bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybrid 4DVAR with a Local Ensemble Tangent Linear Model: Application to the Shallow-Water Model
Authors: Allen Douglas R. , Bishop Craig H. , Frolov Sergey , Hoppel Karl W. , Kuhl David D. , Nedoluha Gerald E. 
Published: October 2016

Abstract
An ensemble-based tangent linear model (TLM) is described and tested in data assimilation experiments using a global shallow-water model (SWM). A hybrid variational data assimilation system was developed with a 4D variational (4DVAR) solver that could be run either with a conventional TLM or a local ensemble TLM (LETLM) that propagates analysis corrections using only ensemble statistics. An offline ensemble Kalman filter (EnKF) is used to generate and maintain the ensemble. The LETLM uses data within a local influence volume, similar to the local ensemble transform Kalman filter, to linearly propagate the state variables at the central grid point. After tuning the LETLM with offline 6-h forecasts of analysis corrections, cycling experiments were performed that assimilated randomly located SWM height observations, based on a truth run with forced bottom topography. The performance using the LETLM is similar to that of the conventional TLM, suggesting that a well-constructed LETLM could free 4D variational methods from dependence on conventional TLMs. This is a first demonstration of the LETLM application within a context of a hybrid-4DVAR system applied to a complex two-dimensional fluid dynamics problem. Sensitivity tests are included that examine LETLM dependence on several factors including length of cycling window, size of analysis correction, spread of initial ensemble perturbations, ensemble size, and model error. LETLM errors are shown to increase linearly with correction size in the linear regime, while TLM errors increase quadratically. As nonlinearity (or forecast model error) increases, the two schemes asymptote to the same solution.
The Royal Air Force, Bomber Command and the Use of Benzedrine Sulphate: An Examination of Policy and Practice During the Second World War
Authors: Pugh James 
Published: October 2016

This article explores the development of policy in the Royal Air Force (RAF) relating to the use of Benzedrine, a potent amphetamine, by aircrews during the Second World War. This policy evolved from total prohibition in September 1939 to cautious approval for the use of the drug on operations in November 1942. Such caution reflected the subjective evidence available about Benzedrine, the media profile of the substance, and wider social and cultural factors relating to the use of drugs during this period. This challenges our understanding of drug history, demonstrating that while amphetamines were framed as a ‘miracle drug’, more nuanced, functional interpretations of the substance were in evidence. In turn, the article examines evidence from the operational context, including new data gathered from questionnaires and interviews with former Bomber Command aircrew and existing oral history material held by the Imperial War Museum. Both policy discussions and operational evidence allows for a re-evaluation of the arguments of Nicholas Rasmussen, who suggests the RAF made use of Benzedrine as a frontline ‘psychiatric medicine’. Such conclusions downplay the significance the RAF attached to the drug’s effects on wakefulness and concerns about the drug’s effects on wellbeing.
Concussions and Head Injuries in English Community Rugby Union Match Play
Authors: Roberts Simon P. , Trewartha Grant , England Michael , Goodison William , Stokes Keith A. 
Published: October 2016

Background: Previous research has described general injury patterns in community-level rugby union, but specific information on time-loss head injuries has not been reported. Purpose: To establish the incidence and nature of significant time-loss head injuries in English community rugby match play, and to identify the injury risk for specific contact events. Study Design: Descriptive epidemiology study. Methods: Over 6 seasons, injury information was collected from 46 (2009-2010), 67 (2010-2011), 76 (2011-2012), 50 (2012-2013), 67 (2013-2014), and 58 (2014-2015) English community rugby clubs (Rugby Football Union levels 3-9) over a total of 175,940 hours of player match exposure. Club injury management staff reported information for all head injuries sustained during match play whereby the player was absent for 8 days or greater. Clubs were subdivided into semiprofessional (mean player age, 24.6 ± 4.7 years), amateur (24.9 ± 5.1 years), and recreational (25.6 ± 6.1 years) playing levels. Contact events from a sample of 30 matches filmed over seasons 2009-2010, 2010-2011, and 2011-2012 provided mean values for the frequency of contact events. Results: The overall incidence for time-loss head injuries was 2.43 injuries per 1000 player match hours, with a higher incidence for the amateur (2.78; 95% CI, 2.37-3.20) compared with recreational (2.20; 95% CI, 1.86-2.53) ( P = .032) playing level but not different to the semiprofessional (2.31; 95% CI, 1.83-2.79) playing level. Concussion was the most common time-loss head injury, with 1.46 per 1000 player match hours. The tackle event was associated with 64% of all head injuries and 74% of all concussions. There was also a higher risk of injuries per tackle (0.33 per 1000 events; 95% CI, 0.30-0.37) compared with all other contact events. Conclusion: Concussion was the most common head injury diagnosis, although it is likely that this injury was underreported. Continuing education programs for medical staff and players are essential for the improved identification and management of these injuries. With the majority of head injuries occurring during a tackle, an improved technique in this contact event through coach and player education may be effective in reducing these injuries.
A unique antiphospholipid assay recognizing phospholipid mixture compared with criteria antiphospholipid immunoassays in lupus patients
Authors: Zuo Y , Willis R , Papalardo E , Petri M , Harris E N , Schleh A , DeCeulaer K , Smikle M , Vilá L M , Reveille J D , Alarcón G S , Gonzalez E B 
Published: October 2016

