bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of viral eradication with sofosbuvir‐based therapy on the outcome of post‐transplant hepatitis C with severe fibrosis
Authors: Martini Silvia , Sacco Marco , Strona Silvia , Arese Daniele , Tandoi Francesco , Dell Olio Dominic , Stradella Davide , Cocchis Donatella , Mirabella Stefano , Rizza Giorgia , Magistroni Paola , Moschini Pamela , Ottobrelli Antonio , Amoroso Antonio , Rizzetto Mario , Salizzoni Mauro , Saracco Giorgio M. , Romagnoli Renato
Published: June 2016

Background & Aims

Several studies have shown that new direct‐acting antivirals maintain their efficacy in liver transplant (LT) recipients with severe hepatitis C virus (HCV) recurrence. We determined the clinical impact of sofosbuvir/ribavirin in LT through the changes in liver function and fibrosis state at 24 and 48 weeks after treatment.

Methods

Between June 2014 and July 2015, 126 patients (30 F3, 96 F4 Metavir stage) were enrolled to receive sofosbuvir + ribavirin (24 weeks, 118 patients) or sofosbuvir + simeprevir + ribavirin (12 weeks, 8 patients); treatment was initiated at a median time of 4.3 years from LT. Median follow‐up after therapy completion was 461 days.

Results

All 30 F3 patients achieved a sustained virological response at week 24 after treatment (SVR24) and showed a distinct amelioration of the AST‐to‐platelet ratio index (APRI), FIB‐4 and liver stiffness at elastography by week 24 post‐therapy, which were maintained at week 48.

Of the 96 F4 cirrhotic patients, 72 (75%) achieved SVR24 accompanied by significant improvement of liver function, which was maintained at week 48 (Child B‐C 22% baseline, 11% week 24, 7% week 48); APRI, FIB‐4 and liver stiffness further improved significantly between weeks 24 and 48 of follow‐up. Among the 77 responders (27 F3, 50 F4) who underwent elastography at baseline and at the end of follow‐up, 39 (50.6%; 18 F3, 21 F4) exhibited a regression in fibrosis stage.

Conclusion

At about 1 year from the completion of successful sofosbuvir‐based therapy, patients with post‐LT HCV and severe fibrosis experienced a long‐term liver function improvement accompanied by a regression of fibrosis stage in half of them.
sandflyDST: a dynamic web‐based decision support tool for the morphological identification of sandflies present in Anatolia and mainland Europe, and user study
Authors: KARAKÜLAH G. , KARAKUŞ M. , SUNER A. , DEMİR S. , ARSERİM S. K. , TÖZ S. , ÖZBEL Y.
Published: June 2016

Species identification of sandflies is mainly performed according to morphological characters using classical written identification keys. This study introduces a new web‐based decision support tool (sandflyDST) for guiding the morphological identification of sandfly species present in Anatolia and mainland Europe and classified in the Phlebotomus and Sergentomyia genera (both: Diptera: Psychodidae). The current version of the tool consists of 111 questions and 36 drawings obtained from classical written keys, and 107 photographs for the quick and easy identification of 26 species of the genus Phlebotomus and four species of the genus Sergentomyia. The tool guides users through a decision tree using yes/no questions about the morphological characters of the specimen. The tool was applied by 30 individuals, who then completed study questionnaires. The results of subsequent analyses indicated that the usability () and users' level of appreciation (86.6%) of the tool were quite high; almost all of the participants considered recommending the tool to others. The tool may also be useful in training new entomologists and maintaining their level of expertise. This is a dynamic tool and can be improved or upgraded according to feedback. The tool is now available online at
http://parasitology.ege.edu.tr/sandflyDST/index.php.
The miR393a/target module regulates seed germination and seedling establishment under submergence in rice (Oryza sativa L.)
Authors: Guo Fu , Han Ning , Xie Yakun , Fang Ke , Yang Yinong , Zhu Muyuan , Wang Junhui , Bian Hongwu
Published: June 2016

The conserved miRNA393 family is thought to be involved in root elongation, leaf development and stress responses, but its role during seed germination and seedling establishment remains unclear. In this study, expression of the MIR393a/target module and its role in germinating rice (Oryza sativa L.) seeds were investigated. β‐Glucuronidase (GUS) analysis showed that MIR393a and OsTIR1 had spatial–temporal transcriptional activities in radicle roots, coleoptile tips and stomata cells, corresponding to a dynamic auxin response. miR393a promoted primary root elongation when rice seeds were germinated in air and inhibited coleoptile elongation and stomatal development when seeds were submerged. Under submergence, the expression of miR393a was inhibited, and then the auxin response was induced. In the process, OsTIR1 and OsAFB2, auxin receptor genes, were negatively regulated by miR393. We found that miR393a inhibited stomatal development and coleoptile elongation but promoted free indole acetic acid (IAA) accumulation in the rice coleoptile tips. In addition, exogenous abscisic acid (ABA) enhanced the expression of miR393 and inhibited coleoptile growth. Together, miR393a/target plays a role in coleoptile elongation and stomatal development via modulation of auxin signalling during seed germination and seedling establishment under submergence. This study provides new perspectives on the direct sowing of rice seeds in flooded paddy fields.
Growth inhibition by selenium is associated with changes in primary metabolism and nutrient levels in Arabidopsis thaliana
Authors: Ribeiro Dimas M. , Silva Júnior Dalton D. , Cardoso Flávio Barcellos , Martins Auxiliadora O. , Silva Welder A. , Nascimento Vitor L. , Araújo Wagner L.
Published: June 2016

