bluuebunny/crossref_metadata_2025 huggingface dataset:
FUSCA3 activates triacylglycerol accumulation in Arabidopsis seedlings and tobacco BY2 cells
Authors: Zhang Meng , Cao Xia , Jia Qingli , Ohlrogge John
Published: June 2016

Triacylglycerol (TAG) is the main storage lipid in plant seeds and the major form of plant oil used for food and, increasingly, for industrial and biofuel applications. Several transcription factors, including FUSCA3 (At3 g26790, FUS3), are associated with embryo maturation and oil biosynthesis in seeds. However, the ability of FUS3 to increase TAG biosynthesis in other tissues has not been quantitatively examined. Here, we evaluated the ability of FUS3 to activate TAG accumulation in non‐seed tissues. Overexpression of FUS3 driven by an estradiol‐inducible promoter increased oil contents in Arabidopsis seedlings up to 6% of dry weight; more than 50‐fold over controls. Eicosenoic acid, a characteristic fatty acid of Arabidopsis seed oil, accumulated to over 20% of fatty acids in cotyledons and leaves. These large increases depended on added sucrose, although without sucrose TAG increased three‐ to four‐fold. Inducing the expression of FUS3 in tobacco BY2 cells also increased TAG accumulation, and co‐expression of FUS3 and diacylglycerol acyltransferase 1 (DGAT1) further increased TAG levels to 4% of dry weight. BY2 cell growth was not altered by FUS3 expression, although Arabidopsis seedling development was impaired, consistent with the ability of FUS3 to induce embryo characteristics in non‐seed tissues. Microarrays of Arabidopsis seedlings revealed that FUS3 overexpression increased the expression of a higher proportion of genes involved in TAG biosynthesis than genes involved in fatty acid biosynthesis or other lipid pathways. Together these results provide additional insights into FUS3 functions in TAG metabolism and suggest complementary strategies for engineering vegetative oil accumulation.
Rab11 Regulates the Mast Cell Exocytic Response
Authors: Wilson Joshua D. , Shelby Sarah A. , Holowka David , Baird Barbara
Published: June 2016

Stimulated exocytic events provide a means for physiological communication and are a hallmark of the mast cell‐mediated allergic response. In mast cells these processes are triggered by antigen crosslinking of IgE bound to its high‐affinity receptor, FcϵRI, on the cell surface. Here we use the endosomal v‐SNARE VAMP8, and the lysosomal hydrolase β‐hexosaminidase (β‐Hex), each C‐terminally fused to super‐ecliptic pHluorin, to monitor stimulated exocytosis. Using these pHluorin‐tagged constructs, we monitor stimulated exocytosis by fluorimetry and visualize individual exocytic events with total internal reflection (TIRF) microscopy. Similar to constitutive recycling endosome (RE) trafficking, we find that stimulated RE exocytosis, monitored by VAMP8, is attenuated by expression of dominant negative (S25N) Rab11. Stimulated β‐Hex exocytosis is also reduced in the presence of S25N Rab11, suggesting that expression of this mutant broadly impacts exocytosis. Interestingly, pretreatment with inhibitors of actin polymerization, cytochalasin D or latrunculin A, substantially restores both RE and lysosome exocytosis in cells expressing S25N Rab11. Conversely, stabilizing F‐actin with jasplakinolide inhibits antigen‐stimulated exocytosis but is not additive with S25N Rab11‐mediated inhibition, suggesting that these reagents inhibit related processes. Together, our results suggest that Rab11 participates in the regulation necessary for depolymerization of the actin cytoskeleton during stimulated exocytosis in mast cells.
Enhanced economic connectivity to foster heat stress–related losses
Authors: Wenz Leonie , Levermann Anders
Published: June 2016

Susceptibility of global economic network to production loss has increased since the beginning of this century.
Highly sensitive sequencing reveals dynamic modifications and activities of small RNAs in mouse oocytes and early embryos
Authors: Yang Qiyuan , Lin Jimin , Liu Miao , Li Ronghong , Tian Bin , Zhang Xue , Xu Beiying , Liu Mofang , Zhang Xuan , Li Yiping , Shi Huijuan , Wu Ligang
Published: June 2016

Expression, modification, and activity of microRNAs are dynamically regulated in early mouse embryos unveiled by sensitive sequencing.
Women’s connectivity in extreme networks
Authors: Manrique Pedro , Cao Zhenfeng , Gabriel Andrew , Horgan John , Gill Paul , Qi Hong , Restrepo Elvira M. , Johnson Daniela , Wuchty Stefan , Song Chaoming , Johnson Neil
Published: June 2016

Women show superior connectivity to men in extreme networks, even though they are typically outnumbered.
Differential Regulation of the Two Ferrochelatase Paralogues in Shewanella loihica PV-4 in Response to Environmental Stresses
Authors: Qiu Dongru , Xie Ming , Dai Jingcheng , An Weixing , Wei Hehong , Tian Chunyuan , Kempher Megan L. , Zhou Aifen , He Zhili , Gu Baohua , Zhou Jizhong
Published: June 2016

