bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a multisectoral National Action Plan for Health Security (NAPHS) to implement the International Health Regulations (IHR 2005) in Tanzania
Authors: Mghamba Janneth M , Talisuna Ambrose O , Suryantoro Ludy , Saguti Grace Elizabeth , Muita Martin , Bakari Muhammad , Rusibamayila Neema , Ally Mohamed , Bernard Jubilate , Banda Richard , Mapunda Maximillian , Eidex Rachel , Sreedharan Rajesh , Sliter Karen , Nikkari Simo , Saikat Sohel , Lolong Glenn P M , Verboom Paul , Yahaya Ali Ahmed , Chungong Stella , Rodier Guenael , Fall Ibrahima Soce
Published: March 2018

The Ebola outbreak in West Africa precipitated a renewed momentum to ensure global health security through the expedited and full implementation of the International Health Regulations (IHR) (2005) in all WHO member states. The updated IHR (2005) Monitoring and Evaluation Framework was shared with Member States in 2015 with one mandatory component, that is, States Parties annual reporting to the World Health Assembly (WHA) on compliance and three voluntary components: Joint External Evaluation (JEE), After Action Reviews and Simulation Exercises. In February 2016, Tanzania, was the first country globally to volunteer to do a JEE and the first to use the recommendations for priority actions from the JEE to develop a National Action Plan for Health Security (NAPHS) by February 2017. The JEE demonstrated that within the majority of the 47 indicators within the 19 technical areas, Tanzania had either ‘limited capacity’ or ‘developed capacity’. None had ‘sustainable capacity’. With JEE recommendations for priority actions, recommendations from other relevant assessments and complementary objectives, Tanzania developed the NAPHS through a nationwide consultative and participatory process. The 5-year cost estimate came out to approximately US$86.6 million (22 million for prevent, 50 million for detect, 4.8 million for respond and 9.2 million for other IHR hazards and points of entry). However, with the inclusion of vaccines for zoonotic diseases in animals increases the cost sevenfold. The importance of strong country ownership and committed leadership were identified as instrumental for the development of operationally focused NAPHS that are aligned with broader national plans across multiple sectors. Key lessons learnt by Tanzania can help guide and encourage other countries to translate their JEE priority actions into a realistic costed NAPHS for funding and implementation for IHR (2005).
Building a safety culture in global health: lessons from Guatemala
Authors: Rice Henry E , Lou-Meda Randall , Saxton Anthony T , Johnston Bria E , Ramirez Carla C , Mendez Sindy , Rice Eli N , Aidar Bernardo , Taicher Brad , Baumgartner Joy Noel , Milne Judy , Frankel Allan S , Sexton J Bryan
Published: March 2018

Programmes to modify the safety culture have led to lasting improvements in patient safety and quality of care in high-income settings around the world, although their use in low-income and middle-income countries (LMICs) has been limited. This analysis explores (1) how to measure the safety culture using a health culture survey in an LMIC and (2) how to use survey data to develop targeted safety initiatives using a paediatric nephrology unit in Guatemala as a field test case. We used the Safety, Communication, Operational Reliability, and Engagement survey to assess staff views towards 13 health climate and engagement domains. Domains with low scores included personal burnout, local leadership, teamwork and work–life balance. We held a series of debriefings to implement interventions targeted towards areas of need as defined by the survey. Programmes included the use of morning briefings, expansion of staff break resources and use of teamwork tools. Implementation challenges included the need for education of leadership, limited resources and hierarchical work relationships. This report can serve as an operational guide for providers in LMICs for use of a health culture survey to promote a strong safety culture and to guide their quality improvement and safety programmes.
Temporal prediction of in-hospital falls using tensor factorisation
Authors: Wang Haolin , Zhang Qingpeng , So Hing-Yu , Kwok Angela , Wong Zoie Shui-Yee
Published: March 2018

In-hospital fall incidence is a critical indicator of healthcare outcome. Predictive models for fall incidents could facilitate optimal resource planning and allocation for healthcare providers. In this paper, we proposed a tensor factorisation-based framework to capture the latent features for fall incidents prediction over time. Experiments with real-world data from local hospitals in Hong Kong demonstrated that the proposed method could predict the fall incidents reasonably well (with an area under the curve score around 0.9). As compared with the baseline time series models, the proposed tensor based models were able to successfully identify high-risk locations without records of fall incidents during the past few months.
Effectiveness of evidence-based treatments of fetal alcohol spectrum disorders in children and adolescents: a systematic review protocol
Authors: Singal Deepa , Menard Chantalle , Neilson Christine J , Brownell Marni , Hanlon-Dearman Ana , Chudley Albert , Zarychanski Ryan , Abou-Setta Ahmed
Published: March 2018

Introduction

The aim of this paper is to provide a protocol for a systematic review assessing the effectiveness of evidence from randomised controlled trials comparing fetal alcohol spectrum disorders pharmacological and non-pharmacological interventions with placebo/dummy interventions or usual standards of care in children and adolescents (<18 years old).

