bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits and risks of the Sanofi-Pasteur dengue vaccine: Modeling optimal deployment
Authors: Ferguson Neil M. , Rodríguez-Barraquer Isabel , Dorigatti Ilaria , Mier-y-Teran-Romero Luis , Laydon Daniel J. , Cummings Derek A. T.
Published: September 2016

The first approved dengue vaccine has now been licensed in six countries. We propose that this live attenuated vaccine acts like a silent natural infection in priming or boosting host immunity. A transmission dynamic model incorporating this hypothesis fits recent clinical trial data well and predicts that vaccine effectiveness depends strongly on the age group vaccinated and local transmission intensity. Vaccination in low-transmission settings may increase the incidence of more severe “secondary-like” infection and, thus, the numbers hospitalized for dengue. In moderate transmission settings, we predict positive impacts overall but increased risks of hospitalization with dengue disease for individuals who are vaccinated when seronegative. However, in high-transmission settings, vaccination benefits both the whole population and seronegative recipients. Our analysis can help inform policy-makers evaluating this and other candidate dengue vaccines.
Nanoporous fabrics could keep you cool
Authors: Boriskina Svetlana V.
Published: September 2016

Engineered polyethylene materials are opaque but allow heat to radiate
Tumors set time
Authors: Shakhmantsir Iryna , Sehgal Amita
Published: September 2016

Lung tumors in mice distally alter circadian cycling of transcripts and metabolites in the liver
The science–policy interface
Authors: Gluckman Peter
Published: September 2016

How do we ensure the effective role of science in public policy-making? This well-worn, long-standing question reflects the fact that the answer is not simple. Later this month in Brussels, scientists and policy-makers will convene at the International Network for Government Science Advice (INGSA) Forum to consider the most promising ways forward.
Small-Volume Adenosine, Lidocaine, and Mg
2+
4-Hour Infusion Leads to 88% Survival after 6 Days of Experimental Sepsis in the Rat without Antibiotics
Authors: Griffin Maddison Jade , Letson Hayley Louise , Dobson Geoffrey Phillip
Published: September 2016

Innovative host-directed drug therapies are urgently required to treat sepsis. We tested the effect of a small-volume 0.9% NaCl adenosine, lidocaine, and Mg
2+
(ALM) bolus and a 4-h intravenous infusion on survivability in the rat model of polymicrobial sepsis over 6 days. ALM treatment led to a significant increase in survivability (88%) compared to that of controls (25%). Four controls died on day 2 to 3, and two died on day 5. Early death was associated with elevated plasma and lung inflammatory markers (interleukin-6 [IL-6], IL-1β, C-reactive protein), reduced white blood cell (WBC) count, hypoxemia, hypercapnia, acidosis, hyperkalemia, and elevated lactate, whereas late death was associated with a massive cytokine storm, a neutrophil-dominated WBC rebound/overshoot, increased lung oxidant injury, edema, and persistent ischemia. On day 6, seven of eight ALM survivors had inflammatory and immunological profiles not significantly different from those of sham-treated animals. We conclude in the rat model of experimental sepsis that small-volume ALM treatment led to higher survivability at 6 days (88%) than that of controls (25%). Early death in controls (day 2 to 3) was associated with significantly elevated plasma levels of IL-1β, IL-6, and C-reactive protein, severe plasma lymphocyte deficiency, reduced neutrophils, and acute lung injury. Late death (day 5) was associated with a massive neutrophil inflammatory storm, increased lung injury, and persistent ischemia. Possible mechanisms of ALM protection are discussed.
Antibody Responses to Immunizations in Children with Type I Diabetes Mellitus: a Case-Control Study
Authors: Eisenhut Michael , Chesover Alexander , Misquith Ronald , Nathwani Nisha , Walters Andrew
Published: September 2016

Type I diabetes mellitus (DM) has been associated with abnormalities of T cells. Our objective was to assess whether antibody responses to T-cell-dependent and -independent antigens in children with DM are lower than those of children without DM. We performed a case-control study matching children with DM to children without DM by age and by assessing antibody levels to pneumococcal serotypes,
Haemophilus influenzae
, and tetanus and diphtheria toxoids and reassessing antibody levels in patients with antibody levels below protective thresholds after booster immunization. We recruited 36 children with DM and 36 age-matched controls. The mean age was 10 years. There was no difference between groups in antibody levels against the antigens tested. Pneumococcal antibody levels below the protective threshold were found in 35.9% of DM patients after conjugate pneumococcal vaccination with no difference between groups. Booster immunization with unconjugated pneumococcal vaccine resulted in a median level against pneumococcal serotypes of 2.3 μg/ml (range, 0.05 to 664.7 μg/ml) in children with DM and 6.1 μg/ml (0.12 to 203.36 μg/ml) in children without DM (
P
= 0.013). Over 85% of children had levels above the protective threshold after booster immunization with no difference between groups. There was no evidence for a reduced antibody response to T-cell-dependent antigens given during childhood immunizations in children with DM. There was a reduced antibody response to antigens of pneumococcal strains in children with DM given unconjugated pneumococcal polysaccharide vaccine compared to that of children without DM without being associated with a difference in percentage of antibody levels below the protective threshold between groups.
Identification and Analysis of Informative Single Nucleotide Polymorphisms in 16S rRNA Gene Sequences of the Bacillus cereus Group
Authors: Hakovirta Janetta R. , Prezioso Samantha , Hodge David , Pillai Segaran P. , Weigel Linda M.
Published: September 2016

