bluuebunny/crossref_metadata_2025 huggingface dataset:
Accessory Gene Regulator-1 Locus Is Essential for Virulence and Pathogenesis of Clostridium difficile
Authors: Darkoh Charles , Odo Chioma , DuPont Herbert L.
Published: August 2016

Clostridium difficile
infection (CDI) is responsible for most of the definable cases of antibiotic- and hospital-associated diarrhea worldwide and is a frequent cause of morbidity and mortality in older patients.
C. difficile
, a multidrug-resistant anaerobic pathogen, causes disease by producing toxins A and B, which are controlled by an accessory gene regulator (Agr) quorum signaling system. Some
C. difficile
strains encode two Agr loci in their genomes, designated
agr1
and
agr2
. The
agr1
locus is present in all of the
C. difficile
strains sequenced to date, whereas the
agr2
locus is present in a few strains. The functional roles of
agr1
and
agr2
in
C. difficile
toxin regulation and pathogenesis were unknown until now. Using allelic exchange, we deleted components of both
agr
loci and examined the mutants for toxin production and virulence. The results showed that the
agr1
mutant cannot produce toxins A and B; toxin production can be restored by complementation with wild-type
agr1
. Furthermore, the
agr1
mutant is able to colonize but unable to cause disease in a murine CDI model. These findings have profound implications for CDI treatment because we have uncovered a promising therapeutic target for the development of nonantibiotic drugs to treat this life-threatening emerging pathogen by targeting the toxins directly responsible for disease.

IMPORTANCE
Within the last decade, the number of cases of
C. difficile
infections has been increasing exponentially in the United States, resulting in about 4.8 billion U.S. dollars in health care costs annually. As a multidrug-resistant, spore-forming, anaerobic pathogen,
C. difficile
overpopulates the colon after the gut microbiota has been altered by antibiotic therapy. With increasing resistance to antibiotic treatment of
C. difficile
infections, patients are experiencing higher costs of health care and a lower quality of life as treatment options decrease. During infection,
C. difficile
produces toxins A and B, which directly cause disease. As a result, the toxins have become promising nonantibiotic treatment targets. Here, we have identified a pathway responsible for activating the production of the toxins. This important finding opens up a unique therapeutic target for the development of a novel nonantibiotic therapy for
C. difficile
infections.
Outer Membrane Vesicle Biosynthesis in
Salmonella
: Is There More to Gram-Negative Bacteria?
Authors: Reidl Joachim
Published: August 2016

Recent research has focused on the biological role of outer membrane vesicles (OMVs), which are derived from the outer membranes (OMs) of Gram-negative bacteria, and their potential exploitation as therapeutics. OMVs have been characterized in many ways and functions. Until recently, research focused on hypothetical and empirical models that addressed the molecular mechanisms of OMV biogenesis, such as vesicles bulging from the OM in various ways. The recently reported study by Elhenawy et al. (mBio 7:e00940-16, 2016,
http://dx.doi.org/10.1128/mBio.00940-16
) provided further insights into OMV biogenesis of
Salmonella enterica
serovar Typhimurium. That study showed that deacylation of lipopolysaccharides (LPS) influences the level of OMV production and, furthermore, determines a sorting of high versus low acylated LPS in OMs and OMVs, respectively. Interestingly, deacylation may inversely correlate with other LPS modifications, suggesting some synergy toward optimized host resistance via best OM compositions for
S
. Typhimurium.
Challenging neck mass: non-functional giant parathyroid adenoma
Authors: Mossinelli Chiara , Saibene Alberto Maria , De Pasquale Loredana , Maccari Alberto
Published: August 2016

A 46-year-old man was referred to our ear, nose and throat department after the accidental discovery of a large retrotracheal mass. In order to obtain the diagnosis and to plan treatment he underwent a full battery of tests (CT, MRI, blood tests, hormonal assays, ultrasounds, thyroid scintigraphy, urine tests and fine-needle aspiration of the mass), but none of these was able to define the true nature of such cervical mass. Only after surgical excision and histological evaluation, it was diagnosed as an exceptional case of giant non-functional parathyroid adenoma.
Cardiovascular diseases in Paralympic athletes
Authors: Pelliccia Antonio , Quattrini Filippo M , Squeo Maria Rosaria , Caselli Stefano , Culasso Franco , Link Mark S , Spataro Antonio , Bernardi Marco
Published: August 2016

Background

Sport participation (SP) of individuals with impairments has recently grown exponentially. Scarce scientific data, however, exist regarding cardiovascular (CV) risk associated with competitive SP.

Objective

Assessing the prevalence of CV abnormalities and the risk for SP in Paralympic athletes (PA).

Methods

PA (n=267; 76% men), aged 35±9 years, engaged in 18 sport disciplines, with a spectrum of lesions including: spinal cord injury (paraplegia and spina bifida) (n=116); amputation, poliomyelitis, cerebral palsy and other neuromuscular and/or skeletal disorders (Les autres) or visual impairment (n=151) entered the study. CV evaluation included history, PE, 12-lead and exercise ECG, echocardiography. Of these, 105 participated in ≥2 consecutive games, and had evaluations available over a 6±4 year follow-up.

