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Showing papers in "PLOS Currents in 2013"


Journal ArticleDOI
TL;DR: A comprehensive molecular phylogeny for bony fishes that includes representatives of all major lineages and the order Perciformes, considered by many a polyphyletic taxonomic waste basket, is defined for the first time as a monophyletic group in the global phylogeny.
Abstract: The tree of life of fishes is in a state of flux because we still lack a comprehensive phylogeny that includes all major groups. The situation is most critical for a large clade of spiny-finned fishes, traditionally referred to as percomorphs, whose uncertain relationships have plagued ichthyologists for over a century. Most of what we know about the higher-level relationships among fish lineages has been based on morphology, but rapid influx of molecular studies is changing many established systematic concepts. We report a comprehensive molecular phylogeny for bony fishes that includes representatives of all major lineages. DNA sequence data for 21 molecular markers (one mitochondrial and 20 nuclear genes) were collected for 1410 bony fish taxa, plus four tetrapod species and two chondrichthyan outgroups (total 1416 terminals). Bony fish diversity is represented by 1093 genera, 369 families, and all traditionally recognized orders. The maximum likelihood tree provides unprecedented resolution and high bootstrap support for most backbone nodes, defining for the first time a global phylogeny of fishes. The general structure of the tree is in agreement with expectations from previous morphological and molecular studies, but significant new clades arise. Most interestingly, the high degree of uncertainty among percomorphs is now resolved into nine well-supported supraordinal groups. The order Perciformes, considered by many a polyphyletic taxonomic waste basket, is defined for the first time as a monophyletic group in the global phylogeny. A new classification that reflects our phylogenetic hypothesis is proposed to facilitate communication about the newly found structure of the tree of life of fishes. Finally, the molecular phylogeny is calibrated using 60 fossil constraints to produce a comprehensive time tree. The new time-calibrated phylogeny will provide the basis for and stimulate new comparative studies to better understand the evolution of the amazing diversity of fishes.

740 citations


Journal ArticleDOI
TL;DR: Findings from the systematic literature review indicate that the primary cause of tsunami-related mortality is drowning, and that females, children and the elderly are at increased mortality risk.
Abstract: Introduction. Population growth and increasing urbanization in earthquake-prone areas suggest that earthquake impacts on human populations will increase in the coming decades. Recent large earthquakes affecting large populations in Japan, Haiti, Chile and New Zealand are evidence of this trend and also illustrate significant variations in outcomes such damage and mortality levels. The objectives of this review were to describe the impact of earthquakes on human populations in terms of mortality, injury and displacement and, to the extent possible, identify risk factors associated with these outcomes. This is one of five reviews on the human impact of natural disasters. Methods. Data on the impact of earthquakes were compiled using two methods, a historical review from 1980 to mid 2009 of earthquake events from multiple databases and a systematic literature review of publications, ending in October 2012. Analysis included descriptive statistics and bivariate tests for associations between earthquake mortality and characteristics using STATA 11. Findings. From 1980 through 2009, there were a total of 372,634 deaths (range 314,634-412,599), 995,219 injuries (range: 845,345-1,145,093), and more than 61 million people affected by earthquakes, and mortality was greatest in Asia. Inconsistent reporting across data sources suggests that the numbers injured and affected are likely underestimates. Findings from a systematic review of the literature indicate that the primary cause of earthquake-related death was trauma due to building collapse and, the very young and the elderly were at increased mortality risk, while gender was not consistently associated with mortality risk. Conclusions. Strategies to mitigate the impact of future earthquakes should include improvements to the built environment and a focus on populations most vulnerable to mortality and injury.

364 citations


Journal ArticleDOI
TL;DR: The probability of drought-related health impacts varies widely and largely depends upon drought severity, baseline population vulnerability, existing health and sanitation infrastructure, and available resources with which to mitigate impacts as they occur.
Abstract: Introduction. Climate change projections indicate that droughts will become more intense in the 21 century in some areas of the world. The El Nino Southern Oscillation is associated with drought in some countries, and forecasts can provide advance warning of the increased risk of adverse climate conditions. The most recent available data from EMDAT estimates that over 50 million people globally were affected by drought in 2011. Documentation of the health effects of drought is difficult, given the complexity in assigning a beginning/end and because effects tend to accumulate over time. Most health impacts are indirect because of its link to other mediating circumstances like loss of livelihoods. Methods. The following databases were searched: MEDLINE; CINAHL; Embase; PsychINFO, Cochrane Collection. Key references from extracted papers were hand-searched, and advice from experts was sought for further sources of literature. Inclusion criteria for papers summarised in tables include: explicit link made between drought as exposure and human health outcomes; all study designs/methods; all countries/contexts; any year of publication. Exclusion criteria include: drought meaning shortage unrelated to climate; papers not published in English; studies on dry/arid climates unless drought was noted as an abnormal climatological event. No formal quality evaluation was used on papers meeting inclusion criteria. Results. 87 papers meeting the inclusion criteria are summarised in tables. Additionally, 59 papers not strictly meeting the inclusion criteria are used as supporting text in relevant parts of the results section. Main categories of findings include: nutrition-related effects (including general malnutrition and mortality, micronutrient malnutrition, and anti-nutrient consumption); water-related disease (including E coli, cholera and algal bloom); airborne and dust-related disease (including silo gas exposure and coccidioidomycosis); vector borne disease (including malaria, dengue and West Nile Virus); mental health effects (including distress and other emotional consequences); and other health effects (including wildfire, effects of migration, and damage to infrastructure). Conclusions. The probability of drought-related health impacts varies widely and largely depends upon drought severity, baseline population vulnerability, existing health and sanitation infrastructure, and available resources with which to mitigate impacts as they occur. The socio-economic environment in which drought occurs influences the resilience of the affected population. Forecasting can be used to provide advance warning of the increased risk of adverse climate conditions and can support the disaster risk reduction process. Despite the complexities involved in documentation, research should continue and results should be shared widely in an effort to strengthen drought preparedness and response activities.

282 citations


Journal ArticleDOI
TL;DR: Establishing a new phylogenetic pattern with accurate divergence dates for bony fishes illustrates several areas where the fossil record is incomplete and provides critical new insights on diversification of this important vertebrate group.
Abstract: Over half of all vertebrates are "fishes", which exhibit enormous diversity in morphology, physiology, behavior, reproductive biology, and ecology. Investigation of fundamental areas of vertebrate biology depend critically on a robust phylogeny of fishes, yet evolutionary relationships among the major actinopterygian and sarcopterygian lineages have not been conclusively resolved. Although a consensus phylogeny of teleosts has been emerging recently, it has been based on analyses of various subsets of actinopterygian taxa, but not on a full sample of all bony fishes. Here we conducted a comprehensive phylogenetic study on a broad taxonomic sample of 61 actinopterygian and sarcopterygian lineages (with a chondrichthyan outgroup) using a molecular data set of 21 independent loci. These data yielded a resolved phylogenetic hypothesis for extant Osteichthyes, including 1) reciprocally monophyletic Sarcopterygii and Actinopterygii, as currently understood, with polypteriforms as the first diverging lineage within Actinopterygii; 2) a monophyletic group containing gars and bowfin (= Holostei) as sister group to teleosts; and 3) the earliest diverging lineage among teleosts being Elopomorpha, rather than Osteoglossomorpha. Relaxed-clock dating analysis employing a set of 24 newly applied fossil calibrations reveals divergence times that are more consistent with paleontological estimates than previous studies. Establishing a new phylogenetic pattern with accurate divergence dates for bony fishes illustrates several areas where the fossil record is incomplete and provides critical new insights on diversification of this important vertebrate group.