Methods and analysis

The following electronic databases will be searched: Medline (Ovid), Cumulative Index of Nursing and Allied Health Plus with Full text (EBSCO), Cochrane Central Register of Controlled Trials (Cochrane Library—Wiley), PsycINFO (ProQuest) and Proquest DissertationsandTheses will be searched from inception to March 2017 for relevant citations of published trials using individualised search strategies prepared for database. We will also search the reference lists of relevant articles and conference proceedings. Two reviewers will independently assess each study against predetermined inclusion/exclusion criteria and extract data including population characteristics, types and duration of interventions and outcomes from included trials. Internal validity will be assessed using the Cochrane Risk of Bias Tool. Primary outcome measures will be improvements in symptoms, including: hyperactivity, impulsivity and attention as measured by standard rating scales. Secondary outcome measures will include improvements in physical and mental health domains, as well as cognitive, behavioural, social and educational skills as measured by rating scales, standardised psychometric tests of IQ and memory, grade repetition, literacy tests and diagnosis of mental health disorder.

Ethics and dissemination

Ethical approval will not be obtained since it is not required for systematic reviews as there are no concerns regarding patient privacy. The results of this review will be disseminated through publication in a peer-review journal and presented at relevant conferences.

PROSPERO registration number

CRD42013005996.
Steps Towards Alcohol Misuse Prevention Programme (STAMPP): a school-based and community-based cluster randomised controlled trial
Authors: McKay Michael , Agus Ashley , Cole Jonathan , Doherty Paul , Foxcroft David , Harvey Séamus , Murphy Lynn , Percy Andrew , Sumnall Harry
Published: March 2018

Objectives

To assess the effectiveness of a combined classroom curriculum and parental intervention (the Steps Towards Alcohol Misuse Prevention Programme (STAMPP)), compared with alcohol education as normal (EAN), in reducing self-reported heavy episodic drinking (HED) and alcohol-related harms (ARHs) in adolescents.

Setting

105 high schools in Northern Ireland (NI) and in Scotland.

Participants

Schools were stratified by free school meal provision. Schools in NI were also stratified by school type (male/female/coeducational). Eligible students were in school year 8/S1 (aged 11–12 years) at baseline (June 2012).

Intervention

A classroom-based alcohol education intervention, coupled with a brief alcohol intervention for parents/carers.

Primary outcomes

(1) The prevalence of self-reported HED in the previous 30 days and (2) the number of self-reported ARHs in the previous 6 months. Outcomes were assessed using two-level random intercepts models (logistic regression for HED and negative binomial for number of ARHs).

Results

At 33 months, data were available for 5160 intervention and 5073 control students (HED outcome), and 5234 and 5146 students (ARH outcome), respectively. Of those who completed a questionnaire at either baseline or 12 months (n=12 738), 10 405 also completed the questionnaire at 33 months (81.7%). Fewer students in the intervention group reported HED compared with EAN (17%vs26%; OR=0.60, 95% CI 0.49 to 0.73), with no significant difference in the number of self-reported ARHs (incident rate ratio=0.92, 95% CI 0.78 to 1.05). Although the classroom component was largely delivered as intended, there was low uptake of the parental component. There were no reported adverse effects.

Conclusions

Results suggest that STAMPP could be an effective programme to reduce HED prevalence. While there was no significant reduction in ARH, it is plausible that effects on harms would manifest later.

Trial registration number

ISRCTN47028486; Post-results.
Evaluation of the district health management fellowship training programme: a case study in Iran
Authors: Gholipour Kamal , Tabrizi Jafar Sadegh , Farahbakhsh Mostafa , Iezadi Shabnam , Ghiasi Akbar , Jahanbin Hasan
Published: March 2018

Objective

To evaluate the district health management fellowship training programme in the north-west of Iran.

Data sources/study setting

The programme was introduced to build the managerial capacity of district health managers in Iran. Eighty-nine heads of units in the province’s health centre, district health managers and the health deputies of the district health centres in the north-west provinces of Iran had registered for the district health management fellowship training programme in Tabriz in 2015–2016.

Study design

This was an educational evaluation study to evaluate training courses to measure participants' reactions and learning and, to a lesser extent, application of training to their job and the organisational impact.

Data collection/extraction methods

Valid and reliable questionnaires were used to assess learning techniques and views towards the fellowship, and self-assessment of health managers’ knowledge and skills. Also, pretest and post-test examinations were conducted in each course and a portfolio was provided to the trainees to be completed in their work settings.

Principal findings

About 63% of the participants were medical doctors and 42.3% of them had over 20 years of experience. Learning by practice (scored 18.37 out of 20) and access to publications (17.27) were the most useful methods of training in health planning and management from the participants’ perspective. Moreover, meeting peers from other districts and the academic credibility of teachers were the most important features of the current programme. Based on the managers’ self-assessment, they were most skilful in quality improvement, managing, planning and evaluation of the district. The results of the post-test analysis on data collected from district health managers showed the highest scores in managing the district (77 out of 100) and planning and evaluation (69) of the courses.

Conclusion

The results of this study indicated that training courses, methods and improvement in managers' knowledge about the health system and the skills necessary to manage their organisation were acceptable.
Organisational perspectives on addressing differential attainment in postgraduate medical education: a qualitative study in the UK
Authors: Woolf Katherine , Viney Rowena , Rich Antonia , Jayaweera Hirosha , Griffin Ann
Published: March 2018

Objectives

To explore how representatives from organisations with responsibility for doctors in training perceive risks to the educational progression of UK medical graduates from black and minority ethnic groups (BME UKGs), and graduates of non-UK medical schools (international medical graduates (IMGs)). To identify the barriers to and facilitators of change.

