bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol for a systematic review of telephone delivered psychosocial interventions on relapse prevention, adherence to psychiatric medication and health risk behaviours in adults with a psychotic disorder
Authors: Beck Alison K , Baker Amanda , Turner Alyna , Haddock Gillian , Kelly Peter J , Berry Katherine , Bucci Sandra
Published: December 2015

Introduction

The mental and physical health of individuals with a psychotic illness are typically poor. When adhered to, medication can reduce relapse. However, despite adherence, relapse remains common and functional outcomes often remain compromised. Compliance is also typically low. Cardiovascular-related morbidity and mortality is also elevated, along with several important modifiable health risk behaviours. Access to psychosocial interventions is therefore important, but currently limited. Telephone delivered interventions represent a promising solution, although further clarity is needed. Accordingly, we aim to provide an overview and critical analysis of the current state of evidence for telephone delivered psychosocial interventions targeting key health priorities in adults with a psychotic disorder, including (1) relapse, (2) adherence to psychiatric medication and/or (3) modifiable cardiovascular health risk behaviours.

Methods and analysis

Our methods are informed by published guidelines. The review is registered and any protocol amendments will be tracked. Ten electronic peer-reviewed and four grey literature databases have been identified. Preliminary searches have been conducted for literature on psychosocial telephone interventions targeting relapse, medication adherence and/or health risk behaviours in adults with a psychotic disorder. Articles classified as ‘evaluation’ will be assessed against standardised criteria and checked by an independent assessor. The searches will be re-run just before final analyses and further studies retrieved for inclusion. A narrative synthesis will be reported, structured around intervention type and content, population characteristics and outcomes. Where possible, ‘summary of findings’ tables will be generated for each comparison. For the primary outcome of each trial, when data are available, we will calculate a risk ratio and its 95% CI (dichotomous outcomes) and/or effect size according to Cohen's formula (continuous outcomes).

Ethics and dissemination

No ethical issues are foreseen. Findings will be disseminated widely to clinicians and researchers via journal publication and conference presentation(s).

Trial registration number

PROSPERO CRD42015025402.
Achieving change in primary care—effectiveness of strategies for improving implementation of complex interventions: systematic review of reviews
Authors: Lau Rosa , Stevenson Fiona , Ong Bie Nio , Dziedzic Krysia , Treweek Shaun , Eldridge Sandra , Everitt Hazel , Kennedy Anne , Qureshi Nadeem , Rogers Anne , Peacock Richard , Murray Elizabeth
Published: December 2015

Objective

To identify, summarise and synthesise available literature on the effectiveness of implementation strategies for optimising implementation of complex interventions in primary care.

Design

Systematic review of reviews.

Data sources

MEDLINE, EMBASE, CINAHL, Cochrane Library and PsychINFO were searched, from first publication until December 2013; the bibliographies of relevant articles were screened for additional reports.

Eligibility criteria for selecting studies

Eligible reviews had to (1) examine effectiveness of single or multifaceted implementation strategies, (2) measure health professional practice or process outcomes and (3) include studies from predominantly primary care in developed countries. Two reviewers independently screened titles/abstracts and full-text articles of potentially eligible reviews for inclusion.

Data synthesis

Extracted data were synthesised using a narrative approach.

Results

91 reviews were included. The most commonly evaluated strategies were those targeted at the level of individual professionals, rather than those targeting organisations or context. These strategies (eg, audit and feedback, educational meetings, educational outreach, reminders) on their own demonstrated a small to modest improvement (2–9%) in professional practice or behaviour with considerable variability in the observed effects. The effects of multifaceted strategies targeted at professionals were mixed and not necessarily more effective than single strategies alone. There was relatively little review evidence on implementation strategies at the levels of organisation and wider context. Evidence on cost-effectiveness was limited and data on costs of different strategies were scarce and/or of low quality.

Conclusions

There is a substantial literature on implementation strategies aimed at changing professional practices or behaviour. It remains unclear which implementation strategies are more likely to be effective than others and under what conditions. Future research should focus on identifying and assessing the effectiveness of strategies targeted at the wider context and organisational levels and examining the costs and cost-effectiveness of implementation strategies.

PROSPERO registration number

CRD42014009410.
Clinical effectiveness and cost-effectiveness of the Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) facilitated self-care rehabilitation intervention in heart failure patients and caregivers: rationale and protocol for a multicentre randomised controlled trial
Authors: Taylor R S , Hayward C , Eyre V , Austin J , Davies R , Doherty P , Jolly K , Wingham J , Van Lingen R , Abraham C , Green C , Warren FC , Britten N , Greaves C J , Singh S , Buckingham S , Paul K , Dalal H
Published: December 2015

Introduction

The Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) trial is part of a research programme designed to develop and evaluate a health professional facilitated, home-based, self-help rehabilitation intervention to improve self-care and health-related quality of life in people with heart failure and their caregivers. The trial will assess the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in patients with systolic heart failure and impact on the outcomes of their caregivers.