188 citations


Journal ArticleDOI
TL;DR: Mid-upper-arm circumference (MUAC) was identified as the preferential indicator of choice because of its relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings) and it does not require prior knowledge of gestational age.
Abstract: Currently there is no consensus on how to identify pregnant women as acutely malnourished and when to enroll them in nutritional programmes. Medecins Sans Frontieres Switzerland undertook a literature review with the purpose of determining values of anthropometric indicators for acute malnutrition that are associated with adverse birth outcomes (such as low birth weight (LBW)), pre-term birth and intra-uterine growth retardation (IUGR). A literature search in PUBMED was done covering 1 January 1995 to 12 September 2012 with the key terms maternal anthropometry and pregnancy. The review focused on the humanitarian context. Mid-upper-arm circumference (MUAC) was identified as the preferential indicator of choice because of its relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings) and it does not require prior knowledge of gestational age. The MUAC values below which most adverse effects were identified were <22 and <23 cm. A conservative cut-off of <23 cm is recommended to include most pregnant women at risk of LBW for their infants in the African and Asian contexts.

161 citations


Journal ArticleDOI
TL;DR: The objective of this review was to describe the impact of cyclones on human populations in terms of mortality, injury, and displacement and, to the extent possible, identify risk factors associated with these outcomes.
Abstract: Background. Cyclones have significantly affected populations in Southeast Asia, the Western Pacific, and the Americas over the past quarter of a century. Future vulnerability to cyclones will increase due to factors including population growth, urbanization, increasing coastal settlement, and global warming. The objectives of this review were to describe the impact of cyclones on human populations in terms of mortality, injury, and displacement and, to the extent possible, identify risk factors associated with these outcomes. This is one of five reviews on the human impact of natural disasters. Methods. Data on the impact of cyclones were compiled using two methods, a historical review from 1980 to 2009 of cyclone events from multiple databases and a systematic literature review of publications ending in October 2012. Analysis included descriptive statistics and bivariate tests for associations between cyclone characteristics and mortality using Stata 11.0. Findings. There were 412,644 deaths, 290,654 injured, and 466.1 million people affected by cyclones between 1980 and 2009, and the mortality and injury burden was concentrated in less developed nations of Southeast Asia and the Western Pacific. Inconsistent reporting suggests this is an underestimate, particularly in terms of the injured and affected populations. The primary cause of cyclone-related mortality is drowning; in developed countries male gender was associated with increased mortality risk, whereas females experienced higher mortality in less developed countries. Conclusions. Additional attention to preparedness and early warning, particularly in Asia, can lessen the impact of future cyclones.

131 citations


Journal ArticleDOI
TL;DR: It is suggested that expedited manufacture and distribution of influenza vaccines after mild winters has the potential to mitigate the severity of future influenza epidemics.
Abstract: The 2012-13 influenza season had an unusually early and severe start in the US, succeeding the record mild 2011-12 influenza season, which occurred during the fourth warmest winter on record. Our analysis of climate and past US influenza epidemic seasons between 1997-98 to present indicates that warm winters tend to be followed by severe epidemics with early onset, and that these patterns are seen for both influenza A and B. We posit that fewer people are infected with influenza during warm winters, thereby leaving an unnaturally large fraction of susceptible individuals in the population going into the next season, which can lead to early and severe epidemics. In the event of continued global warming, warm winters such as that of 2011-12 are expected to occur more frequently. Our results thus suggest that expedited manufacture and distribution of influenza vaccines after mild winters has the potential to mitigate the severity of future influenza epidemics.

125 citations


Journal ArticleDOI
TL;DR: The social media messages posted immediately after and around the Boston Marathon bombings are examined, and it is found that specific keywords appear frequently prior to official public safety and news media reports.
Abstract: Immediately following the Boston Marathon attacks, individuals near the scene posted a deluge of data to social media sites. Previous work has shown that these data can be leveraged to provide rapid insight during natural disasters, disease outbreaks and ongoing conflicts that can assist in the public health and medical response. Here, we examine and discuss the social media messages posted immediately after and around the Boston Marathon bombings, and find that specific keywords appear frequently prior to official public safety and news media reports. Individuals immediately adjacent to the explosions posted messages within minutes via Twitter which identify the location and specifics of events, demonstrating a role for social media in the early recognition and characterization of emergency events. *Christopher Cassa and Rumi Chunara contributed equally to this work. Language: en

117 citations


Journal ArticleDOI
TL;DR: At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life (QoL) instrument scores, while at higher levels offunction, larger increases may be necessary to achieve the same QoL change score.
Abstract: Introduction: Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test (6MWT) in Duchenne muscular dystrophy as a minimal clinically important difference andclinically meaningfulperson-reported outcomes (PROs) at differing levels of ambulatory ability. Methods: We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures for the six-minute walk test (6MWT), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection Instrument (PODCI) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important differences (MCID) of PROs contribute to different estimates of 6-minute walk distance (6MWD) change at differing levels of ability. Results: PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated significant differences between DMD and controls (p Discussion: At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life (QoL) instrument scores. At higher levels of function, larger increases may be necessary to achieve the same QoL change score. Abstract Introduction: Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test (6MWT) in Duchenne muscular dystrophy as a minimal clinically important difference andclinically meaningfulperson-reported outcomes (PROs) at differing levels of ambulatory ability. Methods: We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures for the six-minute walk test (6MWT), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection Instrument (PODCI) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important differences (MCID) of PROs contribute to different estimates of 6-minute walk distance (6MWD) change at differing levels of ability. Results: PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated significant differences between DMD and controls (p Discussion: At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life (QoL) instrument scores. At higher levels of function, larger increases may be necessary to achieve the same QoL change score. Abstract Introduction: Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test (6MWT) in Duchenne muscular dystrophy as a minimal clinically important difference andclinically meaningfulperson-reported outcomes (PROs) at differing levels of ambulatory ability. Methods: We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures for the six-minute walk test (6MWT), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection Instrument (PODCI) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important differences (MCID) of PROs contribute to different estimates of 6-minute walk distance (6MWD) change at differing levels of ability. Results: PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated significant differences between DMD and controls (p Discussion: At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life (QoL) instrument scores. At higher levels of function, larger increases may be necessary to achieve the same QoL change score.