Results

Structural CV abnormalities were identified in 33 athletes (12%), including arrhythmogenic cardiomyopathies in 3, aortic root dilation in 3, valvular diseases in 7 (mitral valve prolapse in 4, bicuspid aortic valve in 3) and systemic hypertension in 11 (4%). In addition, ventricular (polymorphic, couplets or non-sustained ventricular tachycardia) or supraventricular tachyarrhythmias (atrial flutter, paroxysmal atrial fibrillation or SVT) were identified in 9 others. Over a 6-year follow-up, 6 of the 105 athletes (6%) developed CV diseases, including dilated cardiomyopathy in 1 and systemic hypertension in 5.

Conclusions

PA present an unexpected high prevalence of CV abnormalities (12%), including a non-trivial proportion of diseases at risk for sudden death (2%), such as arrhythmogenic cardiomyopathies and dilated aortic root. This observation suggests that tailored recommendations for preparticipation screening and safe SP in this special athletic population are timely and appropriate.
Can standardised clinical examination of athletes with acute groin injuries predict the presence and location of MRI findings?
Authors: Serner Andreas , Weir Adam , Tol Johannes L , Thorborg Kristian , Roemer Frank , Guermazi Ali , Hölmich Per
Published: August 2016

Background

Little is known about the value of clinical examination in relation to diagnostic imaging for acute groin injuries in athletes. Primary aim: to investigate whether clinical examination tests predict a positive or negative MRI result (MRI±). Secondary aim: to assess accuracy of clinical tests to localise injury in MRI+ cases.

Methods

We consecutively included 81 male athletes with acute groin injuries. Standardised clinical examination (palpation, resistance and stretch tests) and MRI were performed within 7 days of injury. Diagnostic statistics including positive and negative predictive values (PPV/NPV) were calculated.

Results

85 acute injuries were found on MRI in 64 (79%) athletes with 17 (21%) athletes having MRI− injuries. Palpation had the highest NPV (91–96%, (95% CI 69% to 99%)). 3 specific adductor examination tests (resisted outer range adduction, squeeze test with hip neutral and long lever, and passive adductor stretch) showed 80–81% (95% CI 63% to 91%) probability of an MRI+ adductor lesion when positive, all with high accuracy of a correct MRI location (PPV 93–97% (95% CI 76% to 100%)). Hip flexor tests showed poor ability to predict MRI+ lesions (PPV 34–63% (95% CI 20% to 84%)) and low accuracy (PPV 17–71% (95% CI 7% to 85%)).

Conclusions

21% of athletes had negative imaging and the absence of palpation pain was best at predicting an MRI− result. Specific adductor examination tests accurately predicted MRI+ adductor injuries. Hip flexor clinical tests were poor at predicating and localising MRI+ injuries in the hip flexors. Clinical examination appears sufficient to diagnose acute adductor injuries, whereas MRI could assist in accurately locating acute hip flexor injuries.
Association of socioeconomic status with psychiatric problems and violent behaviours in a nationally representative sample of Iranian children and adolescents: the CASPIAN-IV study
Authors: Heshmat Ramin , Qorbani Mostafa , Ghoreshi Behnaz , Djalalinia Shirin , Tabatabaie Omid Reza , Safiri Saeid , Noroozi Mehdi , Motlagh Mohammad-Esmaeil , Ahadi Zeinab , Asayesh Hamid , Kelishadi Roya
Published: August 2016

Objectives

The aim of the present study was to evaluate the association between socioeconomic status (SES) and psychiatric problems and violent behaviours in a nationally representative sample of Iranian children and adolescents, based on nationwide surveillance programme data, 2011–2012.

Methods

Overall, 14 880 students, aged 6–18 years, were selected using a multistage cluster sampling method from rural and urban areas of 30 provinces in Iran. SES was estimated based on a main summarised component, extracted from principle component analysis of family assets and parents' jobs and education. For statistical analysis, SES was classified as ‘low’, ‘middle’ and ‘high’. The WHO-Global School Based Student Health Survey (WHO-GSHS) questionnaire was used to assess psychiatric problems and violent behaviours.

Results

In total, 13 486 students (participation rate 90.6%) completed the study: 50.8% were boys and 75.6% were urban residents, with a mean age of 12.47±3.36 years. In the multivariate model, the ORs of depression, anxiety, feeling worthless, anger, insomnia, confusion and physical fights were lower in students with high SES compared with those with low SES (p<0.05) but physical fights was lower in the high SES group than in the low SES group (p<0.05). No significant relationship was documented between SES and other variables, including getting worried, history of bullying and being victimised.

Conclusions

Children and adolescents with low SES were at higher risk for psychiatric problems and violent behaviours. Mental health policies and public interventional strategies should be considered at the public level, notably for low SES families.
Systematic review of approaches to using patient experience data for quality improvement in healthcare settings
Authors: Gleeson Helen , Calderon Ana , Swami Viren , Deighton Jessica , Wolpert Miranda , Edbrooke-Childs Julian
Published: August 2016

Objectives

Explore how patient-reported experience measures (PREMs) are collected, communicated and used to inform quality improvement (QI) across healthcare settings.

