bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of association of FOXO3 gene with Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy
Authors: Leon Rodriguez D. A. , González C. I. , Martin J.
Published: April 2016

FOXO3, a member of the Forkhead family of proteins, plays a role in controlling immune response. FOXO3 gene variant rs12212067 has been associated to differential severity of infectious diseases like malaria. In this study, we assessed whether this FOXO3 gene polymorphism is related to susceptibility to infection by Trypanosoma cruzi and/or chronic Chagasic cardiomyopathy. A total of 1171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and chronic Chagasic cardiomyopathy (n = 401) were genotyped for the FOXO3 rs12212067 using TaqMan allelic discrimination. Our results showed no statistically significantly differences between allelic and genotypic frequencies of rs12212067 in seronegative individuals compared with seropositive individuals. Similarly, we observed no evidence of association when asymptomatic individuals were compared with chronic Chagasic cardiomyopathy patients. Our data suggest that the FOXO3 genetic variant rs12212067 do not play an important role in Chagas disease.
Defiant Neoliberalism and the Danger of Detroit
Authors: Hackworth Jason
Published: April 2016

Critical geographical studies of neoliberalism have emphasised how local spatialities complicate the implementation and theorisation of top‐down, idealised versions of the ideology. The central assumption is that local circumstances autonomously contradict or disrupt such deployments of neoliberalism. This paper explores the deployment of ‘defiant neoliberalism’, and the use of Detroit as a vehicle to promote and ‘prove’ its veracity. Some geographers have suggested that such defiant ideologies are unworthy of serious critique because they are so self‐evidently contradicted by local circumstances. The case calls into question the assumption that local circumstance naturally challenges ideological framings such as neoliberalism. Many local details contradict the veracity of idealised neoliberalism, yet its promoters are able to actively morph them (or elide them) into a narrative that supports the wider ideology.
Economic Geography of the Australian Mining Industry
Authors: Bayari Celal
Published: April 2016

This paper is a discussion of the economic geography of Australia. It provides a history of foreign investment in mining, and discusses several resources booms that shaped the landscape of the continent and the role of governments (state, federal and territory governments) in this process. The paper presents a chronological account of the development of the Australian mining industry, the primary activities of which are the extraction, and export of unprocessed coal, iron, minerals and increasingly natural gas. The paper analyses the industry's interaction with foreign investment and government assistance (that is, government spending in relation to the industry such as subsidies, loans and infrastructure construction, etc.). Australia's trade and foreign investment environment have long been deregulated. The Australian mining industry has benefited from this deregulation. But its most spectacular period has been the ‘commodities super‐cycle’ of the 2000s–2010s. Overall, its contribution to exports has long typified the mining industry. The discussion herein draws attention to the applicability of the ‘eclectic theory’ in reference to foreign investment in mining. That is, investing mining MNEs (multinational enterprises) have three main types of ‘locational advantages’ in Australia: (i) volume of the availability of resources; (ii) foreign investment regulatory environment; and (iii) government assistance that benefits the mining industry's expansion.
VGDI – Advancing the Concept: Volunteered Geo‐Dynamic Information and its Benefits for Population Dynamics Modeling
Authors: Aubrecht Christoph , Özceylan Aubrecht Dilek , Ungar Joachim , Freire Sérgio , Steinnocher Klaus
Published: April 2016

The concept of Volunteered Geographic Information (VGI) has progressed from being an exotic prospect to making a profound impact on GIScience and geography in general, as initially anticipated. However, while massive and manifold data is continuously produced voluntarily and applications are built for information and knowledge extraction, the initially introduced concept of VGI lacks certain methodological perspectives in this regard which have not been fully elaborated. In this article we highlight and discuss an important gap in this concept, i.e. the lack of formal acknowledgment of temporal aspects. By coining the proposed advanced framework ‘Volunteered Geo‐Dynamic Information’ (VGDI), we attempt to lay the ground for full conceptual and applied spatio‐temporal integration. To illustrate that integrative approach of VGDI and its benefits, we describe the potential impact on the field of dynamic population distribution modeling. While traditional approaches in that domain rely on survey‐based data and statistics as well as static geographic information, the use of VGDI enables a dynamic setup. Foursquare venue and user check‐in data are presented for a test site in Lisbon, Portugal. Two core modules of spatio‐temporal population assessment are thereby addressed, namely time use profiling and target zone characterization, motivated by the potential integration in existing population dynamics frameworks such as the DynaPop model.
Physicians' experiences and views on the role of obstetric ultrasound in rural and urban Rwanda: a qualitative study
Authors: Edvardsson Kristina , Ntaganira Joseph , Åhman Annika , Sengoma Jean Paul Semasaka , Small Rhonda , Mogren Ingrid
Published: April 2016

Objective

To explore Rwandan physicians' experiences and views on the role of obstetric ultrasound in clinical management of pregnancy, and in situations where maternal and fetal health interests conflict.

Methods

Physicians (n = 19) in public and private health facilities in urban and rural Rwanda were interviewed in 2015 as part of the CROss‐Country Ultrasound Study (CROCUS). Data were analysed qualitatively.