107 citations


Journal ArticleDOI
TL;DR: In this article, the reverse transcription isothermal Recombinase polymerase Amplification (RT-RPA) was used to detect Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in patient samples.
Abstract: The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the eastern Mediterranean and imported cases to Europe has alerted public health authorities. Currently, detection of MERS-CoV in patient samples is done by real-time RT-PCR. Samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. A rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. In this study, we describe the development of a reverse transcription isothermal Recombinase Polymerase Amplification (RT-RPA) assay for the identification of MERS- CoV. A partial nucleocapsid gene RNA molecular standard of MERS-coronavirus was used to determine the assay sensitivity. The isothermal (42∞C) MERS-CoV RT-RPA was as sensitive as real-time RT-PCR (10 RNA molecules), rapid (3-7 minutes) and mobile (using tubescanner weighing 1kg). The MERS-CoV RT-RPA showed cross-detection neither of any of the RNAs of several coronaviruses and respiratory viruses affecting humans nor of the human genome. The developed isothermal real-time RT-RPA is ideal for rapid mobile molecular MERS- CoV monitoring in acute patients and may also facilitate the search for the animal reservoir of MERS-CoV. Abstract The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the eastern Mediterranean and imported cases to Europe has alerted public health authorities. Currently, detection of MERS-CoV in patient samples is done by real-time RT-PCR. Samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. A rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. In this study, we describe the development of a reverse transcription isothermal Recombinase Polymerase Amplification (RT-RPA) assay for the identification of MERS- CoV. A partial nucleocapsid gene RNA molecular standard of MERS-coronavirus was used to determine the assay sensitivity. The isothermal (42∞C) MERS-CoV RT-RPA was as sensitive as real-time RT-PCR (10 RNA molecules), rapid (3-7 minutes) and mobile (using tubescanner weighing 1kg). The MERS-CoV RT-RPA showed cross-detection neither of any of the RNAs of several coronaviruses and respiratory viruses affecting humans nor of the human genome. The developed isothermal real-time RT-RPA is ideal for rapid mobile molecular MERS- CoV monitoring in acute patients and may also facilitate the search for the animal reservoir of MERS-CoV. Abstract The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the eastern Mediterranean and imported cases to Europe has alerted public health authorities. Currently, detection of MERS-CoV in patient samples is done by real-time RT-PCR. Samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. A rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. In this study, we describe the development of a reverse transcription isothermal Recombinase Polymerase Amplification (RT-RPA) assay for the identification of MERS- CoV. A partial nucleocapsid gene RNA molecular standard of MERS-coronavirus was used to determine the assay sensitivity. The isothermal (42∞C) MERS-CoV RT-RPA was as sensitive as real-time RT-PCR (10 RNA molecules), rapid (3-7 minutes) and mobile (using tubescanner weighing 1kg). The MERS-CoV RT-RPA showed cross-detection neither of any of the RNAs of several coronaviruses and respiratory viruses affecting humans nor of the human genome. The developed isothermal real-time RT-RPA is ideal for rapid mobile molecular MERS- CoV monitoring in acute patients and may also facilitate the search for the animal reservoir of MERS-CoV.

94 citations


Journal ArticleDOI
TL;DR: This paper reviews several applications of VR-based training in the United States, and reveals advantages as well as potential drawbacks and challenges associated with the implementation of such training platform.
Abstract: The advent of technologically-based approaches to disaster response training through Virtual Reality (VR) environments appears promising in its ability to bridge the gaps of other commonly established training formats. Specifically, the immersive and participatory nature of VR training offers a unique realistic quality that is not generally present in classroom-based or web-based training, yet retains considerable cost advantages over large-scale real-life exercises and other modalities and is gaining increasing acceptance. Currently, numerous government departments and agencies including the U.S. Department of Homeland Security (DHS), the Centers for Disease Control and Prevention (CDC) as well as academic institutions are exploring the unique advantages of VR-based training for disaster preparedness and response. Growing implementation of VR-based training for disaster preparedness and response, conducted either independently or combined with other training formats, is anticipated. This paper reviews several applications of VR-based training in the United States, and reveals advantages as well as potential drawbacks and challenges associated with the implementation of such training platform.

Journal ArticleDOI
TL;DR: The DecisionDx-UM gene expression profile test is a stand-alone platform which requires no other information for maximal prognostic accuracy and circumvents many of the drawbacks of chromosomal methods through the use of a highly sensitive microfluidics, PCR-based platform that simultaneously measures the expression of 15 carefully selected genes from primary uveal melanoma samples obtained by fine needle biopsy.
Abstract: Uveal melanoma (UM) is the most common primary cancer of the eye and has a strong propensity for metastasis. Although there have been many recent improvements in the diagnosis and treatment of UM, and only 2-4% of patients present with detectable metastasis, up to half of patients are at risk for dying of metastatic disease. Clinicopathologic factors are not accurate enough for individualized patient care. Chromosomal alterations have been used for prognostic purposes, but the routine clinical use of these methods is limited by their susceptibility to sampling error resulting from tumor heterogeneity, limited clinical validation, lack of standardized testing platforms, and high technical failure rates. In contrast, the DecisionDx-UM gene expression profile test is a stand-alone platform which requires no other information for maximal prognostic accuracy and which circumvents many of the drawbacks of chromosomal methods through the use of a highly sensitive microfluidics, PCR-based platform that simultaneously measures the expression of 15 carefully selected genes from primary uveal melanoma samples obtained by fine needle biopsy. Low metastatic risk is reported as Class 1, and high metastatic risk as Class 2. The test allows patients to be stratified into risk categories such that high-risk patients can be offered intensive metastatic surveillance and adjuvant therapy while low-risk patients can be spared these interventions. This test is now used as part of the standard of care in many ocular oncology centers.

Journal ArticleDOI
TL;DR: This paper calls on all sectors to recognise and address the specific health challenges posed by noncommunicable diseases in emergencies and disaster situations and highlight the need for increased research on morbidity and mortality patterns due to non Communicable diseases during and following emergencies.
Abstract: Recent years have demonstrated the devastating health consequences of complex emergencies and natural disasters and thereby highlighted the importance of comprehensive and collaborative approaches to humanitarian responses and risk reduction. Simultaneously, noncommunicable diseases are now recognised as a real and growing threat to population health and development; a threat that is magnified by and during emergencies. Noncommunicable diseases, however, continue to receive little attention from humanitarian organisations in the acute phase of disaster and emergency response. This paper calls on all sectors to recognise and address the specific health challenges posed by noncommunicable diseases in emergencies and disaster situations. This publication aims to highlight the need for: • Increased research on morbidity and mortality patterns due to noncommunicable diseases during and following emergencies; • Raised awareness through greater advocacy for the issue and challenges of noncommunicable diseases during and following emergencies; • Incorporation of noncommunicable diseases into existing emergency-related policies, standards, and resources; • Development of technical guidelines on the clinical management of noncommunicable diseases in emergencies; • Greater integration and coordination in health service provision during and following emergencies; • Integrating noncommunicable diseases into practical and academic training of emergency workers and emergency-response coordinators.

Journal ArticleDOI
TL;DR: Rec retrospective forecasts were generated for seasonal influenza epidemics using web-based estimates of influenza activity from Google Flu Trends for 2004-2005, 2007-2008 and 2012-2013 flu seasons.
Abstract: We present a framework for near real-time forecast of influenza epidemics using a simulation optimization approach. The method combines an individual-based model and a simple root finding optimization method for parameter estimation and forecasting. In this study, retrospective forecasts were generated for seasonal influenza epidemics using web-based estimates of influenza activity from Google Flu Trends for 2004-2005, 2007-2008 and 2012-2013 flu seasons. In some cases, the peak could be forecasted 5-6 weeks ahead. This study adds to existing resources for influenza forecasting and the proposed method can be used in conjunction with other approaches in an ensemble framework.

