bluuebunny/crossref_metadata_2025 huggingface dataset:
Distance-Decay Relationship for Biological Wastewater Treatment Plants
Authors: Wang Xiaohui , Wen Xianghua , Deng Ye , Xia Yu , Yang Yunfeng , Zhou Jizhong
Published: May 2016

Patterns in the spatial distribution of organisms provide important information about mechanisms underlying biodiversity and the complexity of ecosystems. One of the most well-documented spatial patterns is the distance-decay relationship, which is a universal biogeographic pattern observed repeatedly for plant and animal communities, particularly for microorganisms in natural ecosystems such as soil, ocean, and salt marsh sediment. However, it is uncertain whether the microorganisms exhibit a distance-decay pattern in engineered ecosystems. Therefore, we measured the distance-decay relationship across various microbial functional and phylogenetic groups in 26 biological wastewater treatment plants (WWTPs) in China using a functional gene array (GeoChip 4.2). We found that microbial communities of activated sludge in WWTPs exhibited a significant but very weak distance-decay relationship. The taxon-area
z
values for different functional and phylogenetic groups were <0.0065, which is about 1 to 2 orders of magnitude lower than those observed in microbial communities elsewhere. Variation-partitioning analysis (VPA) showed that the relationships were driven by both environmental heterogeneity and geographic distance. Collectively, these results provided new insights into the spatial scaling of microbial communities in engineering ecosystems and highlighted the importance of environmental heterogeneity and geographic distance in shaping biogeographic patterns.

IMPORTANCE
Determining the distance-decay relationship of microbial biodiversity is important but challenging in microbial ecology. All studies to date are based on natural environments; thus, it remains unclear whether there is such a relationship in an engineered ecosystem. The present study shows that there is a very weak distance-decay relationship in an engineered ecosystem (WWTPs) at the regional-to-continental scale. This study makes fundamental contributions to a mechanistic, predictive understanding of microbial biogeography.
Phytophthora Species in Rivers and Streams of the Southwestern United States
Authors: Stamler Rio A. , Sanogo Soumalia , Goldberg Natalie P. , Randall Jennifer J.
Published: May 2016

Phytophthora
species were isolated from rivers and streams in the southwestern United States by leaf baiting and identified by sequence analysis of internal transcribed spacer (ITS) ribosomal DNA (rDNA). The major waterways examined included the Rio Grande River, Gila River, Colorado River, and San Juan River. The most prevalent species identified in rivers and streams were
Phytophthora lacustris
and
P. riparia
, both members of
Phytophthora
ITS clade 6.
P. gonapodyides
,
P. cinnamomi
, and an uncharacterized
Phytophthora
species in clade 9 were also recovered. In addition, six isolates recovered from the Rio Grande River were shown to be hybrids of
P. lacustris
×
P. riparia
. Pathogenicity assays using
P. riparia
and
P. lacustris
failed to produce any disease symptoms on commonly grown crops in the southwestern United States. Inoculation of
Capsicum annuum
with
P. riparia
was shown to inhibit disease symptom development when subsequently challenged with
P. capsici
, a pathogenic
Phytophthora
species.

IMPORTANCE
Many
Phytophthora
species are significant plant pathogens causing disease on a large variety of crops worldwide. Closer examinations of streams, rivers, and forest soils have also identified numerous
Phytophthora
species that do not appear to be phytopathogens and likely act as early saprophytes in aquatic and saturated environments. To date, the
Phytophthora
species composition in rivers and streams of the southwestern United States has not been evaluated. This article details a study to determine the identity and prevalence of
Phytophthora
species in rivers and streams located in New Mexico, Arizona, Colorado, Utah, and Texas. Isolated species were evaluated for pathogenicity on crop plants and for their potential to act as biological control agents.
Effects of Bacterial Community Members on the Proteome of the Ammonia-Oxidizing Bacterium Nitrosomonas sp. Strain Is79
Authors: Sedlacek Christopher J. , Nielsen Susanne , Greis Kenneth D. , Haffey Wendy D. , Revsbech Niels Peter , Ticak Tomislav , Laanbroek Hendrikus J. , Bollmann Annette
Published: May 2016

Microorganisms in the environment do not exist as the often-studied pure cultures but as members of complex microbial communities. Characterizing the interactions within microbial communities is essential to understand their function in both natural and engineered environments. In this study, we investigated how the presence of a nitrite-oxidizing bacterium (NOB) and heterotrophic bacteria affect the growth and proteome of the chemolithoautotrophic ammonia-oxidizing bacterium (AOB)Nitrosomonassp. strain Is79. We investigatedNitrosomonassp. Is79 in co-culture withNitrobacter winogradskyi, in co-cultures with selected heterotrophic bacteria, and as a member of the nitrifying enrichment culture G5-7. In batch culture,N. winogradskyiand heterotrophic bacteria had positive effects on the growth ofNitrosomonassp. Is79. An isobaric tag for relative and absolute quantification (iTRAQ) liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach was used to investigate the effect ofN. winogradskyiand the co-cultured heterotrophic bacteria from G5-7 on the proteome ofNitrosomonassp. Is79. In co-culture withN. winogradskyi, severalNitrosomonassp. Is79 oxidative stress response proteins changed in abundance, with periplasmic proteins increasing and cytoplasmic proteins decreasing in abundance. In the presence of heterotrophic bacteria, the abundance of proteins directly related to the ammonia oxidation pathway increased, while the abundance of proteins related to amino acid synthesis and metabolism decreased. In summary, the proteome ofNitrosomonassp. Is79 was differentially influenced by the presence of eitherN. winogradskyior heterotrophic bacteria. Together,N. winogradskyiand heterotrophic bacteria reduced the oxidative stress forNitrosomonassp. Is79, which resulted in more efficient metabolism.

