Σάββατο 19 Ιανουαρίου 2019

Studying the plasticity in deep convolutional neural networks using random pruning

Abstract

Recently, there has been a lot of work on pruning filters from deep convolutional neural networks (CNNs) with the intention of reducing computations. The key idea is to rank the filters based on a certain criterion (say, \(l_1\) -norm, average percentage of zeros, etc.) and retain only the top-ranked filters. Once the low-scoring filters are pruned away, the remainder of the network is fine-tuned and is shown to give performance comparable to the original unpruned network. In this work, we report experiments which suggest that the comparable performance of the pruned network is not due to the specific criterion chosen, but due to the inherent plasticity of deep neural networks which allows them to recover from the loss of pruned filters once the rest of the filters are fine-tuned. Specifically, we show counterintuitive results wherein by randomly pruning 25–50% filters from deep CNNs we are able to obtain the same performance as obtained by using state-of-the-art pruning methods. We empirically validate our claims by doing an exhaustive evaluation with VGG-16 and ResNet-50. Further, we also evaluate a real-world scenario where a CNN trained on all 1000 ImageNet classes needs to be tested on only a small set of classes at test time (say, only animals). We create a new benchmark dataset from ImageNet to evaluate such class-specific pruning and show that even here a random pruning strategy gives close to state-of-the-art performance. Lastly, unlike existing approaches which mainly focus on the task of image classification, in this work we also report results on object detection and image segmentation. We show that using a simple random pruning strategy, we can achieve significant speedup in object detection (74% improvement in fps) while retaining the same accuracy as that of the original Faster-RCNN model. Similarly, we show that the performance of a pruned segmentation network is actually very similar to that of the original unpruned SegNet.



http://bit.ly/2MmG3kL

A Rare Hearing Loss Renders a Woman Unable to Hear Male Voices

​A woman in China has been reported to have sudden-onset reverse-slope hearing loss (RSHL), a rare condition that results in an inability to hear low-pitch noises. Prior to the onset, this woman suffered from nausea and tinnitus the night before. When she woke up the following morning, she could not hear her boyfriend or the male patients at the hospital where she sought help. Her case drew attention to RSHL, also known as low-frequency hearing loss and considered a subtype of idiopathic sudden hearing loss. It shows up as the reverse of the ski-slope hearing loss on an audiogram, and affects 3,000 people in the United States and Canada combined (http://bit.ly/2sCWPTv). Genetic conditions, including Wolfram syndrome, Mondini dysplasia, and inheritance through a dominant gene, have all been identified as sources of RSHL. Diseases that affect hair cells such as sudden hearing loss, Ménière's disease, and viral infection and changes in the pressure of the endolymph have also been linked to RSHL. Research found that this type of hearing loss has a better prognosis than other types of hearing loss, and the 10-year prognosis can be predicted by the clinical course (initial therapy and hearing fluctuations) during the first year after onset (Otolaryngol Head Neck Surg 2010;142[4]:565).

Published: 1/18/2019 11:27:00 AM


from #Audiology via ola Kala on Inoreader http://bit.ly/2R0fwu4
via IFTTT

A Rare Hearing Loss Renders a Woman Unable to Hear Male Voices

​A woman in China has been reported to have sudden-onset reverse-slope hearing loss (RSHL), a rare condition that results in an inability to hear low-pitch noises. Prior to the onset, this woman suffered from nausea and tinnitus the night before. When she woke up the following morning, she could not hear her boyfriend or the male patients at the hospital where she sought help. Her case drew attention to RSHL, also known as low-frequency hearing loss and considered a subtype of idiopathic sudden hearing loss. It shows up as the reverse of the ski-slope hearing loss on an audiogram, and affects 3,000 people in the United States and Canada combined (http://bit.ly/2sCWPTv). Genetic conditions, including Wolfram syndrome, Mondini dysplasia, and inheritance through a dominant gene, have all been identified as sources of RSHL. Diseases that affect hair cells such as sudden hearing loss, Ménière's disease, and viral infection and changes in the pressure of the endolymph have also been linked to RSHL. Research found that this type of hearing loss has a better prognosis than other types of hearing loss, and the 10-year prognosis can be predicted by the clinical course (initial therapy and hearing fluctuations) during the first year after onset (Otolaryngol Head Neck Surg 2010;142[4]:565).

Published: 1/18/2019 11:27:00 AM


from #Audiology via ola Kala on Inoreader http://bit.ly/2R0fwu4

A Rare Hearing Loss Renders a Woman Unable to Hear Male Voices

​A woman in China has been reported to have sudden-onset reverse-slope hearing loss (RSHL), a rare condition that results in an inability to hear low-pitch noises. Prior to the onset, this woman suffered from nausea and tinnitus the night before. When she woke up the following morning, she could not hear her boyfriend or the male patients at the hospital where she sought help. Her case drew attention to RSHL, also known as low-frequency hearing loss and considered a subtype of idiopathic sudden hearing loss. It shows up as the reverse of the ski-slope hearing loss on an audiogram, and affects 3,000 people in the United States and Canada combined (http://bit.ly/2sCWPTv). Genetic conditions, including Wolfram syndrome, Mondini dysplasia, and inheritance through a dominant gene, have all been identified as sources of RSHL. Diseases that affect hair cells such as sudden hearing loss, Ménière's disease, and viral infection and changes in the pressure of the endolymph have also been linked to RSHL. Research found that this type of hearing loss has a better prognosis than other types of hearing loss, and the 10-year prognosis can be predicted by the clinical course (initial therapy and hearing fluctuations) during the first year after onset (Otolaryngol Head Neck Surg 2010;142[4]:565).

Published: 1/18/2019 11:27:00 AM


from #Audiology via ola Kala on Inoreader http://bit.ly/2R0fwu4
via IFTTT

Erythropoietin protects the subventricular zone and inhibits reactive astrogliosis in kaolin-induced hydrocephalic rats

Abstract

Purpose

To elucidate the potential role of erythropoietin (EPO) as a neuroprotective agent against reactive astrogliosis and reducing the thinning rate of subventricular zone (SVZ) in kaolin-induced hydrocephalic rats.

Method

Thirty-six ten-week-old Sprague-Dawley rats were used in this study. Hydrocephalus was induced with 20% kaolin suspension injected into the cistern of thirty rats and leaving the six rats as normal group. The hydrocephalic rats were randomly divided into hydrocephalic and treatment group. The treatment group received daily dose of recombinant human erythropoietin (rhEPO) from day 7 to day 21 after induction. The animals were sacrificed at 7 (only for hydrocephalic group) and 14 or 21 (for both groups) days after induction. Brain was removed and was prepared for histological analysis by hematoxylin and eosin staining as well as immunohistochemistry for 4-HNE, GFAP, Iba-1, and Ki-67.

Results

Histopathological analysis showed that animals treated with rhEPO had a reduced astrocyte reactivity displayed by lower GFAP expression. Hydrocephalic rats received rhEPO also displayed reduced microglial activation shown by lower Iba-1 protein expression. Exogenous rhEPO exerted its protective action in reducing astrogliosis by inhibiting lipid peroxidation that was documented in this study as lower expression of 4-HNE than non-treated group. The SVZ thickness was progressively declining in hydrocephalus group, while the progression rate could be reduced by rhEPO.

Conclusion

Erythropoietin has a potential use for inhibiting lipid peroxidation, and reactive astrogliosis in hydrocephalic animal model. The reduced thinning rate of SVZ demonstrated that EPO also had effect in reducing the hydrocephalus progressivity. Further research is warranted to explore its efficacy and safety to use in clinical setting.



http://bit.ly/2RzHySB

Lack of association of cranial lacunae with intracranial hypertension in children with Crouzon syndrome and Apert syndrome: a 3D morphometric quantitative analysis

Abstract

Purpose

Cranial lacunae (foci of attenuated calvarial bone) are CT equivalents of "copper beating" seen on plain skull radiographs in children with craniosynostosis. The qualitative presence of copper beating has not been found to be useful for the diagnosis of intracranial hypertension (IH) in these patients. 3D morphometric analysis (3DMA) allows a more systematic and quantitative assessment of calvarial attenuation. We used 3DMA to examine the relationship between cranial lacunae and IH in children with Crouzon and Apert syndromic craniosynostosis.

Methods

Patients were divided into IH and non-IH groups defined on an intention-to-treat basis. Pre-operative CT scans were converted into 3D skull models and processed to quantify lacunae as a percentage of calvarium surface area (LCP). This was done on individual bone and whole skull basis.

Results

Eighteen consecutive children with Crouzon's syndrome and 17 with Apert syndrome were identified. Median age at CT scan was 135 days (range 6–1778). Of the 35 children, 21 required surgery for IH at median age of 364 days (range 38–1710). Of these 21 children, 14 had lacunae with mean LCP of 3% (0–28%). Of the 14 non-IH children, 8 had lacunae with mean LCP of 2% (0–8%). LCP was not significantly different between IH and non-IH groups. Parietal bones were most likely to show lacunae (IH 14/21, non-IH 9/14), followed by occipital (IH 8/21, non-IH 3/14), and frontal (IH 6/21, non-IH 2/14).