Journal ArticleDOI
TL;DR: Understanding global population movements out of the Middle East through the end of this year's Hajj could help direct anticipatory MERS-CoV surveillance and public health preparedness to mitigate its potential global health and economic impacts.
Abstract: BACKGROUND A novel coronavirus (MERS-CoV) causing severe, life-threatening respiratory disease has emerged in the Middle East at a time when two international mass gatherings in Saudi Arabia are imminent. While MERS-CoV has already spread to and within other countries, these mass gatherings could further amplify and/or accelerate its international dissemination, especially since the origins and geographic source of the virus remain poorly understood. METHODS We analyzed 2012 worldwide flight itinerary data and historic Hajj pilgrim data to predict population movements out of Saudi Arabia and the broader Middle East to help cities and countries assess their potential for MERS-CoV importation. We compared the magnitude of travel to countries with their World Bank economic status and per capita healthcare expenditures as surrogate markers of their capacity for timely detection of imported MERS-CoV and their ability to mount an effective public health response. RESULTS 16.8 million travelers flew on commercial flights out of Saudi Arabia, Jordan, Qatar, and the United Arab Emirates between June and November 2012, of which 51.6% were destined for India (16.3%), Egypt (10.4%), Pakistan (7.8%), the United Kingdom (4.3%), Kuwait (3.6%), Bangladesh (3.1%), Iran (3.1%) and Bahrain (2.9%). Among the 1.74 million foreign pilgrims who performed the Hajj last year, an estimated 65.1% originated from low and lower-middle income countries. CONCLUSION MERS-CoV is an emerging pathogen with pandemic potential with its apparent epicenter in Saudi Arabia, where millions of pilgrims will imminently congregate for two international mass gatherings. Understanding global population movements out of the Middle East through the end of this year's Hajj could help direct anticipatory MERS-CoV surveillance and public health preparedness to mitigate its potential global health and economic impacts.

Journal ArticleDOI
TL;DR: Results show that disorder prediction can be used as a tool that suggests clues to look for in further epidemiological investigations, and classify coronaviruses according to the hardness of their shells.
Abstract: A novel coronavirus, MERS-CoV (NCoV, HCoV-EMC/2012), originating from the Middle-East, has been discovered. Incoming data reveal that the virus is highly virulent to humans. A model that categorizes coronaviuses according to the hardness of their shells was developed before the discovery of MERS-CoV. Using protein intrinsic disorder prediction, coronaviruses were categorized into three groups that can be linked to the levels of oral-fecal and respiratory transmission regardless of genetic proximity. Using this model, MERS-CoV is placed into disorder group C, which consists of coronaviruses that have relatively hard inner and outer shells. The members of this group are likely to persist in the environment for a longer period of time and possess the highest oral-fecal components but relatively low respiratory transmission components. Oral-urine and saliva transmission are also highly possible since both require harder protective shells. Results show that disorder prediction can be used as a tool that suggests clues to look for in further epidemiological investigations. Abstract A novel coronavirus, MERS-CoV (NCoV, HCoV-EMC/2012), originating from the Middle-East, has been discovered. Incoming data reveal that the virus is highly virulent to humans. A model that categorizes coronaviuses according to the hardness of their shells was developed before the discovery of MERS-CoV. Using protein intrinsic disorder prediction, coronaviruses were categorized into three groups that can be linked to the levels of oral-fecal and respiratory transmission regardless of genetic proximity. Using this model, MERS-CoV is placed into disorder group C, which consists of coronaviruses that have relatively hard inner and outer shells. The members of this group are likely to persist in the environment for a longer period of time and possess the highest oral-fecal components but relatively low respiratory transmission components. Oral-urine and saliva transmission are also highly possible since both require harder protective shells. Results show that disorder prediction can be used as a tool that suggests clues to look for in further epidemiological investigations. Abstract A novel coronavirus, MERS-CoV (NCoV, HCoV-EMC/2012), originating from the Middle-East, has been discovered. Incoming data reveal that the virus is highly virulent to humans. A model that categorizes coronaviuses according to the hardness of their shells was developed before the discovery of MERS-CoV. Using protein intrinsic disorder prediction, coronaviruses were categorized into three groups that can be linked to the levels of oral-fecal and respiratory transmission regardless of genetic proximity. Using this model, MERS-CoV is placed into disorder group C, which consists of coronaviruses that have relatively hard inner and outer shells. The members of this group are likely to persist in the environment for a longer period of time and possess the highest oral-fecal components but relatively low respiratory transmission components. Oral-urine and saliva transmission are also highly possible since both require harder protective shells. Results show that disorder prediction can be used as a tool that suggests clues to look for in further epidemiological investigations.

Journal ArticleDOI
TL;DR: There is no therapeutic difference in EF improvement between lisinopril and losartan over the one-year duration for treatment of boys with DMD-related CM, and inter-observer and intra-ob server reliability studies showed no differences between echocardiographers on serial examinations.
Abstract: Objectives This study sought to compare the effectiveness and safety of an angiotensin converting enzyme inhibitor (ACE-I) (lisinopril) vs. an angiotensin receptor blocker (ARB) (losartan) for the treatment of cardiomyopathy (CM) in boys with Duchenne muscular dystrophy (DMD). Background Development of CM is universal in boys with DMD. ACE-I and ARB have both been suggested as effective treatment options. ARBs have been associated with skeletal muscle regeneration in a mouse model of DMD. The question of which, if either, is more effective for CM treatment in DMD remains. The purpose of this multicenter double-blind prospective study was to compare efficacy and safety of lisinopril versus losartan in the treatment of newly diagnosed CM in boys with DMD. Methods Echocardiographic technician inter- and intraobserver variability were tested on 2 separate days on 2 different boys with DMD CM. Results were compared with paired t-testing. Twenty-two boys with newly diagnosed DMD CM (echocardiographic ejection fraction (EF) 10% EF drop. Three boys in the aCE-I group had 3 visits, due to study funding termination. Two were withdrawn because of low EF. All their data are included in the analysis for as long as they remained in the study. Mean EF's were similar at baseline (47.5%- ACE-I, 48.4%- ARB). After 1 year each group significantly improved to 54.6% and 55.2% respectively (p=.02). There was no difference between the 2 treatment groups at 1 year. Conclusions Inter-observer and intra-observer reliability studies showed no differences between echocardiographers on serial examinations. EF improved equally in the two groups. There is no therapeutic difference in EF improvement between lisinopril and losartan over the one-year duration for treatment of boys with DMD-related CM. Trial registration ClinicalTrials.gov NCT01982695.

