bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies for developing sustainable health research capacity in low and middle-income countries: a prospective, qualitative study investigating the barriers and enablers to locally led clinical trial conduct in Ethiopia, Cameroon and Sri Lanka
Authors: Franzen Samuel R P , Chandler Clare , Siribaddana Sisira , Atashili Julius , Angus Brian , Lang Trudie 
Published: October 2017

ObjectivesIn 2013, the WHO stated that unless low-income and middle-income countries (LMICs) become producers of research, health goals would be hard to achieve. Among the capacities required to build a local evidence base, ability to conduct clinical trials is important. There is no evidence-based guidance for the best ways to develop locally led trial capacity. This research aims to identify the barriers and enablers to locally led clinical trial conduct in LMICs and determine strategies for their sustainable development.DesignProspective, multiple case study design consisting of interviews (n=34), focus group discussions (n=13) and process mapping exercises (n=10).SettingCase studies took place in Ethiopia (2011), Cameroon (2012) and Sri Lanka (2013).ParticipantsLocal health researchers with previous experiences of clinical trials or stakeholders with an interest in trials were purposively selected through registration searches and snowball sampling (n=100).Primary and secondary outcome measuresDiscussion notes and transcripts were analysed using thematic coding analysis. Key themes and mechanisms were identified.ResultsInstitutions and individuals were variably successful at conducting trials, but there were strong commonalities in the barriers and enablers across all levels and functions of the research systems. Transferable mechanisms were summarised into the necessary conditions for trial undertaking, which included: awareness of research, motivation, knowledge and technical skills, leadership capabilities, forming collaborations, inclusive trial operations, policy relevance and uptake and macro and institutional strengthening.ConclusionsBarriers and enablers to locally led trial undertaking exist at all levels and functions of LMIC research systems. Establishing the necessary conditions to facilitate this research will require multiple, coordinated interventions that seek to resolve them in a systemic manner. The strategies presented in the discussion provide an evidence-based framework for a self-sustaining capacity development approach. This represents an important contribution to the literature that will be relevant for research funders, users and producers.
Longitudinal associations between marine omega-3 supplement users and coronary heart disease in a UK population-based cohort
Authors: Lentjes Marleen A H , Keogh Ruth H , Welch Ailsa A , Mulligan Angela A , Luben Robert N , Wareham Nicholas J , Khaw Kay-Tee 
Published: October 2017

ObjectivesAssess the association between marine omega-3 polyunsaturated fatty acid (n-3 PUFA) intake from supplements, mainly cod liver oil, and coronary heart disease (CHD) mortality.DesignProspective cohort study, with three exposure measurements over 22 years.SettingNorfolk-based European Prospective Investigation into Cancer (EPIC-Norfolk, UK).Participants22 035 men and women from the general population, 39–79 years at recruitment.ExposureSupplement use was assessed in three questionnaires (1993–1998; 2002–2004; 2004–2011). Participants were grouped into non-supplement users (NSU), n-3 PUFA supplement users (SU+n3) and non–n-3 PUFA supplement users (SU-n3). Cox regression adjusted for time-point specific variables: age, smoking, prevalent illnesses, body mass index, alcohol consumption, physical activity and season and baseline assessments of sex, social class, education and dietary intake (7-day diet diary).Primary and secondary outcome measuresDuring a median of 19-year follow-up, 1562 CHD deaths were registered for 22 035 included participants.ResultsBaseline supplement use was not associated with CHD mortality, but baseline food and supplement intake of n-3 PUFA was inversely associated with CHD mortality after adjustment for fish consumption. Using time-varying covariate analysis, significant associations were observed for SU+n3 (HR: 0.74, 95% CI 0.66 to 0.84), but not for SU-n3 versus NSU. In further analyses, the association for SU+n3 persisted in those who did not take other supplements (HR: 0.83, 95% CI 0.71 to 0.97). Those who became SU+n3 over time or were consistent SU+n3 versus consistent NSU had a lower hazard of CHD mortality; no association with CHD was observed in those who stopped using n-3 PUFA-containing supplements.ConclusionsRecent use of n-3 PUFA supplements was associated with a lower hazard of CHD mortality in this general population with low fish consumption. Residual confounding cannot be excluded, but the findings observed may be explained by postulated biological mechanisms and the results were specific to SU+n3.
Comorbidity and outcomes in traumatic brain injury: protocol for a systematic review on functional status and risk of death
Authors: Mollayeva Tatyana , Xiong Chen , Hanafy Sara , Chan Vincy , Hu Zheng Jing , Sutton Mitchell , Escobar Michael , Colantonio Angela 
Published: October 2017