IMPORTANCEAerobic ammonia-oxidizing microorganisms play an important role in the global nitrogen cycle, converting ammonia to nitrite. In their natural environment, they coexist and interact with nitrite oxidizers, which convert nitrite to nitrate, and with heterotrophic microorganisms. The presence of nitrite oxidizers and heterotrophic bacteria has a positive influence on the growth of the ammonia oxidizers. Here, we present a study investigating the effect of nitrite oxidizers and heterotrophic bacteria on the proteome of a selected ammonia oxidizer in a defined culture to elucidate how these two groups improve the performance of the ammonia oxidizer. The results show that the presence of a nitrite oxidizer and heterotrophic bacteria reduced the stress for the ammonia oxidizer and resulted in more efficient energy generation. This study contributes to our understanding of microbe-microbe interactions, in particular between ammonia oxidizers and their neighboring microbial community.
Evidence for a Role for the Plasma Membrane in the Nanomechanical Properties of the Cell Wall as Revealed by an Atomic Force Microscopy Study of the Response of Saccharomyces cerevisiae to Ethanol Stress
Authors: Schiavone Marion , Formosa-Dague Cécile , Elsztein Carolina , Teste Marie-Ange , Martin-Yken Helene , De Morais Marcos A. , Dague Etienne , François Jean M.
Published: May 2016

A wealth of biochemical and molecular data have been reported regarding ethanol toxicity in the yeast
Saccharomyces cerevisiae
. However, direct physical data on the effects of ethanol stress on yeast cells are almost nonexistent. This lack of information can now be addressed by using atomic force microscopy (AFM) technology. In this report, we show that the stiffness of glucose-grown yeast cells challenged with 9% (vol/vol) ethanol for 5 h was dramatically reduced, as shown by a 5-fold drop of Young's modulus. Quite unexpectedly, a mutant deficient in the Msn2/Msn4 transcription factor, which is known to mediate the ethanol stress response, exhibited a low level of stiffness similar to that of ethanol-treated wild-type cells. Reciprocally, the stiffness of yeast cells overexpressing
MSN2
was about 35% higher than that of the wild type but was nevertheless reduced 3- to 4-fold upon exposure to ethanol. Based on these and other data presented herein, we postulated that the effect of ethanol on cell stiffness may not be mediated through Msn2/Msn4, even though this transcription factor appears to be a determinant in the nanomechanical properties of the cell wall. On the other hand, we found that as with ethanol, the treatment of yeast with the antifungal amphotericin B caused a significant reduction of cell wall stiffness. Since both this drug and ethanol are known to alter, albeit by different means, the fluidity and structure of the plasma membrane, these data led to the proposition that the cell membrane contributes to the biophysical properties of yeast cells.

IMPORTANCE
Ethanol is the main product of yeast fermentation but is also a toxic compound for this process. Understanding the mechanism of this toxicity is of great importance for industrial applications. While most research has focused on genomic studies of ethanol tolerance, we investigated the effects of ethanol at the biophysical level and found that ethanol causes a strong reduction of the cell wall rigidity (or stiffness). We ascribed this effect to the action of ethanol perturbing the cell membrane integrity and hence proposed that the cell membrane contributes to the cell wall nanomechanical properties.
Regulation of the Cobalt/Nickel Efflux OperondmeRFin Agrobacterium tumefaciens and a Link between the Iron-Sensing Regulator RirA and Cobalt/Nickel Resistance
Authors: Dokpikul Thanittra , Chaoprasid Paweena , Saninjuk Kritsakorn , Sirirakphaisarn Sirin , Johnrod Jaruwan , Nookabkaew Sumontha , Sukchawalit Rojana , Mongkolsuk Skorn
Published: May 2016

TheAgrobacterium tumefaciensC58 genome harbors an operon containing thedmeR(Atu0890) anddmeF(Atu0891) genes, which encode a transcriptional regulatory protein belonging to the RcnR/CsoR family and a metal efflux protein belonging to the cation diffusion facilitator (CDF) family, respectively. ThedmeRFoperon is specifically induced by cobalt and nickel, with cobalt being the more potent inducer. Promoter-lacZtranscriptional fusion, an electrophoretic mobility shift assay, and DNase I footprinting assays revealed that DmeR repressesdmeRFtranscription through direct binding to the promoter region upstream ofdmeR. A strain lackingdmeFshowed increased accumulation of intracellular cobalt and nickel and exhibited hypersensitivity to these metals; however, this strain displayed full virulence, comparable to that of the wild-type strain, when infecting aNicotiana benthamianaplant model under the tested conditions. Cobalt, but not nickel, increased the expression of many iron-responsive genes and reduced the induction of the SoxR-regulated genesodBII. Furthermore, control of iron homeostasis via RirA is important for the ability ofA. tumefaciensto cope with cobalt and nickel toxicity.