Background While essential for the classification of antiphospholipid syndrome (APS), anticardiolipin (aCL) assays lack specificity and anti-β2glycoproteinI (anti-β2GPI) assays lack sensitivity in this regard. Our aim was to perform a comparative analysis of the APhL ELISA assay (IgG/IgM) and criteria antiphospholipid (aPL) immunoassays in identifying APS-related clinical manifestations in a large group of patients with systemic lupus erythematosus (SLE). Methods Serum samples from 1178 patients from the Hopkins ( n = 543), LUMINA ( n = 588) and Jamaican SLE cohorts ( n = 47) were examined for IgG/IgM positivity in aCL (in-house), anti-β2GPI (two commercial kits) and APhL (Louisville APL) ELISA assays. Correlation of assay positivity with clinical manifestations and sensitivity, specificity, positive and negative predictive values and likelihood ratios were evaluated. A case series analysis was also performed in patients for whom there was isolated positivity in the specific aPL assays. Results The prevalence of aCL positivity was 34.9%, anti-β2GPI kit A was 22.6%, APhL was 11.5% and anti-β2GPI kit B was 7.6% in the study population. Anti-β2GPI kit B, aCL and APhL assays were correlated with venous thrombosis, while only APhL was significantly correlated with arterial thrombosis and consistently correlated with pregnancy-related morbidity. No significant correlations were noted for anti-β2GPI kit A. Sensitivity was greatest for aCL assays followed by anti-β2GPI kit A, APhL and anti-β2GPI kit B, while specificity was greatest and equal for anti-β2GPI kit B and APhL assays. Conclusions Overall, APhL antibodies, especially IgG, represent a promising biomarker for the classification of APS patients in the context of autoimmunity and in risk assessment with regards to pregnancy morbidity and thrombotic manifestations.
Importance of early treatment initiation in the clinical course of multiple sclerosis
Authors: Kavaliunas Andrius , Manouchehrinia Ali , Stawiarz Leszek , Ramanujam Ryan , Agholme Jonas , Hedström Anna Karin , Beiki Omid , Glaser Anna , Hillert Jan 
Published: October 2016

Objectives: The aim of this study was to identify factors influencing the long-term clinical progression of multiple sclerosis (MS). A special objective was to investigate whether early treatment decisions influence outcome. Methods: We included 639 patients diagnosed with MS from 2001 to 2007. The median follow-up time was 99 months (8.25 years). Cox regression models were applied to identify factors correlating with the outcome variable defined as time from treatment start to irreversible score 4 of the Expanded Disability Status Scale (EDSS). Results: Patients initiated on treatment later had a greater risk of reaching EDSS 4 (hazard ratio of 1.074 (95% confidence interval (CI), 1.048−1.101)), increased by 7.4% for every year of delay in treatment start after MS onset. Patients who started treatment after 3 years from MS onset reached the outcome sooner with hazard ratio of 2.64 (95% CI, 1.71−4.08) compared with the patients who started treatment within 1 year from MS onset. Baseline EDSS and age at onset were found to be predictive factors of disability progression. Conclusion: Early treatment initiation was associated with a better clinical outcome. In addition, we confirmed the well-established prognostic factors of late age at onset and early disability.
Inter-generational transmission in a minority language setting: Stop consonant production by Bangladeshi heritage children and adults
Authors: Mayr Robert , Siddika Aysha 
Published: October 2016