Methods and analysis

A parallel two group randomised controlled trial with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention group) or usual care alone (control group) in 216 patients with systolic heart failure (ejection fraction <45%) and their caregivers. The intervention comprises a self-help manual delivered by specially trained facilitators over a 12-week period. The primary outcome measure is patients’ disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure questionnaire at 12 months’ follow-up. Secondary outcomes include survival and heart failure related hospitalisation, blood biomarkers, psychological well-being, exercise capacity, physical activity, other measures of quality of life, patient safety and the quality of life, psychological well-being and perceived burden of caregivers at 4, 6 and 12 months’ follow-up. A process evaluation will assess fidelity of intervention delivery and explore potential mediators and moderators of changes in health-related quality of life in intervention and control group patients. Qualitative studies will describe patient and caregiver experiences of the intervention. An economic evaluation will estimate the cost-effectiveness of the REACH-HF intervention plus usual care versus usual care alone in patients with systolic heart failure.

Ethics and dissemination

The study is approved by the North West—Lancaster Research Ethics Committee (ref 14/NW/1351). Findings will be disseminated via journals and presentations to publicise the research to clinicians, commissioners and service users.

Trial registration number

ISRCTN86234930; Pre-results.
Integrated Primary Care Teams (IPCT) pilot project in Quebec: a protocol paper
Authors: Contandriopoulos Damien , Duhoux Arnaud , Roy Bernard , Amar Maxime , Bonin Jean-Pierre , Borges Da Silva Roxane , Brault Isabelle , Dallaire Clémence , Dubois Carl-Ardy , Girard Francine , Jean Emmanuelle , Larue Caroline , Lessard Lily , Mathieu Luc , Pépin Jacinthe , Perroux Mélanie , Cockenpot Aurore
Published: December 2015

Introduction

The overall aim of this project is to help develop knowledge about primary care delivery models likely to improve the accessibility, quality and efficiency of care. Operationally, this objective will be achieved through supporting and evaluating 8 primary care team pilot sites that rely on an expanded nursing role within a more intensive team-based, interdisciplinary setting.

Methods and analysis

The first research component is aimed at supporting the development and implementation of the pilot projects, and is divided into 2 parts. The first part is a logical analysis based on interpreting available scientific data to understand the causal processes by which the objectives of the intervention being studied may be achieved. The second part is a developmental evaluation to support teams in the field in a participatory manner and thereby learn from experience. Operationally, the developmental evaluation phase mainly involves semistructured interviews. The second component of the project design focuses on evaluating pilot project results and assessing their costs. This component is in turn made up of 2 parts. Part 1 is a pre-and-post survey of patients receiving the intervention care to analyse their care experience. In part 2, each patient enrolled in part 1 (around 4000 patients) will be matched with 2 patients followed within a traditional primary care model, so that a comparative analysis of the accessibility, quality and efficiency of the intervention can be performed. The cohorts formed in this way will be followed longitudinally for 4 years.

Ethics and dissemination

The project, as well as all consent forms and research tools, have been accepted by 2 health sciences research ethics committees. The procedures used will conform to best practices regarding the anonymity of patients.
Self-reported symptoms of chronic cough and breathlessness in working-age men in the city of Izhevsk, Russia: associations with cardiovascular disease risk factors and comorbidities
Authors: Cook Sarah , Quint Jennifer K , Vasiljev Maxim , Leon David A
Published: December 2015

Introduction

Very little is known about the prevalence of respiratory symptoms or their associations with other health conditions in Russia.

Methods

Between 2008 and 2010, a sample of 983 men resident in Izhevsk, Russia, took part in a cross-sectional survey. Presence of respiratory symptoms was determined from self-report of chronic productive cough and breathlessness assessed using the British Medical Research Council (MRC) breathlessness scale. Self-reported physical and mental health were measured using the 12-Item Short-Form Health Survey (SF-12). Hypertension was assessed from mean blood pressure measured at the health check and/or self-reported use of antihypertensive medication. Other comorbidities were assessed from self-report. Logistic regression models were fitted assessing the association between respiratory symptoms and comorbidities. Linear regression models were fitted to investigate the association between respiratory symptoms and self-reported health scores. All models were adjusted for age, education and smoking status.

Results

The age-standardised prevalence of cough and breathlessness was 20.9% (prevalence with breathlessness MRC grade 3 or above 3.7%). The majority of men with respiratory symptoms (87.3%) were current smokers. Cough and breathlessness were associated with substantially worse self-reported physical and mental health (test for trend with severity of breathlessness p<0.001). Those with chronic cough and grade 3 or above breathlessness had higher odds of having hypertension (OR 3.03; 95% CI 1.36 to 6.74), diabetes (OR 10.55; 95% CI 2.69 to 41.37), angina pectoris (OR 7.54; 95% CI 3.61 to 15.73), previous myocardial infarction (OR 7.61; 95% CI 2.10 to 27.4) and previous stroke (OR 6.61; 95% CI 1.75 to 23.34) compared with those without respiratory symptoms.