Design

Systematic review.

Setting

Various primary and secondary care settings, including general practice, and acute and chronic care hospitals.

Participants

A full range of patient populations from (children through to the elderly) and staff (from healthcare practitioners to senior managers).

Methods

Scientific databases were searched (CINAHL, PsycINFO, MEDLINE and Cochrane Libraries) as was grey literature. Qualitative and quantitative studies describing collection of PREM data and subsequent QI actions in any healthcare setting were included. Risk of bias was assessed using established criteria. Of 5312 initial hits, 32 full texts were screened, and 11 were included.

Results

Patient experience data were most commonly collected through surveys and used to identify small areas of incremental change to services that do not require a change to clinician behaviour (eg, changes to admission processes and producing educational materials). While staff in most studies reported having made effective improvements, authors struggled to identify what those changes were or the impact they had.

Conclusions

Findings suggest there is no single best way to collect or use PREM data for QI, but they do suggest some key points to consider when planning such an approach. For instance, formal training is recommended, as a lack of expertise in QI and confidence in interpreting patient experience data effectively may continue to be a barrier to a successful shift towards a more patient-centred healthcare service. In the context of QI, more attention is required on how patient experience data will be used to inform changes to practice and, in turn, measure any impact these changes may have on patient experience.
Intimate partner violence experienced by HIV-infected pregnant women in South Africa: a cross-sectional study
Authors: Bernstein Molly , Phillips Tamsin , Zerbe Allison , McIntyre James A , Brittain Kirsty , Petro Greg , Abrams Elaine J , Myer Landon
Published: August 2016

Objectives

Intimate partner violence (IPV) during pregnancy may be common in settings where HIV is prevalent but there are few data on IPV in populations of HIV-infected pregnant women in Southern Africa. We examined the prevalence and correlates of IPV among HIV-infected pregnant women.

Setting

A primary care antenatal clinic in Cape Town, South Africa.

Participants

623 consecutive HIV-infected pregnant women initiating lifelong antiretroviral therapy.

Measures

IPV, depression, substance use and psychological distress were assessed using the 13-item WHO Violence Against Women questionnaire, the Edinburgh Postnatal Depression Scale (EPDS), Alcohol and Drug Use Disorders Identification Tests (AUDIT/DUDIT) and the Kessler 10 (K-10) scale, respectively.

Results

The median age in the sample was 28 years, 97% of women reported being in a relationship, and 70% of women reported not discussing and/or agreeing on pregnancy intentions before conception. 21% of women (n=132) reported experiencing ≥1 act of IPV in the past 12 months, including emotional (15%), physical (15%) and sexual violence (2%). Of those reporting any IPV (n=132), 48% reported experiencing 2 or more types. Emotional and physical violence was most prevalent among women aged 18–24 years, while sexual violence was most commonly reported among women aged 25–29 years. Reported IPV was less likely among married women, and women who experienced IPV were more likely to score above threshold for substance use, depression and psychological distress. In addition, women who reported not discussing and/or not agreeing on pregnancy intentions with their partner prior to conception were significantly more likely to experience violence.

Conclusions

HIV-infected pregnant women in the study reported experiencing multiple forms of IPV. While the impact of IPV on maternal and child health outcomes in the context of HIV infection requires further research attention, IPV screening and support services should be considered within the package of routine care for HIV-infected pregnant women.

Trial registration number

NCT01933477.
Prevalence and determinants of depressive and anxiety symptoms in adults with type 2 diabetes in China: a cross-sectional study
Authors: Sun Nianquan , Lou Peian , Shang Yan , Zhang Pan , Wang Jian , Chang Guiqiu , Shi Chunlei
Published: August 2016

Objectives

To evaluate the prevalence and determinants of anxiety and depression and to assess their impact on glycaemic control in participants with type 2 diabetes mellitus.

Design

A cross-sectional study.

Setting

Community-based investigation in Xuzhou, China.

Participants

893 Chinese men and women aged 18–84 years who fulfilled the inclusion criteria.

Methods

People with type 2 diabetes completed the Pittsburgh Sleep Quality Index and the Zung Self-Rating Anxiety and Depression Scales. Demographic and physiological characteristics were recorded. Multiple logistic regression was used to evaluate the combined effect of factors associated with anxiety and depression and to assess the effects of anxiety and depression on glycaemic control.

Results

The prevalence of depressive symptoms and anxiety symptoms was 56.1% and 43.6%, respectively. Multivariate logistic regression analysis indicated that anxiety symptoms were associated with being woman, low income, chronic disease, depressive symptoms and poor sleep quality. Depressive symptoms were associated with being woman, older age, low education level, being single, diabetes complications, anxiety symptoms and poor sleep quality. Glycaemic control was not related to anxiety symptoms (OR=1.31, 95% CIs 0.94 to 1.67) or depressive symptoms (OR=1.23, 95% CI 0.85 to 1.63). A combination of depressive symptoms and anxiety symptoms was associated with poor glycaemic control (relative excess risk due to interaction: 4.93, 95% CI 2.09 to 7.87; attributable proportion due to interaction: 0.27, 95% CI 0.12 to 0.45).