Determining the function and regulation of paralogues is important in understanding microbial functional genomics and environmental adaptation. Heme homeostasis is crucial for the survival of environmental microorganisms. Most
Shewanella
species encode two paralogues of ferrochelatase, the terminal enzyme in the heme biosynthesis pathway. The function and transcriptional regulation of two ferrochelatase genes,
hemH1
and
hemH2
, were investigated in
Shewanella
loihica
PV-4. The disruption of
hemH1
but not
hemH2
resulted in a significant accumulation of extracellular protoporphyrin IX (PPIX), the precursor to heme, and decreased intracellular heme levels.
hemH1
was constitutively expressed, and the expression of
hemH2
increased when
hemH1
was disrupted. The transcription of
hemH1
was regulated by the housekeeping sigma factor RpoD and potentially regulated by OxyR, while
hemH2
appeared to be regulated by the oxidative stress-associated sigma factor RpoE2. When an oxidative stress condition was mimicked by adding H
2
O
2
to the medium or exposing the culture to light, PPIX accumulation was suppressed in the Δ
hemH1
mutant. Consistently, transcriptome analysis indicated enhanced iron uptake and suppressed heme synthesis in the Δ
hemH1
mutant. These data indicate that the two paralogues are functional in the heme synthesis pathway but regulated by environmental conditions, providing insights into the understanding of bacterial response to environmental stresses and a great potential to commercially produce porphyrin compounds.

IMPORTANCE
Shewanella
is capable of utilizing a variety of electron acceptors for anaerobic respiration because of the existence of multiple
c
-type cytochromes in which heme is an essential component. The cytochrome-mediated electron transfer across cellular membranes could potentially be used for biotechnological purposes, such as electricity generation in microbial fuel cells and dye decolorization. However, the mechanism underlying the regulation of biosynthesis of heme and cytochromes is poorly understood. Our study has demonstrated that two ferrochelatase genes involved in heme biosynthesis are differentially regulated in response to environmental stresses, including light and reactive oxygen species. This is an excellent example showing how bacteria have evolved to maintain cellular heme homeostasis. More interestingly, the high yields of extracellular protoporphyrin IX by the
Shewanella loihica
PV-4 mutants could be utilized for commercial production of this valuable chemical via bacterial fermentation.
Interaction of Uranium with Bacterial Cell Surfaces: Inferences from Phosphatase-Mediated Uranium Precipitation
Authors: Kulkarni Sayali , Misra Chitra Seetharam , Gupta Alka , Ballal Anand , Apte Shree Kumar
Published: June 2016

Deinococcus radiodurans
and
Escherichia coli
expressing either PhoN, a periplasmic acid phosphatase, or PhoK, an extracellular alkaline phosphatase, were evaluated for uranium (U) bioprecipitation under two specific geochemical conditions (GCs): (i) a carbonate-deficient condition at near-neutral pH (GC1), and (ii) a carbonate-abundant condition at alkaline pH (GC2). Transmission electron microscopy revealed that recombinant cells expressing PhoN/PhoK formed cell-associated uranyl phosphate precipitate under GC1, whereas the same cells displayed extracellular precipitation under GC2. These results implied that the cell-bound or extracellular location of the precipitate was governed by the uranyl species prevalent at that particular GC, rather than the location of phosphatase. MINTEQ modeling predicted the formation of predominantly positively charged uranium hydroxide ions under GC1 and negatively charged uranyl carbonate-hydroxide complexes under GC2. Both microbes adsorbed 6- to 10-fold more U under GC1 than under GC2, suggesting that higher biosorption of U to the bacterial cell surface under GC1 may lead to cell-associated U precipitation. In contrast, at alkaline pH and in the presence of excess carbonate under GC2, poor biosorption of negatively charged uranyl carbonate complexes on the cell surface might have resulted in extracellular precipitation. The toxicity of U observed under GC1 being higher than that under GC2 could also be attributed to the preferential adsorption of U on cell surfaces under GC1. This work provides a vivid description of the interaction of U complexes with bacterial cells. The findings have implications for the toxicity of various U species and for developing biological aqueous effluent waste treatment strategies.

IMPORTANCE
The present study provides illustrative insights into the interaction of uranium (U) complexes with recombinant bacterial cells overexpressing phosphatases. This work demonstrates the effects of aqueous speciation of U on the biosorption of U and the localization pattern of uranyl phosphate precipitated as a result of phosphatase action. Transmission electron microscopy revealed that location of uranyl phosphate (cell associated or extracellular) was primarily influenced by aqueous uranyl species present under the given geochemical conditions. The data would be useful for understanding the toxicity of U under different geochemical conditions. Since cell-associated precipitation of metal facilitates easy downstream processing by simple gravity-based settling down of metal-loaded cells, compared to cumbersome separation techniques, the results from this study are of considerable relevance to effluent treatment using such cells.
Relationship of Bacterial Richness to Organic Degradation Rate and Sediment Age in Subseafloor Sediment
Authors: Walsh Emily A. , Kirkpatrick John B. , Pockalny Robert , Sauvage Justine , Spivack Arthur J. , Murray Richard W. , Sogin Mitchell L. , D'Hondt Steven
Published: June 2016