Analysis of 16S rRNA genes is important for phylogenetic classification of known and novel bacterial genera and species and for detection of uncultivable bacteria. PCR amplification of 16S rRNA genes with universal primers produces a mixture of amplicons from all rRNA operons in the genome, and the sequence data generally yield a consensus sequence. Here we describe valuable data that are missing from consensus sequences, variable effects on sequence data generated from nonidentical 16S rRNA amplicons, and the appearance of data displayed by different software programs. These effects are illustrated by analysis of 16S rRNA genes from 50 strains of the
Bacillus cereus
group, i.e.,
Bacillus anthracis
,
Bacillus cereus
,
Bacillus mycoides
, and
Bacillus thuringiensis
. These species have 11 to 14 rRNA operons, and sequence variability occurs among the multiple 16S rRNA genes. A single nucleotide polymorphism (SNP) previously reported to be specific to
B. anthracis
was detected in some
B. cereus
strains. However, a different SNP, at position 1139, was identified as being specific to
B. anthracis
, which is a biothreat agent with high mortality rates. Compared with visual analysis of the electropherograms, basecaller software frequently missed gene sequence variations or could not identify variant bases due to overlapping basecalls. Accurate detection of 16S rRNA gene sequences that include intragenomic variations can improve discrimination among closely related species, improve the utility of 16S rRNA databases, and facilitate rapid bacterial identification by targeted DNA sequence analysis or by whole-genome sequencing performed by clinical or reference laboratories.
Production of Cytomegalovirus Dense Bodies by Scalable Bioprocess Methods Maintains Immunogenicity and Improves Neutralizing Antibody Titers
Authors: Schneider-Ohrum Kirsten , Cayatte Corinne , Liu Yi , Wang Zhaoti , Irrinki Alivelu , Cataniag Floro , Nguyen Nga , Lambert Stacie , Liu Hui , Aslam Shahin , Duke Greg , McCarthy Michael P. , McCormick Louise
Published: September 2016

With the goal of developing a virus-like particle-based vaccine based on dense bodies (DB) produced by human cytomegalovirus (HCMV) infections, we evaluated scalable culture, isolation, and inactivation methods and applied technically advanced assays to determine the relative purity, composition, and immunogenicity of DB particles. Our results increase our understanding of the benefits and disadvantages of methods to recover immunogenic DB and inactivate contaminating viral particles. Our results indicate that (i) HCMV strain Towne replicates in MRC-5 fibroblasts grown on microcarriers, (ii) DB particles recovered from 2-bromo-5,6-dichloro-1-beta-
d
-ribofuranosyl benzimidazole riboside (BDCRB)-treated cultures and purified by tangential flow filtration (TFF-DB) or glycerol tartrate gradient sedimentation (GT-DB) constitute 92% or 98%, respectively, of all particles in the final product, (iii) epithelial cell-tropic DB particles are recovered from a single round of coinfection by AD169 and Towne strain viruses, consistent with complementation between the UL130 and UL131A expressed by these strains and restoration of gH/gL/UL128-UL131A (gH pentamer), (iv) equivalent neutralizing antibody titers are induced in mice following immunization with epithelial cell-tropic DB or gH pentamer-deficient DB preparations, (v) UV-inactivated residual virus in GT-DB or TFF-DB preparations retained immunogenicity and induced neutralizing antibody, preventing viral entry into epithelial cells, and (vi) GT-DB and TFF-DB induced cellular immune responses to multiple HCMV peptides. Collectively, this work provides a foundation for future development of DB as an HCMV-based particle vaccine.

IMPORTANCE
Development of a vaccine to prevent congenital HCMV infection remains a high priority. Vaccination with human cytomegalovirus-derived noninfectious particles, or dense bodies, may constitute a safe vaccination strategy that mimics natural infection. The standard approach for purification of virus particles has been to use a multiple-step, complex gradient that presents a potential barrier to production scale-up and commercialization. In the study described here, we employed an approach that combines treatment with an antiviral terminase inhibitor and purification by a simplified process to produce a vaccine candidate providing broad antiviral humoral and cellular immunity as a foundation for future development.
Imperfect Symmetry of Sp1 and Core Promoter Sequences Regulates Early and Late Virus Gene Expression of the Bidirectional BK Polyomavirus Noncoding Control Region
Authors: Bethge Tobias , Ajuh Elvis , Hirsch Hans H.
Published: September 2016

