Moderate treadmill run worsened static but not dynamic postural stability of healthy individuals

Abstract

Purpose

Running has been demonstrated to be one of the most relevant exercise in altering static postural stability, while limiting attention has been paid to its effects on dynamic postural stability. The aim of the present study was to investigate if 25 min of moderate running on a treadmill altered static and dynamic postural stability in healthy subjects.

Methods

Eight female and six male participants (age 27.7 ± 8.3 years, height 170.9 ± 12.2 cm, weight 63.9 ± 15.6 kg) took part in the study. Before and after the run static postural stability was evaluated on a stabilometric platform (10 trials of 30 s each), while dynamic postural stability was assessed on an instrumented unstable platform (2 trials of 30 s each).

Results

After the treadmill run the area of the confident ellipse (from 67.97 ± 34.56 to 93.08 ± 50.00 mm²), sway path velocity (from 6.92 ± 1.85 to 7.83 ± 2.57 mm/s), sway area velocity (from 6.88 ± 3.27 to 9.54 ± 5.36 mm²/s), and medio-lateral maximal oscillation (from 9.48 ± 2.80 to 11.44 ± 3.64 mm) significantly increased. Stabilogram diffusion analysis showed no statistically significant difference in the diffusion coefficients, both short and long term. No statistically significant differences were reported in all the parameters of the dynamic postural stability test.

Conclusion

The contrasting results of the static and dynamic postural stability tests raise the question of which are the more selective tests to assess the acute effect of physical exercise on postural stability among healthy individuals. The proper interaction of both static and dynamic postural evaluations could represent the next challenge in the postural stability assessment.

http://bit.ly/2swRMnF

Trends in lobular carcinoma in situ management: endocrine therapy use in California and New Jersey

Abstract

Purpose

The diagnosis of lobular carcinoma in situ (LCIS) is a strong risk factor for breast cancer. Endocrine therapy (ET) for LCIS has been shown to decrease breast cancer risk substantially. The purpose of this study was to evaluate the trends of ET use for LCIS in two large geographic locations.

Patients and methods

We identified women, ages 18 through 75, with a microscopic diagnosis of LCIS in California (CA) and New Jersey (NJ) from 2004 to 2014. We evaluated trends in unadjusted ET rates during the study period and used logistic regression to evaluate the relationship between patient, tumor, and treatment characteristics, and ET use.

Results

We identified 3,129 patients in CA and 2,965 patients in NJ. The overall use of ET during the study period was 14%. For the combined sample, women in NJ were significantly less likely to utilize ET then their counterparts in CA (OR 0.77, CI 0.66–0.90, NJ vs. CA). In addition, patients in the later year period (OR 1.27, CI 1.01–1.59, 2012–2014 vs. 2004–2005) and women who received an excisional biopsy (OR 2.35, CI 1.74–3.17), were more likely to utilize ET. Uninsured women were less likely to receive ET (OR 0.61, CI 0.44–0.84, non-insured vs. insured status).

Conclusions

We observed that an increasing proportion of women are using ET for LCIS management, but geographical differences exist. Health insurance status played an important role in the underutilization of ET. Further research is needed to assess patient outcomes given the variations in management of LCIS.

http://bit.ly/2FwmoOS

Occurrence of anti-CCP2 and RF isotypes and their relation to age and disease severity among Sudanese patients with rheumatoid arthritis

Abstract

Objective

Anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2) and rheumatoid factor (RF) in rheumatoid arthritis (RA) has been extensively assessed in industrialized countries. We investigated the diagnostic and prognostic impact of anti-CCP2 and RF isotypes in a Sudanese cross-sectional RA cohort.

Methods

Consecutive RA patients (n = 281) diagnosed according to the 1987 ACR criteria were included 2008–2010. Anti-CCP2 and RF isotypes (IgA, IgM, and IgG) were measured by enzyme immunoassay in 262 patients, with reference intervals aligned to the same diagnostic specificity as for anti-CCP2 (97.6%) using national controls.

Results

IgA RF was the predominant RA-associated autoantibody (56%), followed by IgM RF and anti-CCP2 (both 52%) and IgG RF (49%). In receiver operator characteristic analysis, IgA RF also showed the largest area under the curve. Patients with IgG RF were younger and had 8 years lower median age of disease onset compared to antibody negative patients (p < 0.0001). IgG RF was the only marker associated with a high number of involved joints (p = 0.028), and together with anti-CCP2 were the strongest markers for finger deformities (p = 0.016 and p = 0.012), respectively. No statistical differences were found for disease duration, ESR and Hb levels, and occurrence of erosions/osteopenia for any of the investigated autoantibodies.

Conclusion

Whereas IgA RF showed the best diagnostic performance, IgG RF associated with low age of RA onset, high number of involved joints, and finger deformities. These findings indicate that RA-associated antibodies other than conventional IgM RF and anti-CCP2 might be informative in non-Caucasian RA populations.

http://bit.ly/2FwVR3O

PCR detection of Ehrlichia ruminantium and Babesia bigemina in cattle from Kwara State, Nigeria: unexpected absence of infection

Abstract

Ticks and tick-borne diseases (TBDs) continue to pose an insidious and ever-present threat to livestock and livelihoods across the globe. Two of the most significant TBDs of cattle in Africa are heartwater and babesioisis, caused by Ehrlichia ruminantium and Babesia bigemina respectively. Both pathogens are endemic in Nigeria. However, to date, little data has been published regarding the number of cattle infected. In this study, blood samples were collected from cattle of the Kwara State, north-central Nigeria. Probe-based quantitative PCR (qPCR) and semi-nested PCR were used to investigate the presence of both pathogens, respectively. Our study found all samples (n = 157) to be surprisingly negative for both B. bigemina and E. ruminantium. These results contribute new information on the current burden of these two pathogens in Kwara State and may be helpful in informing more effective targeting of control strategies in Nigeria.

http://bit.ly/2SXtJdi

Infectious diseases physician attitudes to long-term antibiotic use

Abstract

Background In Australia, it is not known how much antibiotic prescribing by infectious diseases physicians is long-term, or how confident they are with the evidence behind this practice. Objective Survey Australian infectious diseases physicians to assess attitudes and prescribing practice prescribing prolonged courses of antibiotics. Methods An online questionnaire was distributed to the mailing group for the Australian Society of Infectious Diseases. Responses were collected from 29th October to 12th November 2015. Results The majority of respondents practiced in Australia as Infectious Diseases physicians, microbiologists, or trainees. 88% had prescribed long-term antibiotics. Heterogeneity was noted in the indications for prescription, including recurrent UTIs, cellulitis or chest infections, prosthetic joint infection and vascular graft infection. Beta-lactams antibiotics were prescribed most frequently. 22% of respondents had prescribed rifampicin/fusidic acid most frequently, while 11% could not identify a single antibiotic that they used most frequently, due to the heterogeneity of indications for prescribing. 95% stated that they would stop long-term antibiotic therapy if appropriate, and 74% were willing to enrol their patients into a randomised control trial looking at stopping long-term therapy. Conclusion Most infectious diseases physicians who responded to the survey prescribe long-term antibiotics, with great heterogeneity in the indications for which these antibiotics are prescribed.

http://bit.ly/2AOxjPZ

The clinical effects of CYP2C19 *2 allele frequency on Palestinian patients receiving clopidogrel after percutaneous coronary intervention

Abstract

BackgroundCYP2C19 loss-of-function polymorphic alleles (*2 and *3) have been documented to impair clopidogrel metabolism, and represent a risk factor for major adverse cardiac events. CYP2C19 polymorphism exhibits marked ethnic heterogeneity. Objective To determine the prevalence of CYP2C19 *2 and *3 alleles in a cohort of Palestinian patients managed with percutaneous coronary intervention and dual antiplatelet therapy, and to determine their role in causing major adverse cardiac events. Setting The blood samples were collected at the European Gaza Hospital, and the molecular techniques performed at the molecular genetics laboratory of the Islamic university of Gaza. Method The frequency of CYP2C19 *2 and *3 alleles was determined in 110 patients managed with percutaneous coronary intervention and clopidogrel. Genotyping was performed by PCR–RFLP. Personal and clinical data was obtained from patient record and 6-month follow-up for major adverse cardiac events. Main outcome measureCYP2C19 genotype, personal and clinical data and incidence of major adverse cardiac events. Results The frequency of CYP2C19 *1, *2 and *3 alleles was 82.3%, 15.5% and 2.3% respectively. Genotyping analysis showed that, 67.3% were homozygotes for CYP2C19 *1, 27.3% were *1/*2, 2.7% with *1/*3 genotype, 1.8% were *2/*3 and 0.9% were *2/*2. These frequencies were consistent with those of Caucasian populations. According to this study the poor metabolizers phenotype frequency was 2.7%, which is in the same range reported in Caucasians (2–5%) and lower than Oriental populations 13–23%. A strong significant relation was found between major adverse cardiac events and carrying the variant allele CYP2C19 *2 (P = 0.001). On the other hand, there was no significant relation between major adverse cardiac events and carrying the variant allele CYP2C19 *3 (P = 0.324). Conclusion The CYP2C19 *2 allele is relatively common in our population, and its associated reduced metabolic activity deserves attention as it leads to an increased incidence of major adverse cardiac events in the follow-up of patients receiving clopidogrel.

http://bit.ly/2SZnbuP

Adsorptive removal of chromium(VI) using spherical resorcinol-formaldehyde beads prepared by inverse suspension polymerization

Abstract

The spherical cross-linked beaded polymers were prepared by condensation of resorcinol and formaldehyde in presence of tri-ethylamine by inverse suspension polymerization technique. The m-cresol, aniline, urea and thiourea were used as co-monomer and polyethylene glycol (PEG 400) was used as porogen. Paraffin oil was used as non-aqueous suspension agent. The polymeric spherical beads were prepared using various types of comonomers exhibiting range of particle size 77.62 to 158.84 μm at 90 °C and 300 rpm for 4 h. The resulting beads were analyzed by elemental analysis, particle size analysis and scanning electron microscope (SEM). The synthesized beads were used for the removal of Cr(VI) from aqueous solutions. A simple and sensitive solid phase extraction procedure was used for the determination of chromium at trace level by spectrophotometric method using 1,5-diphenylcarbazide reagent. The adsorption of Cr(VI) on the resorcinol-formaldehyde beads was monitored by energy-dispersive X-ray spectroscopy (EDX) analysis. The metal adsorption parameters such as contact time, pH, metal ion concentration and adsorbent dose were investigated. For Cr(VI), the maximum adsorption capacity was about 99% at pH 2 for the resorcinol-formaldehyde beads obtained.