Subseafloor sediment hosts a large, taxonomically rich, and metabolically diverse microbial ecosystem. However, the factors that control microbial diversity in subseafloor sediment have rarely been explored. Here, we show that bacterial richness varies with organic degradation rate and sediment age. At three open-ocean sites (in the Bering Sea and equatorial Pacific) and one continental margin site (Indian Ocean), richness decreases exponentially with increasing sediment depth. The rate of decrease in richness with increasing depth varies from site to site. The vertical succession of predominant terminal electron acceptors correlates with abundance-weighted community composition but does not drive the vertical decrease in richness. Vertical patterns of richness at the open-ocean sites closely match organic degradation rates; both properties are highest near the seafloor and decline together as sediment depth increases. This relationship suggests that (i) total catabolic activity and/or electron donor diversity exerts a primary influence on bacterial richness in marine sediment and (ii) many bacterial taxa that are poorly adapted for subseafloor sedimentary conditions are degraded in the geologically young sediment, where respiration rates are high. Richness consistently takes a few hundred thousand years to decline from near-seafloor values to much lower values in deep anoxic subseafloor sediment, regardless of sedimentation rate, predominant terminal electron acceptor, or oceanographic context.

IMPORTANCE
Subseafloor sediment provides a wonderful opportunity to investigate the drivers of microbial diversity in communities that may have been isolated for millions of years. Our paper shows the impact of
in situ
conditions on bacterial community structure in subseafloor sediment. Specifically, it shows that bacterial richness in subseafloor sediment declines exponentially with sediment age, and in parallel with organic-fueled oxidation rate. This result suggests that subseafloor diversity ultimately depends on electron donor diversity and/or total community respiration. This work studied how and why biological richness changes over time in the extraordinary ecosystem of subseafloor sediment.
Elution Is a Critical Step for Recovering Human Adenovirus 40 from Tap Water and Surface Water by Cross-Flow Ultrafiltration
Authors: Shi Hang , Xagoraraki Irene , Parent Kristin N. , Bruening Merlin L. , Tarabara Volodymyr V.
Published: June 2016

This paper examines the recovery of the enteric adenovirus human adenovirus 40 (HAdV 40) by cross-flow ultrafiltration and interprets recovery values in terms of physicochemical interactions of virions during sample concentration. Prior to ultrafiltration, membranes were either blocked by exposure to calf serum (CS) or coated with a polyelectrolyte multilayer (PEM). HAdV 40 is a hydrophobic virus with a point of zero charge between pH 4.0 and pH 4.3. In accordance with predictions from the extended Derjaguin-Landau-Verwey-Overbeek theory, the preelution recovery of HAdV (
r
pre
) from deionized water was higher with PEM-coated membranes (
r
pre
PEM
= 74.8% ± 9.7%) than with CS-blocked membranes (
r
pre
CS
= 54.1% ± 6.2%). With either membrane type, the total virion recovery after elution (
r
post
) was high for both deionized water (
r
post
PEM
= 99.5% ± 6.6% and
r
post
CS
= 98.8% ± 7.7%) and tap water (
r
post
PEM
= 89% ± 15% and
r
post
CS
= 93.7% ± 6.9%). The nearly 100% recoveries suggest that the polyanion (sodium polyphosphate) and surfactant (Tween 80) in the eluent disrupt electrostatic and hydrophobic interactions between the virion and the membrane. Addition of EDTA to the eluent greatly improved the elution efficacy (
r
post
CS
= 88.6% ± 4.3% and
r
post
PEM
= 87.0% ± 6.9%) with surface water, even when the organic carbon concentration in the water was high (9.4 ± 0.1 mg/liter). EDTA likely disrupts cation bridging between virions and particles in the feed water matrix or the fouling layer on the membrane surface. For complex water matrices, the eluent composition is the most important factor for achieving high virion recovery.

IMPORTANCE
Herein we present the results of a comprehensive physicochemical characterization of HAdV 40, an important human pathogen. The data on HAdV 40 surface properties enabled rigorous modeling to gain an understanding of the energetics of virion-virion and virion-filter interactions. Cross-flow filtration for concentration and recovery of HAdV 40 was evaluated, with postelution recoveries from ultrapure water (99%), tap water (∼91%), and high-carbon-content surface water (∼84%) being demonstrated. These results are significant because of the very low adenovirus recoveries that have been reported, to date, for other methods. The recovery data were interpreted in terms of specific interactions, and the eluent composition was designed accordingly to maximize HAdV 40 recovery.
Mini-Tn
7
Insertion in an Artificial
att
Tn
7
Site Enables Depletion of the Essential Master Regulator CtrA in the Phytopathogen Agrobacterium tumefaciens
Authors: Figueroa-Cuilan Wanda , Daniel Jeremy J. , Howell Matthew , Sulaiman Aliyah , Brown Pamela J. B.
Published: June 2016

Mechanistic studies of many processes in
Agrobacterium tumefaciens
have been hampered by a lack of genetic tools for characterization of essential genes. In this study, we used a Tn
7
-based method for inducible control of transcription from an engineered site on the chromosome. We demonstrate that this method enables tighter control of inducible promoters than plasmid-based systems and can be used for depletion studies. The method enables the construction of depletion strains to characterize the roles of essential genes in
A. tumefaciens
. Here, we used the strategy to deplete the alphaproteobacterial master regulator CtrA and found that depletion of this essential gene results in dramatic rounding of cells, which become nonviable.