IMPORTANCEThe molecular mechanism of the regulation ofdmeRFtranscription by DmeR was demonstrated. This work provides evidence of a direct interaction of apo-DmeR with the corresponding DNA operator siteinvitro. The recognition site for apo-DmeR consists of 10-bp AT-rich inverted repeats separated by six C bases (5′-ATATAGTATACCCCCCTATAGTATAT-3′). Cobalt and nickel cause DmeR to dissociate from thedmeRFpromoter, which leads to expression of the metal efflux genedmeF. This work also revealed a connection between iron homeostasis and cobalt/nickel resistance inA. tumefaciens.
The role of financial hardship, mastery and social support in the association between employment status and depression: results from an Australian longitudinal cohort study
Authors: Crowe Laura , Butterworth Peter
Published: May 2016

Objective

There is robust epidemiological and clinical evidence of the harmful effects of unemployment on psychological well-being, but the mechanisms through which this occurs is still strongly debated. In addition, there is even less evidence on the impact of underemployment on mental health. Using longitudinal data collected from a cohort of 20–24 years old, the present study examines a range of employed states and investigates the role of mastery, financial hardship and social support in the relationship between labour status and depression.

Method

Responses were from the Personality and Total Health (PATH) Through Life Project: A representative, community-based survey conducted in Canberra and Queanbeyan (NSW) in Australia, where respondents (n=2404) in their early twenties were followed for 8 years. Depression was measured using the self-report Goldberg Depression Scale, with the likely presence of depression being indicated by scores 7 or greater.

Results

The analyses identified unemployment and underemployment as significant predictors of depression, compared to their employed counterparts. Both unemployment and underemployment remained significantly correlated with depression even after accounting for sociodemographic, economic and psychological variables. Social support, financial hardship and a sense of personal control (mastery) all emerged as important mediators between unemployment and depression.

Conclusions

Both unemployment and underemployment were associated with increased risk of depression. The strength of this relationship was attenuated but remained significant after accounting for key variables (mastery, financial hardship and social support), and extensive sociodemographic and health covariates, indicating that no or inade­quate employment contributes to poorer mental health over and above these factors.
Protocol for a pragmatic cluster randomised controlled trial for reducing irrational antibiotic prescribing among children with upper respiratory infections in rural China
Authors: Zou Guanyang , Wei Xiaolin , Hicks Joseph P , Hu Yanhong , Walley John , Zeng Jun , Elsey Helen , King Rebecca , Zhang Zhitong , Deng Simin , Huang Yuanyuan , Blacklock Claire , Yin Jia , Sun Qiang , Lin Mei
Published: May 2016

Introduction

Irrational use of antibiotics is a serious issue within China and internationally. In 2012, the Chinese Ministry of Health issued a regulation for antibiotic prescriptions limiting them to <20% of all prescriptions for outpatients, but no operational details have been issued regarding policy implementation. This study aims to test the effectiveness of a multidimensional intervention designed to reduce the use of antibiotics among children (aged 2–14 years old) with acute upper respiratory infections in rural primary care settings in China, through changing doctors' prescribing behaviours and educating parents/caregivers.

Methods and analysis

This is a pragmatic, parallel-group, controlled, cluster-randomised superiority trial, with blinded evaluation of outcomes and data analysis, and un-blinded treatment. From two counties in Guangxi Province, 12 township hospitals will be randomised to the intervention arm and 13 to the control arm. In the control arm, the management of antibiotics prescriptions will continue through usual care via clinical consultations. In the intervention arm, a provider and patient/caregiver focused intervention will be embedded within routine primary care practice. The provider intervention includes operational guidelines, systematic training, peer review of antibiotic prescribing and provision of health education to patient caregivers. We will also provide printed educational materials and educational videos to patients' caregivers. The primary outcome is the proportion of all prescriptions issued by providers for upper respiratory infections in children aged 2–14 years old, which include at least one antibiotic.

Ethics and dissemination

The trial has received ethical approval from the Ethics Committee of Guangxi Provincial Centre for Disease Control and Prevention, China. The results will be disseminated through workshops, policy briefs, peer-reviewed publications, local and international conferences.

Trial registration number

ISRCTN14340536; Pre-results.
Longitudinal trends in use of targeted therapies for treatment of malignant neoplasms of the eye: a population-based study in Taiwan
Authors: Hsu Jason C , Gonzalez-Gonzalez Luis A , Lu Vicky H , Lu Christine Y
Published: May 2016

Objectives

This study examined the recent trend in use and costs of antineoplastic agents for treatment of eye malignancies in Taiwan from 2009 to 2012. We also forecasted use and costs of targeted therapies up to and including year 2016 based on the current patterns.

Design

Retrospective observational study focusing on the usage of targeted therapies for treatment of eye malignancy.

Setting

The monthly claims data for eye malignancy-related antineoplastic agents were retrieved from Taiwan's National Health Insurance Research Database (2009–2012).