Results

Ultrasound was described as an important tool in maternity care. Availability and quality of equipment varied across sites, and considerable disparities in obstetric ultrasound utilisation between rural and urban areas were described. The physicians wanted more ultrasound training and saw the potential for midwives to perform basic scans. Information about fetal sex and well‐being was described as women's main expectations of ultrasound. Although women's right to autonomy in pregnancy was supported in principle by participating physicians, fetal rights were sometimes seen as needing physician ‘protection’.

Conclusions

There appears to be increasing use and demand for obstetric ultrasound in Rwanda, particularly in urban areas. It seems important to monitor this development closely to secure wise and fair allocation of scarce obstetric expertise and resources and to prevent overuse or misuse of ultrasound. Raising awareness about the benefits of all aspects of antenatal care, including ultrasound may be an important step to improve pregnant women's uptake of services. Increased opportunities for formal ultrasound training, including the training of midwives to perform basic scans, seem warranted. Moreover, in parallel with the transition to more medico‐technical maternity care, a dialogue about maternal rights to autonomy in pregnancy and childbirth is imperative.
Root‐specific expression of opine genes and opine accumulation in some cultivars of the naturally occurring genetically modified organism Nicotiana tabacum
Authors: Chen Ke , de Borne François Dorlhac , Julio Emilie , Obszynski Julie , Pale Patrick , Otten Léon
Published: April 2016

Previous studies have shown that Nicotiana tabacum contains three Agrobacterium‐derived T‐DNA sequences inherited from its paternal ancestor Nicotiana tomentosiformis. Among these, the TB locus carries an intact mannopine synthase 2′ gene (TB‐mas2′). This gene is similar to the Agrobacterium rhizogenes A4‐mas2′ gene that encodes the synthesis of the Amadori compound deoxyfructosyl‐glutamine (DFG or santhopine). In this study we show that TB‐mas2′ is expressed at very low levels in N. tomentosiformis and in most N. tabacum cultivars; however, some cultivars show high TB‐mas2′ expression levels. The TB‐mas2′ promoter sequences of low‐ and high‐expressing cultivars are identical. The low/high level of expression segregates as a single Mendelian factor in a cross between a low‐ and a high‐expression cultivar. pTB‐mas2′‐GUS and pA4‐mas2′‐GUS reporter genes were stably introduced in N. benthamiana. Both were mainly expressed in the root expansion zone and leaf vasculature. Roots of tobacco cultivars with high TB‐mas2′ expression contain detectable levels of DFG.
Herpesvirus Entry into Host Cells Mediated by Endosomal Low pH
Authors: Nicola Anthony V.
Published: April 2016

Herpesviral pathogenesis stems from infection of multiple cell types including the site of latency and cells that support lytic replication. Herpesviruses utilize distinct cellular pathways, including low pH endocytic pathways, to enter different pathophysiologically relevant target cells. This review details the impact of the mildly acidic milieu of endosomes on the entry of herpesviruses, with particular emphasis on herpes simplex virus 1 (HSV‐1). Epithelial cells, the portal of primary HSV‐1 infection, support entry via low pH endocytosis mechanisms. Mildly acidic pH triggers reversible conformational changes in the HSV‐1 class III fusion protein glycoprotein B (gB). In vitro treatment of herpes simplex virions with a similar pH range inactivates infectivity, likely by prematurely activating the viral entry machinery in the absence of a target membrane. How a given herpesvirus mediates both low pH and pH‐independent entry events is a key unresolved question.
A Genetic Screen Identifies a Critical Role for the WDR81‐WDR91 Complex in the Trafficking and Degradation of Tetherin
Authors: Rapiteanu Radu , Davis Luther J. , Williamson James C. , Timms Richard T. , Paul Luzio J. , Lehner Paul J.
Published: April 2016

Tetherin (BST2/CD317) is a viral restriction factor that anchors enveloped viruses to host cells and limits viral spread. The HIV‐1 Vpu accessory protein counteracts tetherin by decreasing its cell surface expression and targeting it for ubiquitin‐dependent endolysosomal degradation. Although the Vpu‐mediated downregulation of tetherin has been extensively studied, the molecular details are not completely elucidated. We therefore used a forward genetic screen in human haploid KBM7 cells to identify novel genes required for tetherin trafficking. Our screen identified WDR81 as a novel gene required for tetherin trafficking and degradation in both the presence and absence of Vpu. WDR81 is a BEACH‐domain containing protein that is also required for the degradation of EGF‐stimulated epidermal growth factor receptor (EGFR) and functions in a complex with the WDR91 protein. In the absence of WDR81 the endolysosomal compartment appears swollen, with enlarged early and late endosomes and reduced delivery of endocytosed dextran to cathepsin‐active lysosomes. Our data suggest a role for the WDR81‐WDR91 complex in the fusion of endolysosomal compartments and the absence of WDR81 leads to impaired receptor trafficking and degradation.
Transfusion management of factor V deficiency: three case reports and review of the literature
Authors: Gavva Chakri , Yates Sean G. , Rambally Siayareh , Sarode Ravi
Published: April 2016

BACKGROUND

Factor V (FV) deficiency may be inherited as an autosomal recessive disease or acquired as a result of autoantibody formation, either spontaneously or secondary to exposure to bovine thrombin or medications. Congenital FV deficiency has traditionally been treated with plasma transfusions. However, recent evidence has suggested that platelet (PLT) transfusions may be a better alternative as FV stored within PLT alpha granules has greater procoagulant potential and is released locally at sites of vascular injury. We report three cases of FV deficiency, one congenital and two acquired, and emphasize the different management approaches.