Conclusions

The prevalence of respiratory symptoms was high. Strong associations were found between respiratory symptoms and cardiovascular comorbidities. These are of particular importance given the extremely high level of cardiovascular disease mortality in Russia.
Systematic bias in cancer patient-reported outcomes: symptom ‘orphans’ and ‘champions’
Authors: Thomas Shirley , Walsh Declan , Aktas Aynur
Published: December 2015

Introduction

Patient-reported outcomes are an integral part of modern healthcare. We report a comparison of symptom item content from several validated cancer instruments to that of a published checklist, and identify the important differences this revealed.

Methods

We defined orphans as any symptom not assessed in any of the six selected instruments; champions, in contrast, were present in all six. An empirically derived cancer multisymptom checklist was used.

Three symptom categories were identified

Orphan—absent from all 6,

Champion—present in all 6,

Intermediate—underreported.

The contents of each validated instrument were cross-referenced against the checklist.

Results

Eighteen (39%) checklist symptoms were orphans. Five (11%) were champions: fatigue, pain, anorexia, dyspnoea and nausea. Of the 46 checklist symptoms, 23 (50%) were inconsistently recorded. All 18 orphan symptoms were clinically important checklist symptoms. Common gastrointestinal and neuropsychological symptoms that pose great clinical management challenges were among the orphan symptoms.

Conclusions

Of 46 checklist cancer symptoms, over a third were orphans. All orphan symptoms were rated as clinically important and distressing by checklist. Only 5 checklist symptoms were champions: fatigue, pain, anorexia, dyspnoea and nausea. Important—but usually omitted—symptoms included early satiety (6 of 6) and weight loss (5 of 6). The bias appears to disproportionately affect gastrointestinal and neuropsychiatric symptoms. Symptom studies should specifically report the limitations and account for the inherent item bias of any instrument used.
Comparison of two training programmes on paramedic-delivered CPR performance
Authors: Govender Kevin , Sliwa Karen , Wallis Lee , Pillay Yugan
Published: December 2015

Objective

To compare CPR performance in two groups of paramedics who received CPR training from two different CPR training programmes.

Methods

Conducted in June 2014 at the Hamad Medical Corporation Ambulance Service, the national ambulance service of the State of Qatar, the CPR performances of 149 new paramedic recruits were evaluated after they had received training from either a traditional CPR programme or a tailored CPR programme. Both programmes taught the same content but differed in the way in which this content was delivered to learners. Exclusive to the tailored programme was mandatory precourse work, continuous assessments, a locally developed CPR instructional video and pedagogical activities tailored to the background education and learner style preferences of paramedics. At the end of each respective training programme, a single examiner who was blinded to the type of training paramedics had received, rated them as competent or non-competent on basic life support skills, condition specific skills, specific overall skills and non-technical skills during a simulated out-of-hospital cardiac arrest (OHCA) assessment.

Results

Paramedics who received CPR training with the tailored programme were rated competent 70.9% of the time, compared with paramedics who attended the traditional programme and who achieved this rating 7.9% of the time (p<0.001). Specific improvements were seen in the time required to detect cardiac arrest, chest compression quality, and time to first monitored rhythm and delivered shock.

Conclusions

In an OHCA scenario, CPR performance rated as competent was significantly higher when training was received using a tailored CPR programme.
Trends in paediatric sports-related injuries presenting to US emergency departments, 2001–2013
Authors: Bayt Demetria R , Bell Teresa M
Published: December 2015

This descriptive epidemiology study describes trends in paediatric sports-related injuries resulting from 21 selected sports presenting to US emergency departments (EDs) over a 13-year period. The study was a retrospective study using data from the US Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) for years 2001–2013. Inclusion criteria included people in the NEISS for injuries related to one of the 21 selected sports and between the ages of 5 and 18 years. Frequencies and linear regressions were calculated using provided sample weights. The results indicated there was a statistically significant increase of 10 010 nationally estimated selected sports-related injuries per year. Football, basketball, soccer and baseball resulted in 74.7% of the total national estimate for sports-related injuries presenting to US EDs for 2001–2013 for children aged 5–18 years. The results indicate that the number of paediatric sports-related injuries treated in US EDs has increased annually from 2001 to 2013.
Injury deaths in the adolescent population of Finland: a 43-year secular trend analysis between 1971 and 2013
Authors: Parkkari Jari , Sievänen Harri , Niemi Seppo , Mattila Ville M , Kannus Pekka
Published: December 2015

Background

Injuries are a major public health problem worldwide, being the leading cause of death in children and adolescents in developed countries. However, knowledge on recent secular trends in injury deaths of adolescents is sparse.