Main outcome measures

We calculated the number of prescriptions and costs for each class of medications, and analysed their time trends. In addition, using a time series design with ARIMA models, we estimated the market share by prescription volume and the proportion of costs for targeted therapies for year 2016.

Results

The market share by prescription volume of targeted therapies grew from 1.56% in 2009 to 9.98% in 2012 among all antineoplastic agents, and the proportion of costs for targeted therapies rose from 15.12% in 2009 to 58.88% in 2012. Especially, the proportion of costs for protein kinase inhibitors grew from 25.62% to 45.28% among all antineoplastic agents between 2010 and 2012. The market share by prescription volume and the proportion of costs for targeted therapies for treatment of eye malignancies were predicted to reach 27.33% and 91.39% by the fourth quarter in 2016, respectively.

Conclusions

This is the first study that examined and forecasted use and costs of targeted therapies for treatment of eye malignancies in Taiwan. Our findings indicate that, compared with other classes of drugs, targeted therapies are having a more and more relevant share among all treatment strategies for eye malignancies in Taiwan, and due to their high costs they are likely to cause great economic burden.
A cross-sectional study of the effect of health literacy on diabetes prevention and control among elderly individuals with prediabetes in rural China
Authors: Qin Lulu , Xu Huilan
Published: May 2016

Objectives

This study was designed to examine the effect of health literacy on diabetes prevention and control and risk factors for low diabetes health literacy among elderly individuals with prediabetes in rural areas in China.

Design setting and participates

A cross-sectional survey was conducted among elderly individuals in rural communities in Yiyang City in China. Multi-staged cluster random sampling was used to select 42 areas and 434 individuals with prediabetes who were interviewed using a questionnaire on diabetes health literacy in China.

Main outcome measures

Participants were asked for general information (age, gender, marital status, history of hyperglycaemia, family history of diabetes mellitus, presence of other diseases and level of education). Binary logistic regression analysis was used to identify risk factors for poor health literacy concerning diabetes prevention and control among elderly subjects with prediabetes.

Results

The median health literacy score for diabetes prevention and prediabetes control was 10.0 (IQR 7.0–13.0). The level of diabetes health literacy among men was lower than among women (OR 2.831, 95% CI 1.818 to 4.408), and lower among respondents with 1–6 years of education than among those with 6 years or more of education (OR 14.274, 95% CI 5.927 to 34.375). Those with less than 1 year of education had the lowest literacy (OR 31.148, 95% CI 11.661 to 83.204). The level of diabetes health literacy among elderly individuals with prediabetes but no history of hyperglycaemia was lower than among those with a history of hyperglycaemia (OR 2.676, 95% CI 1.101 to 6.504).

Conclusions

Health literacy concerning diabetes prevention and control among elderly individuals with prediabetes was very low in rural China. Appropriate health education for elderly individuals with low educational levels should be incorporated into diabetes prevention efforts.

Trial registration number

ChiCTR-IOR-15007033; Results.
Quality assessment of patient leaflets on misoprostol-induced labour: does written information adhere to international standards for patient involvement and informed consent?
Authors: Clausen Jette Aaroe , Juhl Mette , Rydahl Eva
Published: May 2016

Objectives

The need for thorough patient information is increasing as maternity care becomes more medicalised. The aim was to assess the quality of written patient information on labour induction. In most Danish hospitals, misoprostol is the first-choice drug for induction in low-risk pregnancies. Misoprostol has been associated with adverse side effects and severe outcomes for mother and child and is not registered for obstetric use in Denmark.

Setting

Secondary care hospitals in Denmark.

Data

Patient information leaflets from all hospitals that used misoprostol as an induction agent by June 2015 (N=13).

Design

Patient leaflets were evaluated according to a validated scoring tool (International Patient Decision Aid Standards instrument, IPDAS), core elements in the Danish Health Act, and items regarding off-label use and non-registered medication. Two of the authors scored all leaflets independently.

Outcome measures

Women's involvement in decision-making, information on benefits and harms associated with the treatment, other justifiable treatment options, and non-registered treatment.

Results

Generally, the hospitals scored low on the IPDAS checklist. No hospitals encouraged women to consider their preferences. Information on side effects and adverse outcomes was poorly covered and varied substantially between hospitals. Few hospitals informed about precautions regarding outpatient inductions, and none informed about the lack of evidence on the safety of this procedure. None informed that misoprostol is not registered for induction or explained the meaning of off-label use or use of non-registered medication. Elements such as interprofessional consensus, long-term experience, and health authorities' approval were used to add credibility to the use of misoprostol.

Conclusions

Central criteria for patient involvement and informed consent were not met, and the patient leaflets did not inform according to current evidence on misoprostol-induced labour. Our findings indicate that patients receive very different, sometimes contradictory, information with potential ethical implications. Concerns should be given to outpatient inductions, where precise written information is of particular importance.
Patterns of electronic cigarette use in current and ever users among college students in France: a cross–sectional study
Authors: Tavolacci Marie-Pierre , Vasiliu Anca , Romo Lucia , Kotbagi Gayatri , Kern Laurence , Ladner Joël
Published: May 2016

Objective

There is sparse information on electronic cigarette use and health behaviours among college student populations. Our objectives were to identify the patterns of electronic cigarette use in current and ever users among college students in France.