IMPORTANCE
Agrobacterium tumefaciens
is a bacterial plant pathogen and natural genetic engineer. Thus, studies of essential processes, including cell cycle progression, DNA replication and segregation, cell growth, and division, may provide insights for limiting disease or improving biotechnology applications.
Children with chronic health disorders travelling to the tropics: a prospective observational study
Authors: Ducrocq Camille , Sommet Julie , Levy Dora , Trieu Thanh-Van , Quercia Fabrice , Morin Laurence , Belletre Xavier , Koehl Bérengère , Sorge Frederic , Alberti Corinne , de Pontual Loic , Faye Albert
Published: June 2016

Background

The number of trips to the tropics taken by children with chronic health disorders (CHDs) is increasing.

Methods

All of the children with CHDs who attended two international vaccination centres in France before travelling to the tropics were included in a prospective, exposed/unexposed study. Each child was age-matched with two control children and followed for 1 month after returning from the tropics.

Results

Fifty-six children with CHDs and 107 control children were included. The children's median age was 6 years old (IQR 2–11). Of the study participants, 127/163 (78%) travelled to West Africa, mainly to visit relatives. The median duration of the stay was 42 days (IQR 31–55). The age of the children, the destination and the duration of the trip were similar between the two groups. Sickle cell disease (23/56) and asthma (16/56) were the most common CHDs. Overall, the children with CHDs experienced more clinical events than the control patients did (p<0.05); however, there was no difference when chronic disease exacerbations were excluded (p=0.64) or when only the period abroad was considered (p=0.24). One child with a recent genetic diagnosis of atypical haemolytic uraemic syndrome died from a first disease exacerbation.

Conclusions

Health problems among children with CHDs travelling abroad are mainly related to chronic disease exacerbations, which mostly occur after the children return. Patients with diseases that require highly specialised care for an exacerbation should avoid travelling to resource-limited tropical countries.
Interventions for Menière's disease: protocol for an umbrella systematic review and a network meta-analysis
Authors: van Esch Babette F , van der Zaag-Loonen Hester J , Bruintjes Tjasse D , van Benthem Peter Paul G
Published: June 2016

Introduction

The large number of treatment modalities for patients diagnosed with Menière's disease (MD) complicates the selection of the best available treatment as the comparative efficacy of these interventions is not clear. We aim to identify the treatment or treatments with the highest efficacy of current pharmacological and non-pharmacological treatments for MD.

Methods and analysis

We will identify all available systematic reviews on the treatment of MD. An online database search will be conducted in association with the UK Cochrane Centre, particularly the Ear, Nose and Throat Group. We will screen the systematic reviews for eligible randomised controlled trials (RCTs) to execute a network meta-analysis. In addition, online databases will be checked for eligible RCTs on treatments that were published after the latest systematic search was conducted. The characteristics of each RCT will be summarised, including the general design, the participants, the interventions, the outcome measurements, the duration of therapy and adverse events. The risk of bias will be assessed by means of the Cochrane Collaboration's risk of bias tool. The included studies will be assessed for methodological and statistical heterogeneity; the latter will be quantified by means of the I2statistic. The primary outcome will be the efficacy of treatment in terms of control of vertigo attacks. Secondary outcome measures will be the loss or improvement of hearing, severity of vertigo attacks and tinnitus, perception of aural fullness, quality of life, and the incidence of adverse events and complications.

Ethics and dissemination

Formal ethical approval is not required as primary data will not be collected. The review will be disseminated in peer-reviewed publications and conference presentations.

PROSPERO registration number

CRD42015024243.
Healthy Ageing Through Internet Counselling in the Elderly: the HATICE randomised controlled trial for the prevention of cardiovascular disease and cognitive impairment
Authors: Richard Edo , Jongstra Susan , Soininen Hilkka , Brayne Carol , Moll van Charante Eric P , Meiller Yannick , van der Groep Bram , Beishuizen Cathrien R L , Mangialasche Francesca , Barbera Mariagnese , Ngandu Tiia , Coley Nicola , Guillemont Juliette , Savy Stéphanie , Dijkgraaf Marcel G W , Peters Ron J G , van Gool Willem A , Kivipelto Miia , Andrieu Sandrine
Published: June 2016

Introduction

Cardiovascular disease and dementia share a number of risk factors including hypertension, hypercholesterolaemia, smoking, obesity, diabetes and physical inactivity. The rise of eHealth has led to increasing opportunities for large-scale delivery of prevention programmes encouraging self-management. The aim of this study is to investigate whether a multidomain intervention to optimise self-management of cardiovascular risk factors in older individuals, delivered through an coach-supported interactive internet platform, can improve the cardiovascular risk profile and reduce the risk of cardiovascular disease and cognitive decline.

Methods and analysis

HATICE is a multinational, multicentre, prospective, randomised, open-label blinded end point (PROBE) trial with 18 months intervention. Recruitment of 2600 older people (≥65 years) at increased risk of cardiovascular disease will take place in the Netherlands, Finland and France. Participants randomised to the intervention condition will have access to an interactive internet platform, stimulating self-management of vascular risk factors, with remote support by a coach. Participants in the control group will have access to a static internet platform with basic health information.

The primary outcome is a composite score based on the average z-score of the difference between baseline and 18 months follow-up values of systolic blood pressure, low-density-lipoprotein and body mass index. Main secondary outcomes include the effect on the individual components of the primary outcome, the effect on lifestyle-related risk factors, incident cardiovascular disease, mortality, cognitive functioning, mood and cost-effectiveness.