Although Selenium (Se) stress is relatively well known for causing growth inhibition, its effects on primary metabolism remain rather unclear. Here, we characterized both the modulation of the expression of specific genes and the metabolic adjustments in Arabidopsis thaliana in response to changes in Se level in the soil. Se treatment culminated with strong inhibition of both shoot and root growth. Notably, growth inhibition in Se‐treated plants was associated with an incomplete mobilization of starch during the night. Minor changes in amino acids levels were observed in shoots and roots of plants treated with Se whereas the pool size of tricarboxylic acid (TCA) cycle intermediates in root was not altered in response to Se. By contrast, decreased levels of organic acids involved in the first part of the TCA cycle were observed in shoots of Se‐treated plants. Furthermore, decreased expression levels of expansins and endotransglucosylases/endohydrolases (XHTs) genes were observed after Se treatment, coupled with a significant decrease in the levels of essential elements. Collectively, our results revealed an exquisite interaction between energy metabolism and Se‐mediated control of growth in Arabidopsis thaliana to coordinate cell wall extension, starch turnover and the levels of a few essential nutrients.
Pediatric Erythema Annulare Centrifugum Treated with Oral Fluconazole: A Retrospective Series
Authors: Kruse Lacey L. , Kenner‐Bell Brandi M. , Mancini Anthony J.
Published: June 2016

Objectives

Erythema annulare centrifugum (EAC) is an uncommon eruption that may be a hypersensitivity reaction. Treatment of EAC is best accomplished by eliminating the underlying cause. Although many triggers have been reported, the inciting factor is unknown in most patients. We hypothesized that occult yeast overgrowth may trigger EAC in patients with EAC of unknown etiology.

Methods

Five children with EAC were treated empirically with oral fluconazole. These cases were retrospectively reviewed.

Results

Improvement was noted in all patients; three cleared entirely. Two patients experienced recurrences after successful treatment, which were treated with a second course of fluconazole. The treatment was well tolerated, without adverse effects.

Conclusion

Oral fluconazole was an effective treatment in five children with EAC.
Behavioral and emotional responses to diet‐related support and control among same‐sex couples
Authors: AUGUST KRISTIN J. , ABBAMONTE JOHN M. , MARKEY CHARLOTTE N. , NAVE CHRISTOPHER S. , MARKEY PATRICK M.
Published: June 2016

Members of 63 lesbian and 72 gay couples reported how frequently their partners engaged in diet‐related social support and control (persuasion and pressure) and how they responded behaviorally and emotionally to such attempts. Although lesbian women received more frequent diet‐related social support than gay men, there were no gender differences in the receipt of diet‐related social control. Results of multilevel models that controlled for body mass index revealed that all participants responded to all types of involvement with guilt and to support and persuasion with appreciation. Responses to pressure differed for lesbian women and gay men and acted as a function of relationship quality. Findings from this study may increase awareness of the importance of same‐sex partners' involvement in eating behaviors.
Do occupational therapy interventions improve quality of life in persons with dementia? A meta‐analysis with implications for future directions
Authors: Ojagbemi Akin , Owolabi Mayowa
Published: June 2016

Occupational therapy (OT) interventions have shown positive effects on physical functioning in persons with dementia (PwD). However, their effect on quality of life (QoL) has been inconsistent in individual clinical trials. The present review appraises current evidence for the use ofOTinterventions in improvingQoLofPwD.Records in theCochrane Database,MEDLINE,EMBASE,PsycINFO, andCumulative Index to Nursing and Allied Health Literaturewere searched for relevant citations, andPubMed was searched for in‐process articles. Additional searches of the reference lists of retrieved articles were undertaken. Ten studies involving 1002PwDmet the criteria for syntheses.OTintervention produced small non‐significant improvements in overallQoL. The evidence from the present review does not support the specific use ofOTinterventions for the improvement ofQoLinPwDunder pragmatic clinical conditions at this time. They may be best used as part of a comprehensive range of interventions forPwD. Recommendations are made for future design ofOTinterventions focusing on the improvement ofQoL, which is central to the well‐being ofPwD.
A functional classification of medial frontal negativity ERPs: Theta oscillations and single subject effects
Authors: Van Noordt Stefon J.R. , Campopiano Allan , Segalowitz Sidney J.
Published: June 2016

Theta oscillations in the EEG have been linked to several ERPs that are elicited during performance‐monitoring tasks, including the error‐related negativity (ERN), no‐go N2, and the feedback‐related negativity (FRN). We used a novel paradigm to isolate independent components (ICs) in single subjects' (n = 27) EEG accounting for a medial frontal negativity (MFN) to response cue stimuli that signal a potential change in future response demands. Medial frontal projecting ICs that were sensitive to these response cues also described the ERNs, no‐go N2s, and, to a lesser extent, the FRNs, that were elicited in letter flanker, go/no‐go, and time‐estimation tasks, respectively. In addition, percentile bootstrap tests using trimmed means indicated that the medial frontal ICs show an increase in theta activity during the ERN, no‐go N2, and FRN across tasks and within individuals. Our results provide an important validation of previous studies by showing that increases in medial frontal theta to cognitively challenging events in multiple paradigms is a reliable effect within individuals and can be elicited by basic stimulus cues that signal the potential need to adjust response control. Thus, medial frontal theta reflects a neural response common to all MFN paradigms and characterizes the general process of controlling attention without the need to induce error commission, inhibited responses, or to present negative feedback.
Causal Analysis of Ordinal Treatments and Binary Outcomes Under Truncation by Death
Authors: Wang Linbo , Richardson Thomas S. , Zhou Xiao-Hua
Published: June 2016