Rearrangements or point mutations in the noncoding control region (NCCR) of BK polyomavirus (BKPyV) have been associated with higher viral loads and more pronounced organ pathology in immunocompromised patients. The respective alterations affect a multitude of transcription factor binding sites (TFBS) but consistently cause increased expression of the early viral gene region (EVGR) at the expense of late viral gene region (LVGR) expression. By mutating TFBS, we identified three phenotypic groups leading to strong, intermediate, or impaired EVGR expression and corresponding BKPyV replication. Unexpectedly, Sp1 TFBS mutants either activated or inhibited EVGR expression when located proximal to the LVGR (
sp1-4
) or the EVGR (
sp1-2
), respectively. We now demonstrate that the bidirectional balance of EVGR and LVGR expression is dependent on affinity, strand orientation, and the number of Sp1 sites. Swapping the LVGR-proximal high-affinity
SP1-4
with the EVGR-proximal low-affinity
SP1-2
in site strand flipping or inserting an additional
SP1-2
site caused a rearranged NCCR phenotype of increased EVGR expression and faster BKPyV replication. The 5′ rapid amplification of cDNA ends revealed an imperfect symmetry between the EVGR- and LVGR-proximal parts of the NCCR, consisting of
TATA
and
TATA
-like elements, initiator elements, and downstream promoter elements. Mutation or deletion of the archetypal LVGR promoter, which is found in activated NCCR variants, abrogated LVGR expression, which could be restored by providing large T antigen (LTag) in
trans
. Thus, whereas Sp1 sites control the initial EVGR-LVGR expression balance, LTag expression can override inactivation of the LVGR promoter and acts as a key driver of LVGR expression independently of the Sp1 sites and core promoter elements.

IMPORTANCE
Polyomaviridae
currently comprise more than 70 members, including 13 human polyomaviruses (PyVs), all of which share a bidirectional genome organization mediated by the NCCR, which determines species and host cell specificity, persistence, replication, and virulence. Here, we demonstrate that the BKPyV NCCR is fine-tuned by an imperfect symmetry of core promoter elements centered around
TATA
and
TATA
-like sequences close to the EVGR and LVGR, respectively, which are governed by the directionality and affinity of two Sp1 sites. The data indicated that the BKPyV NCCR is poised toward EVGR expression, which can be readily unlatched by a simple switch affecting Sp1 binding. The resulting LTag, which is the major EVGR protein, drives viral genome replication, renders subsequent LVGR expression independently of archetypal promoter elements, and can overcome enhancer/promoter mutations and deletions. The data are pivotal for understanding how human PyV NCCRs mediate secondary host cell specificity, reactivation, and virulence in their natural hosts.
Differential Control of BST2 Restriction and Plasmacytoid Dendritic Cell Antiviral Response by Antagonists Encoded by HIV-1 Group M and O Strains
Authors: Bego Mariana G. , Cong Lijun , Mack Katharina , Kirchhoff Frank , Cohen Éric A.
Published: September 2016

BST2/tetherin is a type I interferon (IFN-I)-stimulated host factor that restricts the release of HIV-1 by entrapping budding virions at the cell surface. This membrane-associated protein can also engage and activate the plasmacytoid dendritic cell (pDC)-specific immunoglobulin-like transcript 7 (ILT7) inhibitory receptor to downregulate the IFN-I response by pDCs. Pandemic HIV-1 group M uses Vpu (M-Vpu) to counteract the two BST2 isoforms (long and short) that are expressed in human cells. M-Vpu efficiently downregulates surface long BST2, while it displaces short BST2 molecules away from viral assembly sites. We recently found that this attribute is used by M-Vpu to activate the BST2/ILT7-dependent negative-feedback pathway and to suppress pDC IFN-I responses during sensing of infected cells. However, whether this property is conserved in endemic HIV-1 group O, which has evolved Nef (O-Nef) to counteract specifically the long BST2 isoform, remains unknown. In the present study, we validated that O-Nefs have the capacity to downregulate surface BST2 and enhance HIV-1 particle release although less efficiently than M-Vpu. In contrast to M-Vpu, O-Nef did not efficiently enhance viral spread in T cell culture or displace short BST2 from viral assembly sites to prevent its occlusion by tethered HIV-1 particles. Consequently, O-Nef impairs the ability of BST2 to activate negative ILT7 signaling to suppress the IFN-I response by pDC-containing peripheral blood mononuclear cells (PBMCs) during sensing of infected cells. These distinctive features of BST2 counteraction by O-Nefs may in part explain the limited spread of HIV-1 group O in the human population.

IMPORTANCE
The geographical distributions and prevalences of different HIV-1 groups show large variations. Understanding drivers of distinctive viral spread may aid in the development of therapeutic strategies for controlling the spread of HIV-1 pandemic strains. The differential spread of HIV-1 groups appears to be linked to their capacities to antagonize the long and short isoforms of the BST2 restriction factor. We found that the endemic HIV-1 group O-encoded BST2 antagonist Nef is unable to counteract the restriction mediated by short BST2, a condition that impairs its ability to activate ILT7 and suppress pDC antiviral responses. This is in contrast to the pandemic HIV-1 group M-specified BST2 countermeasure Vpu, which displays a diverse array of mechanisms to counteract short and long BST2 isoforms, an attribute that allows the effective control of pDC antiviral responses. These findings may help explain the limited spread of HIV-1 group O as well as the continued predominance of HIV-1 group M throughout the world.
Efficiency in Complexity: Composition and Dynamic Nature of Mimivirus Replication Factories
Authors: Fridmann-Sirkis Yael , Milrot Elad , Mutsafi Yael , Ben-Dor Shifra , Levin Yishai , Savidor Alon , Kartvelishvily Elena , Minsky Abraham
Published: September 2016

