bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacillus thuringiensis Vip3Aa Toxin Resistance in Heliothis virescens (Lepidoptera: Noctuidae)
Authors: Pickett Brian R. , Gulzar Asim , Ferré Juan , Wright Denis J.
Published: February 2017

Laboratory selection with Vip3Aa of a field-derived population of
Heliothis virescens
produced >2,040-fold resistance in 12 generations of selection. The Vip3Aa-selected (Vip-Sel)-resistant population showed little cross-resistance to Cry1Ab and no cross-resistance to Cry1Ac. Resistance was unstable after 15 generations without exposure to the toxin. F
1
reciprocal crosses between Vip3Aa-unselected (Vip-Unsel) and Vip-Sel insects indicated a strong paternal influence on the inheritance of resistance. Resistance ranged from almost completely recessive (mean degree of dominance [
h
] = 0.04 if the resistant parent was female) to incompletely dominant (mean
h
= 0.53 if the resistant parent was male). Results from bioassays on the offspring from backcrosses of the F
1
progeny with Vip-Sel insects indicated that resistance was due to more than one locus. The results described in this article provide useful information for the insecticide resistance management strategies designed to overcome the evolution of resistance to Vip3Aa in insect pests.

IMPORTANCE
Heliothis virescens
is an important pest that has the ability to feed on many plant species. The extensive use of
Bacillus thuringiensis
(Bt) crops or spray has already led to the evolution of insect resistance in the field for some species of Lepidoptera and Coleoptera. The development of resistance in insect pests is the main threat to Bt crops. The effective resistance management strategies are very important to prolong the life of Bt plants. Lab selection is the key step to test the assumption and predictions of management strategies prior to field evaluation. Resistant insects offer useful information to determine the inheritance of resistance and the frequency of resistance alleles and to study the mechanism of resistance to insecticides.
Performance of the FreeStyle Libre Flash glucose monitoring system in patients with type 1 and 2 diabetes mellitus
Authors: Fokkert M J , van Dijk P R , Edens M A , Abbes S , de Jong D , Slingerland R J , Bilo H J G
Published: February 2017

Objective

To evaluate the performance of the FreeStyle Libre Flash continuous glucose monitoring (FSL-CGM) system against established central laboratory methods.

Research design and methods

20 subjects (8 type 1 diabetes mellitus, 12 type 2 diabetes mellitus) were analyzed. FSL-CGM sensor measurements (inserted in arm and abdomen) were compared with capillary blood glucose results analyzed with StatStrip as semigold standard. The glucose response after a standardized oral glucose load was measured by FSL-CGM and capillary samples analyzed by perchloric acid hexokinase (PCA-HK) method, StatStrip and FSL test strip (FSLC), and a commonly used CGM system (iPro2).

Results

FSL-CGM arm sensor readings showed 85.5% of paired readings falling within Clarke Error Grid (ISO 15197:2013) zone A when compared with StatStrip. For FSL-CGM abdomen and FSLC, these percentages were 64% and 98%, respectively. The overall correlation of FSL-CGM in the arm and the StatStrip indicates a performance with lower results with the FSL-CGM in the arm than expected based on the StatStrip in the lower glucose ranges, and higher results than expected in the higher ranges. Following a standardized glucose load, a slower rise in glucose level was observed for FSL-CGM arm as compared with PCA-HK, StatStrip, FSLC, and iPro2 during the first 45–60 min after glucose load ingestion.

Conclusions

Certain matters need attention while using the FSL-CGM in daily life including the observed lower values in the lower ranges, and the underestimation of the effect of a meal on glucose response. These effects of such deviations can partly be overcome by optimizing the available user instructions.

Trial registration number

TC5348; results.
Brighter children? The association between seasonality of birth and child IQ in a population-based birth cohort
Authors: Grootendorst-van Mil Nina H , Steegers-Theunissen Régine P M , Hofman Albert , Jaddoe Vincent W V , Verhulst Frank C , Tiemeier Henning
Published: February 2017

Objective

Season of birth has repeatedly been found to be a risk indicator for adverse neurodevelopmental outcomes. Several explanations for this finding have been put forward but no conclusion has been reached. In the current study, we explored the role of sociodemographic and biological factors in the association between season of birth and child IQ.

Design

In a prenatally recruited birth cohort (born in 2002–2006), we examined the association between season of birth and non-verbal IQ at age 6 years among 6034 children. We explored how adjusting for socioeconomic status and maternal IQ, childbirth outcomes, pregnancy vitamin D status, nutritional intake, exposure to infections, and child age relative to peers in class changed the relation between season of birth and child IQ.

Results

We found that spring birth was associated with lower non-verbal IQ (estimate: more than 1 point; β−1.24 (95% CI −2.31 to −0.17), p=0.02; seasonal trend β−0.40 (95% CI −0.74 to −0.07), p=0.02) than birth in summer. Adjustment for different covariates led to a substantial reduction (−65.0% change, in a seasonal trend analysis) of this association. In particular, sociodemographic factors and maternal IQ (−10.0% and −22.5% change, respectively) contributed.