http://bit.ly/2VXLbjS

Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone

Abstract

Global oxycodone consumption has increased sharply during the last two decades, and, in 2008, oxycodone consumption surpassed that of morphine. As oxycodone was synthesized in 1916 and taken to clinical use a year later, it has not undergone the same approval process required by today's standards. Most of the basic oxycodone pharmacokinetic (PK) data are from the 1990s and from academic research; however, a lot of additional data have been published over the last 10 years. In this review, we describe the latest oxycodone data on special populations, including neonates, children, pregnant and lactating women, and the elderly. A lot of important drug interaction data have been published that must also be taken into account when oxycodone is used concomitantly with cytochrome P450 (CYP) 3A inducers and inhibitors and/or CYP2D6 inhibitors. In addition, we gathered data on abuse-deterrent oxycodone formulations, and the PK of alternate administration routes, i.e. transmucosal and epidural, are also described.

http://bit.ly/2CuFUaf

The role of vasopressin in olfactory and visual processing

Abstract

Neural vasopressin is a potent modulator of behaviour in vertebrates. It acts at both sensory processing regions and within larger regulatory networks to mediate changes in social recognition, affiliation, aggression, communication and other social behaviours. There are multiple populations of vasopressin neurons within the brain, including groups in olfactory and visual processing regions. Some of these vasopressin neurons, such as those in the main and accessory olfactory bulbs, anterior olfactory nucleus, piriform cortex and retina, were recently identified using an enhanced green fluorescent protein-vasopressin (eGFP-VP) transgenic rat. Based on the interconnectivity of vasopressin-producing and sensitive brain areas and in consideration of autocrine, paracrine and neurohormone-like actions associated with somato-dendritic release, we discuss how these different neuronal populations may interact to impact behaviour.

http://bit.ly/2QUnIfI

Disseminated central nervous system hemangioblastoma in a patient with no clinical or genetic evidence of von Hippel-Lindau disease—a case report and literature review

Abstract

Background

Hemangioblastomas (HB) are benign tumors of the central nervous system (CNS) that can appear sporadic or as part of von Hippel-Lindau (VHL) disease. It is often curable with surgical resection, but upon relapse, the disease exhibits a treatment-refractory course.

Case report

A patient treated for sporadic cerebellar HB relapsed 12 years post-surgery. She developed disseminated disease throughout the CNS, including leptomeningeal manifestations. Repeat surgery and craniospinal radiation therapy were unsuccessful.

Conclusion

This case is in line with previous publications on disseminated non-VHL HB. Available treatment options are inefficient, emphasizing the need for improved understanding of HB biology to identify therapeutic targets.

http://bit.ly/2VVqjcS

Pneumocephalus: a rare and life-threatening, but reversible, complication after penetrating lumbar injury

Abstract

Pneumocephalus, the presence of intracranial air, is a complication especially seen after neurotrauma or brain surgery. When it leads to a pressure gradient, a so-called tension pneumocephalus, it may require emergency surgery. Clinical symptomatology, especially in young children, does not differentiate between a pneumocephalus and a tension pneumocephalus. An additional CT scan is therefore warranted. Here, we report on a rare case of pneumocephalus after penetrating lumbar injury. Additionally, the pathophysiology of pneumocephalus, as well as its recommendations for diagnosis and treatment, will be elucidated.

http://bit.ly/2QUmNf1

Reply to letter to the editor on “Infection prevention bundle reduces surgical site infections following cranial surgery”

http://bit.ly/2W1jTsy

Root/valve preservation in aortic dissection

Abstract

Role of root/valve preservation in aortic dissection and the relative merits and demerits of David procedure over Yacoub's remodeling operation have been discussed in a one on one discussion with Dr. O.P. Yadava, Editor-in-Chief, IJTC and Dr. P Davierwala of Heart Center, Leipzig.

http://bit.ly/2CpSrvK

Bronchial injuries: a tale of differing presentations

Abstract

Bronchial disruptions are uncommon but nevertheless grievous injuries and are usually secondary to major thoracic trauma. Although many are associated with other catastrophic injuries causing early mortality, their presentations can be late and they are often difficult to diagnose. Their management is frequently challenging and the ideal course of treatment is not yet clearly defined. Here, we describe two cases of main bronchial injuries presenting to us with post-traumatic collapse lung, albeit with a widely differing post-trauma course. Both required thoracotomy followed by a resection and anastomosis of the disrupted/stenotic segment. Operative results were good with both cases showing a well-expanded lung and no postoperative anastomotic site stenosis during the period of follow-up. Our experience highlights that patients with major bronchial injuries can have varying presentations. High degree of suspicion is necessary for early diagnosis and prompt surgical treatment. Resection of the stenosed/fibrosed segment followed by anastomosis yields good results.

http://bit.ly/2RvD4fE

Congenitally corrected transposition with isolated atrial septal defect and apicocaval juxtaposition: a hitherto undescribed cardiac cause of central cyanosis

Abstract

In our practice, we have been struck by the presence of central hypoxemia in individuals with congenitally corrected transposition of the great arteries (CCTGA) with an atrial septal defect (ASD) as the only association, despite existence of normal pulmonary artery pressures. This right to left shunting at the atrial level occurs only in those patients where there is additional presence of apicocaval juxtaposition (ACJ). Patients with CCTGA but without ACJ manifest only left to right shunting at the level of the ASD. We present a case series of patients with CCTGA with intact ventricular septum and incomplete atrial septum with a possible basis for this phenomenon.

http://bit.ly/2CpROSU

Efficacy of Off-Label Topical Treatments for the Management of Androgenetic Alopecia: A Review

Abstract

Androgenetic alopecia (AGA) is characterized by non-scarring follicle miniaturization. Despite the success of approved therapies, commonly reported side effects and the need for continual use has led to the investigation of alternative therapies. The aim of this paper is to critically review the success of off-label, topical monotherapies for treatment of AGA in men. A literature search was conducted to obtain randomized, controlled and blinded studies that investigated off-label, topical, monotherapies in male patients. Hair density, hair diameter and hair growth were used to evaluate treatment success. Fourteen off-label topical therapies were investigated among the 16 studies that met inclusion criteria. Nine off-label therapies were reported to produce a significantly greater improvement in hair restoration parameters (e.g. mean change from hair count and hair diameter) as compared to placebo (p < 0.05 for all treatments). In two studies, procyanidin oligomers exhibited greater efficacy over vehicle with response to mean change in hair density (hairs/cm²) (p_s < 0.0001 at Week 24). In conclusion, prostaglandin analogs and polyphenols, such as latanoprost and procyanidin oligomers, can improve hair restoration parameters in male AGA patients, possibly through targeting mechanisms proposed in the etiology of AGA. The current evidence suggests short-term (24 weeks) use may provide benefit for hair loss patients; however, long-term efficacy and safety data are required.

http://bit.ly/2QXLIyA

Potential of climate-smart agriculture in reducing women farmers’ drudgery in high climatic risk areas

Abstract

Climate-smart agriculture (CSA) has a significant role to play in reducing the gender gap in labor burden for women in agriculture. A targeted approach to address this gap can be useful in developing a women-responsive climatic risk management plan focused on reducing their labor burden in agriculture, especially in areas with high climate risks. The paper therefore presents a top–down approach to identify potential labor-saving CSA technologies for women farmers in areas facing high climate risks. It involves mapping women in agriculture, climate risks, and poverty hotspots and entails understanding the role of women in agricultural activities to identify the suitable CSA options for reducing the levels of labor drudgery. The study is illustrated for Nepal where feminization of agriculture is rapidly increasing, a high level of climatic risks persists, and adaptive capacity to climate change is very low, especially among women in agriculture. Results are presented for two hotspot districts, Rupandehi and Chitwan. Household socioeconomic characteristics were found to play a major role in women's labor contribution in different crop production activities. Discussions with farmers provided a list of more than 15 CSA interventions with labor reduction as well as yield-improving potential. Accordingly, considering the local crop, agro-climate, and social conditions, and women's participation in different agricultural activities, CSA technologies and practices such as direct seeded rice (zero tillage and low tillage using machine), green manuring (GM), laser land leveling (LLL), and system of rice intensification (SRI) were found to potentially reduce women's drudgery in agriculture along with improvement in productivity and farm income.

http://bit.ly/2TSXvzN

Soil Nitrogen and Mercury Dynamics Seven Decades After a Fire Disturbance: a Case Study at Acadia National Park

Abstract

Forest soils (mainly soil organic carbon) play an important role in the retention of nitrogen and mercury, and loss of the forest floor during wildfires can stimulate N and Hg losses. In this paper, we investigate long-term impacts of forest fire on soil N and Hg concentrations at Acadia National Park (ANP) in Maine. Acadia National Park experienced a severe fire in 1947. Within the national park, Hadlock Brook watershed was left unburned, whereas most of Cadillac Brook watershed was intensely burned, with substantial loss of the forest floor. Post-fire regeneration in Cadillac was mostly as hardwood species, whereas vegetation in Hadlock remained predominantly softwood. We sampled soils in both watersheds in 2015, approximately 70 years after the fire. The soils were analyzed for total carbon (TC), total nitrogen (TN), total mercury (THg), and methylmercury (MeHg) content. Compared to Hadlock, Cadillac soils had ~ 50% lower TC, ~ 40% lower TN, and ~ 50% lower THg content, reflecting the loss of forest floor 70 years ago. Methylmercury concentrations in Cadillac were approximately 2 times the concentrations in Hadlock, indicating that conditions were more conducive to methylation, potentially due to differences in forest type. Long-term comparisons of stream DOC, NO₃⁻, and THg concentrations between the two watersheds demonstrated that concentrations were significantly lower in Cadillac Brook, reflecting greater retention in Cadillac and a legacy of lower atmospheric deposition in the hardwood as compared to softwood watershed. This study provides insights on the multi-decadal recovery from a stand-replacing disturbance and underscores the persistence of altered soil biogeochemistry.

http://bit.ly/2Mh0Xl7

Patient Perspectives on Adherence with Micronutrient Supplementation After Bariatric Surgery

Abstract

Background

Adherence to post-bariatric surgery nutritional supplements can be poor and is associated with higher micronutrient deficiency rates. There is currently no available study specifically seeking patients' perspectives on the reasons behind poor adherence and how to address it.

Methods

Bariatric surgery patients living in the UK were invited to take part in an anonymous survey on SurveyMonkey®.

Results

A total of 529 patients (92.61% females, mean age 47.7 years) took part. Most of these patients had undergone either a Roux-en-Y gastric bypass (63.0%) or sleeve gastrectomy (24.0%). Most of the patients were in full-time (49.0%, n = 260/529) or part-time (15.7%, n = 83/529) employment. Approximately 54.0% (n = 287/529) of the respondents reported having trouble taking all their supplements. Males were significantly more likely to report complete compliance. The most important reported reason for poor compliance was difficulty in remembering (45.6%), followed by too many tablets (16.4%), side effects (14.3%), cost (11.5%), non-prescribing by GP (10.8%), bad taste (10.1%), and not feeling the need to take (9.4%). Patients suggested reducing the number of tablets (41.8%), patient education (25.7%), GP education (24.0%), reducing the cost (18.5%), and more information from a healthcare provider (12.5%) or a pharmacist (5.2%) to improve the compliance.