Design

Qualitative semistructured individual and group interview study.

Setting

Postgraduate medical education in the UK.

Participants

Individuals with roles in examinations and/or curriculum design from UK medical Royal Colleges. Employees of NHS Employers.

Results

Representatives from 11 medical Royal Colleges (n=29) and NHS Employers (n=2) took part (55% medically qualified, 61% male, 71% white British/Irish, 23% Asian/Asian British, 6% missing ethnicity). Risks were perceived as significant, although more so for IMGs than for BME UKGs. Participants based significance ratings on evidence obtained largely through personal experience. A lack of evidence led to downgrading of significance. Participants were pessimistic about effecting change, two main barriers being sensitivities around race and the isolation of interventions. Participants felt that organisations should acknowledge problems, but felt concerned about being transparent without a solution; and talking about race with trainees was felt to be difficult. Participants mentioned 63 schemes aiming to address differential attainment, but these were typically local or specialty-specific, were not aimed at BME UKGs and were largely unevaluated. Participants felt that national change was needed, but only felt empowered to effect change locally or within their specialty.

Conclusions

Representatives from organisations responsible for training doctors perceived the risks faced by BME UKGs and IMGs as significant but difficult to change. Strategies to help organisations address these risks include: increased openness to discussing race (including ethnic differences in attainment among UKGs); better sharing of information and resources nationally to empower organisations to effect change locally and within specialties; and evaluation of evidence-based interventions.
Is it feasible to conduct a randomised controlled trial of pretransplant exercise (prehabilitation) for patients with multiple myeloma awaiting autologous haematopoietic stem cell transplantation? Protocol for the PREeMPT study
Authors: Keen Carol , Skilbeck Julie , Ross Helen , Smith Lauren , Collins Karen , Dixey Joanne , Walters Stephen , Greenfield Diana M , Snowden John A , Mawson Susan
Published: March 2018

Introduction

While myeloma is an incurable malignancy, developments in disease management have led to increased life expectancy in recent years. Treatment typically involves stem-cell transplantation. Increased survival rates equate to more patients living with the burden of both the disease and its treatment for increasing number of years, rendering myeloma a long-term condition.

Evidence exists to demonstrate the benefits of exercise for patients recovering from stem-cell transplantation, and prehabilitation—exercise before treatment—has been shown to be effective in other disease areas. To date there has been no research into prehabilitation in patients with myeloma awaiting transplantation treatment.

Our objective is to determine whether it is feasible to conduct a randomised controlled trial into pretransplant exercise for patients with multiple myeloma who are awaiting autologous stem-cell transplantation.

Methods and analysis

This mixed methods study identifies patients with diagnosis of multiple myeloma who have been assigned to the autologous transplantation list and invites them to participate in six weekly sessions of individualised, supervised exercise while awaiting transplantation.

Quantitative data to determine feasibility targets include rates of recruitment, adherence and adverse events, and outcome measures including 6 min walking distance test and quality of life.

Qualitative interviews are undertaken with a purposive sample of patients to capture their experiences of the study and the intervention.

Ethics and dissemination

Ethics committee approval has been obtained. Dissemination will be through open-access publications and presentations and will seek to reach multiprofessional bases as well as patients and carer groups, addressing the widespread interest in this area of research.

Trial registration number

NCT03135925; Pre-results.
Prospective use of unmanned aerial vehicles for military medical evacuation in future conflicts
Authors: Handford Charles , Reeves F , Parker P
Published: March 2018

In order to continue to deliver outstanding medical care on the battlefield, the UK Defence Medical Services must continue to adapt, overcome and actively embrace change. One potential area is the rapid proliferation and sophistication of automated and remote systems such as unmanned aerial vehicles (UAVs). UAVs are already used to deliver blood to remote military locations in Afghanistan and defibrillators to those that need them in the USA and Sweden. An area of future opportunity would be to facilitate rapid evacuation of wounded personnel from high intensity, high threat, remote and austere areas directly to specialist care. Such a capability would reduce threat to human life while allowing rapid extraction of casualties from high risk or inaccessible environments straight back to Role 3 care, all of which in these situations is either not possible or carries too much risk using conventional aerial assets. The article aims to highlight a potential future capability, stimulate debate and reflection, all of which is essential for innovation and future organisational development. The potential uses and benefits of UAVs are highlighted including both the challenges and rewards of utilising UAVs for casualty evacuation. Key benefits are reduced risk to human life, cost, ability to insert into areas conventional aircraft cannot and the rapidity of transfer. Challenges are likely to be airspace management, decisions on appropriate level of care to deliver during transit and ultimately user acceptability. The article also highlights that in order to maximise our ability to exploit new technologies, all arms and trades within the military must be involved in collective research and development. Furthermore, sensible corroboration with private companies will further enhance our ability to acquire products that best serve our needs.
Forgetting ourselves: epistemic costs and ethical concerns in mindfulness exercises
Authors: Ratnayake Sahanika , Merry David
Published: March 2018