Conclusions

Season of birth is an indicator of many underlying factors related to child IQ. The observed effects on IQ were small and therefore not of clinical significance.
Qualitative study of the BREATHER trial (Short Cycle antiretroviral therapy): is it acceptable to young people living with HIV?
Authors: Bernays Sarah , Paparini Sara , Seeley Janet , Namukwaya Kihika Stella , Gibb Diana , Rhodes Tim
Published: February 2017

Objectives

A qualitative study of the BREATHER (PENTA 16) randomised clinical trial, which compared virological control of Short Cycle Therapy (SCT) (5 days on: 2 days off) with continuous efavirenz (EFV)-based antiretroviral therapy (CT) in children and young people (aged 8–24) living with HIV with viral load <50 c/mL to examine adaptation, acceptability and experience of SCT to inform intervention development.

Setting

Paediatric HIV clinics in the UK (2), Ireland (1), the USA (1) and Uganda (1).

Participants

All BREATHER trial participants who were over the age of 10 and aware of their HIV diagnosis were invited to participate. 49 young people from both arms of the BREATHER trial (31 females and 18 males; 40% of the total trial population in the respective sites; age range 11–24) gave additional consent to participate in the qualitative study.

Results

Young people from both trial arms had initial concerns about the impact of SCT on their health and adherence, but these decreased over the early months in the trial. Young people randomised to SCT reported preference for SCT compared with CT pre-trial. Attitudes to SCT did not vary greatly by gender or country. Once short-term adaptation challenges were overcome, SCT was positively described as reducing impact of side effects, easing the pressure to carry and remember medication and enabling more weekend social activities. Young people on both arms reported frequent medication side effects and occasional missed doses that they had rarely voiced to clinical staff. Participants liked SCT by trial end but were concerned that peers who had most problems adhering could find SCT disruptive and difficult to manage.

Conclusions

To realise the potential of SCT (and mitigate possible risks of longer interruptions), careful dissemination and communication post-trial is needed. SCT should be provided alongside a package of monitoring, support and education over 3 months to allow adaptation.

Trial registration number

NCT 01641016
White cell count in the normal range and short-term and long-term mortality: international comparisons of electronic health record cohorts in England and New Zealand
Authors: Shah Anoop Dinesh , Thornley Simon , Chung Sheng-Chia , Denaxas Spiros , Jackson Rod , Hemingway Harry
Published: February 2017

Objectives

Electronic health records offer the opportunity to discover new clinical implications for established blood tests, but international comparisons have been lacking. We tested the association of total white cell count (WBC) with all-cause mortality in England and New Zealand.

Setting

Primary care practices in England (ClinicAl research using LInked Bespoke studies and Electronic health Records (CALIBER)) and New Zealand (PREDICT).

Design

Analysis of linked electronic health record data sets: CALIBER (primary care, hospitalisation, mortality and acute coronary syndrome registry) and PREDICT (cardiovascular risk assessments in primary care, hospitalisations, mortality, dispensed medication and laboratory results).

Participants

People aged 30–75 years with no prior cardiovascular disease (CALIBER: N=686 475, 92.0% white; PREDICT: N=194 513, 53.5% European, 14.7% Pacific, 13.4% Maori), followed until death, transfer out of practice (in CALIBER) or study end.

Primary outcome measure

HRs for mortality were estimated using Cox models adjusted for age, sex, smoking, diabetes, systolic blood pressure, ethnicity and total:high-density lipoprotein (HDL) cholesterol ratio.

Results

We found ‘J’-shaped associations between WBC and mortality; the second quintile was associated with lowest risk in both cohorts. High WBC within the reference range (8.65–10.05×109/L) was associated with significantly increased mortality compared to the middle quintile (6.25–7.25×109/L); adjusted HR 1.51 (95% CI 1.43 to 1.59) in CALIBER and 1.33 (95% CI 1.06 to 1.65) in PREDICT. WBC outside the reference range was associated with even greater mortality. The association was stronger over the first 6 months of follow-up, but similar across ethnic groups.

Conclusions

Clinically recorded WBC within the range considered ‘normal’ is associated with mortality in ethnically different populations from two countries, particularly within the first 6 months. Large-scale international comparisons of electronic health record cohorts might yield new insights from widely performed clinical tests.

Trial registration number

NCT02014610.
Understanding the epidemiology of avoidable significant harm in primary care: protocol for a retrospective cross-sectional study
Authors: Bell Brian G , Campbell Stephen , Carson-Stevens Andrew , Evans Huw Prosser , Cooper Alison , Sheehan Christina , Rodgers Sarah , Johnson Christine , Edwards Adrian , Armstrong Sarah , Mehta Rajnikant , Chuter Antony , Donnelly Ailsa , Ashcroft Darren M , Lymn Joanne , Smith Pam , Sheikh Aziz , Boyd Matthew , Avery Anthony J
Published: February 2017

Introduction

Most patient safety research has focused on specialist-care settings where there is an appreciation of the frequency and causes of medical errors, and the resulting burden of adverse events. There have, however, been few large-scale robust studies that have investigated the extent and severity of avoidable harm in primary care. To address this, we will conduct a 12-month retrospective cross-sectional study involving case note review of primary care patients.

