bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Food and Drug Administration Advisory Committee Recommendations and Agency Actions, 2008–2015
Authors: ZHANG AUDREY D. , SCHWARTZ JASON L. , ROSS JOSEPH S. 
Published: July 2019

Policy Points
Food and Drug Administration (FDA) advisory committee recommendations and the agency's final actions exhibit high rates of agreement, with cases of disagreement tending to reflect the proposed action type and degree of advisory committee consensus.
In the case of disagreements, the FDA tended to be less likely than its advisory committees to approve new products, approve new supplemental indications, or enact new safety changes.
These findings raise important issues regarding the factors that differentially shape decision making by advisory committees and the FDA as an agency, including institutional or reputational concerns.
ContextThe Food and Drug Administration (FDA) convenes advisory committees to provide external scientific counsel on potential agency actions and to inform regulatory decision making. The degree to which advisory committees and their respective agency divisions disagree on recommendations has not been well characterized across product and action types.MethodsWe examined public documents from FDA advisory committee meetings and medical product databases for all FDA advisory committee meetings from 2008 through 2015. We classified the 376 voting meetings in that period by medical product, regulatory, and advisory committee meeting characteristics. We used multivariable logistic regression to determine the associations between these characteristics and discordance between the advisory committee's recommendations and the FDA's final actions.FindingsTwenty‐two percent of the FDA's final actions were discordant with the advisory committee's recommendations. Of these, 75% resulted in the FDA making more restrictive decisions after favorable committee recommendations, and 25% resulted in the agency making less restrictive decisions after unfavorable committee recommendations. Discordance was associated with lower degrees of advisory committee consensus and was more likely for agency actions focused on medical product safety than for novel approvals or supplemental indications. Statements by public speakers, advisory committee conflicts of interest, and media coverage were not associated with discordance between the committee and the agency.ConclusionsThe FDA disagrees with the recommendation of its advisory committees a minority of the time, and in these cases it tends to be less likely to approve new products or supplemental indications and take safety actions. Deviations from recommendations thus offer an opportunity to understand the factors influencing decisions made by both the agency and its expert advisory groups.
Cases of Kava Impairment in Iowa Drivers
Authors: Berry Jonna , Gilbert Ashley , Grodnitzky Justin 
Published: July 2019

AbstractKava is an Oceanic plant in which the root is consumed as a beverage and is becoming increasingly popular. The effects of kava consumption may include sedation, euphoria, and impairment of motor coordination. This article demonstrates kava impairment through four cases of self‐reported kava use supported with Drug Recognition Expert (DRE) evaluations of each subject. Subject's urines screened negative for common drugs of abuse by immunoassay analysis. Urine from cases 3 and 4 were analyzed by liquid chromatography–tandem mass spectrometry, and gas chromatography–mass spectrometry, which yielded the presence of kavalactones. Subjects exhibited poor driving behavior and signs of intoxication. Indicators of impairment from multiple drug categories, central nervous system (CNS) depressants, CNS stimulants, and cannabis were observed, which may be consistent with the presence of multiple kavalactones and their diverse array of mechanisms of action. The consumption of kava can hinder one's ability to operate a vehicle safely.
Using unmanned aerial vehicles with thermal‐image acquisition cameras for animal surveys: a case study on the Sichuan snub‐nosed monkey in the Qinling Mountains
Authors: HE Gang , YANG Haitao , PAN Ruliang , SUN Yewen , ZHENG Pengbin , WANG Jinghua , JIN Xuelin , ZHANG Jingjie , LI Baoguo , GUO Songtao 
Published: July 2019