CASE REPORTS

Patient 1 was a 30‐year‐old man with congenital FV deficiency who presented with a trauma‐induced hematoma of his lower extremity. He was treated with 5 PLT units over 48 hours. Patient 2 was a 64‐year‐old woman who presented with an upper‐extremity thrombus and was discovered to have a FV inhibitor, likely secondary to antibiotics. Patient 3 was a 75‐year‐old woman with hepatitis C virus (HCV) who presented with minor ecchymosis and was found to have a FV inhibitor secondary to either HCV or antibiotic exposure. Corticosteroids alone were able to eradicate the inhibitors in both patients with acquired inhibitors.

CONCLUSIONS

FV deficiency can present with a diverse range of symptoms. For bleeding patients, PLT transfusions should be the initial therapy. In patients with thrombosis, the risks and benefits of anticoagulation must be carefully assessed before treatment. For patients with minor bleeds, transfusions may be withheld, and elimination of the inhibitor should be the primary objective.
Translocal English in the linguascape of Mongolian popular music
Authors: DOVCHIN SENDER
Published: April 2016

This paper seeks to contribute to the current discussion of world Englishes by revealing the seamless English language incorporation in the linguascape of the popular music scene of post‐socialist Mongolia, a context that has been rarely addressed in previous research. Drawing on sets of linguistic (n)ethnographic data, the paper argues that the role of English in the mixed language practices of young musicians should be understood as ‘translocal language’, which makes its meaning through the contact of transnational linguistic flows and resources embedded within the idea of ‘linguascape’.
Short inter‐set rest blunts resistance exercise‐induced increases in myofibrillar protein synthesis and intracellular signalling in young males
Authors: McKendry James , Pérez‐López Alberto , McLeod Michael , Luo Dan , Dent Jessica R. , Smeuninx Benoit , Yu Jinglei , Taylor Angela E. , Philp Andrew , Breen Leigh
Published: April 2016

New Findings

What is the central question of this study?

Does shorter rest between sets of resistance exercise promote a superior circulating hormonal and acute muscle anabolic response compared with longer rest periods?

What is the main finding and its importance?

We demonstrate that short rest (1 min) between sets of moderate‐intensity, high‐volume resistance exercise blunts the acute muscle anabolic response compared with a longer rest period (5 min), despite a superior circulating hormonal milieu. These data have important implications for the development of training regimens to maximize muscle hypertrophy.

Manipulating the rest‐recovery interval between sets of resistance exercise may influence training‐induced muscle remodelling. The aim of this study was to determine the acute muscle anabolic response to resistance exercise performed with short or long inter‐set rest intervals. In a study with a parallel‐group design, 16 males completed four sets of bilateral leg‐press and knee‐extension exercise at 75% of one‐repetition maximum to momentary muscular failure, followed by ingestion of 25 g of whey protein. Resistance exercise sets were interspersed by 1 min (n = 8) or 5 min of passive rest (n = 8). Muscle biopsies were obtained at rest, 0, 4, 24 and 28 h postexercise during a primed continuous infusion of l‐[ring‐13C6]phenylalanine to determine myofibrillar protein synthesis and intracellular signalling. We found that the rate of myofibrillar protein synthesis increased above resting values from 0 to 4 h postexercise with 1 (76%; P = 0.047) and 5 min inter‐set rest (152%; P < 0.001) and was significantly greater in the 5 min inter‐set rest group (P = 0.001). Myofibrillar protein synthesis rates at 24–28 h postexercise remained elevated above resting values (P < 0.05) and were indistinguishable between groups. Postexercise p70S6KThr389 and rpS6Ser240/244 phosphorylation were reduced with 1 compared with 5 min inter‐set rest, whereas phosphorylation of eEF2Thr56, TSC2Thr1462, AMPKThr172 and REDD1 protein were greater for 1 compared with 5 min inter‐set rest. Serum testosterone was greater at 20–40 min postexercise and plasma lactate greater immediately postexercise for 1 versus 5 min inter‐set rest. Resistance exercise with short (1 min) inter‐set rest duration attenuated myofibrillar protein synthesis during the early postexercise recovery period compared with longer (5 min) rest duration, potentially through compromised activation of intracellular signalling.
Diaphragm muscle sarcopenia in Fischer 344 and Brown Norway rats
Authors: Elliott Jonathan E. , Omar Tanya S. , Mantilla Carlos B. , Sieck Gary C.
Published: April 2016

New Findings

What is the central question of this study?

Several rat models are commonly used to study the physiology of ageing (e.g. Fischer 344 and Brown Norway rats are recommended by the USA National Institute of Ageing). Diaphragm muscle sarcopenia (ageing‐related muscle weakness and atrophy) remains incompletely described in these rat models.