Methods and analysis

We will conduct electronic searches of general practice (GP) clinical computer systems to identify patients with avoidable significant harm. Up to 16 general practices from 3 areas of England (East Midlands, London and the North West) will be recruited based on practice size, to obtain a sample of around 100 000 patients. Our investigations will include an ‘enhanced sample’ of patients with the highest risk of avoidable significant harm. We will estimate the incidence of avoidable significant harm and express this as ‘per 100 000 patients per year’. Univariate and multivariate analysis will be conducted to identify the factors associated with avoidable significant harm.

Ethics/Dissemination

The decision regarding participation by general practices in the study is entirely voluntary; the consent to participate may be withdrawn at any time. We will not seek individual patient consent for the retrospective case note review, but if patients respond to publicity about the project and say they do not wish their records to be included, we will follow these instructions. We will produce a report for the Department of Health's Policy Research Programme and several high-quality peer-reviewed publications in scientific journals. The study has been granted a favourable opinion by the East Midlands Nottingham 2 Research Ethics Committee (reference 15/EM/0411) and Confidentiality Advisory Group approval for access to medical records without consent under section 251 of the NHS Act 2006 (reference 15/CAG/0182).
Women's experiences with cervical cancer screening in a colposcopy referral clinic in Cape Town, South Africa: a qualitative analysis
Authors: Momberg Mariette , Botha Matthys H , Van der Merwe Frederick H , Moodley Jennifer
Published: February 2017

Objective

The aim of this study was to explore and understand women's experience with cervical cancer screening and with the referral pathways for abnormal Papanicolau (Pap) smears.

Design and setting

Focus group discussions were conducted with first time colposcopy clinic attendees at a tertiary hospital colposcopy clinic in Cape Town, South Africa during November 2014. A thematic analysis was conducted to identify key themes. Initial coding categories were drawn from the interview guide.

Participants

27 women participated in 4 focus group discussions.

Results

Participants mean age was 34 years, most did not complete secondary level education and were unemployed. Negative community opinions relating to Pap smears and colposcopy referral might deter women from seeking treatment. Having a gynaecological symptom was the most commonly cited reason for having a Pap smear. Fear of having a HIV test performed at the same time as Pap smear and low encouragement from peers, were factors identified as potential access barriers. Participants commented on insufficient or lack of information from primary providers on referral to the colposcopy clinic and concerns and apprehension during waiting periods between receiving results and the colposcopy appointment were discussed.

Conclusions

There is a strong and urgent need to improve current knowledge about cervical cancer and Pap smears and the necessity and benefits of timely access to screening programmes, results and treatment. Strategies such as community health education programmes and mass media interventions could be employed to disseminate cervical cancer information and address negative community perceptions. Better training and support mechanisms to equip healthcare providers with the skills to convey cervical cancer information to women are needed. The use of short message service (SMS) to deliver Pap smear results and provide patients with more information should be considered to improve waiting times for results and alleviate apprehension during waiting periods.
Efficacy and safety of super selective bronchial artery coil embolisation for haemoptysis: a single-centre retrospective observational study
Authors: Ishikawa Hideo , Hara Masahiko , Ryuge Misaki , Takafuji Jun , Youmoto Mihoko , Akira Masanori , Nagasaka Yukio , Kabata Daijiro , Yamamoto Kouji , Shintani Ayumi
Published: February 2017

Objectives

Evidence on the safety and long-term efficacy of super selective bronchial artery embolisation (ssBAE) using platinum coils in patients with haemoptysis is insufficient. The objective of the present study was to evaluate the safety and the 3-year postprocedure haemoptysis-free survival rate of de novo elective ssBAE using platinum coils rather than particles for the treatment of haemoptysis.

Design

A single-centre retrospective observational study.

Setting

Hemoptysis and Pulmonary Circulation Center in Japan.

Participants

A total of 489 consecutive patients with massive and non-massive haemoptysis who underwent de novo elective ssBAE without malignancy or haemodialysis.

Interventions

ssBAE using platinum coils. All patients underwent CT angiography before the procedure for identifying haemoptysis-related arteries (HRAs) and for procedural planning.

Primary and secondary outcome measures

The composite of the 3-year recurrence of haemoptysis and mortality from the day of the last ssBAE session. Each component of the primary end point and procedural success defined as successful embolisation of all target HRAs were also evaluated.

Results

The median patient age was 69 years, and 46.4% were men. The total number of target vessels was 4 (quartile 2–7), and the procedural success rate was 93.4%. There were 8 (1.6%) major complications: 1 aortic dissection, 2 symptomatic cerebellar infarctions and 5 mediastinal haematoma cases. The haemoptysis-free survival rates were estimated by the Kaplan-Meier analysis at 86.9% (95% CI 83.7% to 90.2%) at 1 year, 79.4% (74.8% to 84.3%) at 2 years and 57.6% (45.1% to 73.4%) at 3 years. Although not statistically significant by the adjusted analysis of variance with multiple imputation of missing variables, cryptogenic haemoptysis tended to show the most favourable outcome and non-tuberculous mycobacterium showed the worst outcome (adjusted p=0.250).