Mindfulness exercises are presented as being compatible with almost any spiritual, religious or philosophical beliefs. In this paper, we argue that they in fact involve imagining and conceptualising rather striking and controversial claims about the self, and the self’s relationship to thoughts and feelings. For this reason, practising mindfulness exercises is likely to be in tension with many people’s core beliefs and values, a tension that should be treated as a downside of therapeutic interventions involving mindfulness exercises, not unlike a side effect. Clients ought to be informed of these metaphysical aspects of the exercises, and mental health providers ought to take them into account in assessing which course of treatment to recommend. Given these concerns, the casual way in which mindfulness exercises are presently distributed by mental health providers to the general public is inappropriate.
Making medical decisions for an incompetent older adult when both a proxy and an advance directive are available: which is more likely to reflect the older adult’s preferences?
Authors: Bravo Gina , Sene Modou , Arcand Marcel
Published: March 2018

Objectives

To investigate which of two sources of information about an older adult’s wishes—choices made in an advance directive or proxy’s opinion—provides better insight into the older adult’s preferences measured in hypothetical clinical situations involving decisional incapacity.

Methods

Secondary analyses of data collected from 157 community-dwelling, decisionally competent adults aged 70 years and over who attended a group information session on advance directives with their proxy. Older adults were invited to complete a directive introduced during the session, designed to express healthcare preferences. An average of 3 months later, older adults were asked during an interview whether they would want to receive each of four medical interventions and what their goals of care would be should they develop one of three sudden health events, assuming that they had severe dementia. Proxies were asked to guess the older adult’s answers in each of the seven scenarios.

Results

Eighty per cent of the older adults completed the directive. Choices they made in the directive were more in line with the preferences they stated during the interview than were their proxies’ guesses at their answers. However, concordance was relatively low, with percentages of agreement ranging from 43% to 83% across scenarios.

Conclusions

Findings suggest that a directive might provide better insight into a person’s wishes than the person’s proxy, although neither source is perfect. A multifaceted decision-making model that includes both sources of information might better serve the interests of older adults who have lost the capacity to make decisions on their own.

Trial registration number

ISRCTN89993391; Post-results.
Resuscitation decisions at the end of life: medical views and the juridification of practice
Authors: MacCormick Fiona MA , Emmett Charlotte , Paes Paul , Hughes Julian C
Published: March 2018

Background

Concerns about decision making related to resuscitation have led to two important challenges in the courts resulting in new legal precedents for decision-making practice. Systematic research investigating the experiences of doctors involved in decisions about resuscitation in light of the recent changes in law remains lacking.

Aim

To analyse the practice of resuscitation decision making on hospital wards from the perspectives of doctors.

Design

The data presented in this paper were collected as part of a wider research study of end-of-life care in an acute hospital setting. Data collection comprised ethnographic non-participant observation on two acute hospital wards and individual interviews with patients, relatives and healthcare professionals caring for patients thought to be approaching the end of life. Data were analysed using a constructivist grounded theory approach.

Results

Discussions and decision making about resuscitation present many challenges for those involved on acute medical wards. The data highlight the potential for multiple interpretations of legal precedents, creating misunderstandings that may impact patient care in less positive ways.

Conclusions

This paper provides unique insights into how doctors respond to the changing medico-legal culture and the subsequent effects on patient care. It demonstrates how the juridification of medical practice can occur. It highlights the potential benefit of a structure to support clinicians, patients and relatives in discussing and navigating decisions around care at the end of life in line with the patient’s wishes and preferences. Recommendations for future research are made and legal ramifications are discussed.
Management of tandem occlusions in acute ischemic stroke – intracranial versus extracranial first and extracranial stenting versus angioplasty alone: a systematic review and meta-analysis
Authors: Wilson Mitchell P , Murad Mohammad H , Krings Timo , Pereira Vitor M , O’Kelly Cian , Rempel Jeremy , Hilditch Christopher A , Brinjikji Waleed
Published: March 2018

Background

Optimal technical approaches of large-vessel anterior circulation acute ischemic strokes with concomitant extracranial internal carotid artery tandem occlusions is controversial.

Purpose

This systematic review and meta-analysis evaluates: the overall outcomes of patients with tandem occlusions treated with second-generation mechanical thrombectomy devices; differences in outcomes of extracranial versus intracranial first approaches; and differences in outcomes of extracranial stenting at time of procedure versus angioplasty alone.

Methods

MEDLINE, EMBASE, and the Web of Science was searched through September 2017 for studies evaluating patients presenting with acute tandem occlusions of the extracranial ICA and intracranial ICA, and/or proximal MCA treated with second-generation mechanical thrombectomy devices. Outcomes were pooled across studies using the random-effects model and expressed as cumulative incidence (event rate) and 95% CI.

Results

Thirty-three studies were included in analysis. Overall mRS≤0–2 at 90 days was 47% (95% CI 42% to 51%). No statistical difference was seen in 90-day mRS≤0–2 for patients treated with extracranial versus intracranial first approaches, 53% (95% CI 44% to 61%) vs 49% (95% CI 44% to 57%) (P=0.58). No statistical difference was seen in 90-day mRS≤0–2 for patients treated with extracranial stenting versus angioplasty alone, 49% (95% CI 42% to 56%) vs 49% (95% CI 33% to 65%) (P=0.39). No other statistical differences in outcome or safety were identified.