Design

Cross-sectional study.

Settings

A multicentre cross-sectional study was conducted on two major campuses in France. Students filled in an anonymous questionnaire on their use of electronic cigarettes and on targeted behaviours such as smoking, alcohol consumption, binge drinking, use of cannabis, practice of sport and eating disorders. Ever use of electronic cigarettes was defined as use but not during the previous 30 days, and current use of electronic cigarettes as any use in the previous 30 days. The opinions and motivations of electronic cigarette users were also sought and collected.

Participants

1134 college students between October 2014 and February 2015.

Results

The 1134 students included had a mean age of 20.8 years. The prevalence of ever use and current use of electronic cigarettes was 23.0% (95% CI (20.5% to 25.3%)) and 5.7% (95% CI (4.4% to 7.1%)), respectively. The prevalence of the combined use of conventional cigarettes and electronic cigarettes was 14.5%. Almost half (45.8%) of the ever users of electronic cigarettes had never smoked conventional cigarettes. Behaviours associated with ever use of electronic cigarettes were current cigarette smoking (adjusted OR (AOR)=3.97, 95% CI 2.71 to 5.83), former smoking (AOR=2.56, 95% CI 1.42 to 4.61), cannabis use (AOR=2.44, 95% CI 1.70 to 3.51) and occasional binge drinking (AOR=1.83, 95% CI 1.28 to 2.64). The only behaviour associated with current use of electronic cigarettes was conventional smoking, either previously (AOR=4.85, 95% CI 1.53 to 15.34) or currently (AOR=14.53, 95% CI 6.81 to 31.02).

Conclusions

The ever users have an experimenter's profile with sensation-seeking while the current users are mostly smokers with intention to quit smoking. Our findings are crucial for the accurate targeting of student populations at risk and to implement appropriate awareness campaigns and health education programmes.
Social and behavioural factors associated with frailty trajectories in a population-based cohort of older adults
Authors: Chamberlain Alanna M , St. Sauver Jennifer L , Jacobson Debra J , Manemann Sheila M , Fan Chun , Roger Véronique L , Yawn Barbara P , Finney Rutten Lila J
Published: May 2016

Objective

The goal of this study was to identify distinct frailty trajectories (clusters of individuals following a similar progression of frailty over time) in an ageing population and to determine social and behavioural factors associated with frailty trajectories.

Design

Population-based cohort study.

Setting

Olmsted County, Minnesota.

Participants

Olmsted County, Minnesota residents aged 60–89 in 2005.

Primary outcome measure

Changes in frailty over an 8-year period from 2005 to 2012, measured by constructing a yearly frailty index. Frailty trajectories by decade of age were determined using k-means cluster modelling for longitudinal data.

Results

After adjustment for age and sex, all social and behavioural factors (education, marital status, living arrangements, smoking status and alcohol use) were significantly associated with frailty trajectories in those aged 60–69 and 70–79 years. After further adjustment for baseline frailty, the likelihood of being in the high frailty trajectory was greatest among those reporting concerns from relatives/friends about alcohol consumption (OR (95% CI) 2.26 (1.19 to 4.29)) and those with less than a high school education (OR (95% CI) 1.98 (1.32 to 2.96)) in the 60–69 year olds. In the 70–79 year olds, the largest associations were observed among those with concerns from oneself about alcohol consumption (OR (95% CI) 1.92 (1.23 to 3.00)), those with less than a high school education (OR (95% CI) 1.57 (1.12 to 2.22)), and those living with family (vs spouse; OR (95% CI) 1.76 (1.05 to 2.94)). No factors remained associated with frailty trajectories in the 80–89 year olds after adjustment for baseline frailty.

Conclusions

Social and behavioural factors are associated with frailty, with stronger associations observed in younger ages. Recognition of social and behavioural factors associated with increasing frailty may inform interventions for individuals at risk of worsening frailty, specifically when targeted at younger individuals.
Barriers and enablers in primary care clinicians' management of osteoarthritis: protocol for a systematic review and qualitative evidence synthesis
Authors: Egerton T , Diamond L , Buchbinder R , Bennell K , Slade S C
Published: May 2016

Introduction

Osteoarthritis is a highly prevalent and disabling condition. Primary care management of osteoarthritis is generally suboptimal despite evidence for several modestly effective interventions and the availability of high-quality clinical practice guidelines. This report describes a planned study to synthesise the views of primary care clinicians on the barriers and enablers to following recommended management of osteoarthritis, with the aim of providing new interpretations that may facilitate the uptake of recommended treatments, and in turn improve patient care.