The recent discovery of multiple giant double-stranded DNA (dsDNA) viruses blurred the consensual distinction between viruses and cells due to their size, as well as to their structural and genetic complexity. A dramatic feature revealed by these viruses as well as by many positive-strand RNA viruses is their ability to rapidly form elaborate intracellular organelles, termed “viral factories,” where viral progeny are continuously generated. Here we report the first isolation of viral factories at progressive postinfection time points. The isolated factories were subjected to mass spectrometry-based proteomics, bioinformatics, and imaging analyses. These analyses revealed that numerous viral proteins are present in the factories but not in mature virions, thus implying that multiple and diverse proteins are required to promote the efficiency of viral factories as “production lines” of viral progeny. Moreover, our results highlight the dynamic and highly complex nature of viral factories, provide new and general insights into viral infection, and substantiate the intriguing notion that viral factories may represent the living state of viruses.

IMPORTANCE
Large dsDNA viruses such as vaccinia virus and the giant mimivirus, as well as many positive-strand RNA viruses, generate elaborate cytoplasmic organelles in which the multiple and diverse transactions required for viral replication and assembly occur. These organelles, which were termed “viral factories,” are attracting much interest due to the increasing realization that the rapid and continuous production of viral progeny is a direct outcome of the elaborate structure and composition of the factories, which act as efficient production lines. To get new insights into the nature and function of viral factories, we devised a method that allows, for the first time, the isolation of these organelles. Analyses of the isolated factories generated at different times postinfection by mass spectrometry-based proteomics provide new perceptions of their role and reveal the highly dynamic nature of these organelles.
Plasmodium Helical Interspersed Subtelomeric (PHIST) Proteins, at the Center of Host Cell Remodeling
Authors: Warncke Jan D. , Vakonakis Ioannis , Beck Hans-Peter
Published: September 2016

During the asexual cycle,
Plasmodium falciparum
extensively remodels the human erythrocyte to make it a suitable host cell. A large number of exported proteins facilitate this remodeling process, which causes erythrocytes to become more rigid, cytoadherent, and permeable for nutrients and metabolic products. Among the exported proteins, a family of 89 proteins, called the
Plasmodium
helical interspersed subtelomeric (PHIST) protein family, has been identified. While also found in other
Plasmodium
species, the PHIST family is greatly expanded in
P. falciparum
. Although a decade has passed since their first description, to date, most PHIST proteins remain uncharacterized and are of unknown function and localization within the host cell, and there are few data on their interactions with other host or parasite proteins. However, over the past few years, PHIST proteins have been mentioned in the literature at an increasing rate owing to their presence at various localizations within the infected erythrocyte. Expression of PHIST proteins has been implicated in molecular and cellular processes such as the surface display of PfEMP1, gametocytogenesis, changes in cell rigidity, and also cerebral and pregnancy-associated malaria. Thus, we conclude that PHIST proteins are central to host cell remodeling, but despite their obvious importance in pathology, PHIST proteins seem to be understudied. Here we review current knowledge, shed light on the definition of PHIST proteins, and discuss these proteins with respect to their localization and probable function. We take into consideration interaction studies, microarray analyses, or data from blood samples from naturally infected patients to combine all available information on this protein family.
The mechanism of partial rupture of a locked megathrust: The role of fault morphology
Authors: Qiu Qiang , Hill Emma M. , Barbot Sylvain , Hubbard Judith , Feng Wanpeng , Lindsey Eric O. , Feng Lujia , Dai Keren , Samsonov Sergey V. , Tapponnier Paul
Published: September 2016

Assessment of seismic hazard relies on estimates of how large an area of a tectonic fault could potentially rupture in a single earthquake. Vital information for these forecasts includes which areas of a fault are locked and how the fault is segmented. Much research has focused on exploring downdip limits to fault rupture from chemical and thermal boundaries, and along-strike barriers from subducted structural features, yet we regularly see only partial rupture of fully locked fault patches that could have ruptured as a whole in a larger earthquake. Here we draw insight into this conundrum from the 25 April 2015 Mw 7.8 Gorkha (Nepal) earthquake. We invert geodetic data with a structural model of the Main Himalayan thrust in the region of Kathmandu, Nepal, showing that this event was generated by rupture of a décollement bounded on all sides by more steeply dipping ramps. The morphological bounds explain why the event ruptured only a small piece of a large fully locked seismic gap. We then use dynamic earthquake cycle modeling on the same fault geometry to reveal that such events are predicted by the physics. Depending on the earthquake history and the details of rupture dynamics, however, great earthquakes that rupture the entire seismogenic zone are also possible. These insights from Nepal should be applicable to understanding bounds on earthquake size on megathrusts worldwide.
Detecting magma-poor orogens in the detrital record
Authors: O’Sullivan G.J. , Chew D.M. , Samson S.D.
Published: September 2016