Conclusions

There was a high prevalence of depressive and anxiety symptoms in this Chinese sample of participants, although depression and anxiety were not singly associated with glycaemic control. However, a combination of depressive and anxiety symptoms was negatively correlated with glycaemic control in participants with type 2 diabetes.
Neighbourhoods for Active Kids: study protocol for a cross-sectional examination of neighbourhood features and children's physical activity, active travel, independent mobility and body size
Authors: Oliver Melody , McPhee Julia , Carroll Penelope , Ikeda Erika , Mavoa Suzanne , Mackay Lisa , Kearns Robin A , Kyttä Marketta , Asiasiga Lanuola , Garrett Nicholas , Lin Judy , Mackett Roger , Zinn Caryn , Moewaka Barnes Helen , Egli Victoria , Prendergast Kate , Witten Karen
Published: August 2016

Introduction

New Zealand children's physical activity, including independent mobility and active travel, has declined markedly over recent decades. The Neighbourhoods for Active Kids (NfAK) study examines how neighbourhood built environments are associated with the independent mobility, active travel, physical activity and neighbourhood experiences of children aged 9–12 years in primary and intermediate schools across Auckland, New Zealand's largest city.

Methods and analysis

Child-specific indices of walkability, destination accessibility and traffic exposure will be constructed to measure the built environment in 8 neighbourhoods in Auckland. Interactive online-mapping software will be used to measure children's independent mobility and transport mode to destinations and to derive measures of neighbourhood use and perceptions. Physical activity will be measured using 7-day accelerometry. Height, weight and waist circumference will be objectively measured. Parent telephone interviews will collect sociodemographic information and parent neighbourhood perceptions. Interviews with school representative will capture supports and barriers for healthy activity and nutrition behaviours at the school level. Multilevel modelling approaches will be used to understand how differing built environment variables are associated with activity, neighbourhood experiences and health outcomes.

Discussion

We anticipate that children who reside in neighbourhoods considered highly walkable will be more physically active, accumulate more independent mobility and active travel, and be more likely to have a healthy body size. This research is timely as cities throughout New Zealand develop and implement plans to improve the liveability of intensifying urban neighbourhoods. Results will be disseminated to participants, local government agencies and through conventional academic avenues.
The global burden of diagnostic errors in primary care
Authors: Singh Hardeep , Schiff Gordon D , Graber Mark L , Onakpoya Igho , Thompson Matthew J
Published: August 2016

Diagnosis is one of the most important tasks performed by primary care physicians. The World Health Organization (WHO) recently prioritized patient safety areas in primary care, and included diagnostic errors as a high-priority problem. In addition, a recent report from the Institute of Medicine in the USA,‘Improving Diagnosis in Health Care’, concluded that most people will likely experience a diagnostic error in their lifetime. In this narrative review, we discuss the global significance, burden and contributory factors related to diagnostic errors in primary care. We synthesize available literature to discuss the types of presenting symptoms and conditions most commonly affected. We then summarize interventions based on available data and suggest next steps to reduce the global burden of diagnostic errors. Research suggests that we are unlikely to find a ‘magic bullet’ and confirms the need for a multifaceted approach to understand and address the many systems and cognitive issues involved in diagnostic error. Because errors involve many common conditions and are prevalent across all countries, the WHO’s leadership at a global level will be instrumental to address the problem. Based on our review, we recommend that the WHO consider bringing together primary care leaders, practicing frontline clinicians, safety experts, policymakers, the health IT community, medical education and accreditation organizations, researchers from multiple disciplines, patient advocates, and funding bodies among others, to address the many common challenges and opportunities to reduce diagnostic error. This could lead to prioritization of practice changes needed to improve primary care as well as setting research priorities for intervention development to reduce diagnostic error.
Cancer and the family: assessment, communication and brief interventions—the development of an educational programme for healthcare professionals when a parent has cancer
Authors: Grant Lucy , Sangha Amrit , Lister Sara , Wiseman Theresa
Published: August 2016

Objective

This study developed and piloted an educational intervention to support healthcare professionals (HCPs) to provide supportive care for families when a parent has cancer.

Methods

Programme development followed the Medical Research Council (MRC) framework, beginning with examination of theory and research, and consultation with experts. The programme content incorporated attachment theory, child development and family systems theory. It was piloted thrice with HCPs from a cancer centre. The evaluation involved a questionnaire, comprising open-ended questions, completed before and after the programme. Data from the questionnaire were analysed using framework analysis.

Results

31 HCPs from varying disciplines participated. The programme was evaluated positively by participants. Before the programme, participants had significant concerns about their professional competence, which included: managing their own emotions; a perceived sensitivity around raising child and family matters with patients and a lack of specialist experience, skills and knowledge. After completing the programme, participants reported greater understanding and knowledge, increased confidence to approach patients about family matters, greater skill to initiate conversations and explore family concerns and guiding parent–child communication according to the child's level of understanding, and an increased engagement and resilience for caring for parents with cancer.