Conclusions

Nearly half of all tandem occlusion patients treated with mechanical thrombectomy have good neurological outcomes. No statistical differences in outcome are identified between extracranial first versus intracranial first approaches, nor extracranial stenting versus angioplasty alone.
Role of ivabradine in management of stable angina in patients with different clinical profiles
Authors: Kaski Juan Carlos , Gloekler Steffen , Ferrari Roberto , Fox Kim , Lévy Bernard I , Komajda Michel , Vardas Panos , Camici Paolo G
Published: March 2018

In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of theIfcurrent, decreases myocardial oxygen consumption while increasing diastolic time, without affecting myocardial contractility or coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina and chronic heart failure (HF). This review examines available evidence regarding the efficacy and safety of ivabradine in stable angina, when used as monotherapy or in combination with beta-blockers, in particular angina subgroups and in patients with stable angina with left ventricular systolic dysfunction (LVSD) or HF. Trials involving more than 45 000 patients receiving treatment with ivabradine have shown that this agent has antianginal and anti-ischaemic effects, regardless of age, sex, severity of angina, revascularisation status or comorbidities. This heart rate-lowering agent might also improve prognosis, reduce hospitalisation rates and improve QOL in angina patients with chronic HF and LVSD.
Identification of monosodium urate crystal deposits in patients with asymptomatic hyperuricemia using dual-energy CT
Authors: Wang Penny , Smith Stacy E , Garg Rajesh , Lu Fengxin , Wohlfahrt Alyssa , Campos Anarosa , Vanni Kathleen , Yu Zhi , Solomon Daniel H , Kim Seoyoung C
Published: March 2018

Objectives

Dual-energy CT (DECT) scan is a sensitive and specific tool used to visualise and quantify monosodium urate (MSU) crystal deposits in the joints. Few studies have examined MSU crystal deposits in patients with asymptomatic hyperuricemia (ie, hyperuricemia in the absence of gout) using DECT.

Methods

We conducted a prospective, non-interventional cross-sectional study to detect MSU crystal deposits on DECT scans among patients with asymptomatic hyperuricemia. We also examined patient factors associated with subclinical MSU crystal deposits. Out of 130 subjects aged ≥40 years with metabolic syndrome screened for serum uric acid (sUA) levels ≥6.5 mg/dL, 46 underwent a foot/ankle DECT scan.

Results

The mean age of the study participants was 62 (±8) years, 41% were men and the mean sUA level was 7.8 (±1.0) mg/dL. Seven (15%) of 46 patients had MSU crystal deposits on DECT with a mean total volume of 0.13 (±0.14) cm3. In the univariable logistic regression analysis, older age had a significant association with presence of MSU crystal deposits (OR 1.20, 95% CI 1.03 to 1.39), but sUA did not (OR 1.36, 95% CI 0.63 to 2.95). In the univariable analysis, sUA levels showed a trend towards a modest linear association (β=0.11, P=0.09) with total volume of MSU crystal deposits.

Conclusions

Fifteen per cent of patients with asymptomatic hyperuricemia had subclinical MSU crystal deposits on foot/ankle DECT scans. Older age, but not sUA, was significantly associated with presence of subclinical MSU crystal deposits among patients with asymptomatic hyperuricemia. Clinical significance of these subclinical MSU crystal deposits needs to be determined.
Registry report on prediction by Pocock cardiovascular score of cerebral microemboli acutely following carotid endarterectomy
Authors: Saedon Mahmud , Saratzis Athanasios , Lee Rachel W S , Hutchinson Charles E , Imray Christopher H E , Singer Donald R J
Published: March 2018

Background

Cerebral microemboli may lead to ischaemic neurological complications after carotid endarterectomy (CEA). The association between classical cardiovascular risk factors and acute cerebral microemboli following carotid surgery has not been studied. The aim of this study was to explore whether an established cardiovascular risk score (Pocock score) predicts the presence of cerebral microemboli acutely after CEA.

Subjects and methods

Pocock scores were assessed for the 670 patients from the Carotid Surgery Registry (age 71±1 (SEM) years, 474 (71%) male, 652 (97%) Caucasian) managed from January 2002 to December 2012 in the Regional Vascular Centre at University Hospitals Coventry and Warwickshire NHS Trust, which serves a population of 950 000. CEA was undertaken in 474 (71%) patients for symptomatic carotid stenosis and in 196 (25%) asymptomatic patients during the same period. 74% of patients were hypertensive, 71% were smokers and 49% had hypercholesterolaemia.

Results

A high Pocock score (≥2.3%) was significantly associated with evidence of cerebral microemboli acutely following CEA (P=0.039, Mann-Whitney (MW) test). A Pocock score (≥2.3%) did not predict patients who required additional antiplatelet therapy (microemboli signal (MES) rate >50 hour-1: P=0.164, MW test). Receiver operating characteristic analysis also showed that the Pocock score predicts acute postoperative microemboli (area under the curve (AUC) 0.546, 95% CI 0.502 to 0.590, P=0.039) but not a high rate of postoperative microemboli (MES >50 hour−1: AUC 0.546, 95% CI 0.482 to 0.610, P=0.164). A Pocock score ≥2.3% showed a sensitivity of 74% for the presence of acute postoperative cerebral microemboli. A Pocock score ≥2.3% also showed a sensitivity of 77% and a negative predictive value of 90% for patients who developed a high microembolic rate >50 hour−1after carotid surgery.