Methods

Using Official Cause-of-Death Statistics of Finland, we examined the nationwide trends in the age- and sex-specific incidence rates of fatal injuries among 10–14-year-old and 15–19-year-old adolescents in Finland between 1971 and 2013.

Results

The incidence rate of fatal injuries decreased considerably in both age groups during the 43-year follow-up period. The decline in injury deaths was mainly due to decreased deaths in traffic accidents. The number of drownings reached the ultimate goal—that is, there were no drownings in Finnish 10–19-year-old adolescents in 2013. The rates of intentional injury deaths remained stable in girls, while in 15–19-year-old boys a decreasing trend was evident. During the deep economic depression in 1990, the incidence of suicide in 15–19-year-old boys was as high as 40.1. At that time, boys’ suicide risk was 7.4 times higher than that of girls. Since then, boys’ risk for suicide has clearly decreased and was 1.6 times higher than the corresponding risk in girls in 2013.

Conclusions

The incidence rate of fatal injuries decreased considerably in Finnish adolescents during the period 1971–2013. The clearest change occurred in road traffic injuries and drownings. The rates of intentional injury deaths remained unaltered in girls while 15–19-year-old boys showed a decreasing trend.
Intelligence and socioeconomic position in childhood in relation to frailty and cumulative allostatic load in later life: the Lothian Birth Cohort 1936
Authors: Gale Catharine R , Booth Tom , Starr John M , Deary Ian J
Published: December 2015

Background

Information on childhood determinants of frailty or allostatic load in later life is sparse. We investigated whether lower intelligence and greater socioeconomic disadvantage in childhood increased the risk of frailty and higher allostatic load, and explored the mediating roles of adult socioeconomic position, educational attainment and health behaviours.

Methods

Participants were 876 members of the Lothian Birth Cohort 1936 whose intelligence was assessed at age 11. At age 70, frailty was assessed using the Fried criteria. Measurements were made of fibrinogen, triglyceride, total and high-density lipoprotein cholesterol, albumin, glycated haemoglobin, C reactive protein, body mass index and blood pressure, from which an allostatic load score was calculated.

Results

In sex-adjusted analyses, lower intelligence and lower social class in childhood were associated with an increased risk of frailty: relative risks (95% CIs) were 1.57 (1.21 to 2.03) for a SD decrease in intelligence and 1.48 (1.12 to 1.96) for a category decrease in social class. In the fully adjusted model, both associations ceased to be significant: relative risks were 1.13 (0.83 to 1.54) and 1.19 (0.86 to 1.61), respectively. Educational attainment had a significant mediating effect. Lower childhood intelligence in childhood, but not social class, was associated with higher allostatic load. The sex-adjusted coefficient for allostatic load for a SD decrease in intelligence was 0.10 (0.07 to 0.14). In the fully adjusted model, this association was attenuated but remained significant (0.05 (0.01 to 0.09)).

Conclusions

Further research will need to investigate the mechanisms whereby lower childhood intelligence is linked to higher allostatic load in later life.
TB-HIV co-infection in the Netherlands: estimating prevalence and under-reporting in national registration databases using a capture–recapture analysis
Authors: van Leth Frank , Evenblij Kirsten , Wit Ferdinand , Kiers Albert , Sprenger Herman , Verhagen Maurits , Hillebregt Mariska , Kalisvaart Nico , Schimmel Henrieke , Verbon Annelies
Published: December 2015

Background

Knowledge of the HIV status in patients with tuberculosis (TB) andvice versais crucial for proper individual patient management, while knowledge of the prevalence of co-infection guides preventive and therapeutic strategies. The aim of the study was to assess if national disease databases on TB and HIV are adequate sources to provide this information.

Methods

A two way capture–recapture analysis to assess the completeness of the registers, and to obtain the prevalence of TB-HIV co-infection in the Netherlands in the years 2002–2012.

Results

HIV testing was performed in less than 50% of the patients with TB. Of the 932 TB-HIV infected patients, just 293 (31.4%) were registered in both registers. Under-reporting of TB-HIV co-infection ranged from 50% to 70% in the national TB register, and from 31% to 37% in the HIV database. Prevalence of TB-HIV co-infection in the Netherlands in 2012 was 7.1% (95% CI 6.0% to 8.3%), which was more than double of the prevalence estimated from the national TB database.