Journal ArticleDOI
TL;DR: The findings suggest that participation in an intensive rehabilitation program is well tolerated among motivated patients with early to mid-stage Huntington’s disease.
Abstract: Objective: To assess effects of a two year intensive, multidisciplinary rehabilitation program for patients with early- to mid-stage Huntington's disease. Design: A prospective intervention study. Setting: One inpatient rehabilitation center in Norway. Subjects: 10 patients, with early- to mid-stage Huntington's disease. Interventions: A two year rehabilitation program, consisting of six admissions of three weeks each, and two evaluation stays approximately three months after the third and sixth rehabilitation admission. The program focused on physical exercise, social activities, and group/teaching sessions. Main outcome measures: Standard measures for motor function, including gait and balance, cognitive function, including MMSE and UHDRS cognitive assessment, anxiety and depression, activities of daily living (ADL), health related quality of life (QoL) and Body Mass Index (BMI). Results: Six out of ten patients completed the full program. Slight, but non-significant, decline was observed for gait and balance from baseline to the evaluation stay after two years. Non-significant improvements were observed in physical QoL, anxiety and depression, and BMI. ADL-function remained stable with no significant decline. None of the cognitive measures showed a significant decline. An analysis of individual cases revealed that four out of the six participants who completed the program sustained or improved their motor function, while motor function declined in two participants. All the six patients who completed the program reported improved or stable QoL throughout the study period. Conclusion: Our findings suggest that participation in an intensive rehabilitation program is well tolerated among motivated patients with early to mid-stage HD. The findings should be interpreted with caution due to the small sample size in this study. Abstract Objective: To assess effects of a two year intensive, multidisciplinary rehabilitation program for patients with early- to mid-stage Huntington's disease. Design: A prospective intervention study. Setting: One inpatient rehabilitation center in Norway. Subjects: 10 patients, with early- to mid-stage Huntington's disease. Interventions: A two year rehabilitation program, consisting of six admissions of three weeks each, and two evaluation stays approximately three months after the third and sixth rehabilitation admission. The program focused on physical exercise, social activities, and group/teaching sessions. Main outcome measures: Standard measures for motor function, including gait and balance, cognitive function, including MMSE and UHDRS cognitive assessment, anxiety and depression, activities of daily living (ADL), health related quality of life (QoL) and Body Mass Index (BMI). Results: Six out of ten patients completed the full program. Slight, but non-significant, decline was observed for gait and balance from baseline to the evaluation stay after two years. Non-significant improvements were observed in physical QoL, anxiety and depression, and BMI. ADL-function remained stable with no significant decline. None of the cognitive measures showed a significant decline. An analysis of individual cases revealed that four out of the six participants who completed the program sustained or improved their motor function, while motor function declined in two participants. All the six patients who completed the program reported improved or stable QoL throughout the study period. Conclusion: Our findings suggest that participation in an intensive rehabilitation program is well tolerated among motivated patients with early to mid-stage HD. The findings should be interpreted with caution due to the small sample size in this study. Abstract Objective: To assess effects of a two year intensive, multidisciplinary rehabilitation program for patients with early- to mid-stage Huntington's disease. Design: A prospective intervention study. Setting: One inpatient rehabilitation center in Norway. Subjects: 10 patients, with early- to mid-stage Huntington's disease. Interventions: A two year rehabilitation program, consisting of six admissions of three weeks each, and two evaluation stays approximately three months after the third and sixth rehabilitation admission. The program focused on physical exercise, social activities, and group/teaching sessions. Main outcome measures: Standard measures for motor function, including gait and balance, cognitive function, including MMSE and UHDRS cognitive assessment, anxiety and depression, activities of daily living (ADL), health related quality of life (QoL) and Body Mass Index (BMI). Results: Six out of ten patients completed the full program. Slight, but non-significant, decline was observed for gait and balance from baseline to the evaluation stay after two years. Non-significant improvements were observed in physical QoL, anxiety and depression, and BMI. ADL-function remained stable with no significant decline. None of the cognitive measures showed a significant decline. An analysis of individual cases revealed that four out of the six participants who completed the program sustained or improved their motor function, while motor function declined in two participants. All the six patients who completed the program reported improved or stable QoL throughout the study period. Conclusion: Our findings suggest that participation in an intensive rehabilitation program is well tolerated among motivated patients with early to mid-stage HD. The findings should be interpreted with caution due to the small sample size in this study.

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TL;DR: Estimates confirm that badgers do play a role in bovine TB transmission, and inform debate even if they do not point to a single way forward.
Abstract: The role of badgers in the transmission and maintenance of bovine tuberculosis (TB) in British cattle is widely debated as part of the wider discussions on whether badger culling and/or badger vaccination should play a role in the government's strategy to eradicate cattle TB. The key source of information on the contribution from badgers within high-cattle-TB-incidence areas of England is the Randomised Badger Culling Trial (RBCT), with two analyses providing estimates of the average overall contribution of badgers to confirmed cattle TB in these areas. A dynamical model characterizing the association between the estimated prevalence of Mycobacterium bovis (the causative agent of bovine TB) among badgers culled in the initial RBCT proactive culls and the incidence among sympatric cattle herds prior to culling is used to estimate the average overall contribution of badgers to confirmed TB herd breakdowns among proactively culled areas. The resulting estimate based on all data (52%) has considerable uncertainty (bootstrap 95% confidence interval (CI): 9.1-100%). Separate analyses of experimental data indicated that the largest estimated reduction in confirmed cattle TB achieved inside the proactive culling areas was 54% (overdispersion-adjusted 95% CI: 38-66%), providing a lower bound for the average overall contribution of badgers to confirmed cattle TB. Thus, taking into account both results, the best estimate of the average overall contribution of badgers is roughly half, with 38% being a robustly estimated lower bound. However, the dynamical model also suggested that only 5.7% (bootstrap 95% CI: 0.9-25%) of the transmission to cattle herds is badger-to-cattle with the remainder of the average overall contribution from badgers being in the form of onward cattle-to-cattle transmission. These estimates, confirming that badgers do play a role in bovine TB transmission, inform debate even if they do not point to a single way forward.

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TL;DR: There is a need for studies comparing the clinical validity of SLCO1B1 rs4149056 genotyping with risk scores for myopathy based on other factors such as racial background, statin type and dose, gender, body mass index, co-medications and co-morbidities.
Abstract: Statin drugs are highly effective in lowering blood concentrations of LDL-cholesterol, with concomitant reduction in risk of major cardiovascular events. Although statins are generally regarded as safe and well-tolerated, some users develop muscle symptoms that are mostly mild but in rare cases can lead to life-threatening rhabdomyolysis. The SEARCH genome-wide association study, which has been independently replicated, found a significant association between the rs4149056 (c.521T>C) single-nucleotide polymorphism (SNP) in the SLCO1B1 gene, and myopathy in individuals taking 80 mg simvastatin per day, with an odds ratio of 4.5 per rs4149056 C allele. The purpose of this paper is to assemble evidence relating to the analytical validity, clinical validity and clinical utility of using SLCO1B1 rs4149056 genotyping to inform choice and dose of statin treatment, with the aim of minimising statin-induced myopathy and increasing adherence to therapy. Genotyping assays for the rs4149056 SNP appear to be robust and accurate, though direct evidence for the performance of array-based platforms in genotyping individual SNPs was not found. Using data from the SEARCH study, calculated values for the clinical sensitivity, specificity, positive- and negative-predictive values of a test for the C allele to predict definite or incipient myopathy during 5 years of 80 mg/day simvastatin use were 70.4%, 73.7%, 4.1% and 99.4% respectively. There is a need for studies comparing the clinical validity of SLCO1B1 rs4149056 genotyping with risk scores for myopathy based on other factors such as racial background, statin type and dose, gender, body mass index, co-medications and co-morbidities. No direct evidence was found for clinical utility of statin prescription guided by SLCO1B1 genotype.