Conclusion

Results suggest that cranial lacunae, measured using quantitative 3DMA, do not correlate with IH, in agreement with evidence from qualitative plain skull radiograph studies.



http://bit.ly/2CA12vS

Cerebellar mutism after posterior fossa tumor resection in children: a multicenter international retrospective study to determine possible modifiable factors

Abstract

Purpose

A preliminary survey of pediatric neurosurgeons working at different centers around the world suggested differences in clinical practice resulting in variation in the risk of pediatric cerebellar mutism (CM) and cerebellar mutism syndrome (CMS) after posterior fossa (PF) tumor resection. The purposes of this study were (1) to determine the incidence and severity of CM and CMS after midline PF tumor resection in children treated at these centers and (2) to identify potentially modifiable factors related to surgical management (rather than tumor biology) that correlate with the incidence of CM/CMS.

Methods

Attending pediatric neurosurgeons at British Columbia's Children's Hospital (BCCH) and neurosurgeons who completed a pediatric neurosurgery fellowship at BCCH were invited to provide data from the center where they currently practiced. Children aged from birth to less than 18 years who underwent initial midline PF tumor resection within a contemporary, center-selected 2-year period were included. Data was obtained by retrospective chart and imaging review. Modifiable surgical factors that were assessed included pre-resection surgical hydrocephalus treatment, surgical positioning, ultrasonic aspirator use, intraoperative external ventricular drain (EVD) use, surgical access route to the tumor, and extent of resection. CM was defined as decreased or absent speech output postoperatively and CMS as CM plus new or worsened irritability.

Results

There were 263 patients from 11 centers in 6 countries (Canada, Germany, the Netherlands, India, Indonesia, and the USA). Median age at surgery was 6 years (range < 1 to 17 years). The overall incidence of postoperative CM was 23.5% (range 14.7–47.6% for centers with data on ≥ 20 patients). The overall incidence of CMS was 6.5% (range 0–10.3% for centers contributing data on ≥ 20 patients). A multivariate logistic regression on the full data set showed no significant association between pre-resection surgical hydrocephalus treatment, prone position, ultrasonic aspirator use, EVD use, telovelar approach, complete or near total resection, or treating center and either postoperative CM or CMS.

Conclusions

While there was variation in surgical management of midline PF tumors among centers participating in this study, the factors in management that were examined did not predict postoperative CM or CMS.



http://bit.ly/2RzKApM

Contralateral facial nerve paresis subsequent to posterior fossa meningioma surgery in a child: case report

Abstract

Introduction

Meningiomas are relatively uncommon neoplasms in the pediatric population and posterior fossa is a very rare location for these tumors. Only a few cases of contralateral cranial nerve deficits have been reported but no cases of pediatric meningioma with contralateral facial nerve paresis have been documented in literature.

Cerebellopontine Angle Meningioma Who Case report

We present a 4 year old girl with found postoperative contralateral facial nerve paresis.

Discussion

The possible pathogenesis and literature review concerning this complication are discussed. The mechanisms leading to this complication could be distortion of brainstem, traction during resection and subsequent compression of brainstem against the contralateral petrous or tentorium.



http://bit.ly/2CuY3oA

Apert syndrome without craniosynostosis

Abstract

Background

Apert syndrome is a rare form of syndromic craniosynostosis, also known as acrocephalosyndactyly, which is a disorder characterized by a unique set of craniofacial, hand, and foot abnormalities. Diagnosis is made through a genetic analysis, where the mutation of FGFR2, Ser252Trp, and Pro253Arg confirms the diagnosis.

Case presentation

Although craniosynostosis is the most common characteristic in clinical presentation, we present an atypical case of a one-and-a-half-year-old girl with Apert syndrome confirmed by genetic testing but without craniosynostosis.



http://bit.ly/2RHj3Db

Effects of Reverberation on the Relation Between Compression Speed and Working Memory for Speech-in-Noise Perception

Objectives: Previous study has suggested that when listening in modulated noise, individuals benefit from different wide dynamic range compression (WDRC) speeds depending on their working memory ability. Reverberation reduces the modulation depth of signals and may impact the relation between WDRC speed and working memory. The purpose of this study was to examine this relation across a range of reverberant conditions. Design: Twenty-eight older listeners with mild-to-moderate sensorineural hearing impairment were recruited in the present study. Individual working memory was measured using a Reading Span test. Sentences were combined with noise at two signal to noise ratios (2 and 5 dB SNR), and reverberation was simulated at a range of reverberation times (0.00, 0.75, 1.50, and 3.00 sec). Speech intelligibility was measured in listeners when listening to the sentences processed with simulated fast-acting and slow-acting WDRC conditions. Results: There was a significant relation between WDRC speed and working memory with minimal or no reverberation. Consistent with previous research, this relation was such that individuals with high working memory had higher speech intelligibility with fast-acting WDRC, and individuals with low working memory performed better with slow-acting WDRC. However, at longer reverberation times, there was no relation between WDRC speed and working memory. Conclusions: Consistent with previous studies, results suggest that there is an advantage of tailoring WDRC speed based on an individual’s working memory under anechoic conditions. However, the present results further suggest that there may not be such a benefit in reverberant listening environments due to reduction in signal modulation. ACKNOWLEDGMENTS: The authors thank Tim Schoof for help with calibration, Laura Mathews and Melissa Sherman for assistance with participant recruitment, and Thomas Lunner for providing the Reading Span test. This research was funded by the National Institutes of Health Grants F31 DC015373 to P.R., R01 DC008168 to P.Z., and R01 DC006014 to P.S. The work presented in this manuscript represents an original contribution that has not been previously published or submitted for publication elsewhere. All authors contributed equally to this study. P.R. and P.S. collected and analyzed data and wrote the main article; P.Z. contributed to the study design and manuscript preparation. All authors discussed the results and implications and commented on the manuscript at all stages. The authors have no conflicts of interest to disclose. Address for correspondence: Pamela Souza, Department of Communication Sciences and Disorders, Northwestern University, 2240 E Campus Drive, Evanston, IL 60208, USA. E-mail: p-souza@northwestern.edu Received May 31, 2018; accepted November 26, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader http://bit.ly/2Hn0LC6
via IFTTT

Use of Direct-Connect for Remote Speech-Perception Testing in Cochlear Implants

Objectives: Previous research has demonstrated the feasibility of programming cochlear implants (CIs) via telepractice. To effectively use telepractice in a comprehensive manner, all components of a clinical CI visit should be validated using remote technology. Speech-perception testing is important for monitoring outcomes with a CI, but it has yet to be validated for remote service delivery. The objective of this study, therefore, was to evaluate the feasibility of using direct audio input (DAI) as an alternative to traditional sound-booth speech-perception testing for serving people with CIs via telepractice. Specifically, our goal was to determine whether there was a significant difference in speech-perception scores between the remote DAI (telepractice) and the traditional (in-person) sound-booth conditions. Design: This study used a prospective, split-half-design to test speech perception in the remote DAI and in-person sound-booth conditions. Thirty-two adults and older children with CIs participated; all had a minimum of 6 months of experience with their device. Speech-perception tests included the consonant–nucleus–consonant (CNC) words, Hearing-in-Noise test (HINT) sentences, and Arizona Biomedical Institute at Arizona State University (AzBio) sentences. All three tests were administered at levels of 50 and 60 dBA in quiet. Sentence stimuli were also presented in 4-talker babble at signal to noise ratios (SNRs) of +10 and +5 dB for both the 50- and 60-dBA presentation levels. A repeated-measures analysis of variance was used to assess the effects of location (remote, in person), stimulus level (50, 60 dBA), and SNR (if applicable; quiet, +10, +5 dB) on each outcome measure (CNC, HINT, AzBio). Results: The results showed no significant effect of location for any of the tests administered (p > 0.1). There was no significant effect of presentation level for CNC words or phonemes (p > 0.2). There was, however, a significant effect of level (p

from #Audiology via ola Kala on Inoreader http://bit.ly/2RU7WGe
via IFTTT

Correlates of Hearing Aid Use in UK Adults: Self-Reported Hearing Difficulties, Social Participation, Living Situation, Health, and Demographics