Methods and analysis

A systematic review and meta-synthesis of qualitative studies. 5 databases will be searched using key search terms for qualitative research, evidence-based practice, clinical practice guidelines, osteoarthritis, beliefs, perceptions, barriers, enablers and adherence. A priori inclusion/exclusion criteria include availability of data from primary care clinicians, reports on views regarding management of osteoarthritis, and studies using qualitative methods for both data collection and analysis. At least 2 independent reviewers will identify eligible reports, conduct a critical appraisal of study conduct, extract data and synthesise reported findings and interpretations. Synthesis will follow thematic analysis within a grounded theory framework of inductive coding and iterative theme identification. The reviewers plus co-authors will contribute to the meta-synthesis to find new themes and theories. The Confidence in the Evidence from Reviews of Qualitative research (CERQual) approach will be used to determine a confidence profile of each finding from the meta-synthesis. The protocol has been registered on PROSPERO and is reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) guidelines.

Ethics and dissemination

Ethical approval is not required. The systematic review will be published in a peer-reviewed journal. The results will help to inform policy and practice and assist in the optimisation of management for people with osteoarthritis.

PROSPERO registration number

CRD42015027543.
Non-specific mechanisms in orthodox and CAM management of low back pain (MOCAM): theoretical framework and protocol for a prospective cohort study
Authors: Bradbury Katherine , Al-Abbadey Miznah , Carnes Dawn , Dimitrov Borislav D , Eardley Susan , Fawkes Carol , Foster Jo , Greville-Harris Maddy , Harvey J Matthew , Leach Janine , Lewith George , MacPherson Hugh , Roberts Lisa , Parry Laura , Yardley Lucy , Bishop Felicity L
Published: May 2016

Introduction

Components other than the active ingredients of treatment can have substantial effects on pain and disability. Such ‘non-specific’ components include: the therapeutic relationship, the healthcare environment, incidental treatment characteristics, patients’ beliefs and practitioners’ beliefs. This study aims to: identify the most powerful non-specific treatment components for low back pain (LBP), compare their effects on patient outcomes across orthodox (physiotherapy) and complementary (osteopathy, acupuncture) therapies, test which theoretically derived mechanistic pathways explain the effects of non-specific components and identify similarities and differences between the therapies on patient–practitioner interactions.

Methods and analysis

This research comprises a prospective questionnaire-based cohort study with a nested mixed-methods study. A minimum of 144 practitioners will be recruited from public and private sector settings (48 physiotherapists, 48 osteopaths and 48 acupuncturists). Practitioners are asked to recruit 10–30 patients each, by handing out invitation packs to adult patients presenting with a new episode of LBP. The planned multilevel analysis requires a final sample size of 690 patients to detect correlations between predictors, hypothesised mediators and the primary outcome (self-reported back-related disability on the Roland-Morris Disability Questionnaire). Practitioners and patients complete questionnaires measuring non-specific treatment components, mediators and outcomes at: baseline (time 1: after the first consultation for a new episode of LBP), during treatment (time 2: 2 weeks post-baseline) and short-term outcome (time 3: 3 months post-baseline). A randomly selected subsample of participants in the questionnaire study will be invited to take part in a nested mixed-methods study of patient–practitioner interactions. In the nested study, 63 consultations (21/therapy) will be audio-recorded and analysed quantitatively and qualitatively, to identify communication practices associated with patient outcomes.

Ethics and dissemination

The protocol is approved by the host institution's ethics committee and the NHS Health Research Authority Research Ethics Committee. Results will be disseminated via peer-reviewed journal articles, conferences and a stakeholder workshop.
The most physically active Danish adolescents are at increased risk for developing spinal pain: a two-year prospective cohort study
Authors: Aartun Ellen , Boyle Eleanor , Hartvigsen Jan , Ferreira Paulo H , Maher Christopher G , Ferreira Manuela L , Hestbaek Lise
Published: May 2016

Background

The overall aim of this study was to determine to what extent objectively measured physical activity in a school-based sample aged 11–13 years predicted incident cases of spinal pain (neck pain, mid back pain or low back pain) over the following 2 years.

Methods

Data were collected at baseline (2010) and 2 years later in a school-based prospective cohort study. Spinal pain was assessed via an e-survey that the participants completed during school time. Participants who, at baseline, reported never having had spinal pain were included in the study. An incident case of spinal pain was defined as a report of pain in at least one spinal area at follow-up. Physical activity was measured objectively using the Actigraph GT3X Triaxial Activity Monitor for 1 week.

Results

Objectively measured sedentary activity, moderate-to-vigorous physical activity and vigorous physical activity were generally not predictive of the 2-year incidence of spinal pain. However, 10% of participants with the highest proportion of the day spent in vigorous physical activity were at increased risk of reporting spinal pain at follow-up with a relative risk (RR) of 1.44 (95% CI 1.09 to 1.91). For the overall physical activity, the RR was 1.03 (95% CI 1.01 to 1.05) for reporting spinal pain at follow-up.

Conclusions

In general, physical activity did not affect the risk of spinal pain during follow-up, but the 10% most active adolescents were at increased risk of developing spinal pain. Thus, vigorous physical activity appears to be a risk factor for spinal pain in adolescents.
Cyclic vomiting syndrome: a case series and review of the literature
Authors: Shearer Jessica , Luthra Pavit , Ford Alexander C
Published: May 2016

Objective

Cyclic vomiting syndrome (CVS) is under-recognised. Treatment is difficult as the pathophysiology is incompletely understood. We report our experience of treating patients with amitriptyline, and review the literature to summarise symptoms and associated features, epidemiology, potential pathophysiological mechanisms, differential diagnoses and treatment.