Conclusions

We demonstrated the safety and long-term efficacy of elective ssBAE using platinum coils and established that it can be a valuable therapeutic option for treating patients with haemoptysis.
Costs of Family Caregiving in Palliative Care (COFAC) questionnaire: development and piloting of a new survey tool
Authors: Gardiner Clare , McDermott Chris , Hulme Claire
Published: February 2017

Background

Family caregivers play an important role in the care of patients receiving palliative care, yet little is known about the financial impact of family caregiving in this context. A lack of existing validated tools for collecting data on the costs of family caregiving in palliative care has resulted in a weak and limited evidence base. The aim of the study was to describe the development and initial piloting of a new survey tool which captures data on the costs of family caregiving in palliative care: the Costs of Family Caregiving (COFAC) questionnaire.

Methods

Development and piloting of the COFAC questionnaire involved 2 phases: (1) questionnaire development based on published evidence and cognitive interviews with service users; and (2) validity testing involving expert review and piloting with bereaved caregivers.

Results

Questionnaire content was generated from previously published research and related to work-related costs, carer time costs and out-of-pocket expenses. 2 group cognitive interviews with 15 service users refined content of the draft questionnaire. Face validity was established through expert review with 9 academics and clinicians. Piloting with 8 bereaved caregivers established acceptability and feasibility of administration.

Conclusions

The COFAC tool has been shown to be valid, acceptable to bereaved caregivers and feasible to administer. The COFAC questionnaire is recommended for economic research in palliative care which seeks to capture data from a broad societal perspective which includes family caregiver costs.
Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy
Authors: Tang Ruqi , Wei Yiran , Li Yanmei , Chen Weihua , Chen Haoyan , Wang Qixia , Yang Fan , Miao Qi , Xiao Xiao , Zhang Haiyan , Lian Min , Jiang Xiang , Zhang Jun , Cao Qin , Fan Zhuping , Wu Maoying , Qiu Dekai , Fang Jing-Yuan , Ansari Aftab , Gershwin M Eric , Ma Xiong
Published: February 2017

Objective

A close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls.

Design

We first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results. Finally, a prospective study was performed in a subgroup of 37 patients with PBC who underwent analysis before and after 6 months of UDCA treatment. Faecal samples were collected, and microbiomes were analysed by 16S ribosomal RNA gene sequencing.

Results

A significant reduction of within-individual microbial diversity was noted in PBC (p=0.03). A signature defined by decreased abundance of four genera and increased abundance of eight genera strongly correlated with PBC (area under curve=0.86, 0.84 in exploration and validation data, respectively). Notably, the abundance of six PBC-associated genera was reversed after 6 months of UDCA treatment. In particular, Faecalibacterium, enriched in controls, was further decreased in gp210-positive than gp210-negative patients (p=0.002). Of interest was the finding that the increased capacity for the inferred pathway, bacterial invasion of epithelial cells in PBC, highly correlated with the abundance of bacteria belonging to Enterobacteriaceae.

Conclusions

This study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.
Effects of dabigatran according to age in atrial fibrillation
Authors: Lauw Mandy N , Eikelboom John W , Coppens Michiel , Wallentin Lars , Yusuf Salim , Ezekowitz Michael , Oldgren Jonas , Nakamya Juliet , Wang Jia , Connolly Stuart J
Published: February 2017

Objective

The prevalence of atrial fibrillation (AF) and the risk of stroke and bleeding vary according to age. To estimate effects of dabigatran, compared with warfarin, on stroke, bleeding and mortality in patients with AF in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial according to age, we analysed treatment effects using age as a continuous variable and using age categories.

Methods

RE-LY included 10 855 (59.9%) patients aged <75 years, 4231 patients (23.4%) aged 75–79 years, 2305 (12.7%) aged 80–84 years and 722 (4.0%) aged ≥85 years at baseline.

Results

Benefits of dabigatran versus warfarin regarding stroke (HR range 0.63 (95% CI 0.46 to 0.86) to 0.70 (0.31 to 1.57) for dabigatran 150 mg twice daily), HR range 0.52 (0.21 to 1.29) to 1.08 (0.73 to 1.60) for dabigatran 110 mg twice daily) and intracranial bleeding were maintained across all age groups (interaction p values all not significant). There was a highly significant interaction (p value interaction <0.001) between age and treatment for extracranial major bleeding, with lower rates with both doses of dabigatran compared with warfarin in younger patients (HR 0.78 (0.62 to 0.97) for 150 mg twice daily, HR 0.72 (0.57 to 0.90) for 110 mg twice daily) but similar (HR 1.50 (1.03 to 2.18) for 110 mg twice daily) or higher rates (HR 1.68 (1.18 to 2.41) for 150 mg twice daily) in older patients (≥80 years).

Conclusion

Effects of dabigatran compared with warfarin on stroke prevention and intracranial bleeding are consistent across all age groups. Effects of dabigatran on extracranial major bleeding are age dependent, supporting selection of dabigatran 110 mg twice daily for elderly patients (age ≥80 years).