Conclusion

These findings demonstrate that the Pocock score could be used as a clinical tool to identify patients at high risk of developing acute postoperative microemboli.
Tracheal growth assessment in mongrel puppies (dogs) through multidetector CT
Authors: Soriano‐Rosales Rosa Eugenia , Pérez‐Guillé Beatriz Eugenia , Jimenez‐Bravo‐Luna Miguel Angel , Monroy‐Santoyo Susana , Villegas‐Alvarez Fernándo , Carmona‐Mancilla Arturo , Jiménez‐Gutiérrez Carlos , Elizalde‐Velázquez Susana Leticia , Gonzalez‐Zamora Jose Francisco
Published: March 2018

The aim of this study was to describe the tracheal growth pattern and its zoometric relationship in related medium‐sized mongrel puppies through adulthood. Fourteen puppies were studied. CT monitoring was performed monthly, starting in the 1st month of life through the 7th month and subsequently at the 9th and 12th months. Additionally, six zoometric measurements were performed. Dorsoventral (DV) and transverse (TV) diameters and the luminal area from C1 to T2 were obtained. The global tracheal growth pattern revealed an increase up to 13 times its initial size, reaching a plateau phase during the last trimester. The relationship between the DV and the TV internal diameters of the tracheal lumen did not change during growth. As previously reported, the cranial tracheal area was wider, while the caudal part gradually decreased towards T1–T2; this consideration is important since the more distal an endotracheal tube is inserted, the greater the risk that injury may occur. The linear correlation between the zoometric measurements and the tracheal ring areas was positive. This study provides evidence for the evaluation of the morphometry of the canine trachea during physiological growth using helicoidal CT as a non‐invasive, accurate tool.
Snow cover variability at Polar Bear Pass, Nunavut
Authors: Young Kathy L. , Brown Laura , Labine Claude
Published: March 2018

Information on arctic snow covers is relevant for climate and hydrology studies and investigations into the sustainability of both arctic fauna and flora. This study aims to (1) highlight the variability of snow cover at Polar Bear Pass (PBP) at a range of scales: point, local, and regional using both in situ snow cover measurements and remote sensing imagery products; and (2) consider how snow cover at PBP might change in the future. Terrain-based snow surveys documented the end-of-winter snowpacks over several seasons (2008–2010, 2012–2013), and snowmelt was measured daily at typical terrain types. MODIS products (snow cover) were used to document spatial snow cover variability across PBP and Bathurst and Cornwallis Islands. Due to limited data, no significant difference in snow cover duration can be identified at PBP over the period of record. Locally, end-of-winter snow cover does vary across a range of terrain types with snow depths and densities reflecting polar oasis sites. Aspect remains a defining factor in terms of snow cover variability at PBP. Northern areas of the Pass melt earlier. Regionally, PBP tends to melt out earlier than most of Bathurst Island. In the future, we surmise that snowpacks at PBP will be thinner and disappear earlier.
MiR-21 regulates the apoptosis of keloid fibroblasts by caspase-8 and the mitochondria-mediated apoptotic signaling pathway via targeting FasL
Authors: Liu Ying , Ren Lihong , Liu Wenjing , Xiao Zhibo
Published: March 2018

MicroRNA-21 (miR-21) has been found to be upregulated in keloid tissue and to affect the proliferation and apoptosis of keloid fibroblasts; however, the possible mechanisms remain unclear. In this study, we aimed to evaluate the role of miR-21 in FasL-induced caspase-8 activation and the mitochondria-mediated apoptotic signaling pathway in keloid fibroblasts. Our study found that the protein level of FasL was decreased by miR-21 over-expression, while being enhanced by miR-21 inhibition in keloid fibroblasts. Subsequently, the mitochondria-mediated apoptosis of keloid fibroblasts was restrained by miR-21 over-expression, as evidenced by enhanced mitochondrial membrane potential and decreased production of mitochondrial ROS. Moreover, over-expression of miR-21 inhibited the activation of the caspase-8 and the mitochondria-mediated apoptotic signaling pathway. As expected, inhibition of miR-21 had the opposite effects. Finally, silencing of FasL suppressed miR-21 inhibition-induced apoptosis by inactivation of caspase-8 and the mitochondria-mediated apoptotic signaling pathway, which was comparable to Z-IETD-FMK, a caspase-8 inhibitor. Taken together, these results suggest that miR-21 regulates the apoptosis of keloid fibroblasts via targeting FasL, and caspase-8 and the mitochondria-mediated apoptotic signaling pathway is involved in this process. Our findings provide evidence that miR-21 may be considered to be a therapeutic target for keloids.
Forecasting primary delay recovery of high-speed railway using multiple linear regression, supporting vector machine, artificial neural network, and random forest regression
Authors: Jiang Chaozhe , Huang Ping , Lessan Javad , Fu Liping , Wen Chao
Published: March 2018