IntroductionReports on the association between comorbidity and functional status and risk of death in patients with traumatic brain injury (TBI) have been inconsistent; it is currently unknown which additional clinical entities (comorbidities) have an adverse influence on the evolution of outcomes across the lifespan of men and women with TBI. The current protocol outlines a strategy for a systematic review of the current evidence examining the impact of comorbidity on functional status and early-term and late-term mortality, taking into account known risk factors of these adverse outcomes (ie, demographic (age and sex) and injury-related characteristics).Methods and analysisA comprehensive search strategy for TBI prognosis, functional (cognitive and physical) status and mortality studies has been developed in collaboration with a medical information specialist of the large rehabilitation teaching hospital. All peer-reviewed English language studies with longitudinal design in adults with TBI of any severity, published from May 1997 to April 2017, found through Medline, Central, Embase, Scopus, PsycINFO and bibliographies of identified articles, will be considered eligible. Study quality will be assessed using published guidelines.Ethics and disseminationThe authors will publish findings from this review in a peer-reviewed scientific journal(s) and present the results at national and international conferences. This work aims to understand how comorbidity may contribute to adverse outcomes in TBI, to inform risk stratification of patients and guide the management of brain injury acutely and at the chronic stages postinjury on a population level.PROSPERO registration numberCRD42017070033.
Phosphate replacement in the critically ill: potential implications for military patients
Authors: Coulden A E , Rickard L J , Crooks N , Arora N 
Published: October 2017

BackgroundSevere hypophosphataemia in the intensive care unit (ICU) setting has been widely associated with adverse clinical outcomes across multiple organ systems, as well as increased mortality. However, the clinical significance of mild or moderate hypophosphataemia remains uncertain. This can lead to heterogeneous phosphate replacement protocols across different institutions. The aim of this study was to assess the significance of mild and moderate hypophosphataemia on clinical outcomes across several organ systems.MethodAll patients over a 3-week period in our ICU were retrospectively analysed with admission serum phosphate compared with subsequent clinical outcomes after admission. Low serum phosphate (0.3–1.0 mmol/L), according to local protocol, was compared with normal serum phosphate (>1.0 mmol/L).ResultsOf the 72 patients admitted to intensive therapy unit during this period, 14/72 (19%) had phosphate levels deemed low (<1.0 mmol/L) and received phosphate supplementation. No significant difference was found between groups in terms of cardiac arrhythmias (p=0.55), capillary blood glucose (p=0.08) and serum lactate (p=0.32). Low phosphate (0.3–1.0 mmol/L) was not associated with increased likelihood of requiring ventilation. Platelet count was significantly lower in the low phosphate group (p=0.008).ConclusionIn our study, mild and moderate hypophosphataemia was not associated with adverse clinical outcome across most organ systems analysed. Given the current evidence and results of this study, we would suggest that there is a trend towards over-replacement of phosphate, representing a potential clinical safety issue as well as clear financial implications.
Sacral dural arteriovenous fistulas: a diagnostic and therapeutic challenge – single-centre experience of 13 cases and review of the literature
Authors: Gioppo Andrea , Faragò Giuseppe , Giannitto Caterina , Caputi Luigi , Saladino Andrea , Acerbi Francesco , Ciceri Elisa 
Published: October 2017