Design

Consecutive adult patients with CVS were identified during a 5-year period from January 2010 until December 2015. Medical records were reviewed retrospectively, and age and sex of the patient, symptoms, associated features and response to treatment with amitriptyline were recorded.

Setting

A luminal gastroenterology clinic at a teaching hospital.

Results

Seventeen patients were identified (mean age 29.8 years, 13 (76.5%) female). Five had a history of cannabis use. Duration of symptoms prior to diagnosis ranged from 5 months to 15 years. Fourteen patients commenced amitriptyline, and in eight (57.1%) symptoms either ceased entirely or improved. Review of the literature suggested the prevalence of CVS was 0.5%. Symptoms are stereotypical, with acute episodes of nausea and vomiting, interspersed by periods when the patient is symptom-free. Proposed pathophysiologies include neuroendocrine dysfunction, mutations in mitochondrial DNA and re-intoxication effects from cannabis stored in fat tissues. Treatment during the acute phase is supportive, with rehydration, sedation and antiemetics. Prophylaxis to prevent future attacks with antihistamines, antimigraine drugs, antiepileptics and tricyclic antidepressants may be beneficial. Complete cessation of cannabis smoking should be advised.

Conclusions

Diagnosis of CVS is often delayed in adults. Once identified, patients respond well to amitriptyline.
The effect of long-term −80°C storage of thyroid biospecimens on RNA quality and ensuring fitness for purpose
Authors: Mathieson William , Betsou Fay , Myshunina Tamara , Pushkarev Viktor , Pushkarev Vladimir , Shinkarkina Anna , Voskoboynyk Laryssa , Thomas Gerry A
Published: May 2016

Aims

To establish whether RNA degrades in long-term storage at −80°C and whether RNA integrity numbers (RINs) determine ‘fitness for purpose’ in severely degraded RNA.

Methods

RNA was extracted from 549 thyroid biospecimens stored at −80°C for 0.1–10.9 years then their RINs correlated with storage time. RT-PCR for 65, 265, 534 and 942 base pair amplicons ofhydroxymethylbilane synthasewas used to measure amplicon length in RNA from cryopreserved and FFPE biospecimens that were equally degraded according to RIN.

Results

Storage time did not correlate with RIN. Longer amplicons were obtained from cryopreserved samples than FFPE samples with equal RINs.

Conclusions

RNA does not degrade in thyroid biospecimens stored for long periods of time at −80°C. Although RINs are known to predict amenability to analytical platforms in good quality samples, this prediction is unreliable in severely degraded samples.
Expression of proliferation genes in formalin-fixed paraffin-embedded (FFPE) tissue from breast carcinomas. Feasibility and relevance for a routine histopathology laboratory
Authors: Thomas Carla , Robinson Cleo , Dessauvagie Ben , Wood Benjamin , Sterrett Greg , Harvey Jennet , Amanuel Benhur
Published: May 2016

Aim

Breast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.

Methods

Expression of five proliferation gene mRNAs;Ki-67, STK 15, CCNB1, CCND1andMYBL2,was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score.

Results

Expression ofKi-67, STK15andMYBL2mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), butCCND1andCCNB1showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007).

Conclusions

This study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.
Gene of the month:BAP1
Authors: Wang Ami , Papneja Anjali , Hyrcza Martin , Al-Habeeb Ayman , Ghazarian Danny
Published: May 2016

TheBAP1gene (BRCA1-associated protein 1) is a tumour suppressor gene that encodes a deubiquitinating enzyme (DUB), regulating key cellular pathways, including cell cycle, cellular differentiation, transcription and DNA damage response. GermlineBAP1mutations cause a novel cancer syndrome characterised by early onset of multiple atypical Spitz tumours and increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma and various other malignancies. Recognising the clinicopathological features of specific BAP1-deficient tumours is crucial for early screening/tumour detection, with significant impact on patient outcome.
Association of Serum Pentraxin 3 Concentrations with Diabetic Nephropathy
Authors: Wang Rui , Zhang Jietao , Hu Wenchao
Published: May 2016

Pentraxin 3 (PTX3), a member of a superfamily of conserved proteins, attenuates renal damage in diabetic mice. This study aims to determine whether serum PTX3 concentrations are correlated with the presence of diabetic nephropathy (DN). A total of 160 patients with type 2 diabetes mellitus (T2DM) and 54 healthy subjects were enrolled in this study. Patients with T2DM were divided into three groups in accordance with the levels of urinary albumin excretion (UAE). Serum PTX3 concentrations were determined using an ELISA kit. Serum PTX3 concentrations were significantly higher in patients with T2DM compared with the controls. Patients with T2DM with macroalbuminuria showed higher serum PTX3 concentrations compared with the other three groups. However, there were no significant differences of serum PTX3 concentrations between patients with T2DM with normoalbuminuria and microalbuminuria. Furthermore, a simple regression analysis has shown that serum PTX3 concentrations in patients with T2DM were negatively correlated with body mass index, and positively correlated with blood urea nitrogen, serum creatinine, and UAE. Serum PTX3 concentrations are correlated with DN.
The Internship Preparation Camp at the University of Maryland
Authors: Bontempo Laura J , Frayha Neda , Dittmar Philip C
Published: May 2016

Background

Specialty-specific ‘boot camps’ boost the competence and confidence of medical school graduates as they prepare to enter a residency programme.