It is common that, in multiarm randomized trials, the outcome of interest is ‘truncated by death’, meaning that it is only observed or well-defined conditioning on an intermediate outcome. In this case, in addition to pairwise contrasts, the joint inference for all treatment arms is also of interest. Under a monotonicity assumption we present methods for both pairwise and joint causal analyses of ordinal treatments and binary outcomes in the presence of truncation by death. We illustrate via examples the appropriateness of our assumptions in different scientific contexts.
Zoophycos in deep‐sea sediments indicates high and seasonal primary productivity: Ichnology as a proxy in palaeoceanography during glacial–interglacial variations
Authors: Dorador Javier , Wetzel Andreas , Rodríguez‐Tovar Francisco J.
Published: June 2016

Trace fossils provide valuable palaeoenvironmental information in hemipelagic settings. This is particularly true in the case of Zoophycos, an easily recognizable trace fossil in core. At IODP site U1385, Zoophycos was found throughout an interval representing 1.5 Ma, covering 45 glacial–interglacial cycles mediated by obliquity (41 ka) and short‐term eccentricity (100 ka). Zoophycos is most common in sediments deposited during glacial times and when the sedimentation rate was intermediate and primary production was high and seasonal. Occurrences of Zoophycos elsewhere support a similar relationship with seasonal organic‐matter deposition. This is particularly significant considering that seasonality of organic‐matter deposition is difficult to decipher from the sediment record. Zoophycos appears to represent a useful proxy to characterize high and seasonal organic‐matter deposition and primary productivity in Neogene hemipelagic deposits.
Draft Genome Sequence of Comamonas thiooxydans Strain PHE2-6 (NBRC 110656), a Chlorinated-Ethene-Degrading Bacterium
Authors: Shimodaira Jun , Yonezuka Kenta , Tabata Michiro , Nagase Shun , Kasai Daisuke , Hosoyama Akira , Yamazoe Atsushi , Fujita Nobuyuki , Fukuda Masao
Published: June 2016

Comamonas thiooxydans
strain PHE2-6 (NBRC 110656), which was isolated from a trichloroethene-contaminated site in Japan, utilizes phenol as a sole source of carbon and cometabolizes
cis-
and
trans-
dichloroethenes. We report here the draft genome sequence of this strain, containing 5,309,680 bp, with 60.6% G+C content.
Draft Genome Sequence and Gene Annotation of the Uropathogenic Bacterium Proteus mirabilis Pr2921
Authors: Giorello F. M. , Romero V. , Farias J. , Scavone P. , Umpiérrez A. , Zunino P. , Sotelo Silveira J. R.
Published: June 2016

Here, we report the genome sequence of
Proteus mirabilis
Pr2921, a uropathogenic bacterium that can cause severe complicated urinary tract infections. After gene annotation, we identified two additional copies of
ucaA
, one of the most studied fimbrial protein genes, and other fimbriae related-proteins that are not present in
P. mirabilis
HI4320.
Complete Genome Sequence of the Methanogen Methanoculleus bourgensis BA1 Isolated from a Biogas Reactor
Authors: Maus Irena , Wibberg Daniel , Winkler Anika , Pühler Alfred , Schnürer Anna , Schlüter Andreas
Published: June 2016

Methanoculleus bourgensis
BA1, a hydrogenotrophic methanogen
,
was isolated from a laboratory-scale biogas reactor operating under an elevated ammonium concentration. Here, the complete genome sequence of
M. bourgensis
BA1 is reported. The availability of the BA1 genome sequence enables detailed comparative analyses involving other
Methanoculleus
spp. representing important members of microbial biogas communities.
Genome Sequences of Gordonia terrae Phages Benczkowski14 and Katyusha
Authors: Pope Welkin H. , Benczkowski Matthew S. , Green Daryn E. , Hwang Melina , Kennedy Bryan , Kocak Bradley , Kruczek Ellen , Lin Leon , Moretti Matthew L. , Onelangsy Faith L. , Mezghani Nadia , Milliken Katherine A. , Toner Chelsea L. , Thompson Paige K. , Ulbrich Megan C. , Furbee Emily C. , Grubb Sarah R. , Warner Marcie H. , Montgomery Matthew T. , Garlena Rebecca A. , Russell Daniel A. , Jacobs-Sera Deborah , Hatfull Graham F.
Published: June 2016

Bacteriophages Katyusha and Benczkowski14 are newly isolated phages that infect
Gordonia terrae
3612. Both have siphoviral morphologies with isometric heads and long tails (500 nm). The genomes are 75,380 bp long and closely related, and the tape measure genes (9 kbp) are among the largest to be identified.
High-Quality Draft Genome Sequence of Biocontrol Strain
Pantoea
sp. OXWO6B1
Authors: Town Jennifer , Audy Patrice , Boyetchko Susan M. , Dumonceaux Tim J.
Published: June 2016