Ethics and dissemination

The study was approved by the medical ethics committee of the Academic Medical Center in Amsterdam, the Comité de Protection des Personnes Sud Ouest et Outre Mer in France and the Northern Savo Hospital District Research Ethics Committee in Finland.

We expect that data from this study will result in a manuscript published in a peer-reviewed clinical open access journal.

Trial registration number

ISRCTN48151589.
Estimating the number of quit attempts it takes to quit smoking successfully in a longitudinal cohort of smokers
Authors: Chaiton Michael , Diemert Lori , Cohen Joanna E , Bondy Susan J , Selby Peter , Philipneri Anne , Schwartz Robert
Published: June 2016

Objectives

The number of quit attempts it takes a smoker to quit successfully is a commonly reported figure among smoking cessation programmes, but previous estimates have been based on lifetime recall in cross-sectional samples of successful quitters only. The purpose of this study is to improve the estimate of number of quit attempts prior to quitting successfully.

Design

We used data from 1277 participants who had made an attempt to quit smoking in the Ontario Tobacco Survey, a longitudinal survey of smokers followed every 6 months for up to 3 years beginning in 2005. We calculated the number of quit attempts prior to quitting successfully under four different sets of assumptions. Our expected best set of assumptions incorporated a life table approach accounting for the declining success rates for subsequent observed quit attempts in the cohort.

Results

The estimated average number of quit attempts expected before quitting successfully ranged from 6.1 under the assumptions consistent with prior research, 19.6 using a constant rate approach, 29.6 using the method with the expected lowest bias, to 142 using an approach including previous recall history.

Conclusions

Previous estimates of number of quit attempts required to quit may be underestimating the average number of attempts as these estimates excluded smokers who have greater difficulty quitting and relied on lifetime recall of number of attempts. Understanding that for many smokers it may take 30 or more quit attempts before being successful may assist with clinical expectations.
SWIM (sickle with ibuprofen and morphine) randomised controlled trial fails to recruit: lessons learnt
Authors: Cho Gavin , Anie Kofi A , Buckton Jacky , Kiilu Patricia , Layton Mark , Alexander Lydia , Hemmaway Claire , Sutton Dorothy , Amos Claire , Doré Caroline J , Kahan Brennan , Meredith Sarah
Published: June 2016

Objectives

Sickle With Ibuprofen and Morphine (SWIM) trial was designed to assess whether co-administration of ibuprofen (a non-steroidal anti-inflammatory drug) resulted in a reduction of opioid consumption delivered by patient-controlled analgesia (PCA) for acute pain in sickle cell disease.

Design

A randomised, placebo-controlled, double-blind trial.

Setting

UK multicentre trial in acute hospital setting.

Participants

Adults with sickle cell disease of any gender and phenotype aged 16 years and over.

Interventions

Oral ibuprofen at a dose of 800 mg three times daily or placebo in addition to opioids (morphine or diamorphine) administered via PCA pump for up to 4 days.

Main outcome measures

The primary outcome measure was opioid consumption over 4 days following randomisation.

Results

The SWIM trial closed early because it failed to randomise to its target of 316 patients within a reasonable time.

Conclusions

The key issues identified include the unanticipated length of time between informed consent and randomisation, difficulties in randomisation of patients in busy emergency departments, availability of trained staff at weekends and out of hours, fewer centres than expected using PCA routinely for sickle cell pain treatment, lack of research staff and support for participation, and the trial design. There are implications for future UK trials in sickle cell disease.

Trial registration number

ISRCTN97241637,NCT00880373; Pre-results.
What factors explain the association between socioeconomic deprivation and reduced likelihood of live-donor kidney transplantation? A questionnaire-based pilot case-control study
Authors: Bailey Phillippa K , Tomson Charles RV , Ben-Shlomo Yoav
Published: June 2016

Objectives

Socioeconomically deprived individuals with renal disease are less likely to receive a live-donor kidney transplant (LDKT) than less deprived individuals. This study aimed to develop and pilot a questionnaire designed to determine what factors explain this association.

Design

Questionnaire development and a pilot case–control study. Primary aims were to develop and evaluate a questionnaire, assess response rates, and to generate data to inform full-scale study design.

Setting

A UK tertiary renal referral hospital and transplant centre.

Participants

Invited participants comprised 30 LDKT recipients (cases) and 30 deceased-donor kidney transplant (DDKT) recipients (controls). Stratified random sampling was used to select cases and controls from all adults who had been transplanted at Southmead Hospital North Bristol National Health Service Trust, between 1 August 2007 and 31 July 2013.

Methods

Participants were posted questionnaires that were accompanied by an invitation letter from the renal consultant responsible for their care, and a patient information leaflet. Non-responders were sent a second questionnaire after 4–6 weeks. Data were extracted from returned questionnaires, and entered onto a Research Electronic Data Capture (REDCap) database.

Results

63% (n=38) of those invited returned questionnaires. 16 (42%) declined to answer the question on income. 58% of participants had not asked any of their potential donors to consider living kidney donation (52% LDKT vs 65% DDKT, p=0.44). There was some evidence of a difference between the R3K-T knowledge score for recipients of LDKTs (mean 6.7, SD 1.8) and for recipients of DDKTs (mean 4.9, SD 2.1), p=0.008. Variables’ distribution for the exposure variables of interest was determined.