What is the main finding and its importance?

Diaphragm muscle sarcopenia is present in both the Fischer 344 and Brown Norway rat strains, but appears more pronounced in Fischer 344 rats.

The risk for respiratory diseases increases in adults >65 years of age, which may be attributable in part to ageing‐related weakening and atrophy (i.e. sarcopenia) of the diaphragm muscle (DIAm). The mechanisms underlying DIAm sarcopenia remain unknown. Based on existing evidence, we hypothesized that sarcopenia is most evident in type IIx and/or IIb DIAm fibres, i.e. more fatigable motor units. Currently, the USA National Institute on Aging supports Fischer 344 (F344) and Brown Norway (BN) rat strains for ageing‐related research, yet DIAm sarcopenia has not been evaluated comprehensively in either strain. Thus, the present study examined DIAm sarcopenia in older adult F344 (24 months old, 50% survival) and BN rats (32 months old, 50% survival), compared with young adult (6‐month‐old) F344 and BN rats. Measurements of contractility, contractile protein concentration, fibre type distribution and fibre cross‐sectional area were obtained from midcostal DIAm strips. Maximal specific force was reduced by ∼24 and ∼13% in older F344 and BN rats, respectively. Additionally, although the cross‐sectional area of type I and IIa DIAm fibres was unchanged in both F344 and BN rats, the cross‐sectional area of type IIx and/or IIb DIAm fibres was reduced by ∼20 and ∼15% in F344 and BN rats, respectively. Thus, although there was ageing‐related DIAm weakness and atrophy, selective to type IIx and/or IIb DIAm fibres, in both F344 and BN rats, the sarcopenic phenotype was more pronounced in F344 rats.
Pre-Gondwanan-breakup origin of
Beauprea
(Proteaceae) explains its historical presence in New Caledonia and New Zealand
Authors: He Tianhua , Lamont Byron B. , Fogliani Bruno
Published: April 2016

The tropical shrub
Beauprea
was already present in Gondwana when Zealandia drifted away from Antarctica 82 million years ago.
There are many ways to spin a photon: Half-quantization of a total optical angular momentum
Authors: Ballantine Kyle E. , Donegan John F. , Eastham Paul R.
Published: April 2016

Photons can have a half-integer angular momentum.
Optical π phase shift created with a single-photon pulse
Authors: Tiarks Daniel , Schmidt Steffen , Rempe Gerhard , Dürr Stephan
Published: April 2016

A single-photon pulse creates a π phase shift for another light pulse, which is important for optical quantum computation.
Influence of Niche-Specific Nutrients on Secondary Metabolism in Vibrionaceae
Authors: Giubergia Sonia , Phippen Christopher , Gotfredsen Charlotte H. , Nielsen Kristian Fog , Gram Lone
Published: April 2016

Many factors, such as the substrate and the growth phase, influence biosynthesis of secondary metabolites in microorganisms. Therefore, it is crucial to consider these factors when establishing a bioprospecting strategy. Mimicking the conditions of the natural environment has been suggested as a means of inducing or influencing microbial secondary metabolite production. The purpose of the present study was to determine how the bioactivity of
Vibrionaceae
was influenced by carbon sources typical of their natural environment. We determined how mannose and chitin, compared to glucose, influenced the antibacterial activity of a collection of
Vibrionaceae
strains isolated because of their ability to produce antibacterial compounds but that in subsequent screenings seemed to have lost this ability. The numbers of bioactive isolates were 2- and 3.5-fold higher when strains were grown on mannose and chitin, respectively, than on glucose. As secondary metabolites are typically produced during late growth, potential producers were also allowed 1 to 2 days of growth before exposure to the pathogen. This strategy led to a 3-fold increase in the number of bioactive strains on glucose and an 8-fold increase on both chitin and mannose. We selected two bioactive strains belonging to species for which antibacterial activity had not previously been identified. Using ultrahigh-performance liquid chromatography–high-resolution mass spectrometry and bioassay-guided fractionation, we found that the siderophore fluvibactin was responsible for the antibacterial activity of
Vibrio furnissii
and
Vibrio fluvialis
. These results suggest a role of chitin in the regulation of secondary metabolism in vibrios and demonstrate that considering bacterial ecophysiology during development of screening strategies will facilitate bioprospecting.

IMPORTANCE
A challenge in microbial natural product discovery is the elicitation of the biosynthetic gene clusters that are silent when microorganisms are grown under standard laboratory conditions. We hypothesized that, since the clusters are not lost during proliferation in the natural niche of the microorganisms, they must, under such conditions, be functional. Here, we demonstrate that an ecology-based approach in which the producer organism is allowed a temporal advantage and where growth conditions are mimicking the natural niche remarkably increases the number of
Vibrionaceae
strains producing antibacterial compounds.
Overlap of Spoilage-Associated Microbiota between Meat and the Meat Processing Environment in Small-Scale and Large-Scale Retail Distributions
Authors: Stellato Giuseppina , La Storia Antonietta , De Filippis Francesca , Borriello Giorgia , Villani Francesco , Ercolini Danilo
Published: April 2016