Conclusions

TB-HIV co-infection is markedly under-reported in national disease databases. There is an urgent need for improved registration and preferably a routine data exchange between the two surveillance systems.
Dental pathology in conventionally fed and pasture managed dairy cattle
Authors: Fadden A. N , Poulsen K. P. , Vanegas J. , Mecham J. , Bildfell R. , Stieger‐Vanegas S. M.
Published: December 2015

Healthy teeth are important in the first stages of digestion for dairy cattle, yet little is known about bovine dental disease. This study aimed to investigate dental pathology of dairy cattle in two parts. First dairy cattle cadaver heads (n=11) were examined at the time of culling. Second, the authors performed oral exams in cattle fed a total mixed ration (TMR) (n=200) and pasture‐based (n=71) grazing cattle. Cadaver heads were imaged using radiography and computed tomography before gross dissection to study dental anatomy and pathology. The most prevalent dental abnormalities were excessive transverse ridging of the occlusal surface, the presence of diastemas and third molar dental overgrowths (M3DO) in cadaver heads. Average thickness of subocclusal dentine ranged from 3.5 mm to 5.8 mm in cheek teeth but was >10 mm in maxillary teeth with M3DO. Radiographic findings were compared with oral examinations in live cattle. Prevalence of M3DO upon oral examination was 19 per cent and 28 per cent in herds of cattle fed a TMR diet and 0 per cent in a herd of grazing cattle. Dental abnormalities are prevalent in dairy cattle but due to thin subocclusal dentine in the cheek teeth, established equine dental treatment methodology is not appropriate for bovine cheek teeth with the exception of those that have developed M3DO.
Do Outsourcing Service Providers Need a Methodology for Service Delivery?
Authors: Marcilla Javier Sáenz , de la Cámara Mercedes , Arcilla-Cobián Magdalena
Published: December 2015

The outsourcing market has been growing in recent years and it is expected to keep doing so in the coming years, but this growth has been limited by the failure of many projects that, in some cases, has led organizations to take back those services (insourcing). These failures have been due mainly to problems with providers: lack of experience and capacity to take on the projects, and difficulties of communication. There are good practices frameworks for managing outsourcing projects for clients, but it is not the same for providers, who base the provision of services on their past experience and technical capabilities. The aim of this paper is to state the need of proposing a methodology that guides providers throughout the whole outsourcing life cycle and facilitates the provision of quality services and their management.
A Soft Sensor Based on the Integration of Tikhonov Extreme Learning Machine and Accelerated Kernels for Real-Time Estimation of Automotive Catalyst Temperatures
Authors: Mozaffari Ahmad , Azad Nasser L.
Published: December 2015

This papers deals with the design of an efficient intelligent tool for automotive engine coldstart monitoring applications. The real-time identification and control of engine coldstart operations have been proven to be very formidable tasks. This refers to the highly nonlinear and transient behavior of the engine system over coldstart operations. As the catalyst temperature is not sufficiently high, the amount of tailpipe hydrocarbon emissions is remarkable over this period. The researchers of systems sciences have investigated the development of soft sensors which are needed to monitor the catalyst temperature for enabling effective coldstart controllers to reduce the emissions. However, most of the conducted researches have focused on using complicated statistical models as well as gradient-based neural networks for the considered problem. This raises several problems regarding the generalization and computational efficiency of the proposed models. In this paper, the authors propose a novel computationally efficient method based on the integration of accelerated kernels and Tikhonov regularized extreme learning machine for the online monitoring of the catalyst temperature over the coldstart period for a given engine. Based on the results of comparative simulations, the authors demonstrate that the proposed soft sensor can be very effective for automotive coldstart applications.
Survey of Uses of Evolutionary Computation Algorithms and Swarm Intelligence for Network Intrusion Detection
Authors: Elsayed Saber , Sarker Ruhul , Essam Daryl
Published: December 2015

Many infrastructures, such as those of finance and banking, transportation, military and telecommunications, are highly dependent on the Internet. However, as the Internet’s underlying structural protocols and governance can be disturbed by intruders, for its smooth operation, it is important to minimize such disturbances. Of the available techniques for achieving this, computational intelligence methodologies, such as evolutionary algorithms and swarm intelligence approaches, are popular and have been successfully applied to detect intrusions. In this paper, we present an overview of these techniques and related literature on intrusion detection, analyze their research contributions, compare their approaches and discuss new research directions which will provide useful insights for intrusion detection researchers and practitioners.
Goldeneye: modelling a depleted field for carbon capture – how much uncertainty is left?
Authors: Marshall John D. , Tucker Owain D. , Lovelock Cliff E.
Published: December 2015

The Lower Cretaceous Goldeneye gas field lies in the Captain turbidite fairway of the Moray Firth and has recently ceased production. Its situation and dimensions have made it an excellent candidate for CO
2
sequestration. The field was extensively modelled for the original development planning when uncertainty was assessed from the perspective of volumetrics and field behaviour. The subsequent need to assess its suitability as a CO
2
store has given the opportunity for a look back at an uncertainty analysis with the benefit of full-field performance, and to perform a new analysis aimed at different issues concerning behaviour during CO
2
injection.