The clastic record is commonly interrogated by analysis of detrital heavy mineral assemblages, with the bulk of modern detrital geochronological studies employing U-Pb dating of detrital zircon. However, the bias of zircon toward felsic igneous sources, and the limited ability of the U-Pb system in zircon to record low- to medium-grade metamorphic events, means that the U-Pb detrital zircon record is largely insensitive to magma-poor orogens. In this study, U-Pb ages were obtained by laser ablation–inductively coupled plasma–mass spectrometry for apatite and rutile extracted from alluvium of the French Broad River (FBR) in the southern Appalachians (southeastern United States). In contrast to previously published FBR U-Pb zircon data sets, which yield essentially no record of the most recent Appalachian metamorphic events (ca. 320 Ma) associated with assembly of Pangea, the U-Pb detrital rutile and especially the U-Pb apatite systems together provide a complete record of complex polyphase Appalachian orogenesis. It is unexpected that the apatite and rutile U-Pb Appalachian age populations differ significantly, with probable low-temperature breakdown of rutile biasing the rutile data set toward the most recent (Alleghanian) metamorphic event. These data make the FBR one of the most intensely studied river systems globally for multiproxy single-grain U-Pb analysis, clearly demonstrate dependence of provenance information on mineral proxy choice, and emphasize the resolving power of multiproxy provenance studies.
Experimental evidence that clay inhibits bacterial decomposers: Implications for preservation of organic fossils
Authors: McMahon Sean , Anderson Ross P. , Saupe Erin E. , Briggs Derek E. G.
Published: September 2016

Exceptionally preserved organic fossils are commonly associated with clay-rich horizons or directly with clay minerals. It has been posited that interactions between clay minerals and organic tissues inhibit enzymatic reactions or protect carcasses in such a way that decay is impeded. However, interactions between clay minerals and the biological agents of decay, especially bacteria, may be at least as important to preservation potential. Here we show that clays of particle size <2 μm in suspensions exceeding 10 mg/ml in concentration inhibit the growth of Pseudoalteromonas luteoviolacea, a marine heterotrophic bacterium involved in the decay of marine animals. Such clay-microbe interactions can contribute to exceptional preservation, and specific examples may play a role in shaping the distribution of Konservat-Lagerstätten through time.
Does physical activity moderate the association between alcohol drinking and all-cause, cancer and cardiovascular diseases mortality? A pooled analysis of eight British population cohorts
Authors: Perreault K , Bauman A , Johnson N , Britton A , Rangul V , Stamatakis E
Published: September 2016

Objective

To examine whether physical activity (PA) moderates the association between alcohol intake and all-cause mortality, cancer mortality and cardiovascular diseases (CVDs) mortality.

Design

Prospective study using 8 British population-based surveys, each linked to cause-specific mortality: Health Survey for England (1994, 1998, 1999, 2003, 2004 and 2006) and Scottish Health Survey (1998 and 2003).

Participants

36 370 men and women aged 40 years and over were included with a corresponding 5735 deaths and a mean of 353 049 person-years of follow-up.

Exposures

6 sex-specific categories of alcohol intake (UK units/week) were defined: (1) never drunk; (2) ex-drinkers; (3) occasional drinkers; (4) within guidelines (<14 (women); <21 (men)); (5) hazardous (14–35 (women); 21–49 (men)) and (6) harmful (>35 (women) >49 (men)). PA was categorised as inactive (≤7 MET-hour/week), active at the lower (>7.5 MET-hour/week) and upper (>15 MET-hour/week) of recommended levels.

Main outcomes and measures

Cox proportional-hazard models were used to examine associations between alcohol consumption and all-cause, cancer and CVD mortality risk after adjusting for several confounders. Stratified analyses were performed to evaluate mortality risks within each PA stratum.

Results

We found a direct association between alcohol consumption and cancer mortality risk starting from drinking within guidelines (HR (95% CI) hazardous drinking: 1.40 (1.11 to 1.78)). Stratified analyses showed that the association between alcohol intake and mortality risk was attenuated (all-cause) or nearly nullified (cancer) among individuals who met the PA recommendations (HR (95% CI)).

Conclusions

Meeting the current PA public health recommendations offsets some of the cancer and all-cause mortality risk associated with alcohol drinking.
Association of Mediterranean diet and cardiorespiratory fitness with the development of pre-diabetes and diabetes: the Coronary Artery Risk Development in Young Adults (CARDIA) study
Authors: Bantle Anne E , Chow Lisa S , Steffen Lyn M , Wang Qi , Hughes John , Durant Nefertiti H , Ingram Katherine H , Reis Jared P , Schreiner Pamela J
Published: September 2016

Objective

To better understand the association between a modified Mediterranean diet pattern in young adulthood, cardiorespiratory fitness in young adulthood, and the odds of developing pre-diabetes or diabetes by middle age.

Research design and methods

Participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study who did not have pre-diabetes or diabetes at baseline (year 0 (Y0), ages 18–30) and who had data available at the Y0 and year 25 (Y25) visits were included in this analysis (n=3358). Polytomous logistic regression models were used to assess the association between baseline dietary intake and fitness data and odds of pre-diabetes or diabetes by middle age (Y25, ages 43–55).

Results

At the Y25 visit, 1319 participants (39%) had pre-diabetes and 393 (12%) had diabetes. Higher baseline fitness was associated with lower odds of pre-diabetes and of diabetes at Y25. After adjustment for covariates, each SD increment in treadmill duration (181 s) was associated with lower odds for pre-diabetes (OR 0.85, 95% CI 0.75 to 0.95, p=0.005) and for diabetes (OR 0.71, 95% CI 0.60 to 0.85, p=0.0002) when compared to normal glycemia. A modified Mediterranean diet pattern was not associated with either pre-diabetes or diabetes. No interaction between cardiorespiratory fitness and dietary intake was observed, but baseline fitness remained independently associated with incident pre-diabetes and diabetes following adjustment for diet.