Objectives: Hearing impairment is ranked fifth globally for years lived with disability, yet hearing aid use is low among individuals with a hearing impairment. Identifying correlates of hearing aid use would be helpful in developing interventions to promote use. To date, however, no studies have investigated a wide range of variables, this has limited intervention development. The aim of the present study was to identify correlates of hearing aid use in adults in the United Kingdom with a hearing impairment. To address limitations in previous studies, we used a cross-sectional analysis to model a wide range of potential correlates simultaneously to provide better evidence to aid intervention development. Design: The research was conducted using the UK Biobank Resource. A cross-sectional analysis of hearing aid use was conducted on 18,730 participants aged 40 to 69 years old with poor hearing, based on performance on the Digit Triplet test. Results: Nine percent of adults with poor hearing in the cross-sectional sample reported using a hearing aid. The strongest correlate of hearing aid use was self-reported hearing difficulties (odds ratio [OR] = 110.69 [95% confidence interval {CI} = 65.12 to 188.16]). Individuals who were older were more likely to use a hearing aid: for each additional year of age, individuals were 5% more likely to use a hearing aid (95% CI = 1.04 to 1.06). People with tinnitus (OR = 1.43 [95% CI = 1.26 to 1.63]) and people with a chronic illness (OR = 1.97 [95% CI = 1.71 to 2.28]) were more likely to use a hearing aid. Those who reported an ethnic minority background (OR = 0.53 [95% CI = 0.39 to 0.72]) and those who lived alone (OR = 0.80 [95% CI = 0.68 to 0.94]) were less likely to use a hearing aid. Conclusions: Interventions to promote hearing aid use need to focus on addressing reasons for the perception of hearing difficulties and how to promote hearing aid use. Interventions to promote hearing aid use may need to target demographic groups that are particularly unlikely to use hearing aids, including younger adults, those who live alone and those from ethnic minority backgrounds. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal’s Web site (www.ear-hearing.com). ACKNOWLEDGMENTS: The research was funded by a doctoral studentship supported by Sonova. The study was supported by the NIHR Manchester Biomedical Research Centre and the NIHR Greater Manchester Patient Safety Translational Research Centre. C.S.S and P.D.D. analyzed the data; C.S.S. wrote the article; P.D.D., C.J.A., K.J.M., and G.S. provided critical revision. All authors discussed the results and implications and commented on the manuscript at all stages. This research was conducted using the UK Biobank Resource. The authors have no conflicts of interest to disclose. Address for correspondence: Chelsea S. Sawyer, University of Manchester, HCD office, Ellen Wilkinson Building, Oxford Road, Manchester M13 9PL. E-mail: chelsea.sawyer@manchester.ac.uk Received February 28, 2018; accepted November 19, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader http://bit.ly/2HmIAN4
via IFTTT

Effects of Reverberation on the Relation Between Compression Speed and Working Memory for Speech-in-Noise Perception

Objectives: Previous study has suggested that when listening in modulated noise, individuals benefit from different wide dynamic range compression (WDRC) speeds depending on their working memory ability. Reverberation reduces the modulation depth of signals and may impact the relation between WDRC speed and working memory. The purpose of this study was to examine this relation across a range of reverberant conditions. Design: Twenty-eight older listeners with mild-to-moderate sensorineural hearing impairment were recruited in the present study. Individual working memory was measured using a Reading Span test. Sentences were combined with noise at two signal to noise ratios (2 and 5 dB SNR), and reverberation was simulated at a range of reverberation times (0.00, 0.75, 1.50, and 3.00 sec). Speech intelligibility was measured in listeners when listening to the sentences processed with simulated fast-acting and slow-acting WDRC conditions. Results: There was a significant relation between WDRC speed and working memory with minimal or no reverberation. Consistent with previous research, this relation was such that individuals with high working memory had higher speech intelligibility with fast-acting WDRC, and individuals with low working memory performed better with slow-acting WDRC. However, at longer reverberation times, there was no relation between WDRC speed and working memory. Conclusions: Consistent with previous studies, results suggest that there is an advantage of tailoring WDRC speed based on an individual’s working memory under anechoic conditions. However, the present results further suggest that there may not be such a benefit in reverberant listening environments due to reduction in signal modulation. ACKNOWLEDGMENTS: The authors thank Tim Schoof for help with calibration, Laura Mathews and Melissa Sherman for assistance with participant recruitment, and Thomas Lunner for providing the Reading Span test. This research was funded by the National Institutes of Health Grants F31 DC015373 to P.R., R01 DC008168 to P.Z., and R01 DC006014 to P.S. The work presented in this manuscript represents an original contribution that has not been previously published or submitted for publication elsewhere. All authors contributed equally to this study. P.R. and P.S. collected and analyzed data and wrote the main article; P.Z. contributed to the study design and manuscript preparation. All authors discussed the results and implications and commented on the manuscript at all stages. The authors have no conflicts of interest to disclose. Address for correspondence: Pamela Souza, Department of Communication Sciences and Disorders, Northwestern University, 2240 E Campus Drive, Evanston, IL 60208, USA. E-mail: p-souza@northwestern.edu Received May 31, 2018; accepted November 26, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader http://bit.ly/2Hn0LC6
via IFTTT

Use of Direct-Connect for Remote Speech-Perception Testing in Cochlear Implants

Objectives: Previous research has demonstrated the feasibility of programming cochlear implants (CIs) via telepractice. To effectively use telepractice in a comprehensive manner, all components of a clinical CI visit should be validated using remote technology. Speech-perception testing is important for monitoring outcomes with a CI, but it has yet to be validated for remote service delivery. The objective of this study, therefore, was to evaluate the feasibility of using direct audio input (DAI) as an alternative to traditional sound-booth speech-perception testing for serving people with CIs via telepractice. Specifically, our goal was to determine whether there was a significant difference in speech-perception scores between the remote DAI (telepractice) and the traditional (in-person) sound-booth conditions. Design: This study used a prospective, split-half-design to test speech perception in the remote DAI and in-person sound-booth conditions. Thirty-two adults and older children with CIs participated; all had a minimum of 6 months of experience with their device. Speech-perception tests included the consonant–nucleus–consonant (CNC) words, Hearing-in-Noise test (HINT) sentences, and Arizona Biomedical Institute at Arizona State University (AzBio) sentences. All three tests were administered at levels of 50 and 60 dBA in quiet. Sentence stimuli were also presented in 4-talker babble at signal to noise ratios (SNRs) of +10 and +5 dB for both the 50- and 60-dBA presentation levels. A repeated-measures analysis of variance was used to assess the effects of location (remote, in person), stimulus level (50, 60 dBA), and SNR (if applicable; quiet, +10, +5 dB) on each outcome measure (CNC, HINT, AzBio). Results: The results showed no significant effect of location for any of the tests administered (p > 0.1). There was no significant effect of presentation level for CNC words or phonemes (p > 0.2). There was, however, a significant effect of level (p

from #Audiology via ola Kala on Inoreader http://bit.ly/2RU7WGe
via IFTTT

Correlates of Hearing Aid Use in UK Adults: Self-Reported Hearing Difficulties, Social Participation, Living Situation, Health, and Demographics

Objectives: Hearing impairment is ranked fifth globally for years lived with disability, yet hearing aid use is low among individuals with a hearing impairment. Identifying correlates of hearing aid use would be helpful in developing interventions to promote use. To date, however, no studies have investigated a wide range of variables, this has limited intervention development. The aim of the present study was to identify correlates of hearing aid use in adults in the United Kingdom with a hearing impairment. To address limitations in previous studies, we used a cross-sectional analysis to model a wide range of potential correlates simultaneously to provide better evidence to aid intervention development. Design: The research was conducted using the UK Biobank Resource. A cross-sectional analysis of hearing aid use was conducted on 18,730 participants aged 40 to 69 years old with poor hearing, based on performance on the Digit Triplet test. Results: Nine percent of adults with poor hearing in the cross-sectional sample reported using a hearing aid. The strongest correlate of hearing aid use was self-reported hearing difficulties (odds ratio [OR] = 110.69 [95% confidence interval {CI} = 65.12 to 188.16]). Individuals who were older were more likely to use a hearing aid: for each additional year of age, individuals were 5% more likely to use a hearing aid (95% CI = 1.04 to 1.06). People with tinnitus (OR = 1.43 [95% CI = 1.26 to 1.63]) and people with a chronic illness (OR = 1.97 [95% CI = 1.71 to 2.28]) were more likely to use a hearing aid. Those who reported an ethnic minority background (OR = 0.53 [95% CI = 0.39 to 0.72]) and those who lived alone (OR = 0.80 [95% CI = 0.68 to 0.94]) were less likely to use a hearing aid. Conclusions: Interventions to promote hearing aid use need to focus on addressing reasons for the perception of hearing difficulties and how to promote hearing aid use. Interventions to promote hearing aid use may need to target demographic groups that are particularly unlikely to use hearing aids, including younger adults, those who live alone and those from ethnic minority backgrounds. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal’s Web site (www.ear-hearing.com). ACKNOWLEDGMENTS: The research was funded by a doctoral studentship supported by Sonova. The study was supported by the NIHR Manchester Biomedical Research Centre and the NIHR Greater Manchester Patient Safety Translational Research Centre. C.S.S and P.D.D. analyzed the data; C.S.S. wrote the article; P.D.D., C.J.A., K.J.M., and G.S. provided critical revision. All authors discussed the results and implications and commented on the manuscript at all stages. This research was conducted using the UK Biobank Resource. The authors have no conflicts of interest to disclose. Address for correspondence: Chelsea S. Sawyer, University of Manchester, HCD office, Ellen Wilkinson Building, Oxford Road, Manchester M13 9PL. E-mail: chelsea.sawyer@manchester.ac.uk Received February 28, 2018; accepted November 19, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader http://bit.ly/2HmIAN4
via IFTTT

Effects of Reverberation on the Relation Between Compression Speed and Working Memory for Speech-in-Noise Perception