Significance of the results

Supporting HCPs to provide family-centred care is likely to reduce psychological difficulties in families where a parent has cancer. Further work is planned to disseminate the programme, evaluate the transfer of skills into practice, assess how HCPs manage the emotional demands of providing supportive care over time, and consider on-going professional support for HCPs.
Adolescent mental health and earnings inequalities in adulthood: evidence from the Young-HUNT Study
Authors: Evensen Miriam , Lyngstad Torkild Hovde , Melkevik Ole , Reneflot Anne , Mykletun Arnstein
Published: August 2016

Background

Previous studies have shown that adolescent mental health problems are associated with lower employment probabilities and risk of unemployment. The evidence on how earnings are affected is much weaker, and few have addressed whether any association reflects unobserved characteristics and whether the consequences of mental health problems vary across the earnings distribution.

Methods

A population-based Norwegian health survey linked to administrative registry data (N=7885) was used to estimate how adolescents' mental health problems (separate indicators of internalising, conduct, and attention problems and total sum scores) affect earnings (≥30 years) in young adulthood. We used linear regression with fixed-effects models comparing either students within schools or siblings within families. Unconditional quantile regressions were used to explore differentials across the earnings distribution.

Results

Mental health problems in adolescence reduce average earnings in adulthood, and associations are robust to control for observed family background and school fixed effects. For some, but not all mental health problems, associations are also robust in sibling fixed-effects models, where all stable family factors are controlled. Further, we found much larger earnings loss below the 25th centile.

Conclusions

Adolescent mental health problems reduce adult earnings, especially among individuals in the lower tail of the earnings distribution. Preventing mental health problems in adolescence may increase future earnings.
Green Tea Egcg, T-Cell Function, and T-Cell-Mediated Autoimmune Encephalomyelitis
Authors: Wu Dayong
Published: August 2016

Autoimmune diseases are common, disabling immune disorders affecting millions of people. Recent studies indicate that dysregulated balance of different CD4+ T-cell subpopulations plays a key role in immune pathogenesis of several major autoimmune diseases. Green tea and its active ingredient, epigallocatechin-3-gallate (EGCG), have been shown to modulate immune cell functions and improve some autoimmune diseases in animal models. In a series of studies we determined EGCG's effect on T-cell functions and its application in autoimmune diseases. We first observed that EGCG inhibited CD4+ T-cell expansion induced by polyclonal (mitogens or anti-CD3/CD28) or antigen-specific stimulation. We then showed that EGCG suppressed expansion and cell cycle progression of naïve CD4+ T by modulating cell cycle-related proteins. EGCG also inhibited naive CD4+ T-cell differentiation into Th1 and Th17 effector subsets by impacting their respective signaling transducers and transcription factors. These results suggest that EGCG may improve T-cell-mediated autoimmune diseases. Using the experimental autoimmune encephalomyelitis (EAE) mice, an animal model for human multiple sclerosis, we found that dietary supplementation with EGCG attenuated the disease's symptoms and pathology. These EGCG-induced changes are associated with findings in the immune and inflammation profiles in lymphoid tissues and the central nervous system: a reduction in proliferation of autoreactive T cells, production of proinflammatory cytokines, and Th1 and Th17 subpopulations, and an increase in regulatory T-cell populations. These results suggest that green tea or its active components may have a preventive and therapeutic potential in dealing with T-cell-mediated autoimmune diseases. However, the translational value of these findings needs to be validated in future human studies.
Response to: ‘Why medical professionals have no moral claim to conscientious objection accommodation in liberal democracies’ by Schuklenk and Smalling
Authors: Lyus Richard John
Published: August 2016

Bioethicists commenting on conscientious objection and abortion should consider the empirical data on abortion providers. Abortion providers do not fall neatly into groups of providers and objectors, and ambivalence is a key theme in their experience. Practical details of abortion services further upset the dichotomy. These empirical facts are important because they demonstrate that the way the issue is described in analytical bioethics does not reflect reality. Addressing conscientious objection as a barrier to patient access requires engaging with those who provide the service and those who are able to but do not. The experiences of doctors facing these decisions potentially challenge and expand our understanding of the issue as an ethical concern.
Acute Recanalization of Thrombo-Embolic Ischemic Stroke with pREset (ARTESp): the impact of occlusion time on clinical outcome of directly admitted and transferred patients
Authors: Prothmann Sascha , Schwaiger Benedikt J , Gersing Alexandra S , Reith Wolfgang , Niederstadt Thomas , Felber Alexandra , Kurre Wiebke
Published: August 2016

Objectives

Acute Recanalization of Thrombo-Embolic Ischemic Stroke with pREset (ARTESp) is a prospective multicenter study assessing the efficacy and safety of the pREset stent retriever for the treatment of intracranial vessel occlusion. Determination of the effect of transfer status on clinical outcome was a secondary objective.

Methods

Efficacy was measured by recanalization success (Thrombolysis in Cerebral Infarction score ≥2b) and favorable clinical outcome at 90 days (modified Rankin Scale 0–2). Intracranial hemorrhage (ICH) and death at 90 days were safety measures. The outcome of directly admitted (DAP) and transferred (TP) patients was investigated using multivariable regression models.