Conclusions

Findings from this study will inform a sample size calculation for a full-scale study. The findings of the full-scale case–control study will help us better understand how socioeconomic deprivation is related to the type of transplant an individual receives. This understanding will help us to design and appropriately tailor an intervention to reduce inequitable access to live-donor kidney transplantation.
Procollagen markers in microdialysate can predict patient outcome after Achilles tendon rupture
Authors: Alim Md Abdul , Svedman Simon , Edman Gunnar , Ackermann Paul W
Published: June 2016

Objective

Patients who sustain acute Achilles tendon rupture (ATR) exhibit variable and mostly impaired long-term functional, and patient-reported outcomes. However, there exists a lack of early predictive markers of long-term outcomes to facilitate the development of improved treatment methods. The aim of this study was to assess markers of tendon callus production in patients with ATR in terms of outcome, pain, and fatigue.

Study design and setting

Prospective cohort study; level of evidence 2. Outpatient orthopaedic/sports medicine department.

Patients

A total of 65 patients (57 men, 8 women; mean age 41±7 years) with ATR were prospectively assessed.

Assessments

Markers of tendon callus production, procollagen type I N-terminal propeptide (PINP) and procollagen type III N-terminal propeptide (PIIINP), were assessed 2 weeks postoperatively using microdialysis followed by enzymatic quantification. Normalised procollagen levels (n-PINP and n-PIIINP) were calculated as the ratio of procollagen to total protein content. Pain and fatigue were assessed at 1 year using reliable questionnaires Achilles tendon Total Rupture Score (ATRS).

Results

Patients exhibited fatigue (77.6%) and pain (44.1%) to some extent. Higher levels of n-PINP (R=0.38, p=0.016) and n-PIIINP (R=0.33, p=0.046) were significantly associated with less pain in the limb. Increased concentrations of PINP (R=−0.47, p=0.002) and PIIINP (R=−0.37, p=0.024) were related to more self-reported fatigue in the leg. The results were corroborated by multiple linear regression analyses.

Conclusions

Assessment of procollagen markers in early tendon healing can predict long-term patient-reported outcomes after ATR. These novel findings suggest that procollagen markers could be used to facilitate the development of improved treatment methods in patients who sustain ATR.

Trial registration numbers

NCT01317160: Results.NCT02318472: Pre-results.
Benefits of a novel concept of home-based exercise with the aim of preventing aspiration pneumonia and falls in frail older women: a pragmatic controlled trial
Authors: Takatori Katsuhiko , Matsumoto Daisuke , Nishida Munenori , Matsushita Shinnichiro , Noda Tatsuya , Imamura Tomoaki
Published: June 2016

Aim

To investigate whether home-based exercise with the aim of preventing aspiration pneumonia and accidental falls improves swallowing-related and physical functions in community-dwelling frail older women.

Methods

Participants were 266 community-dwelling frail older women in a long-term care prevention class (mean (SD): age 75 (5) years). Participants were allocated to either an intervention group or a control group. In the intervention group, participants were asked to perform, at least three times a week for 6 months, a home-based exercise programme that was specifically developed to prevent aspiration pneumonia and accidental falls. Control group participants were instructed to perform general stretching exercises only. Voluntary peak cough flow and lip closure force were measured as swallowing-related functions. Static and dynamic balance function, lower limb strength and flexibility were measured as secondary outcomes. Intervention effects were determined using t tests; effect sizes were calculated using Cohen's d.

Results

Voluntary peak cough flow in the intervention group was significantly greater than in the control group (p<0.01, d=0.5). However, lip closure force did not differ between groups. Regarding physical function, results of the Timed Up and Go Test (p<0.05, d=0.4), Chair Stand Test (p<0.01, d=0.4), maximal knee extension strength (p<0.05, d=0.4), and Sit and Reach Test (p<0.05, d=0.3) showed greater improvement in the intervention group.

Conclusions

Specifically developed home-based exercise as described in this study is simple and can be performed briefly. Improvements in voluntary peak cough flow and physical function indicate the possible usefulness of such exercise in preventing falls and aspiration pneumonia in community-dwelling frail older adults.

Trial registration number

UMIN Clinical Trials Registry (UMIN-CTR): UMIN000014880.
Necessary but not yet sufficient: a survey of aged residential care staff perceptions of palliative care communication, education and delivery
Authors: Frey Rosemary , Boyd Michal , Foster Sue , Robinson Jackie , Gott Merryn
Published: June 2016

Objectives

Previous research has indicated that staff in aged residential care (ARC) may be unprepared for their role in palliative care provision. The need for palliative care knowledge among ARC staff has been characterised as ‘pervasive’. Determining the palliative care education, communication and support needs of ARC clinical care staff is, therefore, of critical importance to the delivery of quality healthcare in this setting.

Methods

A survey of clinical staff (n=431) in 52 ARC facilities in 1 urban district health board was conducted, using a paper-based questionnaire. Instruments included the 3-item Experiences with End of Life scale, developed measures of communication and support (13 items), support accessibility (12 items), and palliative care education (19 items).

Results

Only 199 (46.2%) of staff participants reported undertaking palliative care education. Nurses were more likely to have engaged in palliative care education in comparison with healthcare assistants (HCAs) (χ2(1, N=387)=18.10, p=0.00). Participants (n=347) who wanted further education preferred an interactive, hands-on applied education (13.9%) in comparison to short topic-specific sessions/seminars (6.5%) or lecture-based courses (7.7%).