Objectives: Previous study has suggested that when listening in modulated noise, individuals benefit from different wide dynamic range compression (WDRC) speeds depending on their working memory ability. Reverberation reduces the modulation depth of signals and may impact the relation between WDRC speed and working memory. The purpose of this study was to examine this relation across a range of reverberant conditions. Design: Twenty-eight older listeners with mild-to-moderate sensorineural hearing impairment were recruited in the present study. Individual working memory was measured using a Reading Span test. Sentences were combined with noise at two signal to noise ratios (2 and 5 dB SNR), and reverberation was simulated at a range of reverberation times (0.00, 0.75, 1.50, and 3.00 sec). Speech intelligibility was measured in listeners when listening to the sentences processed with simulated fast-acting and slow-acting WDRC conditions. Results: There was a significant relation between WDRC speed and working memory with minimal or no reverberation. Consistent with previous research, this relation was such that individuals with high working memory had higher speech intelligibility with fast-acting WDRC, and individuals with low working memory performed better with slow-acting WDRC. However, at longer reverberation times, there was no relation between WDRC speed and working memory. Conclusions: Consistent with previous studies, results suggest that there is an advantage of tailoring WDRC speed based on an individual's working memory under anechoic conditions. However, the present results further suggest that there may not be such a benefit in reverberant listening environments due to reduction in signal modulation. ACKNOWLEDGMENTS: The authors thank Tim Schoof for help with calibration, Laura Mathews and Melissa Sherman for assistance with participant recruitment, and Thomas Lunner for providing the Reading Span test. This research was funded by the National Institutes of Health Grants F31 DC015373 to P.R., R01 DC008168 to P.Z., and R01 DC006014 to P.S. The work presented in this manuscript represents an original contribution that has not been previously published or submitted for publication elsewhere. All authors contributed equally to this study. P.R. and P.S. collected and analyzed data and wrote the main article; P.Z. contributed to the study design and manuscript preparation. All authors discussed the results and implications and commented on the manuscript at all stages. The authors have no conflicts of interest to disclose. Address for correspondence: Pamela Souza, Department of Communication Sciences and Disorders, Northwestern University, 2240 E Campus Drive, Evanston, IL 60208, USA. E-mail: p-souza@northwestern.edu Received May 31, 2018; accepted November 26, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader http://bit.ly/2Hn0LC6

Use of Direct-Connect for Remote Speech-Perception Testing in Cochlear Implants

Objectives: Previous research has demonstrated the feasibility of programming cochlear implants (CIs) via telepractice. To effectively use telepractice in a comprehensive manner, all components of a clinical CI visit should be validated using remote technology. Speech-perception testing is important for monitoring outcomes with a CI, but it has yet to be validated for remote service delivery. The objective of this study, therefore, was to evaluate the feasibility of using direct audio input (DAI) as an alternative to traditional sound-booth speech-perception testing for serving people with CIs via telepractice. Specifically, our goal was to determine whether there was a significant difference in speech-perception scores between the remote DAI (telepractice) and the traditional (in-person) sound-booth conditions. Design: This study used a prospective, split-half-design to test speech perception in the remote DAI and in-person sound-booth conditions. Thirty-two adults and older children with CIs participated; all had a minimum of 6 months of experience with their device. Speech-perception tests included the consonant–nucleus–consonant (CNC) words, Hearing-in-Noise test (HINT) sentences, and Arizona Biomedical Institute at Arizona State University (AzBio) sentences. All three tests were administered at levels of 50 and 60 dBA in quiet. Sentence stimuli were also presented in 4-talker babble at signal to noise ratios (SNRs) of +10 and +5 dB for both the 50- and 60-dBA presentation levels. A repeated-measures analysis of variance was used to assess the effects of location (remote, in person), stimulus level (50, 60 dBA), and SNR (if applicable; quiet, +10, +5 dB) on each outcome measure (CNC, HINT, AzBio). Results: The results showed no significant effect of location for any of the tests administered (p > 0.1). There was no significant effect of presentation level for CNC words or phonemes (p > 0.2). There was, however, a significant effect of level (p

from #Audiology via ola Kala on Inoreader http://bit.ly/2RU7WGe

Correlates of Hearing Aid Use in UK Adults: Self-Reported Hearing Difficulties, Social Participation, Living Situation, Health, and Demographics

Objectives: Hearing impairment is ranked fifth globally for years lived with disability, yet hearing aid use is low among individuals with a hearing impairment. Identifying correlates of hearing aid use would be helpful in developing interventions to promote use. To date, however, no studies have investigated a wide range of variables, this has limited intervention development. The aim of the present study was to identify correlates of hearing aid use in adults in the United Kingdom with a hearing impairment. To address limitations in previous studies, we used a cross-sectional analysis to model a wide range of potential correlates simultaneously to provide better evidence to aid intervention development. Design: The research was conducted using the UK Biobank Resource. A cross-sectional analysis of hearing aid use was conducted on 18,730 participants aged 40 to 69 years old with poor hearing, based on performance on the Digit Triplet test. Results: Nine percent of adults with poor hearing in the cross-sectional sample reported using a hearing aid. The strongest correlate of hearing aid use was self-reported hearing difficulties (odds ratio [OR] = 110.69 [95% confidence interval {CI} = 65.12 to 188.16]). Individuals who were older were more likely to use a hearing aid: for each additional year of age, individuals were 5% more likely to use a hearing aid (95% CI = 1.04 to 1.06). People with tinnitus (OR = 1.43 [95% CI = 1.26 to 1.63]) and people with a chronic illness (OR = 1.97 [95% CI = 1.71 to 2.28]) were more likely to use a hearing aid. Those who reported an ethnic minority background (OR = 0.53 [95% CI = 0.39 to 0.72]) and those who lived alone (OR = 0.80 [95% CI = 0.68 to 0.94]) were less likely to use a hearing aid. Conclusions: Interventions to promote hearing aid use need to focus on addressing reasons for the perception of hearing difficulties and how to promote hearing aid use. Interventions to promote hearing aid use may need to target demographic groups that are particularly unlikely to use hearing aids, including younger adults, those who live alone and those from ethnic minority backgrounds. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal's Web site (www.ear-hearing.com). ACKNOWLEDGMENTS: The research was funded by a doctoral studentship supported by Sonova. The study was supported by the NIHR Manchester Biomedical Research Centre and the NIHR Greater Manchester Patient Safety Translational Research Centre. C.S.S and P.D.D. analyzed the data; C.S.S. wrote the article; P.D.D., C.J.A., K.J.M., and G.S. provided critical revision. All authors discussed the results and implications and commented on the manuscript at all stages. This research was conducted using the UK Biobank Resource. The authors have no conflicts of interest to disclose. Address for correspondence: Chelsea S. Sawyer, University of Manchester, HCD office, Ellen Wilkinson Building, Oxford Road, Manchester M13 9PL. E-mail: chelsea.sawyer@manchester.ac.uk Received February 28, 2018; accepted November 19, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader http://bit.ly/2HmIAN4

How do Canadian media report climate change impacts on health? A newspaper review

Abstract

Research on climate change media coverage is growing. Few studies, however, have investigated how the media portrays climate change impacts on human health. This review, therefore, presents a quantitative spatiotemporal analysis of Canadian newspaper coverage of climate change impacts on health between 2005 and 2015. Using the ProQuest® and Eureka® databases, a multiphase systematic review strategy was employed to identify relevant English and French articles from two national and six regional high-circulation newspapers. Quantitative and qualitative data were extracted from 145 articles and analyzed to characterize the range, extent, and nature of climate-health newspaper coverage in Canada and to compare these characteristics by region and over time. Coverage varied by region, with the highest proportion of climate-health coverage in Northern Territories (Yukon, Northwest Territories, Nunavut). Over time, there was a decreasing publication frequency trend. Almost all articles described negative climate change impacts on health, with a predominant focus on infectious and chronic noninfectious diseases; however, less than half of the articles discussed climate change solutions. These trends suggest that current media coverage might not drive widespread public support for policies and actions needed to protect against projected climate-health risks. Consequently, as climate change continues to challenge human health, increasing media emphasis on climate change impacts on human health, as well as a shift toward enabling and empowering climate change communication, in which viable mitigation and adaptation options are emphasized, could help to spur action to reduce climate change health risks.



http://bit.ly/2W3JktH

Distribution of bacterial polycyclic aromatic hydrocarbon (PAH) ring-hydroxylating dioxygenases genes in oilfield soils and mangrove sediments explored by gene-targeted metagenomics

Abstract

PAH ring-hydroxylating dioxygenases (PAH-RHDα) gene, a useful biomarker for PAH-degrading bacteria, has been widely used to examine PAH-degrading bacterial community in different contaminated sites. However, the distribution of PAH-RHDα genes in oilfield soils and mangrove sediments and their relationship with environmental factors still remain largely unclear. In this study, gene-targeted metagenomics was first used to investigate the diversity of PAH-degrading bacterial communities in oilfield soils and mangrove sediments. The results showed that higher diversity of PAH-degrading bacteria in the studied samples was revealed by gene-targeted metagenomics than traditional clone library analysis. Pseudomonas, Burkholderia, Ralstonia, Polymorphum gilvum, Mycobacterium, Sciscionella marina, Rhodococcus, and potential new degraders were prevailed in the oilfield area. For mangrove sediments, novel PAH degraders and Mycobacterium were predominated. The spatial distribution of PAH-RHDα gene was dependent on geographical location and regulated by local environmental variables. PAH content played a key role in shaping PAH-degrading bacterial communities in the studied samples, which would enrich PAH-degrading bacterial population and decrease PAH-degrading bacterial diversity. This work brings a more comprehensive and some new insights into the distribution and biodegradation potential of PAH-degrading bacteria in soil and sediments ecosystems.