Aims and objectives: The purpose of this study was to gain a better understanding of speech development across successive generations of heritage language users, examining how cross-linguistic, developmental and socio-cultural factors affect stop consonant production. Design: To this end, we recorded Sylheti and English stop productions of two sets of Bangladeshi heritage families: (1) first-generation adult migrants from Bangladesh and their (second-generation) UK-born children, and (2) second-generation UK-born adult heritage language users and their (third-generation) UK-born children. Data and analysis: The data were analysed auditorily, using whole-word transcription, and acoustically, examining voice onset time. Comparisons were then made in both languages across the four groups of participants, and cross-linguistically. Findings: The results revealed non-native productions of English stops by the first-generation migrants but largely target-like patterns by the remaining sets of participants. The Sylheti stops exhibited incremental changes across successive generations of speakers, with the third-generation children’s productions showing the greatest influence from English. Originality: This is one of few studies to examine both the host and heritage language in an ethnic minority setting, and the first to demonstrate substantial differences in heritage language accent between age-matched second- and third-generation children. The study shows that current theories of bilingual speech learning do not go far enough in explaining how speech develops in heritage language settings. Implications: These findings have important implications for the maintenance, transmission and long-term survival of heritage languages, and show that investigations need to go beyond second-generation speakers, in particular in communities that do not see a steady influx of new migrants.
ABT-126 monotherapy in mild-to-moderate Alzheimer’s dementia: randomized double-blind, placebo and active controlled adaptive trial and open-label extension
Authors: Gault Laura M. , Lenz Robert A. , Ritchie Craig W. , Meier Andreas , Othman Ahmed A. , Tang Qi , Berry Scott , Pritchett Yili , Robieson Weining Z. 
Published: October 2016

Abstract
Background
Results from a phase 2a study indicated that treatment with the novel α7 nicotinic acetylcholine receptor agonist ABT-126 25 mg once daily (QD) was associated with a trend for improvement in cognition in subjects with mild-to-moderate Alzheimer’s dementia (AD). A phase 2b program was designed to evaluate a broader dose range of ABT-126 as monotherapy in subjects with mild-to-moderate AD. The program consisted of a double-blind, placebo and active controlled study of ABT-126 (dose range 25–75 mg) and an open-label extension study (75 mg).

Methods
The randomized double-blind study enrolled 438 subjects (Mini-Mental Status Examination score of 10–24, inclusive) not currently taking acetylcholinesterase inhibitors or memantine. Subjects received 24 weeks of ABT-126 25 mg QD (n = 77), ABT-126 50 mg QD (n = 108), ABT-126 75 mg QD (n = 73), donepezil 10 mg QD (n = 76), or placebo (n = 104). The primary endpoint was the change from baseline to week 24 in the 11-item Alzheimer's Disease Assessment Scale—Cognitive subscale (ADAS-Cog) total score. Subjects completing the double-blind study could enroll in the 28-week open-label extension study. Adverse events (AEs) and other safety parameters were monitored in both studies.

Results
A total of 367 patients (83.8 %) completed the double-blind study and 349 (79.7 %) entered the open-label study. Compared with placebo, donepezil significantly improved ADAS-Cog 11-item total scores from baseline to week 24 (−2.29 ± 0.95; one-sided P = 0.008). No ABT-126 dose demonstrated a statistically significant improvement vs placebo at week 24 in the ADAS-Cog total score: ABT-126 25 mg, −0.47 ± 0.94 (P = 0.309); ABT-126 50 mg, −0.87 ± 0.85 (P = 0.153); and ABT-126 75 mg, −1.08 ± 0.94 (P = 0.127). Rates of serious AEs and discontinuations due to AEs were similar across treatment groups. The most frequently reported AEs in both studies were constipation, fall, and headache. No clinically meaningful changes were observed in other parameters.

Conclusions
In the double-blind trial, donepezil significantly improved ADAS-Cog scores but no statistically significant improvement was seen with any ABT-126 dose. ABT-126 had an acceptable safety profile in subjects with mild-to-moderate AD in both studies.