Conclusions

This study is the first attempt to understand patient perspectives on poor adherence to post-bariatric surgery nutritional recommendation. Patients offered a number of explanations and also provided with suggestions on how to improve it.

http://bit.ly/2QSsz0P

18F-FDG uptake in the normal appendix in adults: PET/CT evaluation

Abstract

Objective

This study aimed to determine the level of ¹⁸F fluorodeoxyglucose (¹⁸F-FDG) activity in the normal adult appendix using positron emission tomography/computed tomography (PET/CT).

Materials and methods

We performed a retrospective review of PET/CT images using ¹⁸F-FDG in 563 consecutive asymptomatic adult patients without appendiceal pathology. We excluded 257 patients for an undetected or obscured appendix and three patients for appendicitis found on CT imaging. FDG uptake in the appendix was qualitatively and quantitatively assessed. The maximum standardized uptake value (SUV_max) was calculated for quantitative analysis with SUV_max of the normal liver for comparison. A total of 303 patients (200 males, 103 females, mean age of 66 years) were included in this study. Medical charts and histories were evaluated for patients who showed positive FDG accumulation. Pearson's correlations between appendiceal SUV_max and age, body mass index, and blood glucose levels were analyzed.

Results

The mean appendiceal SUV_max was 1.14 (range 0.52–5.12) with an appendix-to-liver SUV_max ratio of 0.34 (range 0.06–1.28). Three patients qualitatively showed a positive FDG accumulation with appendiceal SUV_max greater than 3.00. There were no correlations between appendiceal SUV_max and age, body mass index, or blood glucose levels.

Conclusions

FDG in the normal adult appendix shows a low activity level and is lower compared with normal liver. However, the normal appendix can rarely show high FDG accumulation. In such cases, differentiation from appendiceal pathology solely by PET/CT images would be difficult.

http://bit.ly/2QUceZB

Models for optimally controlling varicella and herpes zoster by varicella vaccination: a comparative study

Abstract

The introduction of mass vaccination against Varicella-Zoster-Virus (VZV) is being delayed in many European countries mainly because of the "fear" of a subsequent boom in natural herpes zoster (HZ) incidence in the first decades after the initiation of vaccination, caused by the expected decline in the protective effect of natural immunity boosting due to reduced virus circulation. Optimal control theory has proven to be a successful tool in understanding ways to curtail the spread of infectious diseases by devising the optimal disease intervention strategies. In this paper, we describe how a reduced 'toy' model can extract the essentials of the dynamics of the VZV transmission and reactivation in case of the study of optimal paths of varicella immunization programs. Results obtained using different optimization approaches are compared with the ones of a more realistic age-structured model. The reduced model shows some unreliable predictions in regards of model time scales about herpes zoster dynamic; nevertheless, it is able to reproduce the main qualitative dynamic of the more realistic model to the different optimization problems, while requiring a minimal number of parameters to be identified.

Graphical abstract

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http://bit.ly/2TVGUeR

A New Era for Surgical Neurotherapeutics

http://bit.ly/2QRG1lG

Stereoelectroencephalography Versus Subdural Electrodes for Localization of the Epileptogenic Zone: What Is the Evidence?

Abstract

Accurate and safe localization of epileptic foci is the crux of surgical therapy for focal epilepsy. As an initial evaluation, patients with drug-resistant epilepsy often undergo evaluation by noninvasive methods to identify the epileptic focus (i.e., the epileptogenic zone (EZ)). When there is incongruence of noninvasive neuroimaging, electroencephalographic, and clinical data, direct intracranial recordings of the brain are often necessary to delineate the EZ and determine the best course of treatment. Stereoelectroencephalography (SEEG) and subdural electrodes (SDEs) are the 2 most common methods for recording directly from the cortex to delineate the EZ. For the past several decades, SEEG and SDEs have been used almost exclusively in specific geographic regions (i.e., France and Italy for stereo-EEG and elsewhere for SDEs) for virtually the same indications. In the last decade, however, stereo-EEG has started to spread from select centers in Europe to many locations worldwide. Nevertheless, it is still not the preferred method for invasive localization of the EZ at many centers that continue to employ SDEs exclusively. Despite the increased dissemination of the SEEG method throughout the globe, important questions remain unanswered. Which method (SEEG or SDEs) is superior for identification of the EZ and does it depend on the etiology of epilepsy? Which technique is safer and does this hold for all patient populations? Should these 2 methods have equivalent indications or be used selectively for different focal epilepsies? In this review, we seek to address these questions using current invasive monitoring literature. Available meta-analyses of observational data suggest that SEEG is safer than SDEs, but it is less clear from available data which method is more accurate at delineating the EZ.

http://bit.ly/2VVUuRg

Simultaneous Determination of Selected Trace Contaminants in Drinking Water Using Solid-Phase Extraction-High Performance Liquid Chromatography-Tandem Mass Spectrometry

Abstract

Accurate determination of emerging contaminants in drinking water constitutes a major environmental challenge for which highly sensitive analytical methods are needed. This work details the development of a novel highly sensitive solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method for simultaneous determination of a diverse panel of widely used trace contaminants, including two pharmaceuticals (fluoxetine and gemfibrozil), three pesticides (3-hydroxycarbofuran, azinphos-methyl, and chlorpyrifos), and two hormones (testosterone and progesterone) in water. The method is highly reproducible and sensitive with detection limits at subnanogram per liter level (0.05–0.5 ng/L). It was used to monitor the occurrence of these contaminants in source and drinking water across 18 drinking water treatment facilities in Missouri, USA in 1 year including cold winter and hot summer seasons. The experiment results indicated that all of the monitored contaminant concentrations are very low, lower than or close to the method detection limits, in the selected water treatment facilities. Pesticide concentrations were slightly elevated in some source waters during hot season, whereas slightly higher pharmaceuticals were observed during cold season. The concentrations of two hormones were lower than the limits of detection in all the water samples. These contaminants were present, if any, at below detection limits in all treated drinking water samples analyzed, suggesting that treatment processes effectively removed the contaminants studied herein.

Graphical Abstract

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http://bit.ly/2FsB55i

Τhe minimum fascia–tumor distance (MFTD) criterion is more feasible for benign tumors than for malignant tumors for the localization of parotid tumors. For benign parotid tumors, US is enough to guide operations.

The Diagnostic Performance of Ultrasonography and Computed Tomography in Differentiating Superficial from Deep Lobe Parotid Tumors

Ping‐Chia Cheng  Chih‐Ming Chang  Chun‐Chieh Huang  Wu‐Chia Lo  Tsung‐Wei Huang  Po‐Wen Cheng Li‐Jen Liao

First published: 12 January 2019 https://doi.org/10.1111/coa.13289

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/coa.13289

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Abstract

Objectives

To validate and compare ultrasound (US) versus computed tomography (CT) criteria in the localization of superficial/deep lobe tumors of the parotid gland.

Design and Setting

This was a retrospective study of diagnostic tests performed from January 2008 to June 2017.

Participants

We included adult patients who were referred for a neck ultrasonography examination due to parotid tumors, and who subsequently underwent parotid surgery.

Main outcome measures

We assessed the location of parotid tumors, comparing the minimum fascia–tumor distance (MFTD) criterion on an US with eight CT criteria. We analyzed receiver operating characteristic (ROC) curves of the MFTD for malignant, benign, and all parotid tumors, and compared the accuracy, sensitivity, and specificity of the optimal MFTD with those of CT anatomical criteria.

Results

A total of 166 parotid tumors were included. The mean (SD) MFTD in superficial lobe tumors was significantly shorter than that of deep lobe tumors (1.2 [0.7] vs 2.8 [1.9] mm, effect size: 1.84; 95% CI, 1.27 to 2.41). The areas under the ROC curve were 0.63 for malignant tumors and 0.88 for benign tumors. The optimal MFTD cut point was 2.4 mm for the 154 benign parotid tumors and the accuracy, sensitivity, and specificity were 90%, 80% and 91%, respectively. For the 136 benign parotid tumors that underwent CT examination, three criteria had an accuracy of over 90% (FNline, tMasseter and Conn's arc), but the sensitivities were all below 50%.

Conclusions

MFTD is more feasible for benign tumors than for malignant tumors for the localization of parotid tumors. For benign parotid tumors, US is enough to guide operations.

Harms of Workplace Inspections for Im/Migrant Sex Workers in In-Call Establishments: Enhanced Barriers to Health Access in a Canadian Setting

Abstract

Given shifting sex work criminalization and enforcement in Canada, this study examined worrying about workplace inspections by authorities amongst indoor sex workers in Vancouver (2014–2017). Data were drawn from a community-based prospective cohort of sex workers (AESHA). Bivariate and multivariable logistic regression were used to investigate factors associated with worry about inspections. 23.9% of participants experienced workplace inspections; 51.6% worried about inspections. In multivariable analyses, worrying about inspections was associated with recent im/migration [adjusted odds ratio (AOR) 3.13; 95% confidence interval (CI) 1.77–5.53], police harassment (AOR 3.49; 95% CI 1.92–6.34), and workplace violence (AOR 1.66, 95% CI 1.09–2.51). In a multivariable confounder model, worry was independently associated with barriers to health access (AOR 1.45, 95% CI 1.06–1.98). Im/migrant indoor workers are disproportionately impacted by concerns about workplace inspections, which was independently linked to enhanced barriers to health access. Current criminalization measures may exacerbate health inequities among im/migrant sex workers.

http://bit.ly/2MelsiB

Effect of axial diffusion on impurity adsorption in a circular tube

Abstract

Circular tubes can be used to irreversibly adsorb impurities from a dilute solution of the impurity and a non-adsorbing fluid. An analysis of the unsteady adsorption process over the region \(z = - \infty \) to \(z = \infty \) can be carried out with or without axial diffusion. The transport equation in the presence of axial diffusion can be solved using the complex Fourier transform and the Green's function method. In the absence of axial diffusion, the transport equation can be solved using the Laplace transform method. Previously reported studies over the region \(0\le z\le L\) limited the contribution of axial diffusion. Analytical solutions of the pertinent differential equations are used to determine the impurity concentration everywhere in the circular tube.

http://bit.ly/2Cmnit8

Endoscopic technique for closure of enterocutaneous fistulas

Abstract

Background and objectives

Endoscopic over the scope clip (OTSC) closure represents a new technique for endoscopic management of enteric bleeding and tissue defects such as anastomotic leaks and enterocutaneous (EC) fistulas. We aim to describe our technical approach for OTSC closure of EC fistulas and convey our outcomes.