http://bit.ly/2Cz7VO3

A genome-wide view of mutations in respiration-deficient mutants of Saccharomyces cerevisiae selected following carbon ion beam irradiation

Abstract

Mitochondrial dysfunction in Saccharomyces cerevisiae was selected as a marker of ion penetration following carbon ion beam (CIB) irradiation. Respiration-deficient mutants were screened. Following confirmation of negligible spontaneous mutation, eight genetically stable S. cerevisiae respiration-deficient mutant strains and a control strain were resequenced with ~ 200-fold read depth. Strategies were established to identify and validate the particular mutations induced by CIB irradiation. In the nuclear genome, CIB irradiation mainly caused base substitutions and some small (< 100 bp) insertions/deletions (indels), which were widely distributed across the chromosomes. Although mitochondrial dysfunction was selected as a screening marker, variants in the nuclear genome were detected at a high frequency (10−7) relative to spontaneous mutations (10−9). The transition to transversion ratio for base substitutions was 0.746, which was less than that of spontaneous mutations. In the mitochondrial genome, there were very large deletions including substantial gene areas, resulting in extremely low read coverage. Meanwhile, every mutant possessed a distinctive mutation pattern, for both the nuclear and the mitochondrial genome. Nuclear genomes contained scanty mitochondrial respiration-related genes that were potentially affected by verified mutations, suggesting that variants in the mitochondrial genome may be the main drivers of respiratory deficiencies. Our study confirmed the previous finding that heavy ion beam (HIB) irradiation mainly induces substantial base substitutions and some small indels but also yielded some novel findings, in particular, novel structural variants in the mitochondrial genomes. These data will enhance the understanding of HIB-induced damage and mutations and aid in the HIB-based microbial mutation breeding.



http://bit.ly/2REP7rc

Timing of Gestation After Laparoscopic Sleeve Gastrectomy (LSG): Does It Influence Obstetrical and Neonatal Outcomes of Pregnancies?

Abstract

Aim

We aimed to evaluate the effect of pregnancy timing after laparoscopic sleeve gastrectomy (LSG) on maternal and fetal outcomes.

Methods

Women with LSG were stratified into two groups with surgery-to-conception intervals of ≤ 18 months (early group) or > 18 months (late group). Only the first delivery after LSG was included in this study. We compared maternal characteristics, pregnancy, and neonatal outcomes and adherence to the Institute of Medicine's (IOM) recommendations for gestational weight gain (GWG) in the two groups.

Results

Fifteen patients conceived ≤ 18 months after surgery, with a mean surgery-to-conception interval of 5.6 ± 4.12 months, and 29 women conceived > 18 months following LSG, with a mean surgery-to-conception interval of 32.31 ± 11.38 months, p < 0.05. There was no statistically significant difference between the two groups regarding birth weight, gestational age, cesarean deliveries (CD), preterm birth, whether their child was small or large for their gestational age, or in the need of neonatal intensive care. There was no correlation between mean weight loss from operation till conception, mean weight gain during pregnancy, and mean body mass index (BMI) at conception between birth weight in either study group. Inadequate and normal GWG was significantly higher in the early group, whereas excessive GWG was significantly higher in the late group (X2, 20.780; p = < 0.001).

Conclusion

The interval between LSG and conception did not impact maternal and neonatal outcomes. Pregnancy after LSG was overall safe and well-tolerated.



http://bit.ly/2W7cKY7

Sleeve Gastrectomy Weight Loss and the Preoperative and Postoperative Predictors: a Systematic Review

Abstract

The sleeve gastrectomy (SG) is the most popular weight loss procedure in the USA. Despite its popularity, little is definitively known about the variables that correlate with weight loss. We performed a literature search to find studies that reported variables that correlated with weight loss following SG. Forty-eight articles were identified and included. These articles covered 36 different factors predictive of weight loss while only including five predictive models. Only 12.5% of multivariate analyses evaluated sufficiently reported their results. The factors that predict weight loss following SG cannot be concluded due to the inconsistency in reporting and the methodological flaws in analysis. Reporting factors that predict weight loss should be standardized, and methods should be changed to allow physicians to use the data presented.



http://bit.ly/2QYwgCg

What is the role of diffusion tensor imaging (DTI) in detecting subclinical pyramidal tract dysfunction in Behçet’s and neuro-Behçet’s cases?

Abstract

The aim of this study is to investigate the pyramidal tract integrity with DTI in Behçet's and neuro-Behçet's cases. We performed this technique in two subgroups of neuro-Behçet's patients (parenchymal and vascular), and Behçet's cases without neurological involvement and control group. Totally, 28 patients were investigated. The control group was composed of 14 healthy people. Cranial MR and DTI were performed in three patient groups and the control group. At DTI, circular regions of interest (ROI) were symmetrically drawn on axial slices on the left and right sides along the pyramidal tract pathway at two levels: middle one third of the cerebral peduncle and posterior limb of the internal capsule. Fractional anisotropy (FA) values for each ROI were obtained by averaging all voxels within the ROI. Calculated FA values on both sides (left and right) of the posterior limb of the internal capsule and cerebral peduncle are significantly lower in all three patient groups when compared to the control group. But there is no any difference of FA values in the selected brain regions of three patient groups. FA values on the posterior limb of the internal capsule and cerebral peduncle do not show a statistically significant difference in parenchymal neuro-Behçet's cases. Our study demonstrates that DTI can detect subclinical pyramidal tract dysfunction in neuro-Behçet's and Behçet's patients. Detection of subclinical nervous system involvement is crucial for morbidity in Behçet's disease. For this reason, studies based on DTI, which include a large number of patients and explore different brain regions, are needed to guide clinicians.



http://bit.ly/2W3lUVj

The Growth Differentiation Factor 11 is Involved in Skin Fibroblast Ageing and is Induced by a Preparation of Peptides and Sugars Derived from Plant Cell Cultures

Abstract

Ageing is a complex and progressive phenomenon, during which the accumulation of morphological and chemical changes seriously compromises the capacity of the cells to proliferate and fulfil their biological tasks. The increase in the average age of the world population, associated with a higher occurrence of age-related diseases, is prompting scientific research to look for new strategies and molecular targets that may help in alleviating age-related phenotypes. Growth factors, responsible for modulating several aging markers in many tissues and organs, represent valuable targets to fight age-associated dysfunctions. The growth differentiation factor GDF11, a TGF-β family member, has been associated with the maintenance of youth phenotypes in different human tissues and organs, and in the skin has been related to an inhibition of the inflammatory response. We investigated the role of GDF11 in skin dermal fibroblasts, and we observed that its expression and activity were reduced in fibroblasts deriving from adult donors compared to neonatal ones. The main effect of GDF11 was the induction of collagen I and III, in both neonatal and adult fibroblasts, by triggering Smad signalling in a TGF-β-like fashion. Moreover, by analysing a number of plant extracts having GDF11 inducing activity, we found that a peptide/sugar preparation, obtained from Lotus japonicus somatic embryo cultures, was capable of restoring GDF11 expression in older fibroblasts and to activate the synthesis of collagen I, collagen III and periostin, an important protein involved in collagen assembly.



http://bit.ly/2RUVuWF

Chemokine-like receptor 1 deficiency leads to lower bone mass in male mice

Abstract

The adipokine Chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), are associated with osteoblastogenic differentiation of mesenchymal stem cells (MSCs) and osteoclastogenic differentiation of osteoclast precursors in vitro, suggesting that CMKLR1 would affect the bone mineral density (BMD). However, the role of CMKLR1 on BMD in vivo remains unknown. Here, using CMKLR1 knockout mouse model, we unveiled that CMKLR1 effected the amount of Leydig cells in testis and regulated androgen-dependent bone maintenance in male mice, which exhibited lower serum testosterone levels, thereby reducing the trabecular bone mass. Correspondingly, the mRNA expression of testosterone synthesis enzymes in testis decreased. The bone tissue also showed decreased mRNAs expression of osteogenic markers and increased mRNA levels for osteoclast markers. Furthermore, by in vitro differentiation models, we found CMKLR1-deficiency could break the balance between osteoblastogenesis and osteoclastogenesis that caused a shift from osteogenic to adipogenic differentiation in MSCs and enhanced osteoclast formation. In addition, bone mass increase in CMKLR1 KO male mice can be promoted by treatment with 5α-dihydrotestosterone (DHT), and the inactivation of CMKLR1 in male wild-type (WT) mice with antagonist treatment can lead to low bone mass. Taken together, these data indicate that CMKLR1 positively regulates bone metabolism through mediating testosterone production and the balance between osteoblast and osteoclast formation.



http://bit.ly/2MinfmF

Disassembly of dying cells in diverse organisms

Abstract

Programmed cell death (PCD) is a conserved phenomenon in multicellular organisms required to maintain homeostasis. Among the regulated cell death pathways, apoptosis is a well-described form of PCD in mammalian cells. One of the characteristic features of apoptosis is the change in cellular morphology, often leading to the fragmentation of the cell into smaller membrane-bound vesicles through a process called apoptotic cell disassembly. Interestingly, some of these morphological changes and cell disassembly are also noted in cells of other organisms including plants, fungi and protists while undergoing 'apoptosis-like PCD'. This review will describe morphologic features leading to apoptotic cell disassembly, as well as its regulation and function in mammalian cells. The occurrence of cell disassembly during cell death in other organisms namely zebrafish, fly and worm, as well as in other eukaryotic cells will also be discussed.