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TL;DR: Only half the patients with severe limb injuries, whether managed with amputation or limb preservation, deemed their functional status satisfactory at 2 years, indicating a worsening of the perceived functional status, significantly more pronounced in amputees, and an increase in pain complaints.
Abstract: Background Severe limb trauma is common in earthquake survivors. Overall medium term outcomes and patient-perceived outcomes are poorly documented. Methods and Findings The prospective study SuTra2 assessed the functional and socio-economic status of a cohort of patients undergoing surgery for limb injury resulting in amputation (A) or limb preservation (LP) one year and two years after the 2010 Haiti earthquake. 305 patients [A: n=199 (65%), LP: n=106 (35%)] were evaluated. Their characteristics were: 57% female; mean age 31 years; 74% of principal injuries involved the lower limb; 46% of patients had an additional severe injury; 60% had fractures, of which two-thirds were compound or associated with severe soft tissue damage; 15% of amputations were traumatic. At 2 years, 51% of patients were satisfied with the functional outcome (A: 52%, LP: 49%, ns). Comparison with the 1-year status indicates a worsening of the perceived functional status, significantly more pronounced in amputees, and an increase in pain complaints, mainly in amputees (62% and 80% of pain in overall population at 1- and 2-year respectively). Twenty eight percent (28%) of LP and 66% of A considered themselves as "cured". 100% of LP and 79% of A would have chosen a conservative approach if an amputation was medically avoidable. Two years after the earthquake, 23·5 % of patients were still living in a tent, 30% were working, and 25·5% needed ongoing surgical management. Conclusions Only half the patients with severe limb injuries, whether managed with amputation or limb preservation, deemed their functional status satisfactory at 2 years. The patients' perspective, clearly favors limb conservative management whenever possible. Prolonged care and rehabilitation are needed to optimize the outcome for earthquake survivors with limb injuries. Humanitarian respondents to catastrophes have professional and ethical obligations to provide optimal immediate care and ensure scrupulous attention to long-term management. Keywords Haiti earthquake, limb injury, two-year outcome, patients' perspective, amputation, limb salvage.

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TL;DR: Differences in age categorization of pediatric patients, and in the injury classification system make quantifying the burden of earthquake-related injuries in the pediatric population difficult.
Abstract: Background Children are a special population, particularly susceptible to injury. Registries for various injury types in the pediatric population are important, not only for epidemiological purposes but also for their implications on intervention programs. Although injury registries already exist, there is no uniform injury classification system for traumatic mass casualty events such as earthquakes. Objective To systematically review peer-reviewed literature on the patterns of earthquake-related injuries in the pediatric population. Methods On May 14, 2012, the authors performed a systematic review of literature from 1950 to 2012 indexed in Pubmed, EMBASE, Scopus, Web of Science, and Cochrane Library. Articles written in English, providing a quantitative description of pediatric injuries were included. Articles focusing on other types of disasters, geological, surgical, conceptual, psychological, indirect injuries, injury complications such as wound infections and acute kidney injury, case reports, reviews, and non-English articles were excluded. Results A total of 2037 articles were retrieved, of which only 10 contained quantitative earthquake-related pediatric injury data. All studies were retrospective, had different age categorization, and reported injuries heterogeneously. Only 2 studies reported patterns of injury for all pediatric patients, including patients admitted and discharged. Seven articles described injuries by anatomic location, 5 articles described injuries by type, and 2 articles described injuries using both systems. Conclusions Differences in age categorization of pediatric patients, and in the injury classification system make quantifying the burden of earthquake-related injuries in the pediatric population difficult. A uniform age categorization and injury classification system are paramount for drawing broader conclusions, enhancing disaster preparation for future disasters, and decreasing morbidity and mortality.

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TL;DR: The goal is to assemble large phenomic datasets built using new methods and to provide the public and scientific community with tools for phenomic data assembly that will enable rapid and automated study of phenotypes across the Tree of Life.
Abstract: The phenotype represents a critical interface between the genome and the environment in which organisms live and evolve. Phenotypic characters also are a rich source of biodiversity data for tree building, and they enable scientists to reconstruct the evolutionary history of organisms, including most fossil taxa, for which genetic data are unavailable. Therefore, phenotypic data are necessary for building a comprehensive Tree of Life. In contrast to recent advances in molecular sequencing, which has become faster and cheaper through recent technological advances, phenotypic data collection remains often prohibitively slow and expensive. The next- generation phenomics project is a collaborative, multidisciplinary effort to leverage advances in image analysis, crowdsourcing, and natural language processing to develop and implement novel approaches for discovering and scoring the phenome, the collection of phentotypic characters for a species. This research represents a new approach to data collection that has the potential to transform phylogenetics research and to enable rapid advances in constructing the Tree of Life. Our goal is to assemble large phenomic datasets built using new methods and to provide the public and scientific community with tools for phenomic data assembly that will enable rapid and automated study of phenotypes across the Tree of Life. Abstract The phenotype represents a critical interface between the genome and the environment in which organisms live and evolve. Phenotypic characters also are a rich source of biodiversity data for tree building, and they enable scientists to reconstruct the evolutionary history of organisms, including most fossil taxa, for which genetic data are unavailable. Therefore, phenotypic data are necessary for building a comprehensive Tree of Life. In contrast to recent advances in molecular sequencing, which has become faster and cheaper through recent technological advances, phenotypic data collection remains often prohibitively slow and expensive. The next- generation phenomics project is a collaborative, multidisciplinary effort to leverage advances in image analysis, crowdsourcing, and natural language processing to develop and implement novel approaches for discovering and scoring the phenome, the collection of phentotypic characters for a species. This research represents a new approach to data collection that has the potential to transform phylogenetics research and to enable rapid advances in constructing the Tree of Life. Our goal is to assemble large phenomic datasets built using new methods and to provide the public and scientific community with tools for phenomic data assembly that will enable rapid and automated study of phenotypes across the Tree of Life. Abstract The phenotype represents a critical interface between the genome and the environment in which organisms live and evolve. Phenotypic characters also are a rich source of biodiversity data for tree building, and they enable scientists to reconstruct the evolutionary history of organisms, including most fossil taxa, for which genetic data are unavailable. Therefore, phenotypic data are necessary for building a comprehensive Tree of Life. In contrast to recent advances in molecular sequencing, which has become faster and cheaper through recent technological advances, phenotypic data collection remains often prohibitively slow and expensive. The next- generation phenomics project is a collaborative, multidisciplinary effort to leverage advances in image analysis, crowdsourcing, and natural language processing to develop and implement novel approaches for discovering and scoring the phenome, the collection of phentotypic characters for a species. This research represents a new approach to data collection that has the potential to transform phylogenetics research and to enable rapid advances in constructing the Tree of Life. Our goal is to assemble large phenomic datasets built using new methods and to provide the public and scientific community with tools for phenomic data assembly that will enable rapid and automated study of phenotypes across the Tree of Life.