Results

Four study centers included 100 patients (mean age 68.3 years, median National Institutes of Health Stroke Scale score 15). Recanalization success was achieved in 84.4% after a mean of 1.7 passes. ICH was detected in 14.0%, with 2.0% being symptomatic. At 90 days, 62.5% of the patients had a favorable outcome and 7.3% died. TP had longer occlusion times (289 vs 180 minutes, p<0.001) and a lower rate of favorable outcome (58.0% vs 78.4%, p=0.046) than DAP. Multivariable regression revealed occlusion time as the critical determinant (OR=0.963, 95% CI 0.931 to 0.997, p=0.032), whereas transfer status itself showed no significant association (OR=0.565, CI 0.133 to 2.393, p=0.438).

Conclusions

pREset proved to be safe and effective for the treatment of acute intracranial vessel occlusion. Increased occlusion time impaired clinical outcome in TP.

Trial registration number

NCT02437409; Results.
Mentoring perception, scientific collaboration and research performance: is there a ‘gender gap’ in academic medicine? An Academic Health Science Centre perspective
Authors: Athanasiou Thanos , Patel Vanash , Garas George , Ashrafian Hutan , Hull Louise , Sevdalis Nick , Harding Sian , Darzi Ara , Paroutis Sotirios
Published: August 2016

Objectives

The ‘gender gap’ in academic medicine remains significant and predominantly favours males. This study investigates gender disparities in research performance in an Academic Health Science Centre, while considering factors such as mentoring and scientific collaboration.

Materials and methods

Professorial registry-based electronic survey (n=215) using bibliometric data, a mentoring perception survey and social network analysis. Survey outcomes were aggregated with measures of research performance (publications, citations and h-index) and measures of scientific collaboration (authorship position, centrality and social capital). Univariate and multivariate regression models were constructed to evaluate inter-relationships and identify gender differences.

Results

One hundred and four professors responded (48% response rate). Males had a significantly higher number of previous publications than females (mean 131.07 (111.13) vs 79.60 (66.52), p=0.049). The distribution of mentoring survey scores between males and females was similar for the quality and frequency of shared core, mentor-specific and mentee-specific skills. In multivariate analysis including gender as a variable, the quality of managing the relationship, frequency of providing corrective feedback and frequency of building trust had a statistically significant positive influence on number of publications (all p<0.05).

Conclusions

This is the first study in healthcare research to investigate the relationship between mentoring perception, scientific collaboration and research performance in the context of gender. It presents a series of initiatives that proved effective in marginalising the gender gap. These include the Athena Scientific Women's Academic Network charter, new recruitment and advertisement strategies, setting up a ‘Research and Family Life’ forum, establishing mentoring circles for women and projecting female role models.
Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis
Authors: Sweeney Shannon R , Kavanaugh Arthur , Lodi Alessia , Wang Bo , Boyle David , Tiziani Stefano , Guma Monica
Published: August 2016

Objective

To determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 MHz spectrometer and a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer were used to acquire1H-NMR and ultra high pressure liquid chromatography (UPLC)–MS/MS spectra, respectively, of serum samples before and after rituximab therapy. Data processing and statistical analysis were performed in MATLAB. 14 patients were characterised as responders, and 9 patients were considered non-responders. 7 polar metabolites (phenylalanine, 2-hydroxyvalerate, succinate, choline, glycine, acetoacetate and tyrosine) and 15 lipid species were different between responders and non-responders at baseline. Phosphatidylethanolamines, phosphatidyserines and phosphatidylglycerols were downregulated in responders. An opposite trend was observed in phosphatidylinositols. At 6 months, 5 polar metabolites (succinate, taurine, lactate, pyruvate and aspartate) and 37 lipids were different between groups. The relationship between serum metabolic profiles and clinical response to rituximab suggests that1H-NMR and UPLC–MS/MS may be promising tools for predicting response to rituximab.
Streptococcus equi subspecies equi in horses in Israel: seroprevalence and strain types
Authors: Tirosh‐Levy S. , Blum S. E. , Steward K. F. , Waller A. S. , Steinman A.
Published: August 2016

The purpose of this cross‐sectional study was to determine the seroprevalence of Streptococcus equi in Israel, to monitor seropositive horses over time and to identify archived strains that were recovered from Israeli horses. A serological survey of 200 healthy horses on 20 farms throughout Israel was performed to detect recent exposure to S equi antigens A and C via indirect ELISA. Seroprevalence was 9.5 per cent (19/200) and positive horses were found in 30 per cent (6/20) of the farms. Sixteen horses that returned a positive serology result were retested three and six months later. Most (12/16) positive horses remained positive, which suggests the presence of animals with persistent infection. Molecular characterisation of S equi strains by sequencing of the SeM gene of 16 archived isolates of S equi that were recovered from clinical cases of strangles between 2008 and 2012 identified two strains: SeM‐2 and SeM‐28.
Client‐assessed long‐term outcome in dogs with surgical site infection following tibial plateau levelling osteotomy
Authors: Brown G. , Maddox T. , Baglietto Siles M. M.
Published: August 2016