Trial registration number

Clinical trial registration number: https://clinicaltrials.govNCT00262600.
Flexural deformities Part 1: Congenital
Authors: Kidd Jessica
Published: February 2017

Flexural deformities of foals and growing horses can be divided into congenital (present at birth) and acquired (developing after birth) groups. Although the content of this article could apply to both groups, this first article in the series will focus on congenital flexural deformities, while a second article, to be published in a subsequent issue of In Practice, will discuss acquired deformities.
Primary care requests for anaemia chemistry tests in Spain: potential iron, transferrin and folate over-requesting
Authors: Salinas Maria , López-Garrigós Maite , Flores Emilio , Leiva-Salinas Carlos
Published: February 2017

Aim

To study the regional variability of requests for anaemia chemistry tests in primary care in Spain and the associated economic costs of potential over-requesting.

Methods

Requests for anaemia tests were examined in a cross-sectional study. Clinical laboratories from different autonomous communities (AACCs) were invited to report on primary care anaemia chemistry tests requested during 2014. Demand for iron, ferritin, vitamin B12 and folate tests per 1000 inhabitants and the ratios of the folate/vitamin B12 and transferrin/ferritin requests were compared between AACCs. We also calculated reagent costs and the number of iron, transferrin and folate tests and the economic saving if every AACC had obtained the results achieved by the AACC with best practice.

Results

110 laboratories participated (59.8% of the Spanish population). More than 12 million tests were requested, resulting in reagent costs exceeding €16.5 million. The serum iron test was the most often requested, and the ferritin test was the most costly (over €7 million). Close to €4.5 million could potentially have been saved if iron, transferrin and folate had been appropriately requested (€6 million when extrapolated to the whole Spanish population).

Conclusions

The demand for and expenditure on anaemia chemistry tests in primary care in Spain is high, with significant regional differences between different AACCs.
Effectiveness of Acarbose in Treating Elderly Patients with Diabetes with Postprandial Hypotension
Authors: Zhang Jie , Guo Lixin
Published: February 2017

Postprandial hypotension (PPH) is a common condition that occurs primarily in elderly patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness of acarbose for PPH; it also investigated possible mechanisms behind PPH development. This single-blind, randomized controlled trial included 91 elderly patients with T2DM, aged between 60 and 80 years, who were inpatients at Beijing Hospital between March 2012 and November 2014. The patients were included into one of three groups: Group A, patients with T2DM without PPH; Group B, patients with T2DM with PPH receiving placebo; and Group C, patients with T2DM with PPH receiving acarbose. After an overnight fast, patients received a single dose of acarbose (100 mg) or placebo and then consumed a standardized 450 kcal meal. Blood pressure, glucose levels, heart rate (HR), and catecholamine levels were evaluated. Acarbose ameliorated PPH as determined by significant improvements in the duration and maximal fall in blood pressure (both p<0.001); however, no differences in HR and blood glucose levels were observed. In patients with PPH, blood pressure was correlated with blood glucose and HR variability values (p<0.05). Correlations between epinephrine and glucagon-like peptide-1 with blood pressure in groups A and C were largely lost in group B. Acarbose reduced postprandial blood pressure fluctuations in elderly patients with diabetes. PPH may be related to impaired autonomic nervous system function, reduced catecholamine secretion, and postprandial fluctuations in blood glucose levels.

Trial registration number

Chinese Clinical Trial Registry ChiCTR-IPR-15006177.
Intensive blood pressure lowering in patients with acute intracerebral haemorrhage: clinical outcomes and haemorrhage expansion. Systematic review and meta-analysis of randomised trials
Authors: Boulouis Gregoire , Morotti Andrea , Goldstein Joshua N , Charidimou Andreas
Published: February 2017

Introduction

It is unclear whether intensive lowering of blood pressure (BP) at the acute phase of intracerebral haemorrhage (ICH) is beneficial. We performed a meta-analysis of randomised controlled trials (RCTs) to assess whether intensive BP lowering in patients with acute ICH is safe and effective in improving clinical outcomes.

Methods

We searched PubMed, EMBASE and the Cochrane databases for relevant RCTs and calculated pooled OR for 3-month mortality (safety outcome) and 3-month death or dependency (modified Rankin Scale (mRs) ≥3;efficacy outcome), in patients with acute ICH randomised to either intensive BP-lowering or standard BP-lowering treatment protocols. We also investigated the association between treatment arm and ICH expansion at 24 hours. Random effects models with DerSimonian-Laird weights were used.

Results

Five eligible studies including 4360 patients with acute ICH were pooled in meta-analysis. The risk of 3-month mortality was similar between patients randomised to intensive BP-lowering treatment and standard BP-lowering treatment (OR: 0.99; 95% CI: 0.82 to 1.20, p=0.909). Intensive BP-lowering treatment showed a (non-significant) trend for an association with lower 3-month death or dependency risk compared with standard treatment (OR: 0.91; 95% CI: 0.80 to 1.02), p=0.106). Intensive BP reduction was associated with a trend for lower risk of significant ICH expansion compared with standard treatment (OR: 0.82; 95% CI: 0.68 to 1.00, p=0.056), especially in larger RCTs.