AbstractFollowing significant developments in technology, alternative devices have been applied in fieldwork for animal and plant surveys. Thermal‐image acquisition cameras installed on unmanned aerial vehicles (UAVs) have been used in animal surveys in the wilderness. This article demonstrates an example of how UAVs can be used in high mountainous regions, presenting a case study on the Sichuan snub‐nosed monkey with a detection rate of 65.19% for positive individual identification. It also presents a model that can prospectively predict population size for a given animal species, which is based on combined initial work using UAVs and traditional surveys on the ground. A great potential advantage of UAVs is significantly shortening survey procedures, particularly for areas with high mountains and plateaus, such as the Himalayas, the Qinghai–Tibet Plateau, Hengduan Mountains, the Yunnan‐Gui Plateau and Qinling Mountains in China, where carrying out a traditional survey is extremely difficult, so that species and population surveys, particularly for critically endangered animals, are largely absent. This lack of data has impacted the management of endangered animals as well as the formulation and amendment of conservation strategies.
The association between depressive mood and ischemic heart disease: a twin study
Authors: Wium‐Andersen M. K. , Wium‐Andersen I. K. , Jørgensen M. B. , McGue M. , Jørgensen T. S. H. , Christensen K. , Osler M. 
Published: July 2019

ObjectiveIndividuals with mood disorders have increased risk of cardiovascular disease. The aims of this study were to evaluate if the risk of cardiovascular disease in individuals with mood disorder could be explained by shared genetic and early environmental factors.MethodsWe included 6714 Danish middle and old aged twins from two large population‐based studies. Cox proportional hazards regression was used to perform individual‐level and intra‐pair analyses of the association between self‐reported depression symptomatology scores and register‐based diagnoses of ischemic heart disease.ResultsHigher depression symptomatology scores (both total, affective, and somatic) were associated with higher incidence of ischemic heart disease after multivariable adjustment in individual‐level analyses. In intra‐pair analyses, this association was similar but with slightly larger confidence intervals. There was no interaction with gender and no major differences between mono‐ or dizygotic twins. Within twin pairs, the twin scoring highest on depressive symptoms developed ischemic heart disease more often or earlier than the lower scoring twin. A sensitivity analysis including a 2‐year time lag of depression symptomatology to limit the risk of reverse causality showed similar results.ConclusionGenetic factors and early life environment do not seem to explain the association between depressive mood and ischemic heart disease.
Cost‐effectiveness of scaling‐up HCV prevention and treatment in the United States for people who inject drugs
Authors: Barbosa Carolina , Fraser Hannah , Hoerger Thomas J. , Leib Alyssa , Havens Jennifer R. , Young April , Kral Alex , Page Kimberly , Evans Jennifer , Zibbell Jon , Hariri Susan , Vellozzi Claudia , Nerlander Lina , Ward John W. , Vickerman Peter 
Published: July 2019

AbstractAimsTo examine the cost‐effectiveness of hepatitis C virus (HCV) treatment of people who inject drugs (PWID), combined with medication‐assisted treatment (MAT) and syringe‐service programs (SSP), to tackle the increasing HCV epidemic in the United States.DesignHCV transmission and disease progression models with cost‐effectiveness analysis using a health‐care perspective.SettingRural Perry County, KY (PC) and urban San Francisco, CA (SF), USA. Compared with PC, SF has a greater proportion of PWID with access to MAT or SSP. HCV treatment of PWID is negligible in both settings.ParticipantsPWID data were collected between 1998 and 2015 from Social Networks Among Appalachian People, U Find Out, Urban Health Study and National HIV Behavioral Surveillance System studies.Interventions and comparatorThree intervention scenarios modeled: baseline—existing SSP and MAT coverage with HCV screening and treatment with direct‐acting antiviral for ex‐injectors only as per standard of care; intervention 1—scale‐up of SSP and MAT without changes to treatment; and intervention 2—scale‐up as intervention 1 combined with HCV screening and treatment for current PWID.MeasurementsIncremental cost‐effectiveness ratios (ICERs) and uncertainty using cost‐effectiveness acceptability curves. Benefits were measured in quality‐adjusted life‐years (QALYs).FindingsFor both settings, intervention 2 is preferred to intervention 1 and the appropriate comparator for intervention 2 is the baseline scenario. Relative to baseline, for PC intervention 2 averts 1852 more HCV infections, increases QALYS by 3095, costs $21.6 million more and has an ICER of $6975/QALY. For SF, intervention 2 averts 36 473 more HCV infections, increases QALYs by 7893, costs $872 million more and has an ICER of $11 044/QALY. The cost‐effectiveness of intervention 2 was robust to several sensitivity analysis.ConclusionsHepatitis C screening and treatment for people who inject drugs, combined with medication‐assisted treatment and syringe‐service programs, is a cost‐effective strategy for reducing hepatitis C burden in the United States.
Buprenorphine prescribing for opioid use disorder in medical practices: can office‐based out‐patient care address the opiate crisis in the United States?
Authors: Rhee Taeho Greg , Rosenheck Robert A. 
Published: July 2019