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TL;DR: There is a strong bias towards victimisation of young people, the elderly and women in the data set covering the 308 fatalities in the L'Aquila earthquake, and age and gender biases need to be taken into account in seismic mitigation initiatives.
Abstract: This paper presents the results of an analysis of data on mortality in the magnitude 63 earthquake that struck the central Italian city and province of L'Aquila during the night of 6 April 2009 The aim is to create a profile of the deaths in terms of age, gender, location, behaviour during the tremors, and other aspects This could help predict the pattern of casualties and priorities for protection in future earthquakes To establish a basis for analysis, the literature on seismic mortality is surveyed The conclusions of previous studies are synthesised regarding patterns of mortality, entrapment, survival times, self-protective behaviour, gender and age These factors are investigated for the data set covering the 308 fatalities in the L'Aquila earthquake, with help from interview data on behavioural factors obtained from 250 survivors In this data set, there is a strong bias towards victimisation of young people, the elderly and women Part of this can be explained by geographical factors regarding building performance: the rest of the explanation refers to the vulnerability of the elderly and the relationship between perception and action among female victims, who tend to be more fatalistic than men and thus did not abandon their homes between a major foreshock and the main shock of the earthquake, three hours later In terms of casualties, earthquakes commonly discriminate against the elderly and women Age and gender biases need further investigation and should be taken into account in seismic mitigation initiatives

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TL;DR: The data support the concept that autophagy is impaired in the tibialis anterior muscle of mdx mice and that the regulation of autphagy is muscle type dependent, and differences between muscle groups should be considered during the pre-clinical development of therapeutic strategies addressing muscle metabolism.
Abstract: Background Duchenne muscular dystrophy is a lethal, progressive, muscle-wasting disease caused by mutations in the DMD gene. Structural remodelling processes are responsible for muscle atrophy and replacement of myofibers by fibrotic and adipose tissues. Molecular interventions modulating catabolic pathways, such as the ubiquitin-proteasome and the autophagy-lysosome systems, are under development for Duchenne and other muscular dystrophies. The Akt signaling cascade is one of the main pathways involved in protein synthesis and autophagy repression and is known to be up-regulated in dystrophin null mdx mice. Results We report that autophagy is triggered by fasting in the tibialis anterior muscle of control mice but not in mdx mice. Mdx mice show persistent Akt activation upon fasting and failure to increase the expression of FoxO3 regulated autophagy and atrophy genes, such as Bnip3 and Atrogin1. We also provide evidence that autophagy is differentially regulated in mdx tibialis anterior and diaphragm muscles. Conclusions Our data support the concept that autophagy is impaired in the tibialis anterior muscle of mdx mice and that the regulation of autophagy is muscle type dependent. Differences between muscle groups should be considered during the pre-clinical development of therapeutic strategies addressing muscle metabolism. Abstract Background Duchenne muscular dystrophy is a lethal, progressive, muscle-wasting disease caused by mutations in the DMD gene. Structural remodelling processes are responsible for muscle atrophy and replacement of myofibers by fibrotic and adipose tissues. Molecular interventions modulating catabolic pathways, such as the ubiquitin-proteasome and the autophagy-lysosome systems, are under development for Duchenne and other muscular dystrophies. The Akt signaling cascade is one of the main pathways involved in protein synthesis and autophagy repression and is known to be up-regulated in dystrophin null mdx mice. Results We report that autophagy is triggered by fasting in the tibialis anterior muscle of control mice but not in mdx mice. Mdx mice show persistent Akt activation upon fasting and failure to increase the expression of FoxO3 regulated autophagy and atrophy genes, such as Bnip3 and Atrogin1. We also provide evidence that autophagy is differentially regulated in mdx tibialis anterior and diaphragm muscles. Conclusions Our data support the concept that autophagy is impaired in the tibialis anterior muscle of mdx mice and that the regulation of autophagy is muscle type dependent. Differences between muscle groups should be considered during the pre-clinical development of therapeutic strategies addressing muscle metabolism. Abstract Background Duchenne muscular dystrophy is a lethal, progressive, muscle-wasting disease caused by mutations in the DMD gene. Structural remodelling processes are responsible for muscle atrophy and replacement of myofibers by fibrotic and adipose tissues. Molecular interventions modulating catabolic pathways, such as the ubiquitin-proteasome and the autophagy-lysosome systems, are under development for Duchenne and other muscular dystrophies. The Akt signaling cascade is one of the main pathways involved in protein synthesis and autophagy repression and is known to be up-regulated in dystrophin null mdx mice. Results We report that autophagy is triggered by fasting in the tibialis anterior muscle of control mice but not in mdx mice. Mdx mice show persistent Akt activation upon fasting and failure to increase the expression of FoxO3 regulated autophagy and atrophy genes, such as Bnip3 and Atrogin1. We also provide evidence that autophagy is differentially regulated in mdx tibialis anterior and diaphragm muscles. Conclusions Our data support the concept that autophagy is impaired in the tibialis anterior muscle of mdx mice and that the regulation of autophagy is muscle type dependent. Differences between muscle groups should be considered during the pre-clinical development of therapeutic strategies addressing muscle metabolism.

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TL;DR: A significant reduction in complex II and complex IV flux control ratios was found in the R6/2 mouse striatum at 12 weeks of age compared to controls, confirming previous findings obtained with spectrophotometric enzyme assays.
Abstract: Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system (ETS). In different models of HD, evidence of enzyme defects have been reported in complex II and complex IV using enzyme assays. However, such assays are highly variable and results have been inconsistent. We investigated the integrated ETS function ex vivo using a sensitive high-resolution respirometric (HRR) method. The O2 flux in a whole-cell sample combined with the addition of mitochondrial substrates, uncouplers and inhibitors enabled us to accurately quantitate the function of individual mitochondrial complexes in intact mitochondria, while retaining mitochondrial regulation and compensatory mechanisms. We used HRR to examine the mitochondrial function in striata from 12-week old R6/2 mice expressing exon 1 of human HTT with 130 CAG repeats. A significant reduction in complex II and complex IV flux control ratios was found in the R6/2 mouse striatum at 12 weeks of age compared to controls, confirming previous findings obtained with spectrophotometric enzyme assays.