Pantoea
sp. strain OXWO6B1 inhibits the growth of the potato pathogen
Phytophthora infestans
. We determined the 5.2-Mbp genome sequence of this strain, which featured at least 3 confirmed plasmids of up to 250 kbp. The genome sequence of OXWO6B1 is different from that of all previously sequenced strains of
Pantoea
.
Complete Genome Sequence of a Multidrug-Resistant Acinetobacter baumannii Isolate Obtained from a Mexican Hospital (Sequence Type 422)
Authors: Castro-Jaimes Semiramis , Salgado-Camargo Abraham David , Graña-Miraglia Lucía , Lozano Luis , Bocanegra-Ibarias Paola , Volkow-Fernández Patricia , Silva-Sanchez Jesus , Castillo-Ramírez Santiago , Cevallos Miguel A.
Published: June 2016

Acinetobacter baumannii
has emerged as a dangerous nosocomial pathogen, particularly for severely ill patients in intensive care units and patients with hematologic malignancies. Here, we present the complete genome sequence of a multidrug-resistant
A. baumannii
isolate, recovered from a Mexican hospital and classified as sequence type 422 according to the multilocus sequence typing Pasteur scheme.
High-Quality Draft Genome Sequence of Bacillus subtilis Strain WAUSV36
Authors: Town Jennifer , Audy Patrice , Boyetchko Susan M. , Dumonceaux Tim J.
Published: June 2016

Bacillus subtilis
strain WAUSV36 inhibits the growth of and decreases disease symptoms caused by the potato pathogen
Phytophthora infestans
. We determined the sequence of the 4.7-Mbp genome of this strain. WAUSV36 shared very high nucleotide sequence identity with previously sequenced strains of
B. subtilis
.
Complete Genome Sequences of T1-Like Phages JMPW1 and JMPW2
Authors: Shen Mengyu , Zhu Hongbin , Lu Shuguang , Le Shuai , Li Gang , Tan Yinling , Zhao Xia , Shen Wei , Hu Fuquan , Wang Jing
Published: June 2016

We report the complete genome sequences of phages JMPW1 (49,840 bp) and JMPW2 (50,298 bp), two T1-like
Escherichia coli
phages isolated from contaminated experiment samples. Although the genomes of JMPW1 and JMPW2 share high identity with T1, they show some differences, which are mainly located in several genes with unknown functions and genes encoding tail fiber proteins and endonucleases.
Complete Genome Sequence of the First KPC-Type Carbapenemase-Positive Proteus mirabilis Strain from a Bloodstream Infection
Authors: Di Pilato Vincenzo , Chiarelli Adriana , Boinett Christine J. , Riccobono Eleonora , Harris Simon R. , D'Andrea Marco Maria , Thomson Nicholas R. , Rossolini Gian Maria , Giani Tommaso
Published: June 2016

Sequencing of the
bla
KPC
-positive strain
Proteus mirabilis
AOUC-001 was performed using both the MiSeq and PacBio RS II platforms and yielded a single molecule of 4,272,433 bp, representing the complete chromosome. Genome analysis showed the presence of several acquired resistance determinants, including two copies of
bla
KPC-2
carried on a fragment of a KPC-producing plasmid previously described in
Klebsiella pneumoniae
.
Draft Genome Sequence of Shewanella baltica M1 Isolated from Brackish Surface Water of the Gulf of Gdańsk
Authors: Karczewska-Golec Joanna , Strapagiel Dominik , Sadowska Marta , Szalewska-Pałasz Agnieszka , Golec Piotr
Published: June 2016

Here, we present the 5.168-Mbp draft genome sequence of
Shewanella baltica
M1, the first
Shewanella
strain from the Gulf of Gdańsk to have its genome sequenced and annotated. The availability of the genome sequence of strain M1 will promote further global analyses of bacterial stress responses in the unique Gulf of Gdańsk ecosystem.
Draft Genome Sequences of Methanobrevibacter curvatus DSM11111, Methanobrevibacter cuticularis DSM11139, Methanobrevibacter filiformis DSM11501, and Methanobrevibacter oralis DSM7256
Authors: Poehlein Anja , Seedorf Henning
Published: June 2016

Here, the draft genome sequences of four different
Methanobrevibacter
species are presented. Three of the
Methanobrevibacter
species (
M. curvatus, M. cuticularis
, and
M. filiformis
) have been isolated from the termite hindgut, while
M. oralis
was isolated from human subgingival plaque.
Improving the Standards-Based Management-Recognition initiative to provide high-quality, equitable maternal health services in Malawi: an implementation research protocol
Authors: Mumtaz Zubia , Salway Sarah , Nyagero Josephat , Osur Joachim , Chirwa Ellen , Kachale Fannie , Saunders Duncan
Published: June 2016

Background

The Government of Malawi is seeking evidence to improve implementation of its flagship quality of care improvement initiative—the Standards Based Management-Recognition for Reproductive Health (SBM-R(RH)).

Objective

This implementation study will assess the quality of maternal healthcare in facilities where the SBM-R(RH) initiative has been employed, identify factors that support or undermine effectiveness of the initiative and develop strategies to further enhance its operation.