Accurate prediction of recoverable train delay can support the train dispatchers’ decision-making with timetable rescheduling and improving service reliability. In this paper, we present the results of an effort aimed to develop primary delay recovery (PDR) predictor model using train operation records from Wuhan-Guangzhou (W-G) high-speed railway. To this end, we first identified the main variables that contribute to delay, including dwell buffer time, running buffer time, magnitude of primary delay time, and individual sections’ influence. Different models are applied and calibrated to predict the PDR. The validation results on test datasets indicate that the random forest regression (RFR) model outperforms the other three alternative models, namely, multiple linear regression (MLR), support vector machine (SVM), and artificial neural networks (ANN) regarding prediction accuracy measure. Specifically, the evaluation results show that when the prediction tolerance is less than 1 min, the RFR model can achieve up to 80.4% of prediction accuracy, while the accuracy level is 44.4%, 78.5%, and 78.5% for MLR, SVM, and ANN models, respectively.
High glucose causes vascular dysfunction through Akt/eNOS pathway: reciprocal modulation by juglone and resveratrol
Authors: Pektas M. Bilgehan , Turan Ozge , Ozturk Bingol Gozde , Sumlu Esra , Sadi Gökhan , Akar Fatma
Published: March 2018

Transient elevations in blood glucose level may lead to changes in vascular function. Herein, we investigated the effects of high-glucose or high-fructose challenge, as well as potential influence of juglone or resveratrol on vascular reactivity, Akt/eNOS, and insulin signaling effectors in rat aorta. Aortic segments of rats were incubated with high glucose (30 mmol/L) or high fructose (2 mmol/L) in the absence and presence of juglone (5 μmol/L) or resveratrol (10 μmol/L). Acute high-glucose incubation markedly decreased acetylcholine-induced relaxation, which is further inhibited by juglone, but ameliorated by resveratrol. Incubation with high glucose caused significant reduction in pAkt/total Akt and peNOS/total eNOS ratios, as well as in the expression of some genes involved in insulin signaling. Juglone produced a further impairment, whereas resveratrol resulted in an improvement on the expression profiles of these proteins and genes. Acute exposure of aortic segments to high glucose causes a reduction in acetylcholine-induced relaxation in association with suppression of Akt/eNOS pathway, as well as several genes in insulin signaling pathway. Juglone and resveratrol have opposite actions on vascular relaxation and the above signaling targets. These findings could be relevant for the treatment of hyperglycemia-induced vascular complications.
The waning of the WIMP? A review of models, searches, and constraints
Authors: Arcadi Giorgio , Dutra Maíra , Ghosh Pradipta , Lindner Manfred , Mambrini Yann , Pierre Mathias , Profumo Stefano , Queiroz Farinaldo S.
Published: March 2018

Weakly Interacting Massive Particles (WIMPs) are among the best-motivated dark matter candidates. No conclusive signal, despite an extensive search program that combines, often in a complementary way, direct, indirect, and collider probes, has been detected so far. This situation might change in near future due to the advent of one/multi-TON Direct Detection experiments. We thus, find it timely to provide a review of the WIMP paradigm with focus on a few models which can be probed at best by these facilities. Collider and Indirect Detection, nevertheless, will not be neglected when they represent a complementary probe.
Fault system evolution in the Baltic Sea area west of Rügen, NE Germany
Authors: Deutschmann André , Meschede Martin , Obst Karsten
Published: March 2018

Based on reprocessed offshore seismic lines acquired during oil and gas exploration in the 1980s, we reconstruct the formation and reactivation of major fault systems in the southern Baltic Sea area since the late Paleozoic. The geological evolution of different crustal blocks from the Caledonian Avalonia–Baltica collision until the Late Cretaceous–Paleogene inversion tectonics is also examined. The detected fault systems occur in the northern part of the Trans-European Suture Zone (TESZ) and belong either to the late Paleozoic Tornquist Fan or to the complex Western Pomeranian Fault System (WPFS) generated during Mesozoic extensional movements. While the NW–SE-trending deep Wiek Fault separates the Arkona High from the Middle Rügen Block, the NNW–SSE-trending Agricola Fault demarcates the Middle Rügen Block to the Falster Block in the west. Together with the Plantagenet Fault and numerous younger faults in the Mesozoic cover, it forms the Agricola Fault System. Furthermore, structural analyses of the Prerow Fault Zone above the Prerow salt pillow and the Werre Fault Zone crossing the Grimmen High indicate a complex fault history.
Economics of Water Recovery in the Murray-Darling Basin, Australia
Authors: Grafton R. Quentin , Wheeler Sarah Ann
Published: March 2018

We review recent water reforms and the consequences of water recovery intended to increase stream flows in the Murray-Darling Basin (MDB), Australia. The MDB provides a natural experiment of water recovery for the environment that includes ( a) the voluntary buy-back of water rights from willing sellers and ( b) the subsidization of irrigation infrastructure. We find that ( a) the actual increase in the volumes of water in terms of stream flows is much less than claimed by the Australian government; ( b) subsidies to increase irrigation efficiency have reduced stream and groundwater return flows; ( c) buy-backs are much more cost effective than subsidies; ( d) many of the gains from water recovery have accrued as private benefits to irrigators; and ( e) more than a decade after water recovery began, there is no observable basin-wide relationship between volumes of water recovered and flows at the mouth of the River Murray.
Functional Toll-like Receptor 4 Overexpression in Papillary Thyroid Cancer by MAPK/ERK–Induced ETS1 Transcriptional Activity
Authors: Peyret Victoria , Nazar Magalí , Martín Mariano , Quintar Amado A. , Fernandez Elmer A. , Geysels Romina C. , Fuziwara Cesar S. , Montesinos María M. , Maldonado Cristina A. , Santisteban Pilar , Kimura Edna T. , Pellizas Claudia G. , Nicola Juan P. , Masini-Repiso Ana M.
Published: March 2018