Objective

We sought to evaluate the efficacy of a specialty-neutral Internship Preparation Camp (IPC) that we developed and made available to senior medical students at our medical school. The primary goal of the IPC is to educate students in the cognitive and procedural skills that are applicable to postgraduate year 1 trainees in all fields of specialisation.

Methods

The curriculum was developed through input from senior medical students and faculty from multiple specialties. The course used small-group sessions and skills labs led by distinguished speakers from various professions (medicine, nursing and pharmacy) to teach senior medical students the information and skills common to the needs of all new physicians, regardless of the specialty they have chosen. The course was presented across 3 half-days and was offered just prior to graduation.

Results

Of 166 possible participants, 65 attended the course; 39 (60%) of them completed evaluations immediately following the course and 29 (45%) of participants completed a follow-up evaluation 3 months later. All respondents reported increased confidence in caring for patients in all subject areas taught. In the follow-up survey, 82% of respondents reported using information learned during the course on an hourly, daily or weekly basis in their care of patients.

Conclusions

A specialty-neutral IPC is of benefit to its attendees, regardless of the medical specialty in which they train.
Patient-centred mountain medicine
Authors: Szawarski Piotr , Hillebrandt David
Published: May 2016

Venturing into the mountains, doctors have accompanied expeditions to provide routine care to the teams, undertake research and occasionally take on a rescue role. The role of doctors practicing mountain medicine is evolving. Public health issues involving concepts of health and safety have become necessary with the coming of commercial and youth expeditions. Increasingly individuals with a disability or a medical diagnosis choose to ascend to high altitudes. Doctors become involved in assessment of risk and providing advice for such individuals. The field of mountain medicine is perhaps unique in that acceptance of risk is part of the ethos of climbing and adventure. The pursuit of mountaineering goals may represent the ultimate conquest of a disability. Knowledge of mountain environment is essential in facilitating mountain ascents for those who choose to undertake them, in spite of a disability or medical condition.
Buried pipelines with bends: analytical verification against permanent ground displacements
Authors: Karamitros Dimitris K. , Zoupantis Christos , Bouckovalas George D.
Published: May 2016

Available analytical methodologies for the stress analysis of buried pipelines against large permanent ground displacements (PGDs) apply only to straight pipeline segments. Hence, a new methodology is proposed herein for the analytical computation of pipeline strains in bends of arbitrary angle and radius of curvature, located outside the PGD high-curvature zone, but within the pipeline’s unanchored length. The methodology is based on the equivalent-linear analysis of the bend, assuming that it will perform as an elastic arched beam subjected to uniformly distributed ultimate axial and transverse horizontal soil reactions. The end of the bend towards the PGD zone is subjected to an axial displacement, calculated on the basis of overall displacement compatibility along the pipeline, while the other end is restrained by the unanchored pipeline segment beyond the bend. Using this approach, the maximum axial force at the vicinity of the PGD zone can also be calculated and consequently used for the estimation of corresponding pipeline strains with any of the available numerical or analytical methodologies for straight pipeline segments. Parametric nonlinear finite element analyses are performed to verify the analytical methodology and also derive conclusions of practical interest regarding the effect of bends on pipeline design.
Brief history of geological and mining exploration in nineteenth century Mexico
Authors: Morelos-Rodríguez Lucero
Published: May 2016

In the nineteenth century, both Mexican and foreign scientific travellers, explorers, naturalists, engineers, mining entrepreneurs and enthusiasts made several scientific trips and expeditions across the whole of Mexico to prospect for its natural and mineral wealth. As they did so, they wrote records and articles and drew maps. This article discusses the state-organized geological and mining commissions and writings that promoted extraction activities in the country, offering an overview of the developments in geological and mining exploration through the scientific literature published by earth science pioneers in Mexico.
Intracrine angiotensin II functions originate from noncanonical pathways in the human heart
Authors: Ferrario Carlos M. , Ahmad Sarfaraz , Varagic Jasmina , Cheng Che Ping , Groban Leanne , Wang Hao , Collawn James F. , Dell′Italia Louis J.
Published: May 2016

Although it is well-known that excess renin angiotensin system (RAS) activity contributes to the pathophysiology of cardiac and vascular disease, tissue-based expression of RAS genes has given rise to the possibility that intracellularly produced angiotensin II (Ang II) may be a critical contributor to disease processes. An extended form of angiotensin I (Ang I), the dodecapeptide angiotensin-(1–12) [Ang-(1–12)], that generates Ang II directly from chymase, particularly in the human heart, reinforces the possibility that an alternative noncanonical renin independent pathway for Ang II formation may be important in explaining the mechanisms by which the hormone contributes to adverse cardiac and vascular remodeling. This review summarizes the work that has been done in evaluating the functional significance of Ang-(1–12) and how this substrate generated from angiotensinogen by a yet to be identified enzyme enhances knowledge about Ang II pathological actions.