BackgroundSacral dural arteriovenous fistulas (DAVFs) are rare vascular abnormalities of the spine characterised by slowly progressive symptoms that can mimic different myelopathy disorders.ObjectTo report our single Institution experience with sacral DAVFs.MethodsWe retrospectively reviewed the clinical records of patients admitted from 1 January 2006 to 31 December 2016 with a diagnosis of sacral DAVFs, treated by endovascular embolisation or surgical clipping. Clinical presentation, imaging characteristics, treatment results and follow-up were analysed.ResultsWe identify 13 patients with sacral DAVFs supplied by lateral sacral arteries. Clinical presentation was characterised by different degrees of motor weakness and sphincter disturbances. In all patients, spinal MRI showed spinal cord hyperintensities with enhancement and prominent perimedullary vessels. Selective internal iliac angiography was mandatory to identify the exact location of the fistula. A complete embolisation was achieved in eight patients performing a single endovascular embolisation and in three patients performing a single surgical disconnection: two patients required combined procedures. Follow-up imaging showed a complete resolution of the spinal cord hyperintensities in 81% of patients and a reduction of the intramedullary enhancement in 91%. Gait improvement was observed in 73% of patients, while remaining stable in 27%. Sphincter disturbances improved in 36% of patients and remained stable in 64%.ConclusionAwareness of sacral location of DAVFs is critical because standard spinal angiography will not identify sacral supplies, unless internal iliac arteries are properly examined. In our experience, the endovascular treatment show results comparable to surgery when the fistula point is correctly disconnected.
Routinely collected health data to study inherited heart disease: a systematic review (2000–2016)
Authors: Blanch Bianca , Sweeting Joanna , Semsarian Christopher , Ingles Jodie 
Published: October 2017

ObjectiveOur understanding of inherited heart disease is predominantly based on retrospective specialised clinic cohorts, which have inherent selection bias. Population-based routinely collected data can provide insight into unbiased, large-scale patterns of treatment and care but may be limited by the granularity of clinical information available. We sought to synthesise the global literature to determine whether we can identify patients with inherited heart diseases using routinely collected health data.MethodsMedline, Embase, CINAHL, PreMEDLINE and Google Scholar citation databases were searched for relevant articles published between 1 January 2000 and 31 October 2016.ResultsA total of 5641 titles/abstracts were screened and 46 full-text articles were retrieved. Twelve peer-reviewed, English-language manuscripts met our inclusion criteria. Studies predominantly focused on Marfan syndrome (41%) or hypertrophic cardiomyopathy (29%). All studies used International Classification of Disease diagnosis codes to define inherited heart disease populations; three studies also used procedure codes. Nine of the 17 definitions for inherited heart disease were repeated across studies.ConclusionsInherited heart disease populations can be identified using routinely collected health data, though challenges relate to existing diagnosis codes. This is an underutilised resource with the potential to inform patterns of care, patient outcomes and overall disease burden.
NONLINEAR ANALYSIS OF CORONARY ARTERY DISEASE, MYOCARDIAL INFARCTION, AND NORMAL ECG SIGNALS
Authors: HAGIWARA YUKI , FAUST OLIVER 
Published: October 2017

In this study, we analyze nonlinear feature extraction methods in terms of their ability to support the diagnosis of coronary artery disease (CAD) and myocardial infarction (MI). The nonlinear features were extracted from electrocardiogram (ECG) signals that were measured from CAD patients, MI patients as well as normal controls.We tested 34 recurrence quantification analysis (RQA) features, 14 bispectrum, and 136 cumulant features. The features were extracted from 10,546 normal, 41,545 CAD, and 40,182 MI heart beats. The feature quality was assessed with Student’s [Formula: see text]-test and the [Formula: see text]-value was used for feature ranking.We found that nonlinear features can effectively represent the physiological realities of the human heart.
Efficient logging in non-volatile memory by exploiting coherency protocols
Authors: Cohen Nachshon , Friedman Michal , Larus James R. 
Published: October 2017

Non-volatile memory technologies such as PCM, ReRAM and STT-RAM allow data to be saved to persistent storage significantly faster than hard drives or SSDs. Many of the use cases for non-volatile memory requires persistent logging since it enables a set of operations to execute in an atomic manner. However, a logging protocol must handle reordering, which causes a write to reach the non-volatile memory before a previous write operation.
In this paper, we show that reordering results from two parts of the system: the out-of-order execution in the CPU and the cache coherence protocol. By carefully considering the properties of these reorderings, we present a logging protocol that requires only one round trip to non-volatile memory while avoiding expensive computations, thus increasing performance. We also show how the logging protocol can be extended to building a durable set (hash map) that also requires a single round trip to non-volatile memory for inserting, updating, or deleting operations.
Monadic composition for deterministic, parallel batch processing
Authors: Scott Ryan G. , Navarro Leija Omar S. , Devietti Joseph , Newton Ryan R. 
Published: October 2017