Trial registration
ClinicalTrials.gov NCT01527916, Registered 3 February 2012 (randomized trial). ClinicalTrials.gov NCT01676935. Registered 29 August 2012 (open-label extension study).
Ectopic parathyroid adenoma in the soft palate: A case report
Authors: Chang Brent A. , Sharma Anil , Anderson Donald W. 
Published: October 2016

Background Ectopic parathyroid adenomas can occur in numerous anatomic locations. While ectopic parathyroid adenomas can rarely occur in the pharyngeal region, this has not previously been described in the soft palate. Case presentation We report the first case of ectopic parathyroid adenoma within the soft palate. A 59 year old woman presented with hyperparathyroidism. She remained persistently hyperparathyroid after initial parathyroidectomy. Repeat exploration for a lesion suspicious on PET-CT for an ectopic parathyroid adenoma in the parapharyngeal region was unsuccessful in treating the hyperparathyroidism. An ectopic adenoma in the soft palate was eventually discovered. Removal through a transoral approach was successful in treating the hyperparathyroidism. Conclusions Ectopic parathyroid adenomas can occur in various anatomical locations that may be missed even with the use of the various imaging modalities. The soft palate should be added to the list of possible ectopic locations high in the neck.
Phenotypic and functional characteristics of HLA-DR+ neutrophils in Brazilians with cutaneous leishmaniasis
Authors: Davis Richard E , Sharma Smriti , Conceicão Jacilara , Carneiro Pedro , Novais Fernanda , Scott Phillip , Sundar Shyam , Bacellar Olivia , Carvalho Edgar M , Wilson Mary E 
Published: October 2016

Abstract
The protozoan Leishmania braziliensis causes cutaneous leishmaniasis (CL) in endemic regions. In murine models, neutrophils (PMNs) are recruited to the site of infection soon after parasite inoculation. However, the roles of neutrophils during chronic infection and in human disease remain undefined. We hypothesized that neutrophils help maintain a systemic inflammatory state in subjects with CL. Lesion biopsies from all patients with CL tested contained neutrophils expressing HLA-DR, a molecule thought to be restricted to professional antigen-presenting cells. Although CL is a localized disease, a subset of patients with CL also had circulating neutrophils expressing HLA-DR and the costimulatory molecules CD80, CD86, and CD40. PMNs isolated from a low-density leukocyte blood fraction (LD-PMNs) contained a higher percentage of HLA-DR+ PMNs than did normal-density PMNs. In vitro coculture experiments suggested LD-PMNs do not suppress T cell responses, differentiating them from MDSCs. Flow-sorted HLA-DR+ PMNs morphologically resembled conventional PMNs, and they exhibited functional properties of PMNs. Compared with conventional PMNs, HLA-DR+ PMNs showed increased activation, degranulation, DHR123 oxidation, and phagocytic capacity. A few HLA-DR+ PMNs were observed in healthy subjects, and that proportion could be increased by incubation in either inflammatory cytokines or in plasma from a patient with CL. This was accompanied by an increase in PMN hladrb1 mRNA, suggesting a possible connection between neutrophil “priming” and up-regulation of HLA-DR. These data suggest that PMNs that are primed for activation and that also express surface markers of antigen-presenting cells emerge in the circulation and infected tissue lesions of patients with CL.
Identification of a novel putative interaction partner of the nucleoporin ALADIN
Authors: Jühlen Ramona , Landgraf Dana , Huebner Angela , Koehler Katrin 
Published: October 2016

ABSTRACT
It has been shown that the nucleoporin ALADIN plays a significant role in the redox homeostasis of the cell, but its function in steroidogenesis contributing to adrenal atrophy in triple A syndrome remains largely unknown. In an attempt to identify new interaction partners of ALADIN, co-immunoprecipitation followed by proteome analysis was conducted in different expression models using the human adrenocortical tumour cell line NCI-H295R. Our results suggest an interaction of ALADIN with the microsomal protein PGRMC2. PGRMC2 is shown to be activity regulator of CYP P450 enzymes and, therefore, to be a possible target for adrenal dysregulation in triple A syndrome. We show that there is a sexual dimorphism regarding the expression of Pgrmc2 in adrenals and gonads of wild-type (WT) and Aaas knock-out (KO) mice. Female Aaas KO mice are sterile due to delayed oocyte maturation and meiotic spindle assembly. A participation in meiotic spindle assembly confirms the recently investigated involvement of ALADIN in mitosis and emphasises an interaction with PGRMC2 which is a regulator of the cell cycle. By identification of a novel interaction partner of ALADIN, we provide novel aspects for future research of the function of ALADIN during cell cycle and for new insights into the pathogenesis of triple A syndrome.
A sensitive 301V BSE serial PMCA assay
Authors: Gough Kevin C. , Bishop Keith , Somerville Robert A. , Hunter Nora , Maddison Ben C. 
Published: October 2016