Both sets of analyses required coupled static–dynamic modelling runs in which the key static parameter ranges of the field were varied, including depth conversion, internal geometries and aquifer properties. For the field development work the parameter ranges were explored to assess in-place volumes and field behaviour under natural aquifer and depletion drive; for the CO
2
uncertainty work, however, parameter ranges were explored to demonstrate storage capacity and CO
2
containment. The look-back showed that the field volumes indicated by production data landed in the upper part of the original uncertainty range and that there was definitive spare capacity in the field relative to the planned injection volume.
Evaluating pyrite-induced swelling in Dublin mudrocks
Authors: Matheson George D. , Quigley Paul
Published: December 2015

Expansion of structural backfill used as hardcore aggregate under floor slabs in the Dublin area of Ireland has resulted in significant structural damage and distress to buildings recorded since 2006. The hardcore or backfill aggregate typically comprises mudrocks of Carboniferous age that contain pyrite. The most recent estimates suggest that pyrite-induced reactions have resulted in structural damage affecting in excess of 10000 buildings in the Dublin area. This has a severe impact on the value of property and the remediation costs are set to run to hundreds of millions of euros. A court case held in the High Court in Dublin in 2010 (upheld in 2014 on appeal to the Supreme Court) found that structural damage to Ballymun Youth Centre, Dublin had been caused by pyrite-induced reactions leading to swelling of the backfill as a result of forceful crystallization of gypsum. This paper describes the logic, chemical, X-ray diffraction and petrological techniques and procedures used to evaluate pyrite-induced swelling for this court case and in many hundreds of evaluations since. The paper also suggests procedures to reduce the costs of testing.
From seafloor spreading to obduction: Jurassic–Cretaceous evolution of the northern branch of the Neotethys in the Northeastern Anatolian and Lesser Caucasus regions
Authors: Hässig M. , Rolland Y. , Sosson M.
Published: December 2015

We present arguments for an innovative tectonic set-up just prior to the Northern Neotethys obduction event in the NE Anatolian and Lesser Caucasus area. Along the Northern Neotethyan suture (the Ankara–Erzincan–Amasia–Sevan–Akera suture zone), relicts of the northern branch of the Neotethys oceanic domain outcrop as preserved unmetamorphosed slivers obducted over the northern edge of the South Armenian Block (SAB) and Taurides–Anatolides Platform (TAP) margins. Recent studies have shown that the ophiolitic bodies are formed of similar lithologies of Middle Jurassic age, all bearing mid-ocean ridge basalt chemical compositions enriched in large ion lithophile elements. This extensive database supports a model in which these ophiolites are derived from a single obducted nappe. This model is supported by the metamorphic pressure–temperature–time paths of the sole lithologies under the outcrops of the suture zone ophiolites. Palaeontological dating of sediment deposits directly under or sealing the obduction contact also support this model by temporally linking the emplacement of distant ophiolite outcrops. General emplacement during early Late Cretaceous time has been determined. A south-dipping subduction under the SAB shortly predating obduction has recently been proposed from the metamorphic and magmatic evolution preserved in the SAB crystalline basement, founding a model featuring opposite-direction subduction from at least late Middle Jurassic to Early Cretaceous times. The emplacement of alkaline pillow basalts directly on the oceanic crust is dated as Early to mid-Cretaceous. These dates argue the existence of abnormal mantle heat flows which may be responsible for a decrease in the density of the 80 Ma-old oceanic lithosphere prior to its obduction onto the SAB–TAP. We present a detailed review of recent data to further constrain the structural and geodynamic evolution of this sector and to define the tectonic set-up just prior to the obduction event.
The Campanian quartz ‘claystone’ conundrum of the African Transform Margin
Authors: Brown Allen , Birkhead Scott , McLean David , Towle Philip , White Howard , Wu Yafei
Published: December 2015

An unusual deep-water lithofacies has been penetrated by numerous wells along the equatorial margin of West Africa by Anadarko Petroleum and other operators. An exploration well drilled in 2009 was initially thought to contain very thick, high-quality sands in the Lower Campanian section. Wireline log interpretations calculated the section to be a quartz-rich reservoir rock with 67–83% quartz based on X-ray diffraction analysis and effective porosity values as high as 25%. This petrophysical analysis appeared to differ from the well site geological description of 200 m of ‘claystone’. The conflict between field observations and the interpreted wireline data led to the re-evaluation of earlier wells and interest in gathering data from this unusual lithofacies from subsequent wells. Field observations (from wellsite geologists) derived from this Lower Campanian section have been consistent in describing this lithofacies as ‘claystone’. Sidewall cores from several of the deep-water wells that penetrated this lithofacies were also consistently described as claystones. These descriptions were from visual inspection and conclusions from laboratory analysis utilizing scanning electron microscopy, X-ray diffraction analysis, laser particle size analysis and thin section point counts as evaluation tools. The sidewall cores typically contain >90% silt- and clay-sized particles with extremely low measured permeability as a result of highly reduced pore throat diameters. With the presence of such small grain sizes, these samples have high measured seal capacities. It is important to recognize that this unusual lithofacies exists and can easily be mistaken for a high-quality, quartz-rich sand when, in fact, it is a very low permeability ‘claystone’ with a high percentage of quartz. Wireline data over this lithofacies alone can be very misleading and rock samples must be analysed to validate or invalidate the log interpretations. Misidentifying this lithofacies as an exploration target could have obvious financial ramifications. The challenge of this regional study was to formulate a model that could explain the presence of this deep-water lithofacies over an extensive area encompassing several basins with different sediment source provenances. Based on well sample analysis, palaeoclimatic research and the use of modern day analogue examples, the deposition of aeolian-derived clay-sized quartz particles is proposed as the most likely source of this lithofacies.
Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity
Authors: Hartmann Phillipp , Seebauer Caroline T. , Mazagova Magdalena , Horvath Angela , Wang Lirui , Llorente Cristina , Varki Nissi M. , Brandl Katharina , Ho Samuel B. , Schnabl Bernd
Published: December 2015