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TL;DR: This work extends the prior demonstration that PhenoCube™ can characterize circadian dysfunction in BACHD mice and shows that this system is a sensitive and efficient tool for a first pass high-throughput screening of mouse disease models in general and mouse models of neurodegeneration in particular.
Abstract: Phenotyping with traditional behavioral assays constitutes a major bottleneck in the primary screening, characterization, and validation of genetic mouse models of disease, leading to downstream delays in drug discovery efforts. We present a novel and comprehensive one-stop approach to phenotyping, the PhenoCube!". This system simultaneously captures the cognitive performance, motor activity, and circadian patterns of group- housed mice by use of home-cage operant conditioning modules (IntelliCage) and custom-built computer vision software. We evaluated two different mouse models of Huntingtons Disease (HD), the R6/2 and the BACHD in the PhenoCube!" system. Our results demonstrated that this system can efficiently capture and track alterations in both cognitive performance and locomotor activity patterns associated with these disease models. This work extends our prior demonstration that PhenoCube!" can characterize circadian dysfunction in BACHD mice and shows that this system, with the experimental protocols used, is a sensitive and efficient tool for a first pass high-throughput screening of mouse disease models in general and mouse models of neurodegeneration in particular. Abstract Phenotyping with traditional behavioral assays constitutes a major bottleneck in the primary screening, characterization, and validation of genetic mouse models of disease, leading to downstream delays in drug discovery efforts. We present a novel and comprehensive one-stop approach to phenotyping, the PhenoCube!". This system simultaneously captures the cognitive performance, motor activity, and circadian patterns of group- housed mice by use of home-cage operant conditioning modules (IntelliCage) and custom-built computer vision software. We evaluated two different mouse models of Huntingtons Disease (HD), the R6/2 and the BACHD in the PhenoCube!" system. Our results demonstrated that this system can efficiently capture and track alterations in both cognitive performance and locomotor activity patterns associated with these disease models. This work extends our prior demonstration that PhenoCube!" can characterize circadian dysfunction in BACHD mice and shows that this system, with the experimental protocols used, is a sensitive and efficient tool for a first pass high-throughput screening of mouse disease models in general and mouse models of neurodegeneration in particular. Abstract Phenotyping with traditional behavioral assays constitutes a major bottleneck in the primary screening, characterization, and validation of genetic mouse models of disease, leading to downstream delays in drug discovery efforts. We present a novel and comprehensive one-stop approach to phenotyping, the PhenoCube!". This system simultaneously captures the cognitive performance, motor activity, and circadian patterns of group- housed mice by use of home-cage operant conditioning modules (IntelliCage) and custom-built computer vision software. We evaluated two different mouse models of Huntingtons Disease (HD), the R6/2 and the BACHD in the PhenoCube!" system. Our results demonstrated that this system can efficiently capture and track alterations in both cognitive performance and locomotor activity patterns associated with these disease models. This work extends our prior demonstration that PhenoCube!" can characterize circadian dysfunction in BACHD mice and shows that this system, with the experimental protocols used, is a sensitive and efficient tool for a first pass high-throughput screening of mouse disease models in general and mouse models of neurodegeneration in particular.

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TL;DR: An overview of the health needs following the Great East Japan Earthquake Disaster and the lessons identified highlighted the specific health needs of the vulnerable populations, particularly the elderly and those with non-communicable diseases.
Abstract: Objective To provide an overview of the health needs following the Great East Japan Earthquake Disaster and the lessons identified. Methods The relevant of peer review and grey literature articles in English and Japanese, and books in Japanese, published from March 2011 to September 2012 were searched. Medline, Embase, PsycINFO, and HMIC were searched for journal articles in English, CiNii for those in Japanese, and Amazon.co.jp. for books. Descriptions of the health needs at the time of the disaster were identified using search terms and relevant articles were reviewed. Findings 85 English articles, 246 Japanese articles and 13 books were identified, the majority of which were experience/activity reports. Regarding health care needs, chronic conditions such as hypertension and diabetes were reported to be the greatest burden from the early stages of the disaster. Loss of medication and medical records appeared to worsen the situation. Many sub-acute symptoms were attributed to the contaminated sludge of the tsunamis and the poor living environment at the evacuation centres. Particularly vulnerable groups were identified as the elderly, those with mental health illnesses and the disabled. Although the response of the rescue activities was prompt, it sometimes failed to meet the on-site needs due to the lack of communication and coordination. Conclusion The lessons identified from this mega-disaster highlighted the specific health needs of the vulnerable populations, particularly the elderly and those with non-communicable diseases. Further research is needed so that the lessons identified can be incorporated into future contingency plans in Japan and elsewhere.

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TL;DR: These preliminary findings from the Evidence Aid survey emphasise the need for “global” evidence but also the need that this be supplemented by local and context-specific knowledge.
Abstract: Objectives: This paper presents the initial data analysis for a survey to identify the attitudes towards systematic reviews and research of those involved in the humanitarian response to natural disasters and other crises; their priorities for evidence, and their preferences for accessing this information. Methods: Snowballing sampling techniques were used to recruit participants who identified themselves as humanitarian aid workers, with or without experience in providing funding to aid agencies. An online questionnaire with both quantitative and qualitative questions was made available to participants using a variety of e-mail lists. Quantitative responses from 85 participants to a selection of questions were descriptively analysed using SPSS. Abstract Objectives: This paper presents the initial data analysis for a survey to identify the attitudes towards systematic reviews and research of those involved in the humanitarian response to natural disasters and other crises; their priorities for evidence, and their preferences for accessing this information. Methods: Snowballing sampling techniques were used to recruit participants who identified themselves as humanitarian aid workers, with or without experience in providing funding to aid agencies. An online questionnaire with both quantitative and qualitative questions was made available to participants using a variety of e-mail lists. Quantitative responses from 85 participants to a selection of questions were descriptively analysed using SPSS. Abstract Objectives: This paper presents the initial data analysis for a survey to identify the attitudes towards systematic reviews and research of those involved in the humanitarian response to natural disasters and other crises; their priorities for evidence, and their preferences for accessing this information. Methods: Snowballing sampling techniques were used to recruit participants who identified themselves as humanitarian aid workers, with or without experience in providing funding to aid agencies. An online questionnaire with both quantitative and qualitative questions was made available to participants using a variety of e-mail lists. Quantitative responses from 85 participants to a selection of questions were descriptively analysed using SPSS.

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TL;DR: It is hypothesized that some areas of lingering cholera transmission during the dry season could play an important role in the re-emergence of outbreaks during the rainy season and a deficiency in the fight against cholERA, especially at a period when transmission is weak, may explain the persistence of the disease even in the absence of significant aquatic reservoirs in Haiti.
Abstract: BACKGROUND: Since the beginning of the cholera epidemic in Haiti, attack rates have varied drastically with alternating peak and lull phases, which were partly associated with the fluctuating dry, rainy and cyclonic seasons. According to a study conducted in 2012, the toxigenic V. cholerae O1 strain responsible for the outbreak did not settle at a significant level in the Haitian aquatic environment. Therefore, we hypothesize that some areas of lingering cholera transmission during the dry season could play an important role in the re-emergence of outbreaks during the rainy season. Our objective was therefore to describe the dynamics of cholera and assess the fight against the disease during the dry season. METHODS: A field study was conducted from February 19 to March 29, 2013. After identifying the affected communes by analyzing the national cholera database, we visited corresponding health facilities to identify patient origins. We then conducted a field assessment of these foci to confirm the presence of cholera, assess factors associated with transmission and examine the activities implemented to control the epidemic since the beginning of the current dry season. RESULTS: We found that the great majority of Haitian communes (109/140) presented no sign of cholera transmission in February and March 2013. Suspected cases were concentrated in a small number of urban and rural areas, almost all of which were located in the northern half of the country and often in inland locales. In these areas, community health activities appeared insufficient and were often inappropriately targeted. Out of 49 analyzed foci, only 10 had benefited from at least one intervention involving the distribution of water treatment products together with an awareness campaign since December 2012. CONCLUSION: Cholera continues to affect Haiti as observed in early 2013; however, activities implemented to interrupt cholera transmission appear insufficient and poorly suited. This deficiency in the fight against cholera, especially at a period when transmission is weak, may explain the persistence of cholera even in the absence of significant aquatic reservoirs in Haiti.