Methods and procedures

This retrospective review includes ten patients who underwent OTSC application for EC fistulas by surgical endoscopists at a US tertiary care hospital from July 2015 to October 2017. Demographic data, along with type of defect, location, duration of lesion, success or failure of OTSC, and nutritional status were compiled. The ACS NSQIP surgical risk calculator was used to project the risk of mortality, complications, length of stay, and risk of readmission had our patients undergone surgical correction of their fistula.

Results

Overall success for EC fistula closure was 70%. Acute fistulas were closed with a success rate of 86%. Chronic fistulas were closed successfully in only 33% of cases. Of patients successfully closed, NSQIP-predicted rates of mortality, any complication, and median length of stay were 21.1%, 34.5%, and 9.5 days, respectively. With OTSC, these patients experienced 0 mortalities, 0 complications, and had a median length of stay of 4 days.

Conclusion

OTSC is an effective adjunctive measure to improving rates of successful closure of EC fistulas and compromised anastomosis. OTSC conveys a markedly improved procedural risk profile as compared to standard surgical correction.

http://bit.ly/2RYaN0V

Assessment of Environmental Quality in the Tamaulipas Laguna Madre, Gulf of Mexico, by Integrated Biomarker Response Using the Cross-Barred Venus Clam Chione elevata

Abstract

The entire Laguna Madre of Tamaulipas is a natural protected area and a Priority Marine Region of Mexico. However, its important biodiversity and high levels of endemism are threatened by the discharge of different pollutants and activities related to the ocean oil and gas industry. Therefore, the assessment of these effects on this marine ecosystem is of paramount importance. At present, the joint approach of monitoring chemical contaminant levels, alongside the use of pollution biomarkers as surrogate measures of biological impact within the environment, provides the better evaluation of the environmental hazard. Within this context, a biomonitoring study using native Chione elevata mussels sampled from four locations along the Mexican Laguna Madre coasts evaluated whether a battery of select biomarkers was suitable for identifying and quantifying pollution-induced stress in mussels. The levels of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carboxylesterase (CaE), alkaline phosphatase (ALP), glutathione s-transferase (GST), and the oxygen radical absorbance capacity (ORAC) were measured in soft tissues samples. Different metals (Cd, Pb, Cu, Zn, and Fe) as well as total heavy hydrocarbons were also determined in sediments. Higher concentrations of metals were observed in sampling localities with marine influence possibly related to the presence of marine grass. The concentration of total heavy hydrocarbons, as expected, was higher in sites with intensive fishing activity. The integrated biomarker response (IBR) and the condition index of mussels allowed discriminating between localities of continental and marine influence, revealing that the sampling stations with continental influence were subjected to a greater stress as a result of anthropogenic effects.

http://bit.ly/2RPhhz2

A 5-Year History of Laparoscopic Gastric Band Removals: an Analysis of Complications and Associated Comorbidities

Abstract

Objective

This study was undertaken to examine the factors contributing to laparoscopic adjustable gastric band (LAGB) removals among adults > 18 years of age. We hypothesized that female patients with multiple comorbidities would have increased removals.

Design

This retrospective exploratory study uses internal records and standard statistical methods of analysis.

Results

Eighty-five bands were removed (11.8% males, 88.2% females). The average BMI was 40.7 (n = 83). 2.4% of patients had removals between 0 and 12 months, 18.8% between 39 and 51 months, and 35.3% between 39 and 64 months. 8.2% of treatment times were unknown. The average treatment time was 67.9 months. 48.2% of patients had ≥ 2 comorbidities, GERD (44.2%) being the most frequent. 49.4% of patients reported dysphagia as the reason for band removal. 22.4% of removals were associated with band failures, none with port complications. The reason for band removal was unknown in 21.2% of patients. 67.1%, 32.9%, and 23.5% attended 30-, 60-, and 90-day follow-up appointments, respectively. Weight post-band removal surgery at 30, 60, and 90 days was noted to be − 0.4%., 0.9%, and 0.4%, respectively.

Conclusion

This study supports current literature suggesting LAGB may not be an effective long-term surgical intervention for obesity. Patients with > 2 comorbidities had increased rates of removal. Dysphagia was noted to be the primary reason cited for LAGB removal. Postoperative follow-up was found to be a significant challenge for LAGB removal patients. Further study is warranted to explore if these poor follow-up rates should be considered when risk stratifying LAGB patients for revisional surgery.

http://bit.ly/2Ctv0BB

The effect of pollutant fog deposition on the wood anatomy of subalpine Norway spruce

Abstract

In recent decades, significant changes have been observed in the atmospheric pollutant emissions and deposition in the mountain regions of Central Europe. Pollution caused significant deforestation, but the level of tree damage differs, even between neighboring locations. Thus, it is particularly important to examine the relationships between pollutant deposition rate and detrimental changes in the subalpine spruce ecosystems, and to correlate these with the intensity and structure of pollutant deposition. Radial wood cores were extracted at breast height from trees located in different montane areas: the Sudetes and both Western and Eastern Carpathians. Specific features of the secondary xylem, i.e., annual ring width as well as the width and lumen of early- and latewood tracheids, were analyzed for three decades: before the intense of environmental pollution (1950–1960), during essential stage of the ecological disaster (1980–1990) and after cessation of pollution (2000–2010). The narrowest annual rings and earlywood tracheids were formed in the 1980s in areas where fog was the main source of the pollutant deposition. In conclusion, it has been shown that fog could be an important factor increasing the destructive role of pollutants on wood formation. It was manifested in decreasing of cambial activity resulting in formation of narrower annual rings as well as in reduction in radial dimensions of earlywood tracheids.

http://bit.ly/2ssABDM

Isolation and Expression Analysis of Three Types of α-Carbonic Anhydrases from the Antarctic Alga Chlamydomonas sp. ICE-L under Different Light Stress Treatments

Abstract

Carbonic anhydrases (CAs) are a class of zinc-containing metalloenzymes that can reversibly catalyse the hydration reaction of carbon dioxide. Antarctic algae are the most critical component of the Antarctic ecosystem; algae can enter the carbon cycle food chain by fixing carbon dioxide from the air. In this study, the complete open reading frames (ORFs) of CA1 (GenBank ID KY826431), CA2 (GenBank ID KY826432), and CA3 (GenBank ID KY826433), encoding CAs in the Antarctic ice microalga Chlamydomonas. sp. ICE-L, were successfully cloned using reverse transcription-polymerase chain reaction (RT-PCR). In addition, the expression patterns of CAs under blue light, under UV light, and in the dark were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The CA1, CA2, and CA3 ORFs encode proteins of 376, 430, and 419 amino acids, respectively. Phylogenetic analysis revealed that all amino acid sequences showed high homology with those of C. sp. ICE-L. There are six types of algal CAs; we hypothesised that the CAs studied here are most likely α-CAs. Expression analysis showed that the transcription level of the CAs was influenced by both UV light and blue light. These findings provide additional insight into the molecular mechanisms of CAs and will accelerate the development of CAs for applications in agriculture and environmental governance.

http://bit.ly/2HgHX7w

Production of a Recombinant Dermaseptin Peptide in Nicotiana tabacum Hairy Roots with Enhanced Antimicrobial Activity

Abstract

Expression of strong antimicrobial peptides in plants is of great interest to combat a wide range of plant pathogens. To bring the Dermaseptin B1 (DrsB1) peptide to the intimate contact of the plant pathogens cell wall surface, the DrsB1 encoding sequence was fused to the C-terminal part of the two copies of the chitin-binding domain (CBD) of the Avr4 effector protein and used for Agrobacterium rhizogenes-mediated transformation. The expression of the recombinant protein in the tobacco hairy roots (HRs) was confirmed by molecular analysis. Antimicrobial activity analysis of the recombinant protein purified from the transgenic HRs showed that the (CBD)2-DrsB1 recombinant protein had a significant (p < 0.01) antimicrobial effect on the growth of different fungal and bacterial pathogens. The results of this study indicated that the recombinant protein had a higher antifungal activity against chitin-producing Alternaria alternata than Pythium spp. Scanning electron microscopy images demonstrated that the recombinant protein led to fungal hypha deformation, fragmentation, and agglutination of growing hypha, possibly by dissociating fungal cell wall components. In vitro evidences suggest that the expression of the (CBD)2-DrsB1 recombinant protein in plants by generating transgenic lines is a promising approach to produce disease-resistant plants, resistance to chitin-producing pathogenic fungi.

http://bit.ly/2RP7ysp

Identification of a novel plant RNA virus species of the genus Amalgavirus in the family Amalgaviridae from chia ( Salvia hispanica )

Abstract

Background

Chia (Salvia hispanica) is a flowering plant in the family Lamiaceae, which produces seeds that are a rich source of various nutritional compounds.

Objective

To identify a novel RNA virus potentially associated with chia.

Methods

Transcriptome data obtained from developing chia seeds were assembled into contigs. Sequence contigs containing an open reading frame (ORF) that showed amino acid identities with a viral RNA-dependent RNA polymerase (RdRp) were identified and analyzed.

Results

A genomic sequence of a novel plant RNA virus named Salvia hispanica RNA virus 1 (ShRV1) was identified in a chia seed transcriptome dataset. The ShRV1 genome sequence has two ORFs that showed high sequence identities with ORFs of known members of the genus Amalgavirus in the family Amalgaviridae. Amalgaviridae is a family of positive-sense double-stranded non-segmented RNA viruses that infect plants, fungi, and animals. The ShRV1 genome encodes two proteins: a putative replication factory matrix-like protein from ORF1 and an RdRp from the fused ORF of ORF1 and ORF2 by a + 1 programmed ribosomal frameshifting (PRF) mechanism. A conserved + 1 PRF motif sequence UUU_CGU was found at the ORF1/ORF2 boundary. A comparison of 31 amalgavirus ORF1 + 2 fusion proteins revealed that only three positions were repeatedly used as a + 1 PRF site during amalgavirus evolution.

Conclusion

ShRV1 is a novel virus found to be associated with chia and may be useful for studying the molecular features of amalgaviruses.

http://bit.ly/2FtU937

Evaluation of Antibody Properties and Clinically Relevant Immunogenicity, Anaphylaxis, and Hypersensitivity Reactions in Two Phase III Trials of Tralokinumab in Severe, Uncontrolled Asthma

Abstract

Introduction

Tralokinumab is a monoclonal antibody (mAb) that neutralizes interleukin (IL)-13, a cytokine involved in the pathogenesis of asthma.

Objective

The objectives of this study were to characterize the potential immunogenic properties of tralokinumab and report data for anti-drug antibodies (ADAs) and hypersensitivity reactions from two phase III clinical trials.