Emerging evidence suggests that unregulated Toll-like receptor (TLR) signaling promotes tumor survival signals, thus favoring tumor progression. Here, the mechanism underlying TLR4 overexpression in papillary thyroid carcinomas (PTC) mainly harboring the BRAFV600E mutation was studied. TLR4 was overexpressed in PTC compared with nonneoplastic thyroid tissue. Moreover, paired clinical specimens of primary PTC and its lymph node metastasis showed a significant upregulation of TLR4 levels in the metastatic tissues. In agreement, conditional BRAFV600E expression in normal rat thyroid cells and mouse thyroid tissue upregulated TLR4 expression levels. Furthermore, functional TLR4 expression was demonstrated in PTC cells by increased NF-κB transcriptional activity in response to the exogenous TLR4-agonist lipopolysaccharide. Of note, The Cancer Genome Atlas data analysis revealed that BRAFV600E-positive tumors with high TLR4 expression were associated with shorter disease-free survival. Transcriptomic data analysis indicated a positive correlation between TLR4 expression levels and MAPK/ERK signaling activation. Consistently, chemical blockade of MAPK/ERK signaling abrogated BRAFV600E-induced TLR4 expression. A detailed study of the TLR4 promoter revealed a critical MAPK/ERK–sensitive Ets-binding site involved in BRAFV600E responsiveness. Subsequent investigation revealed that the Ets-binding factor ETS1 is critical for BRAFV600E-induced MAPK/ERK signaling-dependent TLR4 gene expression. Together, these data indicate that functional TLR4 overexpression in PTCs is a consequence of thyroid tumor-oncogenic driver dysregulation of MAPK/ERK/ETS1 signaling.

Implications: Considering the participation of aberrant NF-κB signaling activation in the promotion of thyroid tumor growth and the association of high TLR4 expression with more aggressive tumors, this study suggests a prooncogenic potential of TLR4 downstream signaling in thyroid tumorigenesis. Mol Cancer Res; 16(5); 833–45. ©2018 AACR.
Targeting CREB Pathway Suppresses Small Cell Lung Cancer
Authors: Xia Yifeng , Zhan Cheng , Feng Mingxiang , Leblanc Mathias , Ke Eugene , Yeddula Narayana , Verma Inder M.
Published: March 2018

Small cell lung cancer (SCLC) is the most deadly subtype of lung cancer due to its dismal prognosis. We have developed a lentiviral vector-mediated SCLC mouse model and have explored the role of both the NF-κB and CREB families of transcription factors in this model. Surprisingly, induction of NF-κB activity, which promotes tumor progression in many cancer types including non–small cell lung carcinoma (NSCLC), is dispensable in SCLC. Instead, suppression of NF-κB activity in SCLC tumors moderately accelerated tumor development. Examination of gene expression signatures of both mouse and human SCLC tumors revealed overall low NF-κB but high CREB activity. Blocking CREB activation by a dominant-negative form of PKA (dnPKA) completely abolished the development of SCLC. Similarly, expression of dnPKA or treatment with PKA inhibitor H89 greatly reduced the growth of SCLC tumors in syngeneic transplantation models. Altogether, our results strongly suggest that targeting CREB is a promising therapeutic strategy against SCLC.

Implications: Activity of the transcription factor CREB is elevated in SCLC tumors, which helps to maintain its neuroendocrine signature and cell proliferation. Our results highlight the importance of targeting the CREB pathway to develop new therapeutics to combat SCLC. Mol Cancer Res; 16(5); 825–32. ©2018 AACR.
Molecular Response to Neoadjuvant Chemotherapy in High-Grade Serous Ovarian Carcinoma
Authors: Arend Rebecca C. , Londoño Angelina I. , Montgomery Allison M. , Smith Haller J. , Dobbin Zachary C. , Katre Ashwini A. , Martinez Alba , Yang Eddy S. , Alvarez Ronald D. , Huh Warner K. , Bevis Kerri S. , Straughn J. Michael , Estes Jacob M. , Novak Lea , Crossman David K. , Cooper Sara J. , Landen Charles N. , Leath Charles A.
Published: March 2018

While high-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants [by DNA next-generation sequencing (NGS) using a 50 gene Ion Torrent panel] and gene expression (using the NanoString PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT). NGS was performed on plasma cell free DNA (cfDNA) on a select group of patients (n = 14) to assess the utility of using cfDNA to monitor these changes. A total of 86 genes had significant changes in RNA expression after NACT. Thirty-eight genetic variants (including SNPs) from 6 genes were identified in tumors pre-NACT, while 59 variants from 19 genes were detected in the cfDNA. The number of DNA variants were similar after NACT. Of the 59 variants in the plasma pre-NACT, only 6 persisted, whereas 33 of 38 specific variants in the tumor DNA remained unchanged. Pathway analysis showed the most significant alterations in the cell cycle and DNA damage pathways.

Implications: Gene expression profiles at the time of interval debulking provide additional genetic information that could help impact treatment decisions after NACT; although, continued collection and analysis of matched tumor and cfDNA from multiple time points are needed to determine the role of cfDNA in the management of HGSOC. Mol Cancer Res; 16(5); 813–24. ©2018 AACR.