Methods

Data will be collected in 4 interlinked modules using quantitative and qualitative research methods. Module 1 will develop the programme theory underlying the SBM-R(RH) initiative, using document review and in-depth interviews with policymakers and programme managers. Module 2 will quantitatively assess the quality and equity of maternal healthcare provided in facilities where the SBM-R(RH) initiative has been implemented, using the Malawi Integrated Performance Standards for Reproductive Health. Module 3 will conduct an organisational ethnography to explore the structures and processes through which SBM-R(RH) is currently operationalised. Barriers and facilitators will be identified. Module 4 will involve coordinated co-production of knowledge by researchers, policymakers and the public, to identify and test strategies to improve implementation of the initiative.

Potential impact

The research outcomes will provide empirical evidence of strategies that will enhance the facilitators and address the barriers to effective implementation of the initiative. It will also contribute to the theoretical advances in the emerging science of implementation research.
Measuring engagement in advance care planning: a cross-sectional multicentre feasibility study
Authors: Howard Michelle , Bonham Aaron J , Heyland Daren K , Sudore Rebecca , Fassbender Konrad , Robinson Carole A , McKenzie Michael , Elston Dawn , You John J
Published: June 2016

Objectives

To assess the feasibility, acceptability and clinical sensibility of a novel survey, the advance care planning (ACP) Engagement Survey, in various healthcare settings.

Setting

A target sample of 50 patients from each of primary care, hospital, cancer care and dialysis care settings.

Participants

A convenience sample of patients without cognitive impairment who could speak and read English was recruited. Patients 50 and older were eligible in primary care; patients 80 and older or 55 and older with clinical markers of advanced chronic disease were recruited in hospital; patients aged 19 and older were recruited in cancer and renal dialysis centres.

Outcomes

We assessed feasibility, acceptability and clinical sensibility of the ACP Engagement Survey using a 6-point scale. The ACP Engagement Survey measures ACP processes (knowledge, contemplation, self-efficacy and readiness) on 5-point Likert scales and actions (yes/no).

Results

196 patients (38–96 years old, 50.5% women) participated. Mean (±SD) time to administer was 48.8±19.6 min. Mean acceptability scores ranged from 3.2±1.3 in hospital to 4.7±0.9 in primary care, and mean relevance ranged from 3.5±1.0 in hospital to 4.9±0.9 in dialysis centres (p<0.001 for both). The mean process score was 3.1±0.6 and the mean action score was 11.2±5.6 (of a possible 25).

Conclusions

The ACP Engagement Survey demonstrated feasibility and acceptability in outpatient settings but was less feasible and acceptable among hospitalised patients due to length. A shorter version may improve feasibility. Engagement in ACP was low to moderate.
An explorative study to assess the association between health-related quality of life and the recommended phase II dose in a phase I trial: idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma
Authors: Anota Amélie , Boulin Mathieu , Dabakuyo-Yonli Sandrine , Hillon Patrick , Cercueil Jean-Pierre , Minello Anne , Jouve Jean-Louis , Paoletti Xavier , Bedenne Laurent , Guiu Boris , Bonnetain Franck
Published: June 2016

Objectives

The objective of this study was to explore the association between health-related quality of life (HRQoL) and the recommended phase 2 dose in a phase I clinical trial according to the Time to HRQoL deterioration approach (TTD).

Setting

This is a phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads performed in cirrhotic patients with hepatocellular carcinoma. Patients had to complete the EORTC QLQ-C30 HRQoL questionnaire at baseline and at days 15, 30 and 60 after TACE.

Participants

Patients aged ≥18 years with HCC unsuitable for curative treatments were evaluated for the study (N=21).

Primary and secondary outcome measurements

The primary objective was to determine the maximum tolerated dose (MTD) of idarubicin loaded after a single TACE session. MTD was defined as the dose level closest to that causing dose-limiting toxicity in 20% of patients. HRQoL was the secondary end point.

Results

Between March 2010 and March 2011, 9, 6 and 6 patients were included at idarubicin dose levels of 5, 10 and 15 mg, respectively. Calculated MTD of idarubicin was 10 mg. At the 10 mg idarubicin dose, patients presented a longer TTD than at 5 mg, for global health status (HR=0.91 (95% CI 0.18 to 4.72)), physical functioning (HR=0.38 (0.04 to 3.22)), fatigue (HR=0.67 (0.18 to 2.56)) and pain (HR=0.47 (0.05 to 4.24)).

Conclusions

These HRQoL results were consistent with the estimated MTD, with a median TTD for global health status of 41 days (21 to NA) at 5 mg, 23 days (20 to NA) at 10 mg and 25 days (17 to NA) at 15 mg. These results show the importance of studying HRQoL in phase I trials.

Trial registration number

NCT01040559; Post-results.
“You don't immediately stick a label on them”: a qualitative study of influences on general practitioners' recording of anxiety disorders
Authors: Ford Elizabeth , Campion Alice , Chamles Darleen Aixora , Habash-Bailey Haniah , Cooper Maxwell
Published: June 2016

Objectives

Anxiety is a common condition usually managed in general practice (GP) in the UK. GP patient records can be used for epidemiological studies of anxiety as well as clinical audit and service planning. However, it is not clear how general practitioners (GPs) conceptualise, diagnose and document anxiety in these records. We sought to understand these factors through an interview study with GPs.