Conclusions

The study reveals an ongoing need for staff palliative care education. Results suggest the development of an integrated model of care which draws on both hospice and ARC staff expertise.
Use of S-100B, NSE, CRP and ESR to predict neurological outcomes in patients with return of spontaneous circulation and treated with hypothermia
Authors: Choi Seungwoon , Park Kyunam , Ryu Seokyong , Kang Taekyung , Kim Hyejin , Cho Sukjin , Oh Sungchan
Published: June 2016

Background

With the introduction of therapeutic hypothermia (TH), the prediction of neurological outcomes in cardiac arrest (CA) survivors is challenging. Early, accurate determination of prognosis by emergency physicians is important to avoid unnecessarily prolonged critical care with a likely poor neurological outcome.

Methods

This prospective observational study included patients with non-traumatic CA and return of spontaneous circulation (ROSC) between March 2009 and May 2012 at a tertiary academic hospital. Unconscious patients with ROSC were treated with mild TH (32°C–34°C) for 24 hours. Blood samples were collected for S-100B, neuron-specific enolase (NSE), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at 0, 24 and 48 hours post-ROSC. Neurological outcomes were evaluated at hospital discharge and dichotomised as good (cerebral performance category (CPC) 1 or 2) or poor (CPC 3, 4 or 5).

Results

Of the 119 patients (68.1% male, 53±15.6 years old) who underwent TH, 46 patients had a good outcome (38.9%). Poor neurological outcomes were predicted using receiver operating characteristic analyses at cut-off values of 0.12 g/L for S-100B at 24 hours post-ROSC (sensitivity, 95.0%; specificity, 75.6%; area under the curve (AUC) 0.916; 95% CI of AUC: 0.846 to 0.961), 31.03 ng/mL for NSE at 48 hours post-ROSC (sensitivity, 83.9%; specificity, 96.9%; AUC 0.929; 95% CI of AUC: 0.836 to 0.979) and 11.2 mg/dL for CRP at 48 hours post-ROSC (sensitivity, 69.4%; specificity, 75.0%; AUC 0.731; 95% CI of AUC: 0.617 to 0.827). ESR was not significant.

Conclusions

Among the biomarkers, S-100B at 24 hours and NSE at 48 hours post-ROSC were highly predictive of neurological outcomes in patients treated with TH after CA.
Determinants of individuals' participation in integrated chronic disease screening in Singapore
Authors: Venkataraman Kavita , Wee Hwee Lin , Ng Sheryl Hui Xian , Rebello Salome , Tai E Shyong , Lee Jeannette , Tan Chuen Seng
Published: June 2016

Background

A large pool of patients with chronic diseases remains undiagnosed globally and in Singapore. We explored factors associated with participation in a health screening exercise, using revealed preference, that is, actual attendance, to understand why people remain undiagnosed with chronic diseases.

Methods

A cross-sectional, community-based sample of Singapore residents was invited to participate in home interviews, and subsequently to attend centre-based health screening, between 2004 and 2007. Determinants of health screening participation were identified using logistic regression models based on Andersen's Behavioral Model.

Results

Of the 6366 participants who completed health interview, 4092 attended the health screening, while 2274 did not. Older age, Chinese or Indian ethnicity, higher education levels, greater intake of monounsaturated fat, greater transport and leisure-time physical activity were the key predisposing factors associated with greater health screening participation. Greater family cohesion was the key associated enabling factor, while previous diagnosis of dyslipidaemia or musculoskeletal conditions, absence of previously diagnosed diabetes or hypertension and lower perceived physical health were the associated need factors.

Conclusions

Our study suggests that ethnicity, education, family cohesion, healthy behaviour patterns and perceived physical health status were key determinants of health screening participation. Enhancing the cultural competence of preventive health services may help increase participation of these groups in screening efforts and reduce the proportions of undiagnosed chronic disease in the community.
A cardiovascular disease policy model: part 2—preparing for economic evaluation and to assess health inequalities
Authors: Lawson K D , Lewsey J D , Ford I , Fox K , Ritchie L D , Tunstall-Pedoe H , Watt G C M , Woodward M , Kent S , Neilson M , Briggs A H
Published: June 2016

Objectives

This is the second of the two papers introducing a cardiovascular disease (CVD) policy model. The first paper described the structure and statistical underpinning of the state-transition model, demonstrating how life expectancy estimates are generated for individuals defined by ASSIGN risk factors. This second paper describes how the model is prepared to undertake economic evaluation.

Design

To generate quality-adjusted life expectancy (QALE), the Scottish Health Survey was used to estimate background morbidity (health utilities) and the impact of CVD events (utility decrements). The SF-6D algorithm generated utilities and decrements were modelled using ordinary least squares (OLS). To generate lifetime hospital costs, the Scottish Heart Health Extended Cohort (SHHEC) was linked to the Scottish morbidity and death records (SMR) to cost each continuous inpatient stay (CIS). OLS and restricted cubic splines estimated annual costs before and after each of the first four events. A Kaplan-Meier sample average (KMSA) estimator was then used to weight expected health-related quality of life and costs by the probability of survival.