http://bit.ly/2sBuxJq

The role of P2Y 12 receptor in ischemic stroke of atherosclerotic origin

Abstract

Atherosclerosis is a chronic and progressive disease of the arterial walls and a leading cause of non-cardioembolic ischemic stroke. P2Y12 is a well-recognized receptor that is expressed on platelets and is a target of thienopyridine-type antiplatelet drugs. In the last few decades, P2Y12 receptor inhibitors, such as clopidogrel, have been applied for the secondary prevention of non-cardioembolic ischemic stroke. Recent clinical studies have suggested that these P2Y12 receptor inhibitors may be more effective than other antiplatelet drugs in patients with ischemic stroke/transient ischemic attack of atherosclerotic origin. Moreover, animal studies have also shown that the P2Y12 receptor may participate in atherogenesis by promoting the proliferation and migration of vascular smooth muscle cells (VSMCs) and endothelial dysfunction, and affecting inflammatory cell activities in addition to amplifying and maintaining ADP-induced platelet activation and platelet aggregation. P2Y12 receptor inhibitors may also exert neuroprotective effects after ischemic stroke. Thus, P2Y12 receptor inhibitors may be a better choice for secondary prevention in patients with atherosclerotic ischemic stroke subtypes because of their triple functions (i.e., their anti-atherosclerotic, anti-platelet aggregation, and neuroprotective activities), and the P2Y12 receptor may also serve as a noval therapeutic target for atherosclerosis. In this review, we summarize the current knowledge on the P2Y12 receptor and its key roles in atherosclerosis and ischemic stroke of atherosclerotic origin.



http://bit.ly/2MktuXb

Cerebrovascular disorders associated with genetic lesions

Abstract

Cerebrovascular disorders are underlain by perturbations in cerebral blood flow and abnormalities in blood vessel structure. Here, we provide an overview of the current knowledge of select cerebrovascular disorders that are associated with genetic lesions and connect genomic findings with analyses aiming to elucidate the cellular and molecular mechanisms of disease pathogenesis. We argue that a mechanistic understanding of genetic (familial) forms of cerebrovascular disease is a prerequisite for the development of rational therapeutic approaches, and has wider implications for treatment of sporadic (non-familial) forms, which are usually more common.



http://bit.ly/2sBuv4g

mRNA as novel technology for passive immunotherapy

Abstract

While active immunization elicits a lasting immune response by the body, passive immunotherapy transiently equips the body with exogenously generated immunological effectors in the form of either target-specific antibodies or lymphocytes functionalized with target-specific receptors. In either case, administration or expression of recombinant proteins plays a fundamental role. mRNA prepared by in vitro transcription (IVT) is increasingly appreciated as a drug substance for delivery of recombinant proteins. With its biological role as transient carrier of genetic information translated into protein in the cytoplasm, therapeutic application of mRNA combines several advantages. For example, compared to transfected DNA, mRNA harbors inherent safety features. It is not associated with the risk of inducing genomic changes and potential adverse effects are only temporary due to its transient nature. Compared to the administration of recombinant proteins produced in bioreactors, mRNA allows supplying proteins that are difficult to manufacture and offers extended pharmacokinetics for short-lived proteins. Based on great progress in understanding and manipulating mRNA properties, efficacy data in various models have now demonstrated that IVT mRNA constitutes a potent and flexible platform technology. Starting with an introduction into passive immunotherapy, this review summarizes the current status of IVT mRNA technology and its application to such immunological interventions.



http://bit.ly/2MhG0qx

The Janus face of HMGB1 in heart disease: a necessary update

Abstract

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein involved in transcription regulation, DNA replication and repair and nucleosome assembly. HMGB1 is passively released by necrotic tissues or actively secreted by stressed cells. Extracellular HMGB1 acts as a damage-associated molecular pattern (DAMPs) molecule and gives rise to several redox forms that by binding to different receptors and interactors promote a variety of cellular responses, including tissue inflammation or regeneration. Inhibition of extracellular HMGB1 in experimental models of myocardial ischemia/reperfusion injury, myocarditis, cardiomyopathies induced by mechanical stress, diabetes, bacterial infection or chemotherapeutic drugs reduces inflammation and is protective. In contrast, administration of HMGB1 after myocardial infarction induced by permanent coronary artery ligation ameliorates cardiac performance by promoting tissue regeneration. HMGB1 decreases contractility and induces hypertrophy and apoptosis in cardiomyocytes, stimulates cardiac fibroblast activities, and promotes cardiac stem cell proliferation and differentiation. Interestingly, maintenance of appropriate nuclear HMGB1 levels protects cardiomyocytes from apoptosis by preventing DNA oxidative stress, and mice with HMGB1cardiomyocyte-specific overexpression are partially protected from cardiac damage. Finally, higher levels of circulating HMGB1 are associated to human heart diseases. Hence, during cardiac injury, HMGB1 elicits both harmful and beneficial responses that may in part depend on the generation and stability of the diverse redox forms, whose specific functions in this context remain mostly unexplored. This review summarizes recent findings on HMGB1 biology and heart dysfunctions and discusses the therapeutic potential of modulating its expression, localization, and oxidative-dependent activities.



http://bit.ly/2sBusp6

Activities of daily living and patient satisfaction after long fusion for adult spinal deformity: a retrospective study

Abstract

Purpose

Spinal instrumented arthrodesis improves health-related quality of life (HRQOL), although mobility is impaired. This study evaluates activities of daily livings after thoracolumbosacroiliac arthrodesis for adult spinal deformity and patient satisfaction.

Methods

Fifty patients who underwent surgery filled self-administered questionnaires (1-year preoperative and postoperative conditions), and 36 patients (3 men and 33 women; mean age 71.4 years) participated in the study. Twenty-five activities, including weeding, snow shoveling, toilet activities, and sleeping postures, were examined. Spinal alignment with Scoliosis Research Society (SRS)—Schwab classification, HRQOL with SRS-22, complications, and patient satisfaction were evaluated. Pre- and postoperative conditions were statistically compared.

Results

Spinal alignment improved postoperatively. Comparison data revealed that strenuous activities, such as weeding and farm work, significantly deteriorated postoperatively in 42.1–87.5% patients. Other basic activities, excluding Western toilet usage, sleeping supine, laundry and kitchen chores, and changing jacket/pants, also significantly deteriorated in 21–88% patients. Only activities such as sleeping supine, standing upright, vacuuming, doing laundry, and reaching for objects placed at heights became possible with significant difference postoperatively among activities that could not be performed preoperatively. Light activities were continued, but strenuous activities were restricted. Nevertheless, the patient satisfaction rate was 70%. Six patients exhibited complications; however, none were dissatisfied with surgery outcomes. Instrumentation or proximal junctional failures were associated with at least one strenuous work activity.

Conclusions

Thoracolumbosacroiliac arthrodesis does not always improve activities postoperatively. Therefore, surgical indication for patients who continue activities preoperatively should be carefully decided.

Level of Evidence

Level 3.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.



http://bit.ly/2Mku7Qy

New technologies provide more metabolic engineering strategies for bioethanol production in Zymomonas mobilis

Abstract

Bioethanol has been considered as a potentially renewable energy source, and metabolic engineering plays an important role in the production of biofuels. As an efficient ethanol-producing bacterium, Zymomonas mobilis has garnered special attention due to its high sugar uptake, ethanol yield, and tolerance. Different metabolic engineering strategies have been used to establish new metabolic pathways for Z. mobilis to broaden its substrate range, remove competing pathways, and enhance its tolerance to ethanol and lignocellulosic hydrolysate inhibitors. Recent advances in omics technology, computational modeling and simulation, system biology, and synthetic biology contribute to the efficient re-design and manipulation of microbes via metabolic engineering at the whole-cell level. In this review, we summarize the progress of some new technologies used for metabolic engineering to improve bioethanol production and tolerance in Z. mobilis. Some successful examples of metabolic engineering used to develop strains for ethanol production are described in detail. Lastly, some important strategies for future metabolic engineering efforts are also highlighted.



http://bit.ly/2AW88uC

Real-World Postmarketing Study of the Impact of Adalimumab Treatment on Work Productivity and Activity Impairment in Patients with Psoriatic Arthritis

Abstract

Introduction

This study investigated the effectiveness of adalimumab treatment in improving Work Productivity and Activity Impairment (WPAI) in patients with psoriatic arthritis (PsA) in real-world settings in Japan.

Methods

This 24-week, single-arm, postmarketing surveillance study (2014–2017), conducted at 75 centers in Japan, enrolled adalimumab-naïve patients (paid workers, including part-time) meeting ClASsification criteria for Psoriatic ARthritis (CASPAR). The primary endpoint was improvement in overall work impairment (OWI) scores from baseline to week 24. Secondary endpoints included changes in WPAI-PsA (OWI, absenteeism, presenteeism, and activity impairment), Psoriasis Area and Severity Index (PASI), psoriatic arthritis screening and evaluation (PASE) scores, Disease Activity Scores in 28 joints using C-reactive protein (DAS28[CRP]), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and PASI75/90 and American College of Rheumatology (ACR) 20/50/70 rates.