Nonalcoholic fatty liver disease (NAFLD) and obesity are characterized by altered gut microbiota, inflammation, and gut barrier dysfunction. Here, we investigated the role of mucin-2 (Muc2) as the major component of the intestinal mucus layer in the development of fatty liver disease and obesity. We studied experimental fatty liver disease and obesity induced by feeding wild-type and Muc2-knockout mice a high-fat diet (HFD) for 16 wk. Muc2 deficiency protected mice from HFD-induced fatty liver disease and obesity. Compared with wild-type mice, after a 16-wk HFD, Muc2-knockout mice exhibited better glucose homeostasis, reduced inflammation, and upregulated expression of genes involved in lipolysis and fatty acid β-oxidation in white adipose tissue. Compared with wild-type mice that were fed the HFD as well, Muc2-knockout mice also displayed higher intestinal and plasma levels of IL-22 and higher intestinal levels of the IL-22 target genes Reg3b and Reg3g. Our findings indicate that absence of the intestinal mucus layer activates the mucosal immune system. Higher IL-22 levels protect mice from diet-induced features of the metabolic syndrome.
Pathophysiological roles of proteases in gastrointestinal disease
Authors: Edgington-Mitchell Laura E.
Published: December 2015

Gastrointestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, and colorectal cancer, affect a large proportion of the population and are associated with many unpleasant symptoms. Although the causes of these diseases remain largely unknown, there is increasing evidence to suggest that dysregulated protease activity may be a contributing factor. Proteases are enzymes that cleave other proteins, and their activity is normally very tightly regulated. During disease, however, the balance between proteases and their inhibitors is often shifted, leading to altered spatial and temporal control of substrate cleavage. Evaluating protease levels in normal physiology and disease has relied heavily on the use of chemical tools. Although these tools have greatly advanced the field, they are not without caveats. This review provides an introduction to these tools, their application in the gut, and a summary of the current knowledge on the contribution of protease activity to gastrointestinal disease.
Dissecting the role of the myofilament in diaphragm dysfunction during the development of heart failure in mice
Authors: Gillis Todd E. , Klaiman Jordan M. , Foster Andrew , Platt Mathew J. , Huber Jason S. , Corso Melissa Y. , Simpson Jeremy A.
Published: December 2015

Dyspnea and reduced exercise capacity, caused, in part, by respiratory muscle dysfunction, are common symptoms in patients with heart failure (HF). However, the etiology of diaphragmatic dysfunction has not been identified. To investigate the effects of HF on diaphragmatic function, models of HF were surgically induced in CD-1 mice by transverse aortic constriction (TAC) and acute myocardial infarction (AMI), respectively. Assessment of myocardial function, isolated diaphragmatic strip function, myofilament force-pCa relationship, and phosphorylation status of myofilament proteins was performed at either 2 or 18 wk postsurgery. Echocardiography and invasive hemodynamics revealed development of HF by 18 wk postsurgery in both models. In vitro diaphragmatic force production was preserved in all groups while morphometric analysis revealed diaphragmatic atrophy and fibrosis in 18 wk TAC and AMI groups. Isometric force-pCa measurements of myofilament preparations revealed reduced Ca2+sensitivity of force generation and force generation at half-maximum and maximum Ca2+activation in 18 wk TAC. The rate of force redevelopment ( ktr) was reduced in all HF groups at high levels of Ca2+activation. Finally, there were significant changes in the myofilament phosphorylation status of the 18 wk TAC group. This includes a decrease in the phosphorylation of troponin T, desmin, myosin light chain (MLC) 1, and MLC 2 as well as a shift in myosin isoforms. These results indicate that there are multiple changes in diaphragmatic myofilament function, which are specific to the type and stage of HF and occur before overt impairment of in vitro force production.
Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation
Authors: Frisbee Jefferson C. , Butcher Joshua T. , Frisbee Stephanie J. , Olfert I. Mark , Chantler Paul D. , Tabone Lawrence E. , d'Audiffret Alexandre C. , Shrader Carl D. , Goodwill Adam G. , Stapleton Phoebe A. , Brooks Steven D. , Brock Robert W. , Lombard Julian H.
Published: December 2015