Microbial contamination in food processing plants can play a fundamental role in food quality and safety. The aims of this study were to learn more about the possible influence of the meat processing environment on initial fresh meat contamination and to investigate the differences between small-scale retail distribution (SD) and large-scale retail distribution (LD) facilities. Samples were collected from butcheries (n= 20), including LD (n= 10) and SD (n= 10) facilities, over two sampling campaigns. Samples included fresh beef and pork cuts and swab samples from the knife, the chopping board, and the butcher's hand. The microbiota of both meat samples and environmental swabs were very complex, including more than 800 operational taxonomic units (OTUs) collapsed at the species level. The 16S rRNA sequencing analysis showed that core microbiota were shared by 80% of the samples and includedPseudomonasspp.,Streptococcusspp.,Brochothrixspp.,Psychrobacterspp., andAcinetobacterspp. Hierarchical clustering of the samples based on the microbiota showed a certain separation between meat and environmental samples, with higher levels ofProteobacteriain meat. In particular, levels ofPseudomonasand severalEnterobacteriaceaemembers were significantly higher in meat samples, whileBrochothrix,Staphylococcus, lactic acid bacteria, andPsychrobacterprevailed in environmental swab samples. Consistent clustering was also observed when metabolic activities were considered by predictive metagenomic analysis of the samples. An increase in carbohydrate metabolism was predicted for the environmental swabs and was consistently linked toFirmicutes, while increases in pathways related to amino acid and lipid metabolism were predicted for the meat samples and were positively correlated withProteobacteria. Our results highlighted the importance of the processing environment in contributing to the initial microbial levels of meat and clearly showed that the type of retail facility (LD or SD) did not apparently affect the contamination.

IMPORTANCEThe study provides an in-depth description of the microbiota of meat and meat processing environments. It highlights the importance of the environment as a contamination source of spoilage bacteria, and it shows that the size of the retail facility does not affect the level and type of contamination.
‘FIFA 11 for Health’ for Europe. 1: effect on health knowledge and well-being of 10- to 12-year-old Danish school children
Authors: Fuller Colin W , Ørntoft Christina , Larsen Malte Nejst , Elbe Anne-Marie , Ottesen Laila , Junge Astrid , Dvorak Jiri , Krustrup Peter
Published: April 2016

Aim

To modify the ‘FIFA 11 for Health’ programme to the European situation, and to assess its effects on health knowledge and well-being in Danish school children.

Method

A two-cohort study with seven intervention and two control schools. Of the 546 Danish children (boys 269; girls 277) of mean age 11.1 (±0.4) years from five city and four country-side schools, 402 undertook the ‘FIFA 11 for Health’ programme and 144 acted as controls. As part of each school's PE curriculum, seven intervention schools received a 45 min Play Football period (football skills and 3 vs 3 games) and a 45 min Play Fair period (health issues and football drills) on a weekly-basis for 11 weeks. Control participants continued with their regular school PE activities. Participants completed preintervention and postintervention health knowledge and well-being questionnaires.

Results

Overall, health knowledge increase was significantly (p<0.05) greater for the intervention group (11.9%) than the control group (2.6%). Significant (p<0.05) between-group differences were obtained for 8 of 10 health topics (6.1–20.2%) related to physical activity, nutrition, hygiene and well-being. The social dimension of the well-being questionnaire was significantly (p<0.05) improved in the intervention group compared to the control group, but there were no significant between-group effects for the physical, emotional and school dimensions. Positive reporting about the programme was given by 72.4% of the children and only 4.8% reported negatively.

Conclusions

The ‘FIFA 11 for Health’ programme modified for Europe demonstrated positive effects on children's health knowledge and social dimension of well-being, thereby providing evidence that the football-based health education programme can be used effectively within a European school's curriculum to increase physical activity, well-being and health knowledge.
Patients' with type 2 diabetes willingness to pay for insulin therapy and clinical outcomes
Authors: Feher Michael D , Brazier John , Schaper Nicolaas , Vega-Hernandez Gabriela , Nikolajsen Annie , Bøgelund Mette
Published: April 2016

Objectives

This study assessed patient preferences, using willingness to pay as a method to measure different treatment characteristics or attributes associated with injectable insulin therapy in patients with type 2 diabetes.

Research design and methods

Adults with type 2 diabetes in 12 countries, diagnosed >6 months prior and receiving insulin for >3 months, were recruited through a representative online panel. Data were collected via online questionnaire and analyzed using a standard choice model for discrete choice experiment.

Results

A total of 3758 patients from North America (n=646), South America (n=1537), and Europe (n=1575) completed the study. Mean glycated hemoglobin (HbA1c) levels in North America, South America, and Europe were 63 mmol/mol (7.9%), 75 mmol/mol (9.0%), and 64 mmol/mol (8.0%), respectively. In the three regions, monthly willingness to pay was US$116, US$74, and US$92, respectively, for a 1%-point decrease in HbA1c; US$99, US$80, and US$104 for one less major hypoglycemic event per year; and US$64, US$37 and US$60 for a 3 kg weight decrease. To avoid preinjection preparation of insulin, the respective values were US$47, US$18, and US$37, and US$25, US$25, and US$24 for one less injection per day. Among respondents on basal-only insulin who had previously tried a more intensive regimen, reasons for switching back included difficulty in handling multiple injections and risk of hypoglycemic events.