Results

In the effectiveness population (n = 106; 72.6% men; mean ± standard deviation [SD] age, 49.3 ± 10.7 years), OWI scores significantly improved (mean ± SD change, − 25.2 ± 35.3; p < 0.0001) from baseline to week 24. Other WPAI domain scores also improved significantly. Changes in OWI were significantly correlated (p < 0.0001) with PASE (r = 0.6284), DAS28(CRP) (r = 0.6059), BASDAI (r = 0.7281), and HAQ-DI (r = 0.6161) scores and were significantly influenced by previous nonsteroidal anti-inflammatory drug use (p = 0.0142), and baseline PASE (p = 0.0098), DAS28(CRP) (p = 0.0026), HAQ-DI (p = 0.0004), and BASDAI (p < 0.0001) scores. At the last evaluation, rate (95% confidence interval) of PASI 75 and 90 (n = 100) was 58.0% (47.7–67.8) and 39.0% (29.4–49.3), respectively, and that of ACR 20, 50, and 70 (n = 58) was 86.2% (74.6–93.9), 70.7% (57.3–81.9), and 53.4% (39.9–66.7), respectively. No new safety signals were observed in the safety population (n = 148).

Conclusion

Adalimumab treatment improved WPAI in patients with PsA. Improvements in OWI and joint symptoms were significantly associated.

Trial Registration Number

ClinicalTrials.gov identifier: NCT02414633.

Funding

AbbVie GK and Eisai Co., Ltd.



http://bit.ly/2FIXquM

Formative research experiences in pediatric surgeons: a mixed methods study of Pediatric Trauma Society members

Abstract

Purpose

A career in pediatric surgery has historically required extensive research experience, but the optimal research training is not well defined. The purpose of this study was to explore the formative research experiences among pediatric surgeons.

Methods

A 1-h focus group was held with 14 pediatric surgeons at the 2017 Pediatric Trauma Society annual meeting. A 17-item survey was also administered. Questions were intended to elicit discussion of prior research experiences. A qualitative analysis of the dialogue was performed.

Results

Seventy-seven percent of respondents completed a research fellowship. Most (77%) currently conduct clinical research. Participants most frequently desired additional training in study design (50%), NIH funding (43%), and grant preparation (43%). Seven themes were identified from the focus group: (1) Early research exposure is rudimentary; (2) Resume-building was a motivation; (3) Mentorship is important; (4) Institutional resources are vital; (5) Independent learning is necessary; (6) Protected time is limited; and (7) Basic science research is not always practical.

Conclusions

Many pediatric surgeons feel that their research training can be improved upon. Formal mentorship, dedicated research time, and institutional resources were perceived to be important factors. Education in research study design, grant writing, and NIH funding may be beneficial.

Level of evidence

V, expert opinion.



http://bit.ly/2SYl6PA

Is fecal diversion necessary during ileal pouch creation after initial subtotal colectomy in pediatric ulcerative colitis?

Abstract

Background

Pediatric patients with medically refractory ulcerative colitis (UC) often undergo an initial subtotal colectomy end ileostomy (STC-I). The role of fecal diversion in the subsequent completion proctectomy/ileal-pouch anal anastomosis (CP-IPAA) remains controversial.

Methods

A multi-institutional retrospective review was performed of pediatric UC patients who underwent an STC-I followed by CP-IPAA from 2008 to 2016. 37 patients were included [diverted (n = 20), undiverted (n = 17)].

Results

Children who underwent undiverted CP-IPAA had a longer length of stay (days) compared to the diverted group (9, 6.5–13 vs. 6, 5–6, p = 0.002). The 30-day complication rate was significantly higher in the undiverted group (p = 0.003) although the difference in anastomotic leak, readmission rate, unplanned computer tomography use, and reoperation was not statistically significant. Three patients with undiverted CP-IPAA required additional surgery in the perioperative period for fecal diversion. The mean long-term follow-up was 25.68 ± 21.56 months. There were no significant differences in functional pouch outcomes.

Conclusions

Patients who underwent an undiverted CP-IPAA after initial STC-I had significantly more complications in the immediate postoperative period compared to diverted patients, although this did not translate into long-term differences in functional outcomes. Questions remain regarding careful patient selection and counseling for undiverted pouches in the pediatric UC population.



http://bit.ly/2ATTfZX

Meta-analysis of association between Arg326Gln (rs1503185) and Gln276Pro (rs1566734) polymorphisms of PTPRJ gene and cancer risk

Abstract

Protein tyrosine phosphatase receptor type J (PTPRJ, DEP1) is a tumour suppressor gene that negatively regulates such processes as angiogenesis, cell proliferation and migration and is one of the genes important for tumour development. Similar to other phosphatase genes, PTPRJ is also described as an oncogene. Among various genetic changes characteristic for this gene, single nucleotide polymorphisms (SNPs) constituting benign genetic variants that can modulate its function have been described. We focused on Gln276Pro and Arg326Gln missense polymorphisms and performed a meta-analysis using data from 2930 and 852 patients for Gln276Pro and Arg326Gln respectively in different cancers. A meta-analysis was performed based on five articles accessed via the PubMed and Research Gate databases. Our meta-analysis revealed that for Arg326Gln, the presence of the Arg (C) allele was associated with lower risk of some cancers, the strongest association was observed for colorectal cancer patients, and there was no association between Gln276Pro (G>T) polymorphism and cancer risk. The polymorphisms Arg326Gln and Gln276Pro of the PTPRJ gene are not associated with an increased risk of cancer except for the Arg326Gln polymorphism in colorectal cancer. Large-scale studies should be performed to verify the impact of this SNP on individual susceptibility to colorectal cancer for given individuals.



http://bit.ly/2RUVdCX

Preoperative Transversus Abdominis Plane (TAP) Block with Liposomal Bupivacaine for Bariatric Patients to Reduce the Use of Opioid Analgesics

Abstract

Introduction

Postoperative pain remains the most common challenge following inpatient and outpatient surgeries, and, therefore, opioid analgesics are widely used during the perioperative period. The aim of this study is to examine the efficiency of transversus abdominis plane (TAP) block using liposomal bupivacaine in reducing the use of opioid analgesics during the perioperative period of bariatric procedures.

Material and Methods

A retrospective chart review was performed on 191 patients who underwent a laparoscopic bariatric procedure between September 13, 2017, and February 26, 2018. A total of 97 patients received TAP block with liposomal bupivacaine, and 94 patients did not receive TAP block.

Results

Baseline patient characteristics were comparable between the two groups. The mean age was 43.7 and 41.1 years, and the mean preoperative body mass index (BMI) was 45.6 and 46.1 kg/m2 in TAP and non-TAP groups, respectively. In the TAP group, 65 patients (69.2%) received intravenous (IV) hydromorphone or morphine while 93 (95.9%) did in the non-TAP group (p < 0.0001). In the TAP group, 44 (46.8%) received oral opioid analgesic while 73 (75.3%) did in the non-TAP group (p < 0.0001). The odds of receiving IV hydromorphone or morphine for TAP group was about 0.10 times the corresponding odds for non-TAP group, and the odds of receiving oral opioid analgesic for the TAP group was about 0.29 times the corresponding odds for the non-TAP group.

Conclusion

The use of preoperative TAP block with liposomal bupivacaine significantly decreased the use of IV and oral opioid analgesics. A larger prospective study may be needed to further validate the results.



http://bit.ly/2Cy4yqR

Investigation of Pediatric Anemia in the Commonwealth of the Northern Mariana Islands

Abstract

Objective To report on the prevalence and etiology of pediatric anemia in the Commonwealth of the Northern Mariana Islands (CNMI). Method A retrospective chart review was conducted that included patients up to 19 years of age who presented for well child care and whose hemoglobin or hematocrit was checked in the CNMI from 2014 to 2015. Lab values, diagnoses and treatment plans, patient reported ethnicity, and follow-up results were collected from eligible patients. Results The records for 1483 pediatric patients who had 1584 well child visits were reviewed. The prevalence of anemia amongst all eligible patients was 8.0% (5.4–10.7). This included 292 9 to 18 months old patients, which is estimated to be 40% of the total pediatric population of CNMI in that age group. Among the 9 to 18 months old patients, the prevalence of anemia is 5.5% (2.6–8.4). Etiology of anemia was investigated and of the patients treated with iron, 55.2% had a documented response. The majority of those without documentation of improvement with iron were patients who were lost to follow-up. In addition, a total of 10 patients were found to have an alpha or beta thalassemia variant discovered initially by anemia screening or sibling tracing. Discussion In this United States Commonwealth, prevalence of anemia appears lower than prevalence reported for other independent Pacific Island nations and closer to that of the US. Thalassemia is documented within this population. Limitations to this data were use of a convenient sample that may be hampered by lack of presentation to well-child care. This study will guide future public health studies on anemia prevalence and can guide public health intervention decisions to improve pediatric care in the CNMI.



http://bit.ly/2sC7ii6

Review: the Roles and Mechanisms of Glycoprotein 130 Cytokines in the Regulation of Adipocyte Biological Function