AbstractBackground and aimsOpioid use disorder (OUD) remains a serious public health issue, and treating adults with OUD is a major priority in the United States. Little is known about trends in the diagnosis of OUD and in buprenorphine prescribing by physicians in office‐based medical practices. We sought to characterize OUD diagnoses and buprenorphine prescribing among adults with OUD in the United States between 2006 and 2015.Design and settingsWe used a repeated cross‐sectional design, based on data from the 2006–15 National Ambulatory Medical Care Surveys that surveyed nationally representative samples of office‐based out‐patient physician visits.ParticipantsAdult patients aged 18 years or older with a diagnosis of OUD (n = 1034 unweighted) were included.MeasurementsBuprenorphine prescribing was defined by whether visits involved buprenorphine or buprenorphine–naloxone, or not. We also examined other covariates (e.g. age, gender, race and psychiatric comorbidities).FindingsWe observed an almost tripling of the diagnosis of OUD from 0.14% in 2006–10 to 0.38% in 2011–15 in office‐based medical practices (P < 0.001). Among adults diagnosed with OUD, buprenorphine prescribing increased from 56.1% in 2006–10 to 73.6% in 2011–15 (P = 0.126). Adults with OUD were less likely to receive buprenorphine prescriptions if they were Hispanic [adjusted odds ratio (aOR) = 0.26; 95% confidence interval (CI) = 0.11, 0.60], had Medicaid insurance (aOR = 0.27; 95% CI = 0.10, 0.74) or were diagnosed with other psychiatric disorders (aOR = 0.45; 95% CI = 0.25, 0.83) or substance use disorders (aOR = 0.19; 95% CI = 0.09, 0.41).ConclusionsIn office‐based medical practices in the United States, diagnoses for opioid use disorder and buprenorphine prescriptions for adults with opioid use disorder increased from 0.14 and 56.1%, respectively, in 2006–10 to 0.38 and 73.6% in 2011–15.
Whole‐genome SNP data unravel population structure and signatures of selection for black plumage of indigenous chicken breeds from Jiangxi province, China
Authors: Mao H. , Wang X. , Fan Y. , Cheng D. , Chen K. , Liu S. , Xi S. , Wan L. , Li X. , Ren J. 
Published: July 2019

SummaryTen indigenous chicken breeds were originally distributed in Jiangxi Province, China, and they define a critical component of Chinese chicken genetic resources. We have investigated the population genetics of seven Jiangxi chicken breeds using 600K chicken BeadChip SNP data. To provide a genome‐wide perspective for the population structure of all 10 Jiangxi chicken breeds, we herein genotyped 78 additional individuals from the seven breeds and 63 chickens from three uninvestigated breeds—Yugan Black (YG), Nancheng Black (NC) and Wanzai Yellow using 55K chicken SNP arrays. We then explored merged data of 17 101 SNPs from 235 individuals to infer the population structure of the 10 breeds. We showed that NC and YG are two regional populations of the same breed, as individuals from the two populations clustered together to form a branch separate from the other breeds in the neighbor‐joining tree, they always grouped together in multidimensional principal component analyses and they displayed an identical pattern of ancestral lineage composition. Hence, NC and YG should be considered a single breed in the state‐supported conservation scheme. Moreover, we conducted a genome scan for signatures of selection for black plumage. bayescan and hapflk analyses of two contrasting groups (three black‐feathered breeds vs. six non‐black‐feathered breeds) consistently detected 25 putative regions under selection. Nine pigmentation‐ associated genes (DCT, SLC24A5, SLC30A4, MYO5A, CYP19A1, NADK2, SLC45A2, GNAQ and DCP2) reside within these regions, and these genes are interesting candidates for black plumage and provide a starting point for further identification of causative mutations for black feathers in chicken.
Venom immunotherapy in patients with clonal mast cell disorders: IgG4 correlates with protection
Authors: Jarkvist Jesper , Salehi Clara , Akin Cem , Gülen Theo 
Published: July 2019