Conclusions

Reducing HbA1c, frequency of major hypoglycemic events and weight decrease were the highest valued outcomes in each region. The administrative burden of injections was also considered important.
Effect of tighter glycemic control on cardiac function, exercise capacity, and muscle strength in heart failure patients with type 2 diabetes: a randomized study
Authors: Nielsen Roni , Wiggers Henrik , Thomsen Henrik Holm , Bovin Ann , Refsgaard Jens , Abrahamsen Jan , Møller Niels , Bøtker Hans Erik , Nørrelund Helene
Published: April 2016

Objectives

In patients with type 2 diabetes (T2D) and heart failure (HF), the optimal glycemic target is uncertain, and evidence-based data are lacking. Therefore, we performed a randomized study on the effect of optimized glycemic control on left ventricular function, exercise capacity, muscle strength, and body composition.

Design and methods

40 patients with T2D and HF (left ventricular ejection fraction (LVEF) 35±12% and hemoglobin A1c (HbA1c) 8.4±0.7% (68±0.8 mmol/mol)) were randomized to either 4-month optimization (OPT group) or non-optimization (non-OPT group) of glycemic control. Patients underwent dobutamine stress echocardiography, cardiopulmonary exercise test, 6 min hall-walk test (6-MWT), muscle strength examination, and dual X-ray absorptiometry scanning at baseline and at follow-up.

Results

39 patients completed the study. HbA1c decreased in the OPT versus the non-OPT group (8.4±0.8% (68±9 mmol/mol) to 7.6±0.7% (60±7 mmol/mol) vs 8.3±0.7% (67±10 mmol/mol) to 8.4±1.0% (68±11 mmol/mol); p<0.001). There was no difference between the groups with respect to changes in myocardial contractile reserve (LVEF (p=0.18)), oxygen consumption (p=0.55), exercise capacity (p=0.12), and 6-MWT (p=0.84). Muscle strength decreased in the non-OPT compared with the OPT group (37.2±8.1 to 34.8±8.3 kg vs 34.9±10.2 to 35.4±10.7 kg; p=0.01), in line with a non-significant decrease in lean (p=0.07) and fat (p=0.07) tissue mass in the non-OPT group. Hypoglycemia and fluid retention did not differ between groups.

Conclusions

4 months of optimization of glycemic control was associated with preserved muscle strength and lean body mass in patients with T2D and HF compared with lenient control, and had no deleterious effect on left ventricular contractile function and seemed to be safe.

Trial registration number

NCT01213784; pre-results.
Retrospective cohort study of the performance of the Pinnacle metal on metal (MoM) total hip replacement: a single-centre investigation in combination with the findings of a national retrieval centre
Authors: Langton David John , Sidaginamale Raghavendra Prasad , Avery Peter , Waller Sue , Tank Ghanshyabhai , Lord James , Joyce Thomas , Cooke Nick , Logishetty Raj , Nargol Antoni Viraf Francis
Published: April 2016

Objectives

To determine risk factors for revision in patients implanted with a commonly used metal on metal (MoM) hip replacement.

Design

Retrospective cohort study in combination with a prospective national retrieval study (Northern Retrieval Registry (NRR)).

Setting

Combined orthopaedic unit in combination with the NRR.

Participants

All patients implanted with a DePuy Pinnacle MoM hip prostheses by the 2 senior authors were invited to attend for a review which included clinical examination, blood metal ion measurements, radiographs and targeted imaging. Explanted components underwent wear analysis using validated methodology and these results were compared with those obtained from the NRR.

Results

489 MoM Pinnacle hips were implanted into 434 patients (243 females and 191 males). Of these, 352 patients attended the MoM recall clinics. 64 patients had died during the study period. For the purposes of survival analysis, non-attendees were assumed to have well-functioning prostheses. The mean follow-up of the cohort as a whole was 89 months. 71 hips were revised. Prosthetic survival for the whole cohort was 83.6% (79.9–87.3) at 9 years. The majority of explanted devices exhibited signs of taper junction failure. Risk factors for revision were bilateral MoM prostheses, smaller Pinnacle liners, and implantation in 2006 and later years. A significant number of devices were found to be manufactured out of their specifications. This was confirmed with analysis of the wider data set from the NRR.

Conclusions

This device was found to have an unacceptably high revision rate. Bilateral prostheses, those implanted into female patients and devices implanted in later years were found to be at greater risk. A significant number of explanted components were found to be manufactured with bearing diameters outside of the manufacturer's stated tolerances. Our findings highlight the clinical importance of hitherto unrecognised variations in device production.
How has the extent of institutional mental healthcare changed in Western Europe? Analysis of data since 1990
Authors: Chow Winnie S , Priebe Stefan
Published: April 2016

Objectives

It has been suggested that since 1990, de-institutionalisation of mental healthcare in Western Europe has been reversed into re-institutionalisation with more forensic beds, places in protected housing services and people with mental disorders in prisons. This study aimed to identify changes in the numbers of places in built institutions providing mental healthcare in Western Europe from 1990 to 2012, and to explore the association between changes in psychiatric bed numbers and changes in other institutions.