To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning “healthy” to “high PVD risk” and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk.
Therapeutic potential of endothelin receptor antagonism in kidney disease
Authors: Czopek Alicja , Moorhouse Rebecca , Webb David J. , Dhaun Neeraj
Published: December 2015

Our growing understanding of the role of the endothelin (ET) system in renal physiology and pathophysiology is from emerging studies of renal disease in animal models and humans. ET receptor antagonists reduce blood pressure and proteinuria in chronic kidney disease and cause regression of renal injury in animals. However, the therapeutic potential of ET receptor antagonism has not been fully explored and clinical studies have been largely limited to patients with diabetic nephropathy. There remains a need for more work in nondiabetic chronic kidney disease, end-stage renal disease (patients requiring maintenance dialysis and those with a functioning kidney transplant), ischemia reperfusion injury, and sickle cell disease. The current review summarizes the most recent advances in both preclinical and clinical studies of ET receptor antagonists in the field of kidney disease.
G protein α12(Gα12) is a negative regulator of kidney injury molecule-1-mediated efferocytosis
Authors: Ismail Ola Z. , Zhang Xizhong , Bonventre Joseph V. , Gunaratnam Lakshman
Published: December 2015

Kidney injury molecule-1 (KIM-1) is a receptor for the “eat me” signal, phosphatidylserine, on apoptotic cells. The specific upregulation of KIM-1 by injured tubular epithelial cells (TECs) enables them to clear apoptotic cells (also known as efferocytosis), thereby protecting from acute kidney injury. Recently, we uncovered that KIM-1 binds directly to the α-subunit of heterotrimeric G12protein (Gα12) and inhibits its activation by reactive oxygen species during renal ischemia-reperfusion injury (Ismail OZ, Zhang X, Wei J, Haig A, Denker BM, Suri RS, Sener A, Gunaratnam L. Am J Pathol 185: 1207–1215, 2015). Here, we investigated the role that Gα12plays in KIM-1-mediated efferocytosis by TECs. We showed that KIM-1 remains bound to Gα12and suppresses its activity during phagocytosis. When we silenced Gα12expression using small interefering RNA, KIM-1-mediated engulfment of apoptotic cells was increased significantly; in contrast overexpression of constitutively active Gα12( QLGα12) resulted in inhibition of efferocytosis. Inhibition of RhoA, a key effector of Gα12, using a chemical inhibitor or expression of dominant-negative RhoA, had the same effect as inhibition of Gα12on efferocytosis. Consistent with this, silencing Gα12suppressed active RhoA in KIM-1-expressing cells. Finally, using primary TECs from Kim-1+/+and Kim-1−/−mice, we confirmed that engulfment of apoptotic cells requires KIM-1 expression and that silencing Gα12enhanced efferocytosis by primary TECs. Our data reveal a previously unknown role for Gα12in regulating efferocytosis and that renal TECs require KIM-1 to mediate this process. These results may have therapeutic implications given the known harmful role of Gα12in acute kidney injury.
Systemic and renal lipids in kidney disease development and progression
Authors: Wahl Patricia , Ducasa Gloria Michelle , Fornoni Alessia
Published: December 2015

Altered lipid metabolism characterizes proteinuria and chronic kidney diseases. While it is thought that dyslipidemia is a consequence of kidney disease, a large body of clinical and experimental studies support that altered lipid metabolism may contribute to the pathogenesis and progression of kidney disease. In fact, accumulation of renal lipids has been observed in several conditions of genetic and nongenetic origins, linking local fat to the pathogenesis of kidney disease. Statins, which target cholesterol synthesis, have not been proven beneficial to slow the progression of chronic kidney disease. Therefore, other therapeutic strategies to reduce cholesterol accumulation in peripheral organs, such as the kidney, warrant further investigation. Recent advances in the understanding of the biology of high-density lipoprotein (HDL) have revealed that functional HDL, rather than total HDL per se, may protect from both cardiovascular and kidney diseases, strongly supporting a role for altered cholesterol efflux in the pathogenesis of kidney disease. Although the underlying pathophysiological mechanisms responsible for lipid-induced renal damage have yet to be uncovered, several studies suggest novel mechanisms by which cholesterol, free fatty acids, and sphingolipids may affect glomerular and tubular cell function. This review will focus on the clinical and experimental evidence supporting a causative role of lipids in the pathogenesis of proteinuria and kidney disease, with a primary focus on podocytes.