AbstractBackgroundPatients with clonal mast cell disorders (cMCD), systemic mastocytosis (SM) and monoclonal mast cell activation syndrome (MMAS), represent an increased risk for Hymenoptera venom anaphylaxis (HVA). Lifelong venom immunotherapy (VIT) is recommended; however, its efficacy and safety are controversial. Hence, we sought to evaluate the efficacy and safety of VIT in HVA patients with cMCD.MethodsA retrospective study was conducted among 46 patients with Vespula venom allergy who had experienced severe HVA, 32 cMCD (22 with SM and 10 with MMAS) and 14 controls. There were no differences between cMCD patients and controls in age (58 vs 66) and duration of VIT (47 vs 48 months), respectively.ResultsDuring VIT, 11 (34%) cMCD patients experienced adverse reactions (ARs) (7% in controls), including 1 anaphylaxis. There were 23 re‐stings in 17 (53%) patients during VIT. Of episodes, four (17%) presented with anaphylaxis, 14 (60%) presented with local reaction, and five (23%) were asymptomatic. In 11 episodes (48%), the patient did not take epinephrine, of these 8 (73%) presented with local reaction, and 3 (27%) were asymptomatic. Patient‐based protection from anaphylaxis was 76% (4/17) in cMCD vs. 100% in controls during VIT. The venom‐specific IgG4 concentrations increased during VIT (P < .001) although tryptase and IgE were unaltered.ConclusionBoth safety and efficacy of VIT in cMCD patients were slightly reduced than controls. Severe ARs were rare. The elevated IgG4 levels may be a biomarker for efficacy of VIT in cMCD patients, as it correlates with protection from re‐stings.
A realist evaluation of student use of a virtual reality smartphone application in undergraduate legal education
Authors: McFaul Hugh , FitzGerald Elizabeth 
Published: July 2019

AbstractThis paper provides a realist evaluation of the Open Justice virtual reality (VR) smartphone app, designed to develop presentation skills for students on an undergraduate legal education module. This work addresses two research questions: what proportion of students engaged with the Open Justice app, and what worked for whom in what circumstances and why? Questionnaire and interviews were conducted and analysed using a realist evaluation approach. This approach is particularly pertinent to the evaluation of how emerging educational technologies are used, as it can point to the potential affordances of a technological intervention, in addition to assessing its current use. In keeping with the realist evaluation approach, data analysis was completed using the context–mechanism–outcome framework. The findings suggest that more than half of students did not engage with the app during their studies, but this was not surprising as it was a pilot project into using VR with our students and such innovations can be difficult to manage in distance education contexts. Those who did engage with it recognised the potential of immersive VR to contribute to legal skills development, but they found the application of the technology, in this context, to be of limited use. By utilising a realist evaluation framework, this study contributes to the emerging field of programme theory‐based evaluations of educational technology, which might form the basis of further research.
Practitioner NotesWhat is already known about this topic

Smartphone‐based virtual reality technology has developed exponentially and is now widely and cheaply available.
Smartphone‐based virtual reality technology has the potential to develop professional skills, and thereby provide a useful addition to experiential learning pedagogies. This is of particular relevance to the development of professional legal skills in the context of clinical legal education.
Realist evaluation methodology is increasingly common in health literature to evaluate the impact of education programmes.
What this paper adds