Achieving determinism on real software systems remains difficult. Even a batch-processing job, whose task is to map input bits to output bits, risks nondeterminism from thread scheduling, system calls, CPU instructions, and leakage of environmental information such as date or CPU model. In this work, we present a system for achieving low-overhead deterministic execution of batch-processing programs that read and write the file system—turning them into pure functions on files.
We allow multi-process executions where a permissions system prevents races on the file system. Process separation enables different processes to enforce permissions and enforce determinism using distinct mechanisms. Our prototype, DetFlow, allows a statically-typed coordinator process to use shared-memory parallelism, as well as invoking process-trees of sandboxed legacy binaries. DetFlow currently implements the coordinator as a Haskell program with a restricted I/O type for its main function: a new monad we call DetIO. Legacy binaries launched by the coordinator run concurrently, but internally each process schedules threads sequentially, allowing dynamic determinism-enforcement with predictably low overhead.
We evaluate DetFlow by applying it to bioinformatics data pipelines and software build systems. DetFlow enables determinizing these data-processing workflows by porting a small amount of code to become a statically-typed coordinator. This hybrid approach of static and dynamic determinism enforcement permits freedom where possible but restrictions where necessary.
Who guards the guards? formal validation of the Arm v8-m architecture specification
Authors: Reid Alastair 
Published: October 2017

Software and hardware are increasingly being formally verified against specifications, but how can we verify the specifications themselves? This paper explores what it means to formally verify a specification. We solve three challenges: (1) How to create a secondary, higher-level specification that can be effectively reviewed by processor designers who are not experts in formal verification; (2) How to avoid common-mode failures between the specifications; and (3) How to automatically verify the two specifications against each other.
One of the most important specifications for software verification is the processor specification since it defines the behaviour of machine code and of hardware protection features used by operating systems. We demonstrate our approach on ARM's v8-M Processor Specification, which is intended to improve the security of Internet of Things devices. Thus, we focus on establishing the security guarantees the architecture is intended to provide. Despite the fact that the ARM v8-M specification had previously been extensively tested, we found twelve bugs (including two security bugs) that have all been fixed by ARM.
Type test scripts for TypeScript testing
Authors: Kristensen Erik Krogh , Møller Anders 
Published: October 2017

TypeScript applications often use untyped JavaScript libraries. To support static type checking of such applications, the typed APIs of the libraries are expressed as separate declaration files. This raises the challenge of checking that the declaration files are correct with respect to the library implementations. Previous work has shown that mismatches are frequent and cause TypeScript's type checker to misguide the programmers by rejecting correct applications and accepting incorrect ones.
This paper shows how feedback-directed random testing, which is an automated testing technique that has mostly been used for testing Java libraries, can be adapted to effectively detect such type mismatches. Given a JavaScript library with a TypeScript declaration file, our tool TSTEST generates a "type test script", which is an application that interacts with the library and tests that it behaves according to the type declarations. Compared to alternative solutions that involve static analysis, this approach finds significantly more mismatches in a large collection of real-world JavaScript libraries with TypeScript declaration files, and with fewer false positives. It also has the advantage that reported mismatches are easily reproducible with concrete executions, which aids diagnosis and debugging.
Muscle α-adrenergic responsiveness during exercise and ATP-induced vasodilation in chronic obstructive pulmonary disease patients
Authors: Iepsen U. W. , Munch G. W. , Ryrsø C. K. , Secher N. H. , Lange P. , Thaning P. , Pedersen B. K. , Mortensen S. P. 
Published: October 2017