Methods

The oligosaccharide structure of tralokinumab, Fab-arm exchange, and ADAs were characterized by standard techniques. Hypersensitivity adverse events (AEs) were evaluated in two pivotal clinical trials of tralokinumab in severe, uncontrolled asthma: STRATOS 1 and 2 (NCT02161757 and NCT02194699).

Results

No galactose-α-1,3-galactose (α-Gal) epitopes were found in the Fab region of tralokinumab and only 4.5% of glycoforms contained α-Gal in the Fc region. Under non-reducing conditions, Fab-arm exchange did not take place with another immunoglobulin (Ig) G₄ mAb (mavrilimumab). However, following glutathione reduction, a hybrid antibody with monovalent bioactivity was detected. ADA incidences (titers) were as follows: STRATOS 1—every 2 weeks (Q2 W) 0.8% (26.0), every 4 weeks (Q4 W) 0.5% (26.0), placebo 0.8% (52.0); STRATOS 2—Q2 W 1.2% (39.0), placebo 0.8% (13.0). Participant-reported hypersensitivity AE rates were as follows: STRATOS 1—Q2 W 25.9%, Q4 W 25.0%, placebo 25.5%; STRATOS 2—Q2 W 13.2%, placebo 9.0%. External evaluation for anaphylaxis by Sampson criteria found no tralokinumab-related severe hypersensitivity or anaphylaxis reactions.

Conclusion

Preclinical assessments suggested a low likelihood of immunogenicity for tralokinumab. In STRATOS 1 and 2, ADA incidence was low, no differences were found between tralokinumab-treated and placebo groups in reporting of hypersensitivity reactions, and there were no Sampson criteria-evaluated anaphylaxis events with tralokinumab treatment. Together, the results suggest that tralokinumab treatment would not increase the risk for severe hypersensitivity or anaphylactic reactions.

http://bit.ly/2MdWdgl

Dispersion of Love waves in size-dependent substrate containing finite piezoelectric and viscoelastic layers

Abstract

The dispersion properties of Love waves are utilized for the fabrication of sensor devices in the different material environments. This study involves the propagation of Love wave in a double-layered structure consisting of two finite layers of viscoelastic and piezoelectric material lying over the semi-infinite size-dependent micropolar substrate. The bottom substrate of the structure is modeled as, the material with microstructural properties. The real and damping dispersion relations are obtained analytically in closed form expression under both the cases of electrically open and short conditions. The coupling constant and characteristic length that describe the effect of the microstructure of the micropolar substrate, are studied graphically on Love wave propagation. The effects of piezoelectric layer are shown by considering two different materials of a piezoelectric layer, i.e., \(PZT-5H\) or \(BaTiO_3\) , along with the internal friction and heterogeneity parameter associated with a viscoelastic layer. The numerical computation and the graphs are given for aluminium-epoxy (substrate), viscoelastic material and \(PZT-5H\) or \(BaTiO_3\) (piezoelectric layer). Some of the particular cases are derived from the study by using different relevant conditions.

http://bit.ly/2TVqWl0

Medical Provider Promotion of Oral Health and Women’s Receipt of Dental Care During Pregnancy

Abstract

Objectives Dental care during pregnancy is important. We examined whether promotion of oral health by medical providers during pregnancy and pregnant women's receipt of dental care improved between 2009 and 2012 in California. Methods We used population-based postpartum survey data collected during 2009 (n = 3105) and 2012 (n = 6810) to compare the prevalence of women's reports that, during pregnancy, (a) their medical providers discussed oral health and/or suggested they see a dentist, and (b) they received dental care. Results Between 2009 and 2012, the proportion of women reporting that their medical providers talked about oral health or referred them to a dentist increased significantly overall (from 36 to 42%, and 21–26%, respectively, p < 0.001). The proportion of women with a dental visit during pregnancy also increased, from 38% in 2009 to 42% in 2012 (p < 0.005). The improvements were largely among women of lower income and education levels, those covered by Medi-Cal, and Latinas. Women whose medical providers promoted oral health care were approximately two times more likely to report having had a dental visit during pregnancy, even after adjusting for several potential confounders. Conclusions for Practice Characteristics of women reporting that their medical providers promoted, and that they received, dental care during pregnancy in 2012 suggests that the increases in promotion and use of oral health care were largely concentrated among Medi-Cal recipients. Further improvement is needed for all populations of pregnant women. Both public and private providers need to incorporate promotion of and referral for dental care into routine prenatal care protocols.

http://bit.ly/2AYNmLd

Optimization of initiator and activator for reactive thermoplastic pultrusion

Abstract

In order to manufacture continuous fiber reinforced thermoplastic composites with high fiber content, reactive thermoplastic pultrusion was developed by using the anionic polymerization of polyamide-6 in this study. Firstly, based on the polymerization time tests, combination of activator of difunctional hexamethylene-1,6-di carbamoylcaprolactam (C20) and initiator of sodium caprolactamate (C10) were chosen as the most suitable formula combination for pultrusion. Effects of concentrations of the activator C20 and the initiator C10 on the polymerization time, molecular weight of polymer and degree of conversion were also investigated. Then, the range of initial polymerization temperature was determined, which had a great influence on the impregnation of dense fiber reinforcement. Comparing with commercial polyamide-6, the anionic polyamide-6 has a higher modulus and lower elongation. Finally, continuous glass fiber reinforced polyamide-6 composites with 50% volume fraction were successfully pultruded. Great interfacial adhesion between fiber and polymer was observed by the scanning electron microscope.

http://bit.ly/2TTlQ8K

Adverse Drug Events Detection in Clinical Notes by Jointly Modeling Entities and Relations Using Neural Networks

Abstract

Background and Significance

Adverse drug events (ADEs) occur in approximately 2–5% of hospitalized patients, often resulting in poor outcomes or even death. Extraction of ADEs from clinical narratives can accelerate and automate pharmacovigilance. Using state-of-the-art deep-learning neural networks to jointly model concept and relation extraction, we achieved the highest integrated task score in the 2018 Medication and Adverse Drug Event (MADE) 1.0 challenge.

Methods

We used a combined bidirectional long short-term memory (BiLSTM) and conditional random fields (CRF) neural network to detect medical entities relevant to ADEs and a combined BiLSTM and attention network to determine relations, including the adverse drug reaction relation between medication and sign or symptom entities. Using these models, we conducted three experiments: (1) separate and sequential modeling of entities and relations; (2) joint modeling where relations between medications and sign or symptoms determined ADE and indication entities; (3) use of information from external resources such as the US FDA's adverse event database as additional input to the second method.

Results

Joint modeling improved the overall task accuracy from 0.62 to 0.65 F measure, and the additional use of external resources improved the accuracy to 0.66 F measure. Given the gold-standard medical entity labels, the joint model plus external resources method achieved F measures of 0.83 for ADE-relevant medical entity detection and 0.87 for relation detection.

Conclusion

It is important to use joint modeling techniques and external resources for effectively detecting ADEs from clinical narratives in electronic health record (EHR) systems. While the extraction of entities and relations individually achieved high accuracy, the integrated task still has room for further improvement.

http://bit.ly/2su8C6T

Safety and Tolerability of Anti-Angiogenic Protein Kinase Inhibitors and Vascular-Disrupting Agents in Cancer: Focus on Gastrointestinal Malignancies

Abstract

Angiogenesis is an essential process for tumor growth and metastasis. Inhibition of angiogenesis as an anticancer strategy has shown significant results in a plethora of tumors. Anti-angiogenic agents are currently part of many standard-of-care options for several metastatic gastrointestinal cancers. Bevacizumab, aflibercept, ramucirumab, and regorafenib have significantly improved both progression-free and overall survival in different lines of treatment in metastatic colorectal cancer. Second-line ramucirumab and third-line apatinib are effective anti-angiogenic treatments for patients with metastatic gastric cancer. Unfortunately, the anti-angiogenic strategy has major practical limitations: resistance inevitably develops through redundancy of signaling pathways and selection for subclonal populations adapted for hypoxic conditions. Anti-angiogenic agents may be more effective in combination therapies, with not only cytotoxics but also other emerging compounds in the anti-angiogenic class or in the separate class of the so-called vascular-disrupting agents. This review aims to provide an overview of the approved and "under development" anti-angiogenic compounds as well as the vascular-disrupting agents in the treatment of gastrointestinal cancers, focusing on the actual body of knowledge available on therapy challenges, pharmacodynamic and pharmacokinetic mechanisms, safety profiles, promising predictive biomarkers, and future perspectives.

http://bit.ly/2MdsNyO

Safety of Novel Targeted Therapies in Oncology

http://bit.ly/2svs6YQ

Detecting Adverse Drug Events with Rapidly Trained Classification Models

Abstract

Introduction

Identifying occurrences of medication side effects and adverse drug events (ADEs) is an important and challenging task because they are frequently only mentioned in clinical narrative and are not formally reported.

Methods

We developed a natural language processing (NLP) system that aims to identify mentions of symptoms and drugs in clinical notes and label the relationship between the mentions as indications or ADEs. The system leverages an existing word embeddings model with induced word clusters for dimensionality reduction. It employs a conditional random field (CRF) model for named entity recognition (NER) and a random forest model for relation extraction (RE).

Results

Final performance of each model was evaluated separately and then combined on a manually annotated evaluation set. The micro-averaged F1 score was 80.9% for NER, 88.1% for RE, and 61.2% for the integrated systems. Outputs from our systems were submitted to the NLP Challenges for Detecting Medication and Adverse Drug Events from Electronic Health Records (MADE 1.0) competition (Yu et al. in http://bio-nlp.org/index.php/projects/39-nlp-challenges, 2018). System performance was evaluated in three tasks (NER, RE, and complete system) with multiple teams submitting output from their systems for each task. Our RE system placed first in Task 2 of the challenge and our integrated system achieved third place in Task 3.