This is the first empirical study of the use of VR technology to develop professional skills in a distance learning setting.
This is the first paper to use realist methodology to evaluate virtual reality technology in legal education.
It provides a granular analysis of particular contexts and user responses that can facilitate or inhibit learner engagement with VR technology.
Implications for practice and/or policy

It provides an analysis of VR used to support teaching and learning, where the students are distance learners—this highlights issues and challenges to be overcome.
It provides an evidence base to inform the development of, and further research into, smartphone‐based virtual reality for legal education settings.
It provides a detailed example of how realist methodology can be utilised to evaluate educational technology in real‐world settings.
Bleeding and bruising in Osteogenesis Imperfecta: International Society on Thrombosis and Haemostasis bleeding assessment tool and haemostasis laboratory assessment in 22 individuals
Authors: Gooijer Koert , Rondeel Jan M. M. , van Dijk Fleur S. , Harsevoort Arjan G. J. , Janus Guus J. M. , Franken Anton A. M. 
Published: July 2019

SummaryOsteogenesis imperfecta (OI) is characterized by susceptibility to bone fractures. Other symptoms, such as easy bruising and bleeding complications during surgery necessitating transfusions, have also been reported. The aim of the cross‐sectional pilot study was to assess the bleeding and bruising tendency in OI patients and to screen for possible underlying haematological disorders. Bleeding tendency was investigated using the International Society on Thrombosis and Haemostasis bleeding assessment tool (ISTH‐BAT) in 22 adult OI patients. Laboratory testing was performed to investigate for bleeding disorders or abnormal coagulation. Four patients [OI type 1(n = 3), OI type 4(n = 1)] had a bleeding score (BS) fitting with a bleeding tendency, but without test results pointing to a coagulopathy. Two patients [OI type 1(n = 1), OI type 3 (n = 1)] without a bleeding tendency according to the BS had increased fibrinolysis. This is the second largest study to date addressing bleeding tendency in OI and the first study to use ISTH‐BAT and elaborate laboratory testing for coagulopathies. Four patients had an increased bleeding tendency. However, laboratory testing demonstrated no bleeding disorder or abnormal coagulation. Increased fibrinolysis was demonstrated in two patients without bleeding tendency on BS. Vascular fragility as a cause of bleeding tendency in OI has been suggested earlier. Further research on bleeding tendency in OI is important.
A 2‐year retrospective study on pleural effusions: A cancer centre experience
Authors: Valerio Ediel , Nunes Warley , Cardoso Jaqueline , Santos Aline , Bovolim Graziele , Domingos Tabata , De Brot Louise , Saieg Mauro 
Published: July 2019

AbstractBackgroundCytopathological examination of pleural effusions is a fast and minimally invasive method for verification of the presence of neoplastic cells. We report our 2‐year experience using a categorised diagnostic system and reporting risks of malignancy (ROMs) for each defined category.MethodsCytological reports of patients between November 2016 and October 2018 were collected, with results primarily classified into a five‐tiered classification scheme. Immunohistochemistry markers used in cytology and their results were also recorded. Final agreement to histology and overall test performance was calculated for cases with available concomitant (up to 3 months) pleural biopsies.ResultsA total of 519 samples from 385 patients were collected, being 29 (5.6%) classified as non‐diagnostic, 291 (56%) as negative, 28 (5.4%) as atypical, 30 (5.8%) as suspicious and 141 (27.2%) as positive. Most requested markers were calretinin, TTF1, Ber‐EP4 and Gata‐3, being conclusive in 45 (76.3%) cases. Total cyto‐histological agreement was achieved in 49 (80.3%) specimens, with an overall sensitivity and specificity of 69.4% and 93.3%, respectively. Positive predictive value was 96.2% and negative predictive value was of 56%. ROM for each diagnostic category was 50% for non‐diagnostic, 44% for negative, 50% for atypical, 83.3% for suspicious and 96.2% for positive.ConclusionsOur 2‐year retrospective study has shown a high specificity and positive predictive value for pleural cytology. The use of a five‐tiered system has also shown to be highly effective, with a concordantly progressive higher ROM for the assigned diagnostic categories.