The objective of this study was to describe client‐assessed long‐term functional outcome following surgical site infection (SSI) in dogs that underwent tibial plateau levelling osteotomy (TPLO) and identify predictive factors for infection development and management. This study is a retrospective clinical case series. Clinical records of dogs (n=545) undergoing TPLO surgery (n=683) were reviewed. Signalment, clinical details, surgical management and postoperative complications were recorded. Multilevel analysis was used to assess the relationship between signalment and clinical variables and the subsequent development of SSI. Additionally, SSIs were analysed to identify predictors for management. Long‐term functional outcome was evaluated using a previously validated clinical metrology instrument (Liverpool Osteoarthritis in Dogs (LOAD) questionnaire). SSI occurred in 4.7 per cent (95 per cent CI 3.3 per cent to 6.5 per cent) procedures. Of the dogs with SSI, 37.5 per cent required implant retrieval and later onset SSI was associated with increased requirement for retrieval (P=0.04). There was no significant difference in LOAD score (P=0.7) in dogs with or without SSI. Crossbreed dogs had a lower risk of developing SSI (P=0.03). There was no association between SSI and long‐term functional outcome (as assessed by LOAD) in dogs following TPLO. Later onset of SSI is more likely to require implant retrieval to resolve. Crossbreed dogs may be at reduced risk of developing SSI.
Radioprotective potential of Lagenaria siceraria extract against radiation-induced gastrointestinal injury
Authors: Sharma Dhara , Goel Harish Chandra , Chauhan Sonal
Published: August 2016

The cucurbits (prebiotics) were investigated as novel agents for radio-modification against gastrointestinal injury. The cell-cycle fractions and DNA damage were monitored in HCT-15 cells. A cucurbit extract was added to culture medium 2 h before irradiation (6 Gy) and was substituted by fresh medium at 4 h post-irradiation. The whole extract of the fruits of Lagenaria siceraria, Luffa cylindrica, or Cucurbita pepo extract enhanced G2 fractions (42%, 34%, and 37%, respectively) as compared with control (20%) and irradiated control (31%). With cucurbits, the comet tail length remained shorter (L. siceraria, 28 μm; L. cylindrica, 34.2 μm; C. pepo, 36.75 μm) than irradiated control (41.75 μm). For in vivo studies, L. siceraria extract (2 mg/kg body weight) was administered orally to mice at 2 h before and 4 and 24 h after whole-body irradiation (10 Gy). L. siceraria treatment restored the glutathione contents to 48.8 μmol/gm as compared with control (27.6 μmol/gm) and irradiated control (19.6 μmol/gm). Irradiation reduced the villi height from 379 to 350 μm and width from 54 to 27 μm. L. siceraria administration countered the radiation effects (length, 366 μm; width, 30 μm, respectively) and improved the villi morphology and tight junction integrity. This study reveals the therapeutic potential of cucurbits against radiation-induced gastrointestinal injury.
Theory and calibration of the Pierre 2 stochastic rock fall dynamics simulation program
Authors: Mitchell Andrew , Hungr Oldrich
Published: August 2016

The use of computer models to determine rock fall hazards is increasingly common, with increasingly complex models being developed. In most practical applications, slopes potentially affected by rock falls are characterized in general terms only, thus a simpler model is desirable to reduce the parameter uncertainty. The model presented here utilizes a lumped-mass representation of the rocks. Key features are the stochastic roughness angle to represent contact geometry variability, hyperbolic restitution factors, and a stochastic shape factor, which have been developed considering impact mechanics theory. Together, these features can yield realistic results for linear and angular velocity, bounce height, runout distance, and normal restitution factors greater than one while still being easy to calibrate. The model calibration has been carried out using detailed, full-scale experiments from a talus slope in France, a hard rock quarry in Austria, and a weak bedrock and talus slope in Japan. An observed rock fall event in British Columbia was modeled as a pseudoforward analysis to demonstrate the model validity. The usefulness of the model as a design tool has been demonstrated by using the simulation results as inputs for a hypothetical barrier design application, and calculating the reliability of the design values.
Competition during enrichment of pathogenicEscherichia colimay result in culture bias
Authors: Conrad Cheyenne C. , Stanford Kim , McAllister Tim A. , Thomas James , Reuter Tim
Published: August 2016

Deadly outbreaks and illnesses due to Shiga toxin-producing Escherichia coli (STEC) occur worldwide; however, the cultivation methods required for adequate monitoring and traceback investigations are inefficient at best. Detection of STEC relies heavily on enrichment; yet no standard media or protocols exist. Furthermore, whether enrichment may bias detection of multiple STEC serogroups from complex samples is unknown. Thus, 14 STEC strains of serogroups O157 and the top six non-O157s (O26, O45, O103, O111, O121, and O145) were enriched in pairs for 6–78 h in broth and evaluated by quantitative polymerase chain reaction (qPCR). Here we show that a conventional 6-h enrichment protocol did not result in intra-species culture bias for the isolates tested. However, subsequent enrichments often produced biased cultures, with differences in the qPCR gene copy number ≥2 log10apparent in 12%, 38%, and 52% of competitions after 30, 54, and 78 h of consecutive enrichments, respectively. Some strains were able to prevail and (or) out-compete the opponent strain in 100% of competitions. Our results suggest that culture bias should be considered and (or) evaluated further due to the potential implications during routine pathogen screening and outbreak investigations.
Gamma-Ray Observations of Active Galactic Nuclei
Authors: Madejski Grzegorz (Greg) , Sikora Marek
Published: August 2016