Conclusions

Higher cardiorespiratory fitness in young adulthood, but not a modified Mediterranean diet pattern, is associated with lower odds of pre-diabetes and of diabetes in middle age.

Trial registration number

NCT00005130.
Investigating the epidemiology of medication errors and error-related adverse drug events (ADEs) in primary care, ambulatory care and home settings: a systematic review protocol
Authors: Assiri Ghadah Asaad , Grant Liz , Aljadhey Hisham , Sheikh Aziz
Published: September 2016

Introduction

There is a need to better understand the epidemiology of medication errors and error-related adverse events in community care contexts.

Methods and analysis

We will systematically search the following databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Eastern Mediterranean Regional Office of the WHO (EMRO), MEDLINE, PsycINFO and Web of Science. In addition, we will search Google Scholar and contact an international panel of experts to search for unpublished and in progress work. The searches will cover the time period January 1990–December 2015 and will yield data on the incidence or prevalence of and risk factors for medication errors and error-related adverse drug events in adults living in community settings (ie, primary care, ambulatory and home). Study quality will be assessed using the Critical Appraisal Skills Program quality assessment tool for cohort and case–control studies, and cross-sectional studies will be assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Descriptive Studies. Meta-analyses will be undertaken using random-effects modelling using STATA (V.14) statistical software.

Ethics and dissemination

This protocol will be registered with PROSPERO, an international prospective register of systematic reviews, and the systematic review will be reported in the peer-reviewed literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Social facilitation maintenance treatment for adults with obesity: study protocol for a randomised-controlled feasibility study (SFM study)
Authors: Hilbert Anja
Published: September 2016

Introduction

The long-term success of non-surgical weight loss treatment in adults with obesity is limited by substantial relapse, and only a few evidence-based weight loss maintenance treatments exist. This clinical trial investigates the feasibility and efficacy of a social facilitation maintenance programme for weight loss maintenance, tailored to meet the needs of obese adults who have undergone a lifestyle weight loss intervention.

Methods and analysis

In a single-centre, open feasibility trial, 72 adults currently or previously obese or overweight who have undergone a lifestyle weight loss intervention are centrally randomised to 4 months of social facilitation maintenance treatment or treatment as a usual control condition. In 16 outpatient group sessions, the social facilitation maintenance treatment, based on a socioecological model and on evidence supporting social facilitation as a key process in maintaining weight loss, focuses on promoting interpersonal relationships to build up a healthy lifestyle for long-term weight loss maintenance. Primary outcome is the amount of weight regain at 6-month follow-up, compared with pre-treatment weight, derived from measured body weight. Secondary outcomes address feasibility, including recruitment, attrition, assessment non-completion, compliance and patients' programme evaluation; and in comparison with pre-weight loss maintenance, social and interpersonal functioning, eating behaviour and physical activity, psychological and physical symptoms, body composition and risk of comorbidity, and quality of life at post-treatment and follow-up assessments.

Ethics and dissemination

The study was approved by the Ethical Committee at the University of Leipzig (165-13-15072013). The study results will be disseminated through peer-reviewed publications.

Trial registration number

DRKS00005182.
Psychological impact and recovery after involvement in a patient safety incident: a repeated measures analysis
Authors: Van Gerven Eva , Bruyneel Luk , Panella Massimiliano , Euwema Martin , Sermeus Walter , Vanhaecht Kris
Published: September 2016

Objective

To examine individual, situational and organisational aspects that influence psychological impact and recovery of a patient safety incident on physicians, nurses and midwives.

Design

Cross-sectional, retrospective surveys of physicians, midwives and nurses.

Setting

33 Belgian hospitals.

Participants

913 clinicians (186 physicians, 682 nurses, 45 midwives) involved in a patient safety incident.

Main outcome measures

The Impact of Event Scale was used to retrospectively measure psychological impact of the safety incident at the time of the event and compare it with psychological impact at the time of the survey.

Results

Individual, situational as well as organisational aspects influenced psychological impact and recovery of a patient safety incident. Psychological impact is higher when the degree of harm for the patient is more severe, when healthcare professionals feel responsible for the incident and among female healthcare professionals. Impact of degree of harm differed across clinicians. Psychological impact is lower among more optimistic professionals. Overall, impact decreased significantly over time. This effect was more pronounced for women and for those who feel responsible for the incident. The longer ago the incident took place, the stronger impact had decreased. Also, higher psychological impact is related with the use of a more active coping and planning coping strategy, and is unrelated to support seeking coping strategies. Rendered support and a support culture reduce psychological impact, whereas a blame culture increases psychological impact. No associations were found with job experience and resilience of the health professional, the presence of a second victim support team or guideline and working in a learning culture.