Settings and data

Data were identified from 11 countries on psychiatric hospital beds, forensic beds, protected housing places and prison populations. Fixed effects regression models tested the associations between psychiatric hospital beds with other institutions.

Results

The number of psychiatric hospital beds decreased, while forensic beds, places in protected housing and prison populations increased. Overall, the number of reduced beds exceeded additional places in other institutions. There was no evidence for an association of changes in bed numbers with changes in forensic beds and protected housing places. Panel data regression analysis showed that changes in psychiatric bed numbers were negatively associated with rising prison populations, but the significant association disappeared once adjusted for gross domestic product as a potential covariate.

Conclusions

Institutional mental healthcare has substantially changed across Western Europe since 1990. There are ongoing overall trends of a decrease in the number of psychiatric hospital beds and an increase in the number of places in other institutions, including prisons. The exact association between these trends and their drivers remains unclear. More reliable data, information on the characteristics of patients in different institutions, long-term pathway analyses and effectiveness studies are required to arrive at evidence-based policies for the provision of institutional mental healthcare.
Use of heparins in patients with cancer: individual participant data meta-analysis of randomised trials study protocol
Authors: Schünemann Holger J , Ventresca Matthew , Crowther Mark , Briel Matthias , Zhou Qi , Garcia David , Lyman Gary , Noble Simon , Macbeth Fergus , Griffiths Gareth , DiNisio Marcello , Iorio Alfonso , Beyene Joseph , Mbuagbaw Lawrance , Neumann Ignacio , Van Es Nick , Brouwers Melissa , Brozek Jan , Guyatt Gordon , Levine Mark , Moll Stephan , Santesso Nancy , Streiff Michael , Baldeh Tejan , Florez Ivan , Gurunlu Alma Ozlem , Solh Ziad , Ageno Walter , Marcucci Maura , Bozas George , Zulian Gilbert , Maraveyas Anthony , Lebeau Bernard , Buller Harry , Evans Jessica , McBane Robert , Bleker Suzanne , Pelzer Uwe , Akl Elie A
Published: April 2016

Introduction

Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits.

Methods and analysis

First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials.

Ethics and dissemination

Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings.

Trial registration number

PROSPERO CRD42013003526.
Effect of mobile application-based versus DVD-based CPR training on students’ practical CPR skills and willingness to act: a cluster randomised study
Authors: Nord Anette , Svensson Leif , Hult Håkan , Kreitz-Sandberg Susanne , Nilsson Lennart
Published: April 2016

Objectives

The aim was to compare students’ practical cardiopulmonary resuscitation (CPR) skills and willingness to perform bystander CPR, after a 30 min mobile application (app)-based versus a 50 min DVD-based training.

Settings

Seventh grade students in two Swedish municipalities.

Design

A cluster randomised trial. The classes were randomised to receive app-based or DVD-based training. Willingness to act and practical CPR skills were assessed, directly after training and at 6 months, by using a questionnaire and a PC Skill Reporting System. Data on CPR skills were registered in a modified version of the Cardiff test, where scores were given in 12 different categories, adding up to a total score of 12–48 points. Training and measurements were performed from December 2013 to October 2014.

Participants

63 classes or 1232 seventh grade students (13-year-old) were included in the study.

Primary and secondary outcome measures

Primary end point was the total score of the modified Cardiff test. The individual variables of the test and self-reported willingness to make a life-saving intervention were secondary end points.

Results

The DVD-based group was superior to the app-based group in CPR skills; a total score of 36 (33–38) vs 33 (30–36) directly after training (p<0.001) and 33 (30–36) and 31 (28–34) at 6 months (p<0.001), respectively. At 6 months, the DVD group performed significantly better in 8 out of 12 CPR skill components. Both groups improved compression depth from baseline to follow-up. If a friend suffered cardiac arrest, 78% (DVD) versus 75% (app) would do compressions and ventilations, whereas only 31% (DVD) versus 32% (app) would perform standard CPR if the victim was a stranger.

Conclusions

At 6 months follow-up, the 50 min DVD-based group showed superior CPR skills compared with the 30 min app-based group. The groups did not differ in regard to willingness to make a life-saving effort.
Validating the use of Hospital Episode Statistics data and comparison of costing methodologies for economic evaluation: an end-of-life case study from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)
Authors: Thorn Joanna C , Turner Emma L , Hounsome Luke , Walsh Eleanor , Down Liz , Verne Julia , Donovan Jenny L , Neal David E , Hamdy Freddie C , Martin Richard M , Noble Sian M
Published: April 2016

Objectives

To evaluate the accuracy of routine data for costing inpatient resource use in a large clinical trial and to investigate costing methodologies.

Design

Final-year inpatient cost profiles were derived using (1) data extracted from medical records mapped to the National Health Service (NHS) reference costs via service codes and (2) Hospital Episode Statistics (HES) data using NHS reference costs. Trust finance departments were consulted to obtain costs for comparison purposes.