Conclusion

Adding to the growing number of publications that utilize NLP to detect occurrences of ADEs, our study illustrates the benefits of employing innovative feature engineering.

http://bit.ly/2MfXLpU

Safety and Tolerability of Antibody-Drug Conjugates in Cancer

Abstract

Antibody-drug conjugates are monoclonal antibodies attached to biologically active drugs through chemical linkers that deliver and release cytotoxic agents at the tumor site, reducing the likelihood of systemic exposure and therefore toxicity. Currently, there are about 110 ongoing studies implementing antibody-drug conjugates in the treatment of multiple human malignancies. Antibody-drug conjugates carry a feature of the specificity of a monoclonal antibody and the anti-neoplastic potential of a cytotoxin. The first antibody-drug conjugate was approved in 2001, and the field of antibody-drug conjugates has expanded since then with three more antibody-drug conjugates being added to the market. The complex structure of the antibody-drug conjugate poses a challenge in designing a clinically adequate molecule. Antibody-drug conjugates are usually well tolerated with some predictable adverse reactions, as well as new medical issues, that need careful approach. This review provides an outline of the current status of the efficacy and safety of antibody-drug conjugates in malignant diseases.

http://bit.ly/2spRYoS

Safety and Tolerability of Adoptive Cell Therapy in Cancer

Abstract

Adoptive T cell therapy (ACT) is a safe and effective personalized cancer immunotherapy that can comprise naturally occurring ex vivo expanded cells (e.g., tumor-infiltrating lymphocytes [TIL]) or T cells genetically engineered to confer antigen specificity (T-cell receptor [TCR] or chimeric antigen receptor [CAR] engineered T cells) to mediate cancer rejection. In recent years, some ACTs have produced unprecedented breakthrough responses: TIL therapy has moved from melanoma to solid tumor applications, TCR-engineered cells are developed for hematologic and solid tumors, and CAR-engineered T cells have received Food and Drug Administration (FDA) approval for the treatment of patients with certain B-cell malignancies. Although results are encouraging, to date, only a small percentage of patients with advanced malignancies can benefit from ACT. Besides ACT availability and accessibility, treatment-related toxicities represent a major hurdle in the widespread implementation of this therapeutic modality. The large variety of observed toxicities is caused by the infused cell product or as side effects of accompanying medication and chemotherapy. Toxicities can occur immediately or can be delayed. In order to render those highly promising therapeutic approaches safe enough for a wider pool of patients outside of clinical trials, an international consensus for toxicity management needs to be established.

http://bit.ly/2MfXHXc

Safety and Tolerability of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Oncology

Abstract

Tyrosine kinase inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) have dramatically improved progression-free survival in non-small-cell lung cancer (NSCLC) patients who carry sensitizing EGFR-activating mutations and in patients with breast and pancreatic cancers. However, EGFR-TKIs are associated with significant and disabling undesirable effects that adversely impact on quality of life and compliance. These effects include dermatological reactions, diarrhoea, hepatotoxicity, stomatitis, interstitial lung disease and ocular toxicity. Each individual EGFR-TKI is also associated with additional adverse effect(s) that are not shared widely by the other members of its class. Often, these effects call for dose reduction, treatment discontinuation or pharmacotherapeutic intervention. Since dermatological effects result from on-target effects on wild-type EGFR, rash is often considered to be a biomarker of efficacy. A number of studies have reported better outcomes in patients with skin reactions compared with those without. This has led to a 'dosing-to-rash' strategy to optimize therapeutic outcomes. Although conceptually attractive, there is currently insufficient evidence-based support for this strategy. While skin reactions following EGFR-TKIs are believed to result from an effect on wild-type EGFR, their efficacy is related to effects on mutant variants of EGFR. It is noteworthy that newer EGFR-TKIs that spare wild-type EGFR are associated with fewer dermatological reactions. Furthermore, secondary mutations such as T790M in exon 20 often lead to development of resistance to the clinical activity and efficacy of first- and second-generation EGFR-TKIs. This has stimulated the search for later-generations of EGFR-TKIs with the ability to overcome this resistance and with greater target selectivity to spare wild-type EGFR in expectations of an improved safety profile. However, available data reviewed herein indicate that not only are these newer agents associated with the aforementioned adverse effects typical of earlier agents, but they are also susceptible to resistance due to tertiary mutations, most frequently C797S. At least three later-generation EGFR-TKIs, canertinib, naquotinib and rociletinib, have been discontinued from further development in NSCLC following concerns about their safety and risk/benefit.

http://bit.ly/2st7KiH

Development of a Controlled Vocabulary-Based Adverse Drug Reaction Signal Dictionary for Multicenter Electronic Health Record-Based Pharmacovigilance

Abstract

Introduction

Integration of controlled vocabulary-based electronic health record (EHR) observational data is essential for real-time large-scale pharmacovigilance studies.

Objective

To provide a semantically enriched adverse drug reaction (ADR) dictionary for post-market drug safety research and enable multicenter EHR-based extensive ADR signal detection and evaluation, we developed a comprehensive controlled vocabulary-based ADR signal dictionary (CVAD) for pharmacovigilance.

Methods

A CVAD consists of (1) administrative disease classifications of the International Classification of Diseases (ICD) codes mapped to the Medical Dictionary for Regulatory Activities Preferred Terms (MedDRA^® PTs); (2) two teaching hospitals' codes for laboratory test results mapped to the Logical Observation Identifiers Names and Codes (LOINC) terms and MedDRA^® PTs; and (3) clinical narratives and ADRs encoded by standard nursing statements (encoded by the International Classification for Nursing Practice [ICNP]) mapped to the World Health Organization–Adverse Reaction Terminology (WHO-ART) terms and MedDRA^® PTs.

Results

Of the standard 4514 MedDRA^® PTs from Side Effect Resources (SIDER) 4.1, 1130 (25.03%), 942 (20.86%), and 83 (1.83%) terms were systematically mapped to clinical narratives, laboratory test results, and disease classifications, respectively. For the evaluation, we loaded multi-source EHR data. We first performed a clinical expert review of the CVAD clinical relevance and a three-drug ADR case analyses consisting of linezolid-induced thrombocytopenia, warfarin-induced bleeding tendency, and vancomycin-induced acute kidney injury.

Conclusion

CVAD had a high coverage of ADRs and integrated standard controlled vocabularies to the EHR data sources, and researchers can take advantage of these features for EHR observational data-based extensive pharmacovigilance studies to improve sensitivity and specificity.

http://bit.ly/2Mieppe

Safety and Tolerability of Immune Checkpoint Inhibitors (PD-1 and PD-L1) in Cancer

Abstract

Immunotherapy has emerged in recent years and has revolutionized the treatment of cancer. Immune checkpoint inhibitors, including anti-cytotoxic T lymphocyte antigen-4 (CTLA-4), anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) agents, are the first of this new generation of treatments. Anti-PD-1/PD-L1 agents target immune cells by blocking the PD-1/PD-L1 pathway. This blockade leads to enhancement of the immune system and therefore restores the tumour-induced immune deficiency selectively in the tumour microenvironment. However, this shift in the balance of the immune system can also produce adverse effects that involve multiple organs. The pattern of toxicity is different from traditional chemotherapy agents or targeted therapy, and there is still little experience in recognizing and managing it. Thus, toxicity constitutes a real clinical management challenge and any new alteration should be suspected of being treatment-related. The most common toxicities occur in the skin, gastrointestinal tract, lungs, and endocrine, musculoskeletal, renal, nervous, haematologic, cardiovascular and ocular systems. Immune-mediated toxic effects are usually manageable, but toxicities may sometimes lead to treatment withdrawal, and even fulminant and fatal events can occur. Oncologists need to collaborate with internists, clinical immunologists and other specialists to understand, manage and prevent toxicity derived from immunotherapy. This review focuses on the mechanisms of toxicity of anti-PD-1/PD-L1 agents, and its diagnosis and management.

http://bit.ly/2sDtxo9

Safety and Tolerability of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer

Abstract

The chimeric protein echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, resulting from the rearrangement of the homonym genes, is one of the currently targetable oncogenic drivers in anaplastic lymphoma kinase-positive non-small-cell lung cancer. In fact, four first- and second-generation anaplastic lymphoma kinase tyrosine kinase inhibitors, crizotinib (PF-02341066), ceritinib (LDK378), alectinib (CH5424802), and brigatinib (AP26113), are presently approved for clinical practice; however, these agents are not devoid of complications and thus should be administered meaningfully. Furthermore, third-generation inhibitors are currently under development to overcome acquired resistance mechanisms inevitably resulting from treatment with first- and second-generation tyrosine kinase inhibitors. Therefore, this article aims to provide a comprehensive state-of-the-art review about the pharmacodynamics, pharmacokinetics, safety, and tolerability profiles of currently available and promising under-development anaplastic lymphoma kinase tyrosine kinase inhibitors.

http://bit.ly/2Mewbtd

Benefit–Risk Assessment of Plecanatide in the Treatment of Chronic Idiopathic Constipation

Abstract

Plecanatide, a uroguanylin analog, activates the guanylate cyclase C receptors in the epithelial lining of the gastrointestinal tract in a pH-dependent fashion initiating (1) the conversion of intracellular guanosine triphosphate to cyclic guanosine monophosphate, which increases the activity of the cystic fibrosis transmembrane conductance regulator to increase chloride and bicarbonate secretion into the intestinal lumen and (2) a decrease in activity of the sodium-hydrogen ion exchanger. The resulting ionic shifts cause an increase in lumenal fluid to facilitate digestion. Plecanatide has been approved by the FDA for use in chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. This manuscript is a critical assessment of the therapeutic efficacy and potential risks associated with the use of plecanatide in CIC. The discussion of CIC as a clinical and investigative disorder focuses on the importance of this problem as well and the difficulties involved in clinical management and scholarly investigation of a symptom arising from multiple pathophysiologic mechanisms. Clinical data from studies of recently approved drugs for CIC are utilized to construct a platform for thoughtful understanding of CIC and of how changes in investigation guidelines influence the interpretation of study data and guide symptom management. Plecanatide is a safe and effective medication for the management of adults with CIC.

http://bit.ly/2sDtubX

Safety and Tolerability of c-MET Inhibitors in Cancer

Abstract

The role of aberrant hepatocyte growth factor receptor (c-MET, also known as tyrosine-protein kinase MET)/hepatocyte growth factor (HGF) signaling in cancer progression and invasion has been extensively studied. c-MET inhibitors have shown promising pre-clinical and early phase clinical trial anti-tumor activity in several tumor types, although results of most phase III trials with these agents have been negative. To date, two small molecule c-MET inhibitors, cabozantinib and crizotinib, have been approved by regulatory authorities for the treatment of selected cancer types, but several novel c-MET inhibitors (either monoclonal antibodies or small molecule c-MET tyrosine kinase inhibitors) and treatment combinations are currently under study in different settings. Here we provide an overview of the mechanism of action and rationale of c-MET inhibition in cancer, the efficacy of approved agents, and novel promising c-MET-inhibitors and novel targeted combination strategies under development in different cancer types, with a focus on the safety profile and tolerability of these compounds.

http://bit.ly/2MdfNcw

Safety and Tolerability of Histone Deacetylase (HDAC) Inhibitors in Oncology

Abstract

Histone deacetylases (HDACs) are expressed at increased levels in cells of various malignancies, and the use of HDAC inhibitors has improved outcomes in patients with haematological malignancies (T-cell lymphomas and multiple myeloma). However, they are not as effective in solid tumours. Five agents are currently approved under various jurisdictions, namely belinostat, chidamide, panobinostat, romidepsin and vorinostat. These agents are associated with a range of class-related and agent-specific serious and/or severe adverse effects, notably myelosuppression, diarrhoea and various cardiac effects. Among the cardiac effects are ST-T segment abnormalities and QTc interval prolongation of the electrocardiogram, isolated cases of atrial fibrillation and, in rare instances, ventricular tachyarrhythmias. In order to improve the safety profile of this class of drugs as well as their efficacy in indications already approved and to further widen their indications, a large number of newer HDAC inhibitors with varying degrees of HDAC isoform selectivity have been synthesised and are currently under clinical development. Preliminary evidence from early studies suggests that they may be effective in non-haematological cancers as well when used in combination with other therapeutic modalities, but that they too appear to be associated with the above class-related adverse effects. As the database accumulates, the safety, efficacy and risk/benefit of the newer agents and their indications will become clearer.