Conclusions

Healthcare organisations should anticipate on providing their staff appropriate and timely support structures that are tailored to the healthcare professional involved in the incident and to the specific situation of the incident.
Can an ethics officer role reduce delays in research ethics approval? A mixed-method evaluation of an improvement project
Authors: Dixon-Woods Mary , Foy Chris , Hayden Charlotte , Al-Shahi Salman Rustam , Tebbutt Stephen , Schroter Sara
Published: September 2016

Objective

Frustration continues to be directed at delays in gaining approvals for undertaking health research in the UK. We aimed to evaluate the impact of an ethics officer intervention on rates of favourable opinions (approval) and provisional opinions (requiring revision and resubmission) and on the time taken to reach a final opinion by research ethics committees (RECs), to characterise how the role operated in practice, and to investigate applicants' views.

Design

Mixed-method study involving (i) a 2-group, non-randomised before-and-after intervention study of RECs assigned an ethics officer and a matched comparator group; (ii) a process evaluation involving a survey of applicants and documentary analysis.

Participants

6 RECs and 3 associated ethics officers; 18 comparator RECs; REC applicants.

Results

Rates of provisional and favourable opinions between ethics officer and comparator RECs did not show a statistically significant effect of the intervention (logistic regression, p=0.26 for favourable opinions and p=0.31 for provisional opinions). Mean time to reach a decision showed a non-significant reduction (ANOVA, p=0.22) from 33.3 to 32.0 days in the ethics officer RECs compared with the comparator RECs (32.6 to 32.9 days). The survey (30% response rate) indicated applicant satisfaction and also suggested that ethics officer support might be more useful before submission. Ethics officers were successful in identifying many issues with applications, but the intervention did not function exactly as designed: in 31% of applicants, no contact between the applicants and the ethics officer took place before REC review.

Limitations

This study was a non-randomised comparison cohort study. Some data were missing.

Conclusions

An ethics officer intervention, as designed and implemented in this study, did not increase the proportion of applications to RECs that were approved on first review and did not reduce the time to a committee decision.
How policy can help develop and sustain workforce capacity in UK dementia research: insights from a career tracking analysis and stakeholder interviews
Authors: Marjanovic Sonja , Lichten Catherine A , Robin Enora , Parks Sarah , Harte Emma , MacLure Calum , Walton Clare , Pickett James
Published: September 2016

Objectives

To identify research support strategies likely to be effective for strengthening the UK's dementia research landscape and ensuring a sustainable and competitive workforce.

Design

Interviews and qualitative analysis; systematic internet search to track the careers of 1500 holders of UK doctoral degrees in dementia, awarded during 1970–2013, to examine retention in this research field and provide a proxy profile of the research workforce.

Setting and participants

40 interviewees based in the UK, whose primary role is or has been in dementia research (34 individuals), health or social care (3) or research funding (3). Interviewees represented diverse fields, career stages and sectors.

Results

While the UK has diverse strengths in dementia research, needs persist for multidisciplinary collaboration, investment in care-related research, supporting research-active clinicians and translation of research findings. There is also a need to better support junior and midlevel career opportunities to ensure a sustainable research pipeline and future leadership. From a sample of 1500 UK doctorate holders who completed a dementia-related thesis in 1970–2013, we identified current positions for 829 (55%). 651 (43% of 1500) could be traced and identified as still active in research (any field) and 315 (21%) as active in dementia research. Among recent doctoral graduates, nearly 70% left dementia research within 4–6 years of graduation.

Conclusions

A dementia research workforce blueprint should consider support for individuals, institutions and networks. A mix of policy interventions are needed, aiming to attract and retain researchers; tackle bottlenecks in career pathways, particularly at early and midcareer stages (eg, scaling-up fellowship opportunities, rising star programmes, bridge-funding, flexible clinical fellowships, leadership training); and encourage research networks (eg, doctoral training centres, succession and sustainability planning). Interventions should also address the need for coordinated investment to improve multidisciplinary collaboration; balanced research portfolios across prevention, treatment and care; and learning from evaluation.
Nutritionists’ Health Study cohort: a web-based approach of life events, habits and health outcomes
Authors: Folchetti Luciana Gavilan Dias , Silva Isis Tande da , Almeida-Pititto Bianca de , Ferreira Sandra Roberta G
Published: September 2016

Introduction

Non-communicable chronic diseases (NCCDs) represent a burden for public health. Alongside the established cardiometabolic risk factors such as high blood pressure and disorders of glucose and lipid metabolism, living habits and nutritional status at different stages of life are seen as contributors to this scenario. Gut microbiota composition and subclinical inflammation have been pointed out as underlying mechanisms of NCCDs. Studies involving health professionals have brought relevant contributions to the knowledge about risk factors. Technological advances facilitate data collection and analysis for big samples. A web-based survey addressed to collect data from a cohort study, which is able to identify NCCDs risk factors, is highly desirable. The objective of the Brazilian Nutritionists’ Health Study (NutriHS) is to gather online information on early life events, daily habits, emergent cardiometabolic risk factors and health outcomes of a specific subset of the Brazilian population.

Methods and analysis

NutriHS, developed at the School of Public Health—University of Sao Paulo, Brazil, is a research initiative that enrols undergraduates of nutrition courses from Brazilian universities and graduated volunteers. A web-based self-administered system was designed to collect health-related data. After fulfilling online questionnaires (socioeconomic, early life events and lifestyle data), participants are invited to a clinical visit for physical examination and laboratory procedures (blood sampling, faeces collection and body composition). At a 3-year interval, they will be invited to repeat similar procedures.