Setting

UK National Health Service (NHS) General Practice (England and Wales).

Participants

17 UK GPs.

Primary and secondary outcome measures

Semistructured interviews used vignettes to explore the process of diagnosing anxiety in primary care and investigate influences on recording. Interviews were transcribed verbatim and analysed using thematic analysis.

Results

GPs chose 12 different codes for recording anxiety in the 2 vignettes, and reported that history, symptoms and management would be recorded in free text. GPs reported on 4 themes representing influences on recording of anxiety: ‘anxiety or a normal response’, ‘granularity of diagnosis’, ‘giving patients a label’ and ‘time as a tool’; and 3 themes about recording in general: ‘justifying the choice of code’, ‘usefulness of coding’ and ‘practice-specific pressures’. GPs reported using only a regular selection of codes in patient records to help standardise records within the practice and as a time-saving measure.

Conclusions

We have identified a coding culture where GPs feel confident recognising anxiety symptoms; however, due to clinical uncertainty, a long-term perspective and a focus on management, they are reluctant to code firm diagnoses in the initial stages. Researchers using GP patient records should be aware that GPs may prefer free text, symptom codes and other general codes rather than firm diagnostic codes for anxiety.
Sexual counselling for patients with cardiovascular disease: protocol for a pilot study of the CHARMS sexual counselling intervention
Authors: Murphy Patrick J , Mc Sharry Jenny , Casey Dympna , Doherty Sally , Gillespie Paddy , Jaarsma Tiny , Murphy Andrew W , Newell John , O'Donnell Martin , Steinke Elaine E , Toomey Elaine , Byrne Molly
Published: June 2016

Introduction

Sexual problems are common with cardiovascular disease, and can negatively impact quality of life. To address sexual problems, guidelines have identified the importance of sexual counselling during cardiac rehabilitation, yet this is rarely provided. The Cardiac Health and Relationship Management and Sexuality (CHARMS) intervention aims to improve the provision of sexual counselling in cardiac rehabilitation in Ireland.

Methods and analysis

This is a multicentre pilot study for the CHARMS intervention, a complex, multilevel intervention delivered within hospital-based cardiac rehabilitation programmes. The intervention includes (1) training in sexual counselling for staff, (2) a staff-led patient education and support intervention embedded within the cardiac rehabilitation programme, (3) a patient information booklet and (4) an awareness raising poster. The intervention will be delivered in two randomly selected cardiac rehabilitation centres. In each centre 30 patients will be recruited, and partners will also be invited to participate. Data will be collected from staff and patients/partners at T1 (study entry), T2 (3-month follow-up) and T3 (6-month follow-up). The primary outcome for patients/partners will be scores on the Sexual Self-Perception and Adjustment Questionnaire. Secondary outcomes for patients/partners will include relationship satisfaction; satisfaction with and barriers to sexual counselling in services; sexual activity, functioning and knowledge; physical and psychological well-being. Secondary outcomes for staff will include sexuality-related practice; barriers to sexual counselling; self-ratings of capability, opportunity and motivation; sexual attitudes and beliefs; knowledge of cardiovascular disease and sex. Fidelity of intervention delivery will be assessed using trainer self-reports, researcher-coded audio recordings and exit interviews. Longitudinal feasibility data will be gathered from patients/partners and staff via questionnaires and interviews.

Ethics and dissemination

This study is approved by the Research Ethics Committee (REC) of the National University of Ireland, Galway. Findings will be disseminated to cardiac rehabilitation staff, patients/partners and relevant policymakers via appropriate publications and presentations.
β-Blockers in sepsis: protocol for a systematic review and meta-analysis of randomised control trials
Authors: Duan Erick H , Oczkowski Simon J W , Belley-Cote Emilie , Whitlock Richard , Lamontagne Francois , Devereaux Phillip J , Cook Deborah J
Published: June 2016

Introduction

Sepsis is a common and deadly complication of infection. As part of the host response, sympathetic stimulation can result in septic myocardial depression, and metabolic, haematological and immunological dysfunction. Administration of β-blockers may attenuate this pathophysiological response to infection, but the effects on clinical outcomes are unknown. The objective of this systematic review is to determine the efficacy and safety of β-blockers in adults with sepsis using data from randomised control trials.

Methods and analysis

We will identify randomised control trials comparing treatment with β-blockers, versus placebo or standard care in adults with sepsis. Data sources will include MEDLINE, EMBASE, CENTRAL, clinical trial registries and conference proceedings. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, risk of bias assessment and evaluation of the quality of the evidence using the GRADE approach.

Ethics and dissemination

Our systematic review will evaluate the effects of β-blockers in adults with sepsis, comprehensively summarising and appraising the available evidence from randomised control trials. The results of this systematic review will help clinicians treating patients with sepsis to understand the potential role of β-blockade, and inform future research on this topic. Our findings will be disseminated through conference presentation and publication in a peer-reviewed journal.