The prion strain 301V, is a mouse passaged form of bovine spongiform encephalopathy (BSE). It has been used as a model of BSE for more than 20 years, in particular in the investigation of tissue distribution of infectivity, the molecular phenotype and transmission properties of BSE, strain typing assays and prion inactivation studies. Most 301V experiments have required murine bioassay as a method for the quantitation of infectivity. To date this model strain has not been studied with the protein misfolding cyclic amplification assay (PMCA) which detects prion-associated PrPSc protein. The detection of BSE PrPSc by PMCA can be more sensitive than mouse bioassay and is carried out in a much shorter time frame of days as opposed to months/years. Here, we describe the development of a new highly sensitive and specific PMCA assay for murine 301V and assess the sensitivity of the assay in direct comparison with murine bioassay of the same material. This in vitro assay detected, in a few days, 301V at a brain dilution of at least 1x10-9, compared to bioassay of the same material in VM mice that could detect down to a 1x10-8 dilution and took >180 days. The 301V PMCA may therefore offer a faster and more sensitive alternative to live animal bioassay when studying the BSE agent in VM mice.
Hazards and risk: the support worker's role
Authors: Stonehouse David 
Published: October 2016

Within this article, the author will be discussing the vital role that support workers have in managing risk and in maintaining a safe working environment for themselves, their colleagues and service users. The Code of Conduct for Healthcare Support Workers and Adult Social Care Workers in England ( Skills for Care and Skills for Health, 2013 ) clearly states the importance of health and safety in delivering care of the highest standards; relevant clauses of the Code will be identified. The Health and Safety at Work etc. Act 1974 will be highlighted as being a key piece of legislation. The five steps of risk assessment will be discussed, to demonstrate how support workers can use this process to successfully manage risk in their working environments, while following workplace policies and procedures.
UM TRABALHO DE SIMULAÇÃO DE OPERAÇÕES BANCÁRIAS NUM CENÁRIO INVESTIGATIVO COM ALUNOS DOS ANOS INICIAIS
Authors: Borges Fábio Alexandre , Da Silva Eliane Siviero 
Published: October 2016

Com o presente relato de experiência, teve-se como objetivo investigar o potencial pedagógico possibilitado pela adoção de um cenário investigativo nos Anos Iniciais do Ensino Fundamental em aulas de Matemática. Para isso, foram trabalhadas atividades envolvendo as quatro operações fundamentais discutidas nos Anos Iniciais do Ensino Fundamental (adição, subtração, multiplicação e divisão), por meio de simulações de transações comerciais (compras e vendas), a partir da criação de uma moeda fictícia. O trabalho foi desenvolvido durante as aulas de Matemática no período vespertino, de uma turma de 5º ano de uma escola pública localizada no município de Moreira Sales/PR, contando com a participação de 21 alunos, com idades na faixa etária de 9 e 10 anos. Foi criada uma moeda local, denominada pelos alunos de Fisgraus e adquirida inicialmente por meio de uma troca de garrafas do tipo pet. Também foram trabalhados três problemas envolvendo as medidas de volume mililitros (ml) e litros (l), aproveitando, com isso, o recolhimento de tais garrafas pet. Por fim, foi organizado em um dia uma venda de lanches, em que os alunos utilizaram as moedas adquiridas na troca das garrafas pet para a compra destes lanches. A partir da atividade desenvolvida, concluíu-se que o trabalho num cenário investigativo se mostrou um ambiente propício à aprendizagem, uma vez que houve o envolvimento dos alunos. Foi possível diagnosticar algumas das dificuldades apresentadas por eles com relação às quatros operações fundamentais (adição, subtração, divisão e multiplicação). Além disso, proporcionou-se um trabalho autônomo por parte dos alunos nas resoluções dos problemas.