Results

The policy model predicts the change in QALE and lifetime hospital costs as a result of an intervention(s) modifying risk factors. Cost-effectiveness analysis and a full uncertainty analysis can be undertaken, including probabilistic sensitivity analysis. Notably, the impacts according to socioeconomic deprivation status can be made.

Conclusions

The policy model can conduct cost-effectiveness analysis and decision analysis to inform approaches to primary prevention, including individually targeted and population interventions, and to assess impacts on health inequalities.
Cardiac arrest: a missed learning opportunity
Authors: Khpal Muska , Coxwell Matthewman Madeline
Published: June 2016

Aim

The Resuscitation Council advocates debriefing after cardiac arrests, as both a training tool and to improve patient outcomes. There is, however, a large variation between hospitals in their implementation of debriefing. This potentially disadvantages trainees, as they are unable to use the presented opportunity to improve their skills and knowledge. The primary aim of this survey was to investigate the utility and perception of debriefing postcardiac arrest among staff at a district general hospital. The secondary aim was to evaluate our specifically designed postcardiac arrest debrief tool.

Method

A confidential, qualitative survey was distributed to 100 cardiac arrest team members at Lister Hospital, Stevenage, during February 2016.

Results

72% of the participants reported never having debriefed postcardiac arrest at Lister Hospital. 93% believed that debriefing would improve individual performance, 95% felt it would benefit team performance and 88% felt it would improve patient safety. Our postcardiac arrest debrief tool was well received, with 93% stating that they would find the tool useful.

Conclusions

Debriefing postcardiac arrest has been associated with improved return of spontaneous circulation (ROSC) neurological outcomes, hands-off compression times as well as reduced time delay to first compression. Despite the benefits, this survey has shown a lack of debriefing at our hospital. We have developed a concise debriefing tool aimed at providing much-needed training for those involved. The tool allows identification of key concerns in leadership, and teamwork and encourages open discussions around areas of concern. We believe that its implementation may improve resuscitation outcomes, and therefore, recommend its use postcardiac arrests.
Long-term study of the impact of methotrexate on serum cytokines and lymphocyte subsets in patients with active rheumatoid arthritis: correlation with pharmacokinetic measures
Authors: Kremer Joel M , Lawrence David A , Hamilton Robert , McInnes Iain B
Published: June 2016

Objective

To describe changes in immune parameters observed during long-term methotrexate (MTX) therapy in patients with active rheumatoid arthritis (RA) and explore correlations with simultaneously measured MTX pharmacokinetic (PKC) parameters.

Design

Prospective, open-label, long-term mechanism of action study.

Setting

University clinic.

Methods

MTX was initiated at a single weekly oral dose of 7.5 mg and dose adjusted for efficacy and toxicity for the duration of the study. Standard measures of disease activity were performed at baseline and every 6–36 months. Serum cytokine measurements in blood together with lymphocyte surface immunophenotypes and stimulated peripheral blood mononuclear cell (PBMC) cytokine production were assessed at each clinical evaluation.

Results

Cytokine concentrations exhibited multiple significant correlations with disease activity measures over time. The strongest correlations observed were for interleukin (IL)-6 (r=0.45, p<0.0001 for swollen joints and r=0.32, p=0.002 for tender joints) and IL-8 (r=0.25, p=0.01 for swollen joints). Significant decreases from baseline were observed in serum IL-1B, IL-6 and IL-8 concentrations. The most significant changes were observed for IL-6 (p<0.001). Significant increases from baseline were observed in IL-2 release from PBMCs ex vivo (p<0.01). In parallel, multiple statistically significant correlations were observed between MTX PKC measures and immune parameters. The change in swollen joint count correlated inversely with the change in area under the curve (AUC) for MTX (r=−0.63, p=0.007).

Conclusions

MTX therapy of patients with RA is accompanied by a variety of changes in serum cytokine expression, which in turn correlate strongly with clinical disease activity and MTX pharmacokinetics (PKCs). These data strongly support the notion that MTX mediates profound and functionally relevant effects on the immunological hierarchy in the RA lesion.
Reconstructing the eruptive history of a monogenetic volcano through a combination of fieldwork and geophysical surveys: the example of Puig d’Àdri (Garrotxa Volcanic Field)
Authors: Pedrazzi Dario , Bolós Xavier , Barde-Cabusson Stéphanie , Martí Joan
Published: June 2016

Puig d’Àdri is a complex volcano in the Garrotxa Volcanic Field (0.7–0.01 Ma), the youngest part of the Catalan Volcanic Zone (NE Iberian Peninsula). The construction of this volcano involved the superimposition of three volcanic edifices with five lithostratigraphic units, in which several Strombolian and phreatomagmatic episodes alternated. Geological and geophysical surveys performed using electrical resistivity tomography and self-potential have contributed to revealing the internal structure of the volcano and the succession of deposits. The ring–cone morphology of the phreatomagmatic part of the structure shows how a number of variables including the way in which magma and water interacted greatly influenced the eruptive dynamics and the mechanisms of formation. A further major issue reflected in the final structure of the edifice is the process of vent migration, which was controlled by the characteristics of the substrate and its interaction with the magma as it rose.

Supplementary material:
Granulometric and component histograms of the samples not shown in Figure 4 are available at
http://doi.org/10.6084/m9.figshare.c.3262498