Conclusions

For patients with acute ICH similar to those included in RCTs and without contraindication to acute BP treatment, intensive acute BP lowering is safe, but does not seem to provide an incremental clinical benefit in terms of functional outcomes. The effect of intensive BP lowering on significant haematoma expansion at 24 hours warrants further investigation.
A deep ethics for mental difference and disability: the ‘case’ of Vincent van Gogh
Authors: Lewis Bradley
Published: February 2017

Despite a growing prevalence of mental illness diagnoses and treatments, there remains remarkable interpretive diversity regarding the meaning of these diagnoses and their implication for mental healthcare. Humanities scholarship devoted to language, power and ethical cares of the self provides invaluable tools for navigating interpretive diversity in this domain. This scholarship suggests that ethical questions of informed consent regarding mental difference and disability go much deeper than the usual standards. Ethical questions of informed consent go back to the very language choices people use to narrate and navigate the mental difference or disability. Making these ethical choices between different ways of understanding psychic difference is fundamentally about making narrative and lifestyle choices. This article considers these issues in the context of the many interpretations of Vincent van Gogh's life and their ongoing relevance for contemporary approaches to mental difference and disability.
Endovascular mechanical thrombectomy for cerebral venous sinus thrombosis: a systematic review
Authors: Ilyas Adeel , Chen Ching-Jen , Raper Daniel M , Ding Dale , Buell Thomas , Mastorakos Panogiotis , Liu Kenneth C
Published: February 2017

Background

Cerebral venous sinus thrombosis (CVST) is an uncommon form of stroke that, when severe, can be a therapeutic challenge. Endovascular mechanical thrombectomy (EMT) techniques have significantly evolved over the past decade, but data regarding the efficacy and safety of EMT for CVST are poorly defined.

Objective

To summarize the large number of case series on this relatively rare condition and establish trends in the outcomes of EMT for CVST.

Methods

A literature review was performed using PubMed and Medline to identify reports of three or more patients with CVST treated with EMT. Baseline and outcomes data, including radiographic resolution, neurological outcome, recurrence, and treatment-related complications, were extracted for analysis.

Results

A total of 17 studies comprising 235 patients treated with EMT were included for analysis. Based on pooled data, 40.2% of patients presented with encephalopathy or coma. Concurrent endovascular thrombolysis was employed in 87.6% of patients. Complete radiographic resolution of CVST was achieved in 69.0% of patients. At follow-up (range 0.5–3.5 years), 34.7% of patients were neurologically intact and the mortality rate was 14.3%. CVST recurrence was evident in 1.2%. Worsening or new intracranial hemorrhage (ICH) occurred in 8.7% of cases. ORs of good outcome (modified Rankin Scale score 0–2) and development of ICH with sole EMT versus concurrent thrombolytic therapy were 1.51 (95% CI 0.29 to 8.15, p=0.61) and 1.15 (95% CI 0.12 to 10.80, p=0.90), respectively.

Conclusions

EMT is an effective salvage therapy for refractory CVST, with a reasonable safety profile. Chemical thrombolysis, in conjunction with EMT, did not appear to result in additional harm or benefit. Further analysis is warranted to determine predictors of success after EMT for CVST.
Case‐control study on the use of pituitary‐derived hormones from sheep as a potential risk factor for the occurrence of atypical scrapie in Great Britain
Authors: Marier E. , Dawson M. , Simmons M. , Hope J. , Ortiz‐Peláez A.
Published: February 2017

A case‐control study was conducted in 2013 to investigate the use of pituitary‐derived hormones from sheep as a potential risk factor for the presence of atypical scrapie in Great Britain sheep holdings. One hundred and sixty‐five holdings were identified as cases. Two equal sets of controls were selected: no case of scrapie and cases of classical scrapie. A total of 495 holdings were selected for the questionnaire survey, 201 responses were received and 190 (38.3 per cent) were suitable for analysis. The variables ‘use‐of‐heat‐synchronisation/superovulation’ and ‘flock size’ were significantly associated with the occurrence of atypical scrapie. Farms with atypical cases were less likely (OR 0.25, 95 per cent CI 0.07 to 0.89) to implement heat synchronisation/superovulation in the flock than the control group. Atypical cases were 3.3 times (95 per cent CI 1.38 to 8.13) more likely to occur in large holdings (>879 sheep) than in small flocks (<164 sheep). If the ‘use‐of‐heat‐synchronisation/superovulation’ is a proxy for the use of pituitary‐derived hormones, the significant negative association between having a case of atypical scrapie and the use of these practices rules out the initial hypothesis that using these drugs is a risk factor for the occurrence of atypical scrapie. Flock size was a significant risk factor for atypical scrapie, consistent with a previous generic case‐control study.
Leptospira interrogans serogroup Pomona infections in the UK: is there a real threat for farm animals?
Authors: Arent Z. , Gilmore C. , Barlow A. M. , Smith L. , Ellis W. A.
Published: February 2017