Setting

7 UK secondary care centres.

Population

A subsample of 292 men identified as having died at least a year after being diagnosed with prostate cancer in Cluster randomised triAl of PSA testing for Prostate cancer (CAP), a long-running trial to evaluate the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing.

Results

Both inpatient cost profiles showed a rise in costs in the months leading up to death, and were broadly similar. The difference in mean inpatient costs was £899, with HES data yielding ∼8% lower costs than medical record data (differences compatible with chance, p=0.3). Events were missing from both data sets. 11 men (3.8%) had events identified in HES that were all missing from medical record review, while 7 men (2.4%) had events identified in medical record review that were all missing from HES. The response from finance departments to requests for cost data was poor: only 3 of 7 departments returned adequate data sets within 6 months.

Conclusions

Using HES routine data coupled with NHS reference costs resulted in mean annual inpatient costs that were very similar to those derived via medical record review; therefore, routinely available data can be used as the primary method of costing resource use in large clinical trials. Neither HES nor medical record review represent gold standards of data collection. Requesting cost data from finance departments is impractical for large clinical trials.

Trial registration number

ISRCTN92187251; Pre-results.
Exploring situational awareness in emergency medicine: developing a shared mental model to enhance training and assessment
Authors: Lowe David J , Ireland Alastair J , Ross Al , Ker Jean
Published: April 2016

Non-technical skills (NTS) are gaining increasing prominence within the field of emergency medicine. Situational awareness (SA), one key component of NTS, is a key skill for emergency physicians (EPs) during initial training and throughout their career. Furthermore, the majority of frameworks used to evaluate clinical performance incorporate SA as one key component. This review seeks to define and explore the concept of SA within the context of emergency medicine. We describe SA at an individual, team and departmental level. Development of this ability enables EPs to function effectively within the challenging environment of the emergency department (ED). Enhancing our understanding of SA may develop the cognitive process that underpins our clinical performance. We propose a model for consideration to support evaluation and training of SA within the ED, linking the model to the novice expert continuum.
Constraints on synrift intrabasinal horst development from alluvial fan and aeolian deposits (Triassic, Fundy Basin, Nova Scotia)
Authors: Leleu Sophie , Hartley Adrian J.
Published: April 2016

The Triassic Fundy rift basin in Nova Scotia is a large (>70 km wide) half-graben filled with alluvial, lacustrine and aeolian deposits. A major lithospheric lineament, the Cobequid–Chedabucto Fault Zone (CCFZ), which forms the tip of the Newfoundland–Gibraltar Fault Zone, occurs within the Fundy Basin. The timing of early movement on this important fault zone is poorly constrained. We present data from the alluvial and aeolian units that crop out adjacent to the CCFZ in the Minas sub-basin to determine the initiation of fault movement. We use the onset of alluvial fan deposition to infer when the fault became sufficiently active to create the intrabasinal topography and document the influence of fault activity on the intrabasinal drainage. The occurrence and preservation of aeolian deposits immediately adjacent to the CCFZ and concomitant with alluvial fan development suggests a wind shadow effect associated with the fault-generated topography. The onset of alluvial fan deposition associated directly with the fault occurred during Norian times, following an earlier phase of sedimentation in the Fundy Basin, and records a potentially important phase of plate reorganization during early Atlantic rifting.
Mast cells and exosomes in hyperoxia-induced neonatal lung disease
Authors: Veerappan A. , Thompson M. , Savage A. R. , Silverman M. L. , Chan W. S. , Sung B. , Summers B. , Montelione K. C. , Benedict P. , Groh B. , Vicencio A. G. , Peinado H. , Worgall S. , Silver R. B.
Published: April 2016

Chronic lung disease of prematurity (CLD) is a frequent sequela of premature birth and oxygen toxicity is a major associated risk factor. Impaired alveolarization, scarring, and inflammation are hallmarks of CLD. Mast cell hyperplasia is a feature of CLD but the role of mast cells in its pathogenesis is unknown. We hypothesized that mast cell hyperplasia is a consequence of neonatal hyperoxia and contributes to CLD. Additionally, mast cell products may have diagnostic and prognostic value in preterm infants predisposed to CLD. To model CLD, neonatal wild-type and mast cell-deficient mice were placed in an O2chamber delivering hyperoxic gas mixture [inspired O2fraction (FiO2) of 0.8] (HO) for 2 wk and then returned to room air (RA) for an additional 3 wk. Age-matched controls were kept in RA (FiO2of 0.21). Lungs from HO mice had increased numbers of mast cells, alveolar simplification and enlargement, and increased lung compliance. Mast cell deficiency proved protective by preserving air space integrity and lung compliance. The mast cell mediators β-hexosaminidase (β-hex), histamine, and elastase increased in the bronchoalveolar lavage fluid of HO wild-type mice. Tracheal aspirate fluids (TAs) from oxygenated and mechanically ventilated preterm infants were analyzed for mast cell products. In TAs from infants with confirmed cases of CLD, β-hex was elevated over time and correlated with FiO2. Mast cell exosomes were also present in the TAs. Collectively, these data show that mast cells play a significant role in hyperoxia-induced lung injury and their products could serve as potential biomarkers in evolving CLD.