http://bit.ly/2stOSjy

Safety and Tolerability of Sonic Hedgehog Pathway Inhibitors in Cancer

Abstract

The hedgehog pathway, for which sonic hedgehog (Shh) is the most prominent ligand, is highly conserved and is tightly associated with embryonic development in a number of species. This pathway is also tightly associated with the development of several types of cancer, including basal cell carcinoma (BCC) and acute promyelocytic leukemia, among many others. Inactivating mutations in Patched-1 (PTCH1), leading to ligand-independent pathway activation, are frequent in several cancer types, but most prominent in BCC. This has led to the development of several compounds targeting this pathway as a cancer therapeutic. These compounds target the inducers of this pathway in Smoothened (SMO) and the GLI transcription factors, although targeting SMO has had the most success. Despite the many attempts at targeting this pathway, only three US FDA-approved drugs for cancers affect the Shh pathway. Two of these compounds, vismodegib and sonidegib, target SMO to suppress signaling from either PTCH1 or SMO mutations that lead to upregulation of the pathway. The other approved compound is arsenic trioxide, which can suppress this pathway at the level of the GLI proteins, although current evidence suggests it also has other targets. This review focuses on the safety and tolerability of these clinically approved drugs targeting the Shh pathway, along with a discussion on other Shh pathway inhibitors being developed.

http://bit.ly/2McYXdU

Hard negative mining for correlation filters in visual tracking

Abstract

Visual tracking is a fundamental computer vision task. Recent years have seen many tracking methods based on correlation filters exhibiting excellent performance. The strength of these methods comes from their ability to efficiently learn changes of the target appearance over time. A fundamental drawback to these methods is that the background of the object is not modeled over time which results in suboptimal results. In this paper, we propose a robust tracking method in which a hard negative mining scheme is employed in each frame. In addition, a target verification strategy is developed by introducing a peak signal-to-noise ratio (PSNR) criterion. The proposed method achieves strong tracking results, while maintaining a real-time speed of 30 frame per second without further optimization. Extensive experiments over multiple tracking datasets show the superior accuracy of our tracker compared to state-of-the-art methods including those based on deep learning features.

http://bit.ly/2McvSiI

Combination Therapy with Dipyridamole and Clopidogrel for Secondary Stroke Prevention in Aspirin-Intolerant Patients After Myocardial Infarction: Results of a Nationwide Case-Control Study

Abstract

Background and Purpose

Combination therapy with dipyridamole and clopidogrel in stroke prevention and long-term outcomes in aspirin-intolerant patients with acute myocardial infarction (AMI) and previous stroke are unknown. This nationwide study analyzed the impact of dipyridamole and clopidogrel on secondary stroke prevention and long-term outcomes in aspirin-intolerant stroke patients after AMI.

Methods

This was a nationwide, case-control study involving 186,112 first AMI patients, 78,607 of whom had a previous history of stroke. In the final analysis, we included 4637 patients taking clopidogrel alone and 208 patients using a combination of clopidogrel and dipyridamole.

Results

The 12-year survival rate was not different between clopidogrel and clopidogrel–dipyridamole groups (log-rank p = 0.6247). Furthermore, there were no differences in event-free survival after stroke (log-rank p = 0.6842), gastrointestinal (GI) bleeding (log-rank p = 0.9539), or intracerebral hemorrhage (ICH; log-rank p = 0.6191) between the two groups. Dipyridamole did not contribute significantly to AMI survival (hazard ratio 0.98, 95% confidence interval 0.84–1.15), and did not show benefits in any of the subgroups regardless of sex, age (younger or older than 75 years), comorbidities, percutaneous coronary intervention, or medications.

Conclusion

No differences were observed in the 12-year survival rate between clopidogrel and clopidogrel–dipyridamole groups. The two groups had balanced event-free survival in recurrent stroke, ICH, GI bleeding, and myocardial infarction.

http://bit.ly/2FAWx7u

Effects of Treadmill Cushion and Running Speed on Plantar Force and Metabolic Energy Consumption in Running

Publication date: Available online 16 January 2019

Source: Gait & Posture

Author(s): Huijuan Shi, Hanjun Li, Hui Liu, Bing Yu

Abstract

Background

Repetitive loading with high impact forces are considered as a primary risk factor for overuse injuries. Cushion was proposed in running surface and shoe manufacturing to reduce impact forces and prevent injuries in running.

Research Question

To investigate the effects of treadmill cushion and running speed on plantar force and metabolic energy consumption in treadmill running.

Methods

Plantar force data and metabolic data were collected for 20 men during running at 8 km/hour and 10 km/hour on the treadmill with and without cushion. Two-way ANOVAs with repeated measures were performed to determine the treadmill effects and the speed effects.

Results

Participants significantly decreased peak plantar force on the fore foot at both 10 km/hour (P = 0.001) and 8 km/hour (P = 0.001) and peak plantar force on the mid foot only at 10 km/hour (P = 0.011) while running on the treadmill with cushion compared to the treadmill without cushion. The reduction of peak plantar force at 10 km/hour was greater than that at 8 km/hour while running on the treadmill with cushion. Participants significantly increased metabolic energy consumption while running on the treadmill with cushion compared to the treadmill without cushion (P = 0.007).

Significance

Running on the treadmill with cushion significantly decreased plantar force on the fore foot and mid foot, and increased metabolic energy consumption. Running on the treadmill with cushion may be a useful method in the prevention of fore foot injuries and increasing exercise effects.

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The Impact of Ankle-Foot Orthosis Stiffness on Gait: A Systematic Literature Review

Publication date: Available online 15 January 2019

Source: Gait & Posture

Author(s): Deema Totah, Meghna Menon, Carlie Jones-Hershinow, Kira Barton, Deanna H. Gates

Abstract

Background

Ankle-foot orthoses (AFOs) are commonly prescribed to provide ankle support during walking. Current prescription standards provide general guidelines for choosing between AFO types, but are limited in terms of guiding specific design parameter choices. These design parameters affect the ankle stiffness of the AFO.

Research Question

The aim of this review was to investigate the impact of AFO stiffness on walking mechanics.

Methods

A literature search was conducted using three databases: Pubmed, Engineering Village, and Web of Science.

Results

After applying the exclusion criteria, 25 of 287 potential articles were included. The included papers tested a range of stiffnesses (0.02 to 8.17 Nm/deg), a variety of populations (e.g. healthy, post-stroke, cerebral palsy) and various gait outcome measures. Ankle kinematics were the most frequently reported measures and the most consistently affected by stiffness variations. Greater stiffnesses generally resulted in reduced peak ankle plantarflexion, dorsiflexion, and total range of motion, as well as increased dorsiflexion at initial contact. At the knee, a few studies reported increased flexion at initial contact, and decreased peak extension and increased peak flexion during stance when stiffness was increased. Stiffness did not affect hip kinetics and there was low evidence for its effects on hip or pelvis kinematics, ankle and knee kinetics, muscle activity, metabolic cost, ground reaction forces and spatiotemporal parameters. There were no generalizable trends for the impact of stiffness on user preference.

Significance

AFO stiffness is a key factor influencing ankle movement. Clear reporting standards for AFO design parameters, as well as additional high quality research is needed with larger sample sizes and different clinical populations to ascertain the true effect of stiffness on gait.

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Assessment of Gait Kinetics in Post-Menopausal Women Using Tri-Axial Ankle Accelerometers during Barefoot Walking

Publication date: Available online 15 January 2019

Source: Gait & Posture

Author(s): Stefan I. Madansingh, Dennis H. Murphree, Kenton R. Kaufman, Emma Fortune

Abstract

Background

Physical activity (PA) interventions, designed to increase exposure to ground reaction force (GRF) loading, are a common target for reducing fracture risk in post-menopausal women with low bone mineral density (BMD). Unfortunately, accurate tracking of PA in free-living environments and the ability to translate this activity into evaluations of bone health is currently limited.

Research question

This study evaluates the effectiveness of ankle-worn accelerometers to estimate the vertical GRFs responsible for bone and joint loading in post-menopausal women at a range of self-selected walking speeds during barefoot walking.

Methods

Seventy women, at least one year post-menopause, wore Actigraph GT3X + on both ankles and completed walking trials at self-selected speeds (a minimum of five each at fast, normal and slow walking) along a 30 m instrumented walkway with force plates and photocells to measure loading and estimate gait velocity. Repeated measures correlation analysis and step-wise mixed-effects modelling were performed to evaluate significant predictors of peak vertical GRFs normalized to body weight (pVGRFbw), including peak vertical ankle accelerations (pVacc), walking velocity (Vel_w) and age.

Results

A strong repeated measures correlation of r = 0.75 (95%CI [0.71-0.76] via 1000 bootstrap passes) between pVacc and pVGRFbw was observed. Five-fold cross-validation of mixed-model predictions yielded an average mean-absolute-error (MAE[95%CI]) and root-mean-square-error (RMSE) rate of 5.98%[5.61-6.42] and 0.076 [0.069-0.082] with a more complex model (including Vel_w,) and 6.80%[6.37-7.54] and 0.087BW[0.081-0.095] with a simpler model (including only pVacc), when comparing accelerometer-based estimations of pVGRFbw to force plate measures of pVGRFbw. Age was not found to be significant.

Significance

This study is the first to show a strong relationship among ankle accelerometry data and high fidelity lower-limb loading approximations in post-menopausal women. The results provide the first steps necessary for estimation of real-world limb and joint loading supporting the goals of accurate PA tracking and improved individualization of clinical interventions.

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Effects of Treadmill Cushion and Running Speed on Plantar Force and Metabolic Energy Consumption in Running

Publication date: Available online 16 January 2019

Source: Gait & Posture

Author(s): Huijuan Shi, Hanjun Li, Hui Liu, Bing Yu

Abstract

Background

Repetitive loading with high impact forces are considered as a primary risk factor for overuse injuries. Cushion was proposed in running surface and shoe manufacturing to reduce impact forces and prevent injuries in running.

Research Question

To investigate the effects of treadmill cushion and running speed on plantar force and metabolic energy consumption in treadmill running.

Methods

Plantar force data and metabolic data were collected for 20 men during running at 8 km/hour and 10 km/hour on the treadmill with and without cushion. Two-way ANOVAs with repeated measures were performed to determine the treadmill effects and the speed effects.