Current typing of Leptospira strains requires a combination of both serological and molecular methods. Study of the epidemiology of strains within the Pomona serogroup has proved problematic due to the limitations of serological typing methods. This is particularly true of the two main complexes within this group, namely the Pomona, Monjakov, Kennewicki cluster in Leptospira interrogans species and the Mozdok, Tsaratsovo, Kunming, Altodouro cluster in Leptospira kirschneri. Strains from the south of England have been shown previously to belong to L kirschneri serovar Mozdok, strains of which are maintained by small rodents in western Europe. While they may occasionally cause disease in domestic animals, they are unlikely to be of economic importance. In contrast, L interrogans serovar Pomona type Kennewicki strains have been shown to be significant animal pathogens, especially in north America, while L interrogans serovar Pomona types Pomona and Monjakov have not been associated with significant economic loss. The purpose of this study was to examine 10 UK serovar Pomona isolates to assess type as a means of assessing the possible risk they pose to British livestock. All isolates were identified as L interrogans serovar Pomona type Pomona and were therefore unlikely to pose a significant threat to domestic animals in the UK.
Susceptibility and PK/PD relationships of Staphylococcus aureus strains isolated from the milk of sheep and goats with clinical mastitis to five veterinary fluoroquinolones
Authors: Serrano‐Rodríguez J. M. , Cárceles‐García C. , Cárceles‐Rodríguez C. M. , Gabarda M. L. , Serrano‐Caballero J. M. , Fernández‐Varón E.
Published: February 2017

Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of veterinary fluoroquinolones as enrofloxacin, its metabolite ciprofloxacin, danofloxacin, difloxacin and marbofloxacin against Staphylococcus aureus strains (n=24) isolated from milk of sheep and goats affected by clinical mastitis were evaluated. The authors have used the MIC and MPC, as well as the pharmacokinetic‐pharmacodynamic relationships in plasma and milk. MIC values were significantly different between drugs, unlike MPC values. Lower MIC values were obtained for danofloxacin and difloxacin, middle and higher values for enrofloxacin, ciprofloxacin and marbofloxacin. However, differences in MPC values were not found between drugs. At conventional doses, the AUC24/MIC and AUC24/MPC ratios were close to 30–80 hours and 5–30 hours, with exception of danofloxacin, in plasma and milk. The time inside the mutant selection window (TMSW) was close to 3–6 hours for enrofloxacin, ciprofloxacin and marbofloxacin, near to 8 hours for danofloxacin and 12–22 hours for difloxacin. From these data, the mutant selection window could be higher for danofloxacin and difloxacin compared with the other fluoroquinolones tested. The authors concluded that enrofloxacin and marbofloxacin, at conventional doses, could prevent the selection of bacterial subpopulations of S aureus, unlike danofloxacin and difloxacin, where higher doses could be used.
ON CASH SETTLED IRR-SWAPTIONS AND MARKOV FUNCTIONAL MODELING
Authors: BERMIN HANS-PETER , WILLIAMS GARETH
Published: February 2017

In this paper, we show how to consistently price cash settled Internal Rate of Return (IRR)-swaptions and derivatives on these contracts. There are several results worth highlighting. First, if we know at what fixed coupon an IRR-swap values to par, we can compute the price of any IRR-swaption in a way consistent with absence of arbitrage. We show that this fixed coupon, denoted the IRR-forward, carries an additional convexity adjustment. The size of the adjustment depends mainly on the shape of the volatility surface but also on the skew of the forward. The largest convexity adjustments are seen for IRR-forwards referencing long tenors and long expiries. Second, we show that any Markov functional technique, relating a given term-structure model to the market observed IRR-swaptions, should be carried out with respect to the corresponding forward measure. The modification of the forward swap rate is further shown to consistently value the fixed and the floating leg of the underlying IRR-swap correctly.
Mississippian reef development in the Cracoe Limestone Formation of the southern Askrigg Block, North Yorkshire, UK
Authors: Waters C. N. , Haslam R. B. , Cózar P. , Somerville I. D. , Millward D. , Woods M.
Published: February 2017

The southern margin of the Askrigg Block around Cracoe, North Yorkshire, shows a transition from carbonate ramp to reef-rimmed shelf margin, which, based on new foraminiferal/algal data, is now constrained to have initiated during the late Asbian. A late Holkerian to early Asbian ramp facies that included small mudmounds developed in comparatively deeper waters, in a transition zone between the proximal ramp, mudmound-free carbonates of the Scaleber Quarry Limestone Member (Kilnsey Formation) and the distal Hodderense Limestone and lower Pendleside Limestone formations of the adjacent Craven Basin. The ramp is envisaged as structurally fragmented, associated with sudden thickness and facies changes. The late Asbian to early Brigantian apron reefs and isolated reef knolls of the Cracoe Limestone Formation include massive reef core and marginal reef flank facies, the latter also including development of small mudmounds on the deeper water toes of back-reef flanks. The position of the apron/knoll reefs is constrained to the south (hangingwall) of the North Craven Fault, but it is syn-depositional displacement on the Middle Craven Fault that accounts for the thick reefal development. Subsequent inversion of this structure during the early Brigantian caused uplift and abandonment of the reefs and subsequent burial by the Bowland Shale Formation.
Engineering challenges for sustainable road access in the Himalayas
Authors: Hearn G. J. , Shakya N. M.
Published: February 2017