Sympathetic vasoconstriction is blunted in exercising muscle (functional sympatholysis) but becomes attenuated with age. We tested the hypothesis that functional sympatholysis is further impaired in chronic obstructive pulmonary disease (COPD) patients. We determined leg blood flow and calculated leg vascular conductance (LVC) during 1) femoral-arterial Tyramine infusion (evokes endogenous norepinephrine release, 1 µmol·min−1·kg leg mass−1), 2) one-legged knee extensor exercise with and without Tyramine infusion [10 W and 20% of maximal workload (WLmax)], 3) ATP (0.05 µmol·min−1·kg leg mass−1) and Tyramine infusion, and 4) incremental ATP infusions (0.05, 0.3, and 3.0 µmol·min−1·kg leg mass−1). We included 10 patients with moderate to severe COPD and 8 age-matched healthy control subjects. Overall, leg blood flow and LVC were lower in COPD patients during exercise ( P < 0.05). Tyramine reduced LVC in both groups at 10-W exercise (COPD: −3 ± 1 ml·min−1·mmHg−1and controls: −3 ± 1 ml·min−1·mmHg−1, P < 0.05) and 20% WLmax(COPD: −4 ± 1 ml·min−1·mmHg−1and controls: −3 ± 1 ml·min−1·mmHg−1, P < 0.05) with no difference between groups. Incremental ATP infusions induced dose-dependent vasodilation with no difference between groups, and, in addition, the vasoconstrictor response to Tyramine infused together with ATP was not different between groups (COPD: −0.03 ± 0.01 l·min−1·kg leg mass−1vs. controls: −0.04 ± 0.01 l·min−1·kg leg mass−1, P > 0.05). Compared with age-matched healthy control subjects, the vasodilatory response to ATP is intact in COPD patients and their ability to blunt sympathetic vasoconstriction (functional sympatholysis) as evaluated by intra-arterial Tyramine during exercise or ATP infusion is maintained.NEW & NOTEWORTHY The ability to blunt sympathetic vasoconstriction in exercising muscle and ATP-induced dilation in chronic obstructive pulmonary disease patients remains unexplored. Chronic obstructive pulmonary disease patients demonstrated similar sympathetic vasoconstriction in response to intra-arterial Tyramine during exercise and ATP-induced vasodilation compared with age-matched healthy control subjects.
Intermuscular Adipose Tissue and Subclinical Coronary Artery Calcification in Midlife
Authors: Terry James G. , Shay Christina M. , Schreiner Pamela J. , Jacobs David R. , Sanchez Otto A. , Reis Jared P. , Goff David C. , Gidding Samuel S. , Steffen Lyn M. , Carr John Jeffrey 
Published: October 2017

Objective—
Excess deposition of fat within and around vital organs and nonadipose tissues is hypothesized to contribute to cardiovascular disease (CVD) risk. We evaluated the association of abdominal intermuscular adipose tissue (IMAT) volume with coronary artery calcification in the CARDIA study (Coronary Artery Risk Development in Young Adults) participants.

Approach and Results—
We measured IMAT in the abdominal muscles, visceral adipose tissue and pericardial adipose tissue, and coronary artery calcification using computed tomography in 3051 CARDIA participants (56% women) at the CARDIA year 25 examination (2010–2011). Mean IMAT volume and mean IMAT/total muscle volume (IMAT normalized for muscle size) were calculated in a 10-mm block of slices centered at L3–L4. Multivariable analyses included potential confounders and traditional cardiovascular disease risk factors. Compared with the lowest quartile, the upper quartile of abdominal IMAT volume was associated with higher coronary artery calcification prevalence (odds ratio [95% confidence interval], 1.6 [1.2–2.1]) after adjusting for cardiovascular disease risk factors. Results were similar for highest versus lowest quartile of IMAT normalized to total muscle volume (odds ratio [95% confidence interval], 1.5 [1.1–2.0]). Significant associations of higher IMAT and normalized IMAT with coronary artery calcification prevalence persisted when body mass index, visceral adipose tissue, or pericardial adipose tissue were added to the models.

Conclusions—
In a large, community-based, cross-sectional study, we found that higher abdominal skeletal muscle adipose tissue volume was associated with subclinical atherosclerosis independent of traditional cardiovascular disease risk factors and other adipose depots.