This article reviews the recent observational results regarding γ-ray emission from active galaxies. The most numerous discrete extragalactic γ-ray sources are AGNs dominated by relativistic jets pointing in our direction (commonly known as blazars), and they are the main subject of the review. They are detected in all observable energy bands and are highly variable. The advent of the sensitive γ-ray observations, afforded by the launch and continuing operation of the Fermi Gamma-ray Space Telescope and the AGILE Gamma-ray Imaging Detector, as well as by the deployment of current-generation Air Cerenkov Telescope arrays such as VERITAS, MAGIC, and HESS-II, continually provides sensitive γ-ray data over the energy range of ∼100 MeV to multi-TeV. Importantly, it has motivated simultaneous, monitoring observations in other bands, resulting in unprecedented time-resolved broadband spectral coverage. After an introduction, in Sections 3, 4, and 5, we cover the current status and highlights of γ-ray observations with (mainly) Fermi but also AGILE and put those in the context of broadband spectra in Section 6. We discuss the radiation processes operating in blazars in Section 7, and we discuss the content of their jets and the constraints on the location of the energy dissipation regions in, respectively, Sections 8 and 9. Section 10 covers the current ideas for particle acceleration processes in jets, and Section 11 discusses the coupling of the jet to the accretion disk in the host galaxy. Finally, Sections 12, 13, and 14 cover, respectively, the contribution of blazars to the diffuse γ-ray background, the utility of blazars to study the extragalactic background light, and the insight they provide for study of populations of supermassive black holes early in the history of the Universe.
IL-6 ameliorates defective leptin sensitivity in DIO ventromedial hypothalamic nucleus neurons
Authors: Larsen Louise , Le Foll Christelle , Dunn-Meynell Ambrose A. , Levin Barry E.
Published: August 2016

Rats selectively bred to develop diet-induced obesity (DIO) have an early onset reduction in the sensitivity of their ventromedial hypothalamic nucleus (VMN) neurons to leptin compared with diet-resistant (DR) rats. This reduced sensitivity includes decreased leptin receptor (Lepr-b) mRNA expression, leptin receptor binding, leptin-induced phosphorylation of STAT3 (pSTAT3), and impaired leptin excitation (LepE) of VMN neurons. When administered exogenously, the pancreatic peptide, amylin, acts synergistically to reduce food intake and body weight in obese, leptin-resistant DIO rats by increasing VMN leptin signaling, likely by stimulation of microglia IL-6, which acts on its receptor to increase leptin-induced pSTAT3. Here, we demonstrate that incubation of cultured VMN neurons of outbred rats with IL-6 increases their leptin sensitivity. Control, dissociated DIO VMN neurons express 66% less Lepr-b and 75% less Bardet Biedl Syndrome-6 (BBS6) mRNA and have reduced leptin-induced activation of LepE neurons compared with DR neurons. Incubation for 4 days with IL-6 increased DIO neuron Lepr-b expression by 77% and BBS6 by 290% and corrected their defective leptin activation of LepE neurons to DR levels. Since BBS6 enhances trafficking of Lepr-b to the cell membrane, the increases in Lepr-b and BBS6 expression appear to account for correction of the reduced leptin excitation of DIO LepE neurons to that of control DR rats. These data support prior findings suggesting that IL-6 mediates the leptin-sensitizing effects of amylin on VMN neurons and that the inherent leptin resistance of DIO rats can be effectively reversed at a cellular level by IL-6.
Evidence of degraded representation of speech in noise, in the aging midbrain and cortex
Authors: Presacco Alessandro , Simon Jonathan Z. , Anderson Samira
Published: August 2016

Humans have a remarkable ability to track and understand speech in unfavorable conditions, such as in background noise, but speech understanding in noise does deteriorate with age. Results from several studies have shown that in younger adults, low-frequency auditory cortical activity reliably synchronizes to the speech envelope, even when the background noise is considerably louder than the speech signal. However, cortical speech processing may be limited by age-related decreases in the precision of neural synchronization in the midbrain. To understand better the neural mechanisms contributing to impaired speech perception in older adults, we investigated how aging affects midbrain and cortical encoding of speech when presented in quiet and in the presence of a single-competing talker. Our results suggest that central auditory temporal processing deficits in older adults manifest in both the midbrain and in the cortex. Specifically, midbrain frequency following responses to a speech syllable are more degraded in noise in older adults than in younger adults. This suggests a failure of the midbrain auditory mechanisms needed to compensate for the presence of a competing talker. Similarly, in cortical responses, older adults show larger reductions than younger adults in their ability to encode the speech envelope when a competing talker is added. Interestingly, older adults showed an exaggerated cortical representation of speech in both quiet and noise conditions, suggesting a possible imbalance between inhibitory and excitatory processes, or diminished network connectivity that may impair their ability to encode speech efficiently.