Improved road access is fundamental to the current drive for economic development and livelihood improvement in many parts of the Himalayas. There is a history of over one hundred years of road building in the region and an expanding road network that faces serious challenges to its sustainability. These challenges include severe terrain, dynamic geology and heavy rainfall, with earthquakes, landslides, floods, erosion and sediment posing significant hazards. In both India and Nepal there is a large body of published literature that describes the impact of these hazards on roads, and there are a number of manuals, guidelines and standards for sustainable road construction and maintenance. There is also a strong presence of geological and geohazard expertise in both countries that is able to inform decision-making in route selection and road design. However, it is apparent that this expertise is not always being used and that road construction is sometimes taking place without reference to the established manuals and guidelines. Although the guidelines themselves require consolidating and strengthening in certain areas, including a greater infusion of engineering geology, it is paramount that they are used. The future poses major challenges for the engineering sustainability of road access in the Himalayas, but these can be addressed through careful planning, thorough investigation, adherence to best practice, control of construction practices and learning the lessons of the past.
Inferring the properties of the pterosaur wing membrane
Authors: Palmer Colin
Published: February 2017

The preservation of the wing membrane of pterosaurs is very poor and the available fossil evidence does not allow its properties to be reconstructed. In contrast, the fossil record for the wing bones is relatively good and the advent of CT scanning has made it possible to build high-fidelity structural models of the wing spar. The bending strength of the wing spar of a 6 m wingspan ornithocheirid pterosaur is used to infer the likely membrane tension. The tensions required to suppress aeroelastic flutter and to minimize ballooning of the membrane under flight loads are also estimated. All three estimates are of similar magnitude and imply that the membrane must have contained high-modulus material, supporting the view that the reinforcing aktinofibrils were keratinous.
A novel method of standardized myocardial infarction in aged rabbits
Authors: Morrissey Patrick J. , Murphy Kevin R. , Daley Jean M. , Schofield Lorraine , Turan Nilufer N. , Arunachalam Karuppiah , Abbott J. Dawn , Koren Gideon
Published: February 2017

The incidence of both myocardial infarction (MI) and sudden cardiac death increases with age. Here, we describe the development of a minimally invasive large animal model of MI that can be applied to young or aged animals. We demonstrate that rabbit coronary anatomy is highly variable, more so than described in previous literature. In this work, we categorize the coronary pattern of 37 young rabbits and 64 aged rabbits. Aged rabbits had a higher degree of branching from the left main coronary artery. Standardizing the model across age cohorts required a new approach, targeting an area of myocardium rather than a specific vessel. Here, we present a method for achieving a reproducible infarct size, one that yielded a consistent scar encompassing ~30% of the apical left ventricular free wall. The model’s consistency allowed for more valid comparisons of MI sequelae between age cohorts.

NEW & NOTEWORTHY This study describes the coronary angiographic imaging of young and aged rabbits. We developed and improved a novel minimally invasive approach for coil embolization that targets a specific area of myocardium and yielded a consistent scar encompassing ~30% of the left ventricular free wall of young and aged rabbit hearts.
Mitochondria-regulated formation of endothelium-derived extracellular vesicles shifts the mediator of flow-induced vasodilation
Authors: Freed Julie K. , Durand Matthew J. , Hoffmann Brian R. , Densmore John C. , Greene Andrew S. , Gutterman David D.
Published: February 2017

To examine the effect of endothelium-derived extracellular vesicles (eEVs) on the mediator of flow-induced dilation (FID), composition, formation, and functional effects on the mediator of FID were examined from two different eEV subtypes, one produced from ceramide, while the other was produced from plasminogen-activator inhibitor 1 (PAI-1). Using video microscopy, we measured internal-diameter changes in response to increases in flow in human adipose resistance arteries acutely exposed (30 min) to eEVs derived from cultured endothelial cells exposed to ceramide or PAI-1. FID was significantly impaired following exposure to 500K/ml (K = 1,000) of ceramide-induced eEVs (Cer-eEVs) but unaffected by 250K/ml. FID was reduced in the presence of PEG-catalase following administration of 250K/ml of Cer-eEVs and PAI-1 eEVs, whereas Nω-nitro-l-arginine methyl ester (l-NAME) had no effect. Pathway analysis following protein composition examination using liquid chromatography tandem mass spectrometry (LC-MS/MS) demonstrated that both subtypes were strongly linked to similar biological functions, primarily, mitochondrial dysfunction. Flow cytometry was used to quantify eEVs in the presence or absence of l-phenylalanine-4′-boronic acid (PBA) and mitochondria-targeted [93-boronophenyl)methyl]triphenyl-phosphonium (mito-PBA), cytosolic and mitochondrial-targeted antioxidants, respectively. eEV formation was significantly and dramatically reduced with mito-PBA treatment. In conclusion, eEVs have a biphasic effect, with higher doses impairing and lower doses shifting the mediator of FID from nitric oxide (NO) to hydrogen peroxide (H2O2). Despite differences in protein content, eEVs may alter vascular function in similar directions, regardless of the stimulus used for their formation. Furthermore, mitochondrial ROS production is required for the generation of these vesicles.

NEW & NOTEWORTHY The vascular effect of endothelium-derived extracellular vesicles (eEVs) is biphasic, with higher doses decreasing the magnitude of flow-induced dilation (FID) compared with lower doses that shift the mediator of FID from nitric oxide to H2O2. eEVs may cause vascular dysfunction via similar pathways despite being formed from different stimuli, although both require mitochondrial reactive oxygen species for their formation.