Results

Participants significantly decreased peak plantar force on the fore foot at both 10 km/hour (P = 0.001) and 8 km/hour (P = 0.001) and peak plantar force on the mid foot only at 10 km/hour (P = 0.011) while running on the treadmill with cushion compared to the treadmill without cushion. The reduction of peak plantar force at 10 km/hour was greater than that at 8 km/hour while running on the treadmill with cushion. Participants significantly increased metabolic energy consumption while running on the treadmill with cushion compared to the treadmill without cushion (P = 0.007).

Significance

Running on the treadmill with cushion significantly decreased plantar force on the fore foot and mid foot, and increased metabolic energy consumption. Running on the treadmill with cushion may be a useful method in the prevention of fore foot injuries and increasing exercise effects.

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The Impact of Ankle-Foot Orthosis Stiffness on Gait: A Systematic Literature Review

Publication date: Available online 15 January 2019

Source: Gait & Posture

Author(s): Deema Totah, Meghna Menon, Carlie Jones-Hershinow, Kira Barton, Deanna H. Gates

Abstract

Background

Ankle-foot orthoses (AFOs) are commonly prescribed to provide ankle support during walking. Current prescription standards provide general guidelines for choosing between AFO types, but are limited in terms of guiding specific design parameter choices. These design parameters affect the ankle stiffness of the AFO.

Research Question

The aim of this review was to investigate the impact of AFO stiffness on walking mechanics.

Methods

A literature search was conducted using three databases: Pubmed, Engineering Village, and Web of Science.

Results

After applying the exclusion criteria, 25 of 287 potential articles were included. The included papers tested a range of stiffnesses (0.02 to 8.17 Nm/deg), a variety of populations (e.g. healthy, post-stroke, cerebral palsy) and various gait outcome measures. Ankle kinematics were the most frequently reported measures and the most consistently affected by stiffness variations. Greater stiffnesses generally resulted in reduced peak ankle plantarflexion, dorsiflexion, and total range of motion, as well as increased dorsiflexion at initial contact. At the knee, a few studies reported increased flexion at initial contact, and decreased peak extension and increased peak flexion during stance when stiffness was increased. Stiffness did not affect hip kinetics and there was low evidence for its effects on hip or pelvis kinematics, ankle and knee kinetics, muscle activity, metabolic cost, ground reaction forces and spatiotemporal parameters. There were no generalizable trends for the impact of stiffness on user preference.

Significance

AFO stiffness is a key factor influencing ankle movement. Clear reporting standards for AFO design parameters, as well as additional high quality research is needed with larger sample sizes and different clinical populations to ascertain the true effect of stiffness on gait.

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via IFTTT

Assessment of Gait Kinetics in Post-Menopausal Women Using Tri-Axial Ankle Accelerometers during Barefoot Walking

Publication date: Available online 15 January 2019

Source: Gait & Posture

Author(s): Stefan I. Madansingh, Dennis H. Murphree, Kenton R. Kaufman, Emma Fortune

Abstract

Background

Physical activity (PA) interventions, designed to increase exposure to ground reaction force (GRF) loading, are a common target for reducing fracture risk in post-menopausal women with low bone mineral density (BMD). Unfortunately, accurate tracking of PA in free-living environments and the ability to translate this activity into evaluations of bone health is currently limited.

Research question

This study evaluates the effectiveness of ankle-worn accelerometers to estimate the vertical GRFs responsible for bone and joint loading in post-menopausal women at a range of self-selected walking speeds during barefoot walking.

Methods

Seventy women, at least one year post-menopause, wore Actigraph GT3X + on both ankles and completed walking trials at self-selected speeds (a minimum of five each at fast, normal and slow walking) along a 30 m instrumented walkway with force plates and photocells to measure loading and estimate gait velocity. Repeated measures correlation analysis and step-wise mixed-effects modelling were performed to evaluate significant predictors of peak vertical GRFs normalized to body weight (pVGRFbw), including peak vertical ankle accelerations (pVacc), walking velocity (Vel_w) and age.

Results

A strong repeated measures correlation of r = 0.75 (95%CI [0.71-0.76] via 1000 bootstrap passes) between pVacc and pVGRFbw was observed. Five-fold cross-validation of mixed-model predictions yielded an average mean-absolute-error (MAE[95%CI]) and root-mean-square-error (RMSE) rate of 5.98%[5.61-6.42] and 0.076 [0.069-0.082] with a more complex model (including Vel_w,) and 6.80%[6.37-7.54] and 0.087BW[0.081-0.095] with a simpler model (including only pVacc), when comparing accelerometer-based estimations of pVGRFbw to force plate measures of pVGRFbw. Age was not found to be significant.

Significance

This study is the first to show a strong relationship among ankle accelerometry data and high fidelity lower-limb loading approximations in post-menopausal women. The results provide the first steps necessary for estimation of real-world limb and joint loading supporting the goals of accurate PA tracking and improved individualization of clinical interventions.

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via IFTTT

Effects of Treadmill Cushion and Running Speed on Plantar Force and Metabolic Energy Consumption in Running

Publication date: Available online 16 January 2019

Source: Gait & Posture

Author(s): Huijuan Shi, Hanjun Li, Hui Liu, Bing Yu

Abstract

Background

Repetitive loading with high impact forces are considered as a primary risk factor for overuse injuries. Cushion was proposed in running surface and shoe manufacturing to reduce impact forces and prevent injuries in running.

Research Question

To investigate the effects of treadmill cushion and running speed on plantar force and metabolic energy consumption in treadmill running.

Methods

Plantar force data and metabolic data were collected for 20 men during running at 8 km/hour and 10 km/hour on the treadmill with and without cushion. Two-way ANOVAs with repeated measures were performed to determine the treadmill effects and the speed effects.

Results

Participants significantly decreased peak plantar force on the fore foot at both 10 km/hour (P = 0.001) and 8 km/hour (P = 0.001) and peak plantar force on the mid foot only at 10 km/hour (P = 0.011) while running on the treadmill with cushion compared to the treadmill without cushion. The reduction of peak plantar force at 10 km/hour was greater than that at 8 km/hour while running on the treadmill with cushion. Participants significantly increased metabolic energy consumption while running on the treadmill with cushion compared to the treadmill without cushion (P = 0.007).

Significance

Running on the treadmill with cushion significantly decreased plantar force on the fore foot and mid foot, and increased metabolic energy consumption. Running on the treadmill with cushion may be a useful method in the prevention of fore foot injuries and increasing exercise effects.

from #Audiology via ola Kala on Inoreader http://bit.ly/2HdFDhy

The Impact of Ankle-Foot Orthosis Stiffness on Gait: A Systematic Literature Review

Publication date: Available online 15 January 2019

Source: Gait & Posture

Author(s): Deema Totah, Meghna Menon, Carlie Jones-Hershinow, Kira Barton, Deanna H. Gates

Abstract

Background

Ankle-foot orthoses (AFOs) are commonly prescribed to provide ankle support during walking. Current prescription standards provide general guidelines for choosing between AFO types, but are limited in terms of guiding specific design parameter choices. These design parameters affect the ankle stiffness of the AFO.

Research Question

The aim of this review was to investigate the impact of AFO stiffness on walking mechanics.

Methods

A literature search was conducted using three databases: Pubmed, Engineering Village, and Web of Science.

Results

After applying the exclusion criteria, 25 of 287 potential articles were included. The included papers tested a range of stiffnesses (0.02 to 8.17 Nm/deg), a variety of populations (e.g. healthy, post-stroke, cerebral palsy) and various gait outcome measures. Ankle kinematics were the most frequently reported measures and the most consistently affected by stiffness variations. Greater stiffnesses generally resulted in reduced peak ankle plantarflexion, dorsiflexion, and total range of motion, as well as increased dorsiflexion at initial contact. At the knee, a few studies reported increased flexion at initial contact, and decreased peak extension and increased peak flexion during stance when stiffness was increased. Stiffness did not affect hip kinetics and there was low evidence for its effects on hip or pelvis kinematics, ankle and knee kinetics, muscle activity, metabolic cost, ground reaction forces and spatiotemporal parameters. There were no generalizable trends for the impact of stiffness on user preference.

Significance

AFO stiffness is a key factor influencing ankle movement. Clear reporting standards for AFO design parameters, as well as additional high quality research is needed with larger sample sizes and different clinical populations to ascertain the true effect of stiffness on gait.

from #Audiology via ola Kala on Inoreader http://bit.ly/2RTCkjO

Assessment of Gait Kinetics in Post-Menopausal Women Using Tri-Axial Ankle Accelerometers during Barefoot Walking

Publication date: Available online 15 January 2019

Source: Gait & Posture

Author(s): Stefan I. Madansingh, Dennis H. Murphree, Kenton R. Kaufman, Emma Fortune

Abstract

Background

Physical activity (PA) interventions, designed to increase exposure to ground reaction force (GRF) loading, are a common target for reducing fracture risk in post-menopausal women with low bone mineral density (BMD). Unfortunately, accurate tracking of PA in free-living environments and the ability to translate this activity into evaluations of bone health is currently limited.

Research question

This study evaluates the effectiveness of ankle-worn accelerometers to estimate the vertical GRFs responsible for bone and joint loading in post-menopausal women at a range of self-selected walking speeds during barefoot walking.

Methods

Seventy women, at least one year post-menopause, wore Actigraph GT3X + on both ankles and completed walking trials at self-selected speeds (a minimum of five each at fast, normal and slow walking) along a 30 m instrumented walkway with force plates and photocells to measure loading and estimate gait velocity. Repeated measures correlation analysis and step-wise mixed-effects modelling were performed to evaluate significant predictors of peak vertical GRFs normalized to body weight (pVGRFbw), including peak vertical ankle accelerations (pVacc), walking velocity (Vel_w) and age.

Results

A strong repeated measures correlation of r = 0.75 (95%CI [0.71-0.76] via 1000 bootstrap passes) between pVacc and pVGRFbw was observed. Five-fold cross-validation of mixed-model predictions yielded an average mean-absolute-error (MAE[95%CI]) and root-mean-square-error (RMSE) rate of 5.98%[5.61-6.42] and 0.076 [0.069-0.082] with a more complex model (including Vel_w,) and 6.80%[6.37-7.54] and 0.087BW[0.081-0.095] with a simpler model (including only pVacc), when comparing accelerometer-based estimations of pVGRFbw to force plate measures of pVGRFbw. Age was not found to be significant.

Significance

This study is the first to show a strong relationship among ankle accelerometry data and high fidelity lower-limb loading approximations in post-menopausal women. The results provide the first steps necessary for estimation of real-world limb and joint loading supporting the goals of accurate PA tracking and improved individualization of clinical interventions.

from #Audiology via ola Kala on Inoreader http://bit.ly/2HexxVX