Trial registration number

CRD42016036933.
Alcohol and Fat Promote Steatohepatitis: A Critical Role for Fat-Specific Protein 27/Cidec
Authors: Liangpunsakul Suthat , Gao Bin
Published: June 2016

Alcoholic liver disease (ALD) is a major public health problem worldwide and is the leading cause of end-stage liver disease. While the ultimate control of ALD will require the prevention of alcohol abuse, better understanding of the mechanisms of alcohol-induced liver injury may lead to treatments of fatty liver, alcoholic hepatitis, and prevention or delay of occurrence of cirrhosis. The elucidation and the discovery of several new concepts in ALD pathogenesis have raised our understanding on the complex mechanisms and the potential in developing the new strategies for therapeutic benefits. In this review, we provide the most up-to-date information on the basic molecular mechanisms focusing on the role of fat-specific protein 27/CIDEC in the pathogenesis of ALD.
Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study
Authors: Newton Julia L , Finkelmeyer Andreas , Petrides George , Frith James , Hodgson Tim , Maclachlan Laura , MacGowan Guy , Blamire Andrew M
Published: June 2016

Objectives

To explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements.

Methods

Cardiac MR (MR) examinations were performed using 3 T Philips Intera Achieva scanner (Best, NL) in participants with CFS (Fukuda; n=47) and matched case-by-case controls. Total volume (TV), red cell volume (RCV) and plasma volume (PV) measurements were performed (41 CFS and 10 controls) using the indicator dilution technique using simultaneous 51-chromium labelling of red blood cells and 125-iodine labelling of serum albumin.

Results

The CFS group length of history (mean±SD) was 14±10 years. Patients with CFS had significantly reduced end-systolic and end-diastolic volumes together with reduced end-diastolic wall masses (all p<0.0001). Mean±SD RCV was 1565±443 mL with 26/41 (63%) having values below 95% of expected. PV was 2659±529 mL with 13/41 (32%) <95% expected. There were strong positive correlations between TV, RCV and PV and cardiac end-diastolic wall mass (all p<0.0001; r2=0.5). Increasing fatigue severity correlated negatively with lower PV (p=0.04; r2=0.2). There were no relationships between any MR or volume measurements and length of history, suggesting that deconditioning was unlikely to be the cause of these abnormalities.

Conclusions

This study confirms an association between reduced cardiac volumes and blood volume in CFS. Lack of relationship between length of disease, cardiac and plasma volumes suggests findings are not secondary to deconditioning. The relationship between plasma volume and severity of fatigue symptoms suggests a potential therapeutic target in CFS.
Staged re-evaluation of non-culprit lesions in ST segment elevation myocardial infarction: a retrospective study
Authors: Thim Troels , Egholm Gro , Olesen Kevin Kris Warnakula , Kaltoft Anne , Terkelsen Christian Juhl , Krusell Lars Romer , Kristensen Steen Dalby , Bøtker Hans Erik , Christiansen Evald Høj , Maeng Michael
Published: June 2016

Objective

It remains unknown whether complete revascularisation is optimally performed in patients with ST segment elevation myocardial infarction (STEMI) during the index or at staged procedures. The aims of this study were to quantify the number of primary percutaneous coronary intervention (PCI) procedures in which non-culprit lesions needed further evaluation, to determine the consequence of the re-evaluation and to quantify adverse cardiac events during the waiting time for re-evaluation and intervention.

Methods

The study was observational and retrospective and included all patients with STEMI treated with primary PCI during 1 year at our centre.

Results

Among the 507 patients with STEMI, 374 were considered sufficiently treated with culprit lesion PCI only. Complete primary multivessel revascularisation was performed in 11 patients. Non-culprit lesion re-evaluation was planned for 122 patients (24%). Of these 122 patients, 3 patients died during their index admission. Follow-up data were not available for 3 patients. Among the 116 patients, 187 non-culprit lesions were re-evaluated and 77 patients (66.4%) underwent revascularisation with treatment of 119 lesions (63.3%). Re-evaluation was performed after a median of 30 days (25th centile: 9 days, 75th centile: 35 days). During the waiting time for re-evaluation, two patients underwent a new primary PCI due to stent thrombosis of the index culprit lesion.

Conclusions

Staged re-evaluation of non-culprit lesions observed in patients with STEMI was required in 24% of a primary PCI cohort. Intervention was performed in 66.4% of patients scheduled for re-evaluation. We observed no adverse events related to the non-culprit lesions during the waiting time for a staged re-evaluation or intervention.
Oral squamous cell carcinoma in a greater hedgehog tenrec (Setifer setosus)
Authors: Brady Sean , Harrison Tara , Rodriguez Carlos O , Johnson Amanda , Wack Raymund F
Published: June 2016

A five‐year‐old male greater hedgehog tenrec (Setifer setosus) presented with an oral mass and osteolysis of the mandible. Histopathology characterised the mass as a squamous cell carcinoma with extension into the alveolar bone. The patient was treated with intralesional bleomycin, clindamycin, meloxicam and enrofloxacin. After seven weeks of treatment, the animal's condition declined. Radiographs indicated progression of the lesions. Due to its worsening clinical condition and poor response to therapy, the animal was humanely euthanased. This is the first description of squamous cell carcinoma in a greater hedgehog tenrec and the first reported use of intralesional bleomycin in this species.
Chemical erosion of the bentonite buffer: do we observe it in nature?
Authors: Reijonen Heini M. , Marcos Nuria
Published: June 2016