Abstract

Chronic low-grade inflammation is now widely accepted as one of the most important contributors to metabolic disorders. Glycoprotein 130 (gp130) cytokines are involved in the regulation of metabolic activity. Studies have shown that several gp130 cytokines, such as interleukin-6 (IL-6), leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1), have divergent effects on adipogenesis, lipolysis, and insulin sensitivity as well as food intake. In this review, we will summarize the present knowledge about gp130 cytokines, including IL-6, LIF, CNTF, CT-1, and OSM, in adipocyte biology and metabolic activities in conditions such as obesity, cachexia, and type 2 diabetes. It is valuable to explore the diverse actions of these gp130 cytokines on the regulation of the biological functions of adipocytes, which will provide potential therapeutic targets for the treatment of obesity and cachexia.



http://bit.ly/2R1CjG6

Correction to: ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model

The author "Ashish D. Diwan" receives educational consultant fees from Nuvasive Inc.



http://bit.ly/2RBLmmq

Investigation of Pediatric Anemia in the Commonwealth of the Northern Mariana Islands

Abstract

Objective To report on the prevalence and etiology of pediatric anemia in the Commonwealth of the Northern Mariana Islands (CNMI). Method A retrospective chart review was conducted that included patients up to 19 years of age who presented for well child care and whose hemoglobin or hematocrit was checked in the CNMI from 2014 to 2015. Lab values, diagnoses and treatment plans, patient reported ethnicity, and follow-up results were collected from eligible patients. Results The records for 1483 pediatric patients who had 1584 well child visits were reviewed. The prevalence of anemia amongst all eligible patients was 8.0% (5.4–10.7). This included 292 9 to 18 months old patients, which is estimated to be 40% of the total pediatric population of CNMI in that age group. Among the 9 to 18 months old patients, the prevalence of anemia is 5.5% (2.6–8.4). Etiology of anemia was investigated and of the patients treated with iron, 55.2% had a documented response. The majority of those without documentation of improvement with iron were patients who were lost to follow-up. In addition, a total of 10 patients were found to have an alpha or beta thalassemia variant discovered initially by anemia screening or sibling tracing. Discussion In this United States Commonwealth, prevalence of anemia appears lower than prevalence reported for other independent Pacific Island nations and closer to that of the US. Thalassemia is documented within this population. Limitations to this data were use of a convenient sample that may be hampered by lack of presentation to well-child care. This study will guide future public health studies on anemia prevalence and can guide public health intervention decisions to improve pediatric care in the CNMI.



http://bit.ly/2sC7ii6

Acute and overuse injuries among sports club members and non-members: the Finnish Health Promoting Sports Club (FHPSC) study

Abstract

Background

Physical activity in adolescence is promoted for its multi-dimensional health benefits. However, too intensive sports participation is associated with an increased injury risk. Our aim was to compare the occurrence of acute and overuse injuries in Finnish sports club members and non-members and to report training and competing habits associated with a higher injury risk in sports club members.

Methods

In this cross-sectional survey targeted at 14–16-year-old adolescents, a structured questionnaire was completed by 1077 sports club members and 812 non-members. The main outcome measures were self-reported acute and overuse injuries, their location and type.

Results

At least one acute injury in the past year was reported by 44.0% of sports club members and 19.8% of non-members (P < 0.001). The sex-adjusted odds ratio (OR) for acute injury in sports club members compared to non-members was 3.13 (95% confidence interval (95% CI) 2.54–3.87). Thirty-five percent of sports club members and 17.4% of non-members (P < 0.001) reported at least one overuse injury during the past year. The overuse injury OR for sports club members was 2.61 (95% CI 2.09–3.26). Sports club members who trained 7–14 h per week during training (OR 1.61, 95% CI 1.21–2.12, P = 0.001) or competition season (OR 1.55, 95% CI 1.18–2.06, P = 0.002) were more likely to report an injury compared to members who trained 3–6 h per week. Those sports club members who participated in forty competitions or more compared to 7–19 competitions per year were more likely to report an acute injury (OR 1.55, 95% CI 1.05–2.08, P = 0.028) or for an overuse injury (OR 1.53, 95% CI 1.02–2.30, P = 0.038).

Conclusions

Both acute and overuse injuries are common among youth sports club members, and the number increases along with increasing amounts of training and competitions. More effective injury prevention is needed both for adolescents engaging in sports club activities and for other adolescents.



http://bit.ly/2CuRJ0g

In vitro and in vivo cytotoxic activity and human serum albumin interaction for a methoxy-styryl-thiosemicarbazone

Summary

Thiosemicarbazone is a class of compounds with potential applications in medicine, presenting high capacity to inhibit the growth of cancer cells as well as low toxicity. Because of high interest in anticancer studies involving thiosemicarbazones as new chemotherapeutic agents, a synthetic thiosemicarbazone derivative, 4-N-(2′-methoxy-styryl)-thiosemicarbazone (MTSC) was evaluated in vivo against Ehrlich carcinoma in an animal model. In vivo results demonstrated that MTSC treatment induced the survival of mice and altered significantly the body weight of the surviving mice 12 days after tumor inoculation. Treatment with 30 mg/kg of MTSC exhibited effective cytotoxic activity with T/C values of 150.49% (1 dose) and 278% (2 doses). Its interaction with human serum albumin (HSA), which plays a crucial role in the biodistribution of a wide variety of ligands, was investigated by multiple spectroscopic techniques at 296 K, 303 K, and 310 K, as well as by theoretical calculations. The interaction between HSA and MTSC occurs via ground-state association in the subdomain IIA (Sudlow's site I). The binding is moderate (Ka ≈ 104 M–1), spontaneous, entropically, and enthalpically driven. Molecular docking results suggested hydrogen bonding and hydrophobic interactions as the main binding forces. Overall, the interaction HSA:MTSC could provide therapeutic benefits, improving its cytotoxic efficacy and tolerability.



http://bit.ly/2Cv2z6p

An observational study evaluating the demand of major trauma on different surgical specialities in a UK Major Trauma Centre

Abstract

Introduction

Major Trauma Centres (MTCs) should ideally have all key surgical specialities on site. This may not always be the case since trauma is only one factor influencing speciality location. The implications of this can only be understood when the demands on specific specialities are established and this is not well documented. We investigated surgical speciality demand by quantifying the frequency and urgency of surgical trauma interventions.

Patients and methods

Data on adult trauma admissions for a UK MTC were retrieved from the UK Trauma Audit and Research Network for a 2-year period and analysed to establish the frequency and urgency of surgical interventions.

Results

Of 1285 trauma patients with an ISS > 15 presenting in the study year period 713 (55.5%) required surgery. Neurosurgical (59.9%) and orthopaedic (55.1%) operations were most frequent. Cardiothoracic, general surgery, plastic surgery and maxillofacial operations were required infrequently. General surgery was commonly needed urgently, 45% within 4 h of MTC arrival. Urgency was also common in interventional radiology and vascular surgery. Cardiothoracic interventions were mainly urgent interventions (thoracotomy 1/3) and less urgent (rib fixation 2/3).

Discussion

Neurosurgery and orthopaedic surgery are key on-site trauma specialities and required frequently. General surgery, interventional radiology and cardiothoracic interventions are required less frequently but often urgently. This confirms a need for MTC on-site capability and possibly training to maintain competency in occasional trauma operators, particularly in general surgery. Maxillofacial surgery, ENT and urology are required neither frequently nor urgently and on-site presence may be less critical.

Conclusion

Demand for specific surgical specialities was reported in a cohort of UK trauma patients. This confirmed the need for rapid on-site capability in key specialities and highlights possible training requirements for occasional trauma operators in specialities with low frequency but high urgency.



http://bit.ly/2HjBCbF

In vitro and in vivo cytotoxic activity and human serum albumin interaction for a methoxy-styryl-thiosemicarbazone

Summary

Thiosemicarbazone is a class of compounds with potential applications in medicine, presenting high capacity to inhibit the growth of cancer cells as well as low toxicity. Because of high interest in anticancer studies involving thiosemicarbazones as new chemotherapeutic agents, a synthetic thiosemicarbazone derivative, 4-N-(2′-methoxy-styryl)-thiosemicarbazone (MTSC) was evaluated in vivo against Ehrlich carcinoma in an animal model. In vivo results demonstrated that MTSC treatment induced the survival of mice and altered significantly the body weight of the surviving mice 12 days after tumor inoculation. Treatment with 30 mg/kg of MTSC exhibited effective cytotoxic activity with T/C values of 150.49% (1 dose) and 278% (2 doses). Its interaction with human serum albumin (HSA), which plays a crucial role in the biodistribution of a wide variety of ligands, was investigated by multiple spectroscopic techniques at 296 K, 303 K, and 310 K, as well as by theoretical calculations. The interaction between HSA and MTSC occurs via ground-state association in the subdomain IIA (Sudlow's site I). The binding is moderate (Ka ≈ 104 M–1), spontaneous, entropically, and enthalpically driven. Molecular docking results suggested hydrogen bonding and hydrophobic interactions as the main binding forces. Overall, the interaction HSA:MTSC could provide therapeutic benefits, improving its cytotoxic efficacy and tolerability.



http://bit.ly/2Cv2z6p