Ethics and dissemination

The NutriHS research protocol was approved by the Institutional Ethics Committee and is providing promising data which contribute to the understanding of pathophysiological links between early life events, body composition, gut microbiota, and inflammatory and metabolic risk profile. The combination of a friendly tool with the innovative purposes of NutriHS offers a remarkable resource for testing hypotheses about mechanisms of nutrition-related diseases and further planning of preventive programmes in public health.
Implementation of asthma guidelines to West Australian community pharmacies: an exploratory, quasi-experimental study
Authors: Watkins Kim , Trevenen Michelle , Murray Kevin , Kendall Peter A , Schneider Carl R , Clifford Rhonda
Published: September 2016

Objectives

Pharmacy assistants are often the first point of contact for patients presenting in community pharmacies. The current role of pharmacy assistants in the supply of asthma-reliever medications (short-acting β-agonists) was identified as a barrier to appropriate guideline-based care. The aim of this research was to devise and evaluate a team-based intervention to formalise the role of pharmacy assistants and to improve asthma guideline-based care in community pharmacy.

Design

A controlled pre-post intervention study was conducted in 336 metropolitan pharmacies located in Perth, Western Australia. Pharmacies were stratified into 2 groups (187 intervention and 149 control) based on known confounders for asthma control. The intervention was designed using a common-sense approach and resources developed included a checklist, videos and web page. Delivery was via workshops (25 pharmacies) or academic detailing (162 pharmacies). Pharmacy practice was assessed preintervention and postintervention via covert simulated patient methodology. Primary outcome measures included patient medical referral, device use demonstration and counselling, internal referral and/or direct involvement of a pharmacist in consultations.

Results

There was a significant increase in patient medical referral in intervention pharmacies from 32% to 47% (p=0.0007) from preintervention to postintervention, while control pharmacies showed a non-significant decrease from 50% to 44% (p=0.22). Device counselling was not routinely carried out at any stage or in any cohort of this research and no significant changes in internal referral were observed.

Conclusions

Increases in medical referral indicate that asthma guideline compliance can be improved in community pharmacy if implementation employs a team-based approach and involves pharmacy assistants. However, results were variable and the intervention did not improve practice related to device counselling or internal referral/pharmacist involvement. Undertaking more workshops may have improved results. Guideline implementation in community pharmacy should consider the role of pharmacy assistants and how to overcome logistical barriers to pharmacy participation in implementation activities.
Do children who receive an ‘early dose’ of MMR vaccine during a measles outbreak return for their regularly scheduled dose? A retrospective population-based study
Authors: Guo Xiaoyan , Simmonds Kimberley A , Svenson Jill , MacDonald Shannon E
Published: September 2016

Background

Children under the age of 12 months may receive an early dose of measles–mumps–rubella (MMR) vaccine to provide short-term protection in the case of a disease outbreak. Following a measles outbreak in Alberta, Canada, there was concern that children who received an early dose may not be returning for their routinely scheduled dose at 12 months, leaving them vulnerable to disease in the long term.

Methods

This population-based study of children born between 2006 and 2014 used administrative health data to assess coverage and timeliness of the first routine dose of MMR vaccine administered at age 12–24 months for children who received an early dose of the vaccine due to a disease outbreak. We compared this group to children who received an early dose due to travel to a measles-endemic region and to children who did not receive an early dose.

Results

Only 5.5% of 366 351 children received an early dose. Coverage for the routine dose at age 24 months was 96.5% for children receiving an outbreak dose, 92.2% for those travelling to measles-endemic regions and 86.6% for those without an early dose (p<0.0001). The multivariable Cox proportional hazard analysis, controlling for neighbourhood income, place of residence and interaction effects, determined that, as compared to the general cohort, the outbreak group was most likely to obtain the first routine dose (adjusted HR (aHR): 1.52, 95% CI 1.44 to 1.60), followed by the travel group (aHR: 1.26, 95% CI 1.18 to 1.34).

Conclusions

It is reassuring that the majority of children who received an early dose returned for their routine dose and did so in a timely manner.
A Quality Improvement Project to Reduce the ‘No Show’ rate in a Paediatric Neurology Clinic
Authors: Mohamed Khalid , Mustafa Amira , Tahtamouni Sona , Taha Eshraga , Hassan Reham
Published: September 2016

This quality improvement project aimed to reduce the 'no show' rate in a paediatric neurology clinic in Qatar.

No show, in outpatient clinics, is defined as patients who fail to attend their scheduled clinic appointments. It is one of the targets for improving quality of care. It leads to longer waiting times for patients to be seen in outpatient clinics, and the result is patients missing their important appointments. It also results in a waste of the clinic resources, and physician and other healthcare practitioners' time.

This study was undertaken as part of the CCITP (clinical care improvement training programme). A project team was assembled with coaching support. The department chairman and the appointment system personnel were involved. Baseline and ongoing measures were collected and charted.

The baseline no-show rate was identified as 49%. Following three intervention PDSAs, mainly addressing communication and appointment flexibility, the post intervention no-show rate dropped to 18% and was sustained below the target of 25% for two years.

Better communication and appointment flexibility can significantly reduce the no-show rate in outpatient clinics.