It is planned to use bentonites as buffer materials in various types of geological repositories designed to host radioactive waste. For the bentonite materials, the hydrological and hydrogeochemical conditions are two of the main environmental factors affecting their evolution, assessed for a period of up to 1 Ma. Since it has been observed in laboratory tests that smectite, in particular montmorillonite, forms colloids and disperses in very dilute conditions, a scenario for chemical erosion has been discussed at length, especially in relation to geological repositories located in future glaciated terrains and locations otherwise potentially hosting dilute groundwaters. General understanding, based on laboratory experiments, is that bentonite erosion does not occur when the total charge equivalent of cations in groundwater is higher than 4 mM. However, based on current knowledge, it seems that chemical erosion is not observed in repository-relevant natural systems where groundwater conditions are below the given limit. Further investigation is therefore suggested to provide a better scientific understanding of the mechanisms involved in stabilizing smectites in these natural systems.
An improved model for through-diffusion experiments: application to strontium and tritiated water (HTO) diffusion in Boom Clay and compacted illite
Authors: Aertsens M. , Van Laer L. , Maes N. , Govaerts J.
Published: June 2016

Through-diffusion experiments are conventional experiments to measure the transport parameters of radionuclides in clays. Typically, a regular replacement of the outlet volume by a tracer-free volume is performed. In the classical approach, this type of through-diffusion experiment is modelled by assuming a zero concentration in the outlet volume. Nonetheless, this assumption is not always correct, usually because the outlet volume is insufficiently large or the time between two consecutive replacements of the outlet volume is too long. Therefore, a model was developed disregarding this assumption and, instead, considers the tracer concentration in the outlet volume to evolve, as in the experiments: the flux into the outlet volume increases the tracer concentration and, at each replacement, the tracer concentration in the outlet volume is set to zero. The model was used to reproduce the diffusion of strontium (Sr) and tritiated water (HTO) in illite and Boom Clay. Model results yielded good matches with the tracer evolution in the inlet and the outlet, and the tracer profile in the core at the end of the experiment.
On the Complexity of the Orbit Problem
Authors: Chonev Ventsislav , Ouaknine Joël , Worrell James
Published: June 2016

We consider higher-dimensional versions of Kannan and Lipton’s Orbit Problem—determining whether a target vector space ν may be reached from a starting point

x

under repeated applications of a linear transformation

A

. Answering two questions posed by Kannan and Lipton in the 1980s, we show that when ν has dimension one, this problem is solvable in polynomial time, and when ν has dimension two or three, the problem is in

NP
RP

.
A Hardware-Assisted Energy-Efficient Processing Model for Activity Recognition Using Wearables
Authors: Ghasemzadeh Hassan , Fallahzadeh Ramin , Jafari Roozbeh
Published: June 2016

Wearables are being widely utilized in health and wellness applications, primarily due to the recent advances in sensor and wireless communication, which enhance the promise of wearable systems in providing continuous and real-time monitoring and interventions. Wearables are generally composed of hardware/software components for collection, processing, and communication of physiological data. Practical implementation of wearable monitoring in real-life applications is currently limited due to notable obstacles. The wearability and form factor are dominated by the amount of energy needed for sensing, processing, and communication. In this article, we propose an ultra-low-power granular decision-making architecture, also called screening classifier, which can be viewed as a tiered wake-up circuitry, consuming three orders of magnitude-less power than the state-of-the-art low-power microcontrollers. This processing model operates based on computationally simple template matching modules, based on coarse- to fine-grained analysis of the signals with on-demand and gradually increasing the processing power consumption. Initial template matching rejects signals that are clearly not of interest from the signal processing chain, keeping the rest of processing blocks idle. If the signal is likely of interest, the sensitivity and the power of the template matching modules are gradually increased, and ultimately, the main processing unit is activated. We pose optimization techniques to efficiently split a full template into smaller bins, called mini-templates, and activate only a subset of bins during each classification decision. Our experimental results on real data show that this signal screening model reduces power consumption of the processing architecture by a factor of 70% while the sensitivity of detection remains at least 80%.
Improving Unsupervised Dependency Parsing with Knowledge from Query Logs
Authors: Qiao Xiuming , Cao Hailong , Zhao Tiejun
Published: June 2016

Unsupervised dependency parsing becomes more and more popular in recent years because it does not need expensive annotations, such as treebanks, which are required for supervised and semi-supervised dependency parsing. However, its accuracy is still far below that of supervised dependency parsers, partly due to the fact that their parsing model is insufficient to capture linguistic phenomena underlying texts. The performance for unsupervised dependency parsing can be improved by mining knowledge from the texts and by incorporating it into the model. In this article, syntactic knowledge is acquired from query logs to help estimate better probabilities in dependency models with valence. The proposed method is language independent and obtains an improvement of 4.1% unlabeled accuracy on the Penn Chinese Treebank by utilizing additional dependency relations from the Sogou query logs and Baidu query logs. Morever, experiments show that the proposed model achieves improvements of 8.07% on CoNLL 2007 English using the AOL query logs. We believe query logs are useful sources of syntactic knowledge for many natural language processing (NLP) tasks.
Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery
Authors: Shin Su Rin , Kim Won Ho , Kim Dong Joon , Shin Il-Woo , Sohn Ju-Tae
Published: June 2016

The incidence of acute kidney injury after cardiac surgery (CS-AKI) ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI.