Τετάρτη, 25 Μαΐου 2016

Asia Pacific Media Educator

Asia Pacific Media Educator, published by SAGE Publications, last updated on 2016-05-25, available at http://ame.sagepub.com

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Perceptual and Motor Skills

Perceptual and Motor Skills, published by SAGE Publications, last updated on 2016-05-25, available at http://pms.sagepub.com

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County Freeholder on the Road to Recovery - Shorebeat


Shorebeat

County Freeholder on the Road to Recovery
Shorebeat
Ocean County Freeholder John C. Bartlett has successfully completed radiation and chemotherapy treatment for cancer and returned to the board at a work session meeting Wednesday. “I had very little side effects from either of them,” said Bartlett ...



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Hepatic Aryl Hydrocarbon Receptor Attenuates Fibroblast Growth Factor 21 Expression [Gene Regulation]

The Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in many physiological processes. Several studies indicate that AHR is also involved in energy homeostasis. Fibroblast growth factor 21 (FGF21) is an important regulator of the fasting and feeding responses. When administered to various genetic and diet-induced mouse models of obesity, FGF21 can attenuate obesity-associated morbidities. Here, we explore the role of AHR in hepatic Fgf21 expression through the use of a conditional, hepatocyte-targeted AHR knockout mouse model (CreAlbAhrFx/Fx). Compared to the congenic parental strain (AhrFx/Fx), non-fasted CreAlbAhrFx/Fx mice exhibit a 4-fold increase in hepatic Fgf21 expression, as well as elevated expression of FGF21-target gene Igfbp1. Furthermore, in vivo agonist activation of AHR reduces hepatic Fgf21 expression during a fast. The Fgf21 promoter contains several putative dioxin response elements (DREs). Using EMSA, we demonstrate that the AHR/ARNT heterodimer binds to a specific DRE that overlaps binding sequences for peroxisome proliferator-activated receptor alpha (PPARα), carbohydrate response element-binding protein (ChREBP), and cAMP response element binding protein, hepatocyte specific (CREBH). In addition, we reveal that agonist-activated AHR impairs PPARα-, ChREBP-, and CREBH-mediated promoter activity in Hepa-1 cells. Accordingly, agonist treatment in Hepa-1 cells ablates potent ER stress-driven Fgf21 expression, and pre-treatment with AHR antagonist blocks this effect. Finally, we show that pre-treatment of primary human hepatocytes with AHR agonist diminishes PPARα-, glucose-, and ER stress-driven induction of FGF21 expression, indicating the effect is not mouse-specific. Together, our data show that AHR contributes to hepatic energy homeostasis, partly through the regulation of FGF21 expression and signaling.

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Activation of EGFR/p38/HIF-1{alpha} is pivotal for angiogenesis and tumorigenesis of malignantly transformed cells induced by hexavalent chromium [Gene Regulation]

Cr(VI)-containing compounds are well-established environmental carcinogens. Most mechanistic investigations of Cr(VI)-induced carcinogenesis focus on oxidative stress and various cellular responses, leading to malignant cell transformation, or the first stage of metal-induced carcinogenesis. The development of malignantly transformed cells into tumors which require angiogenesis is the second stage. This study focuses on the second stage, in particular, the role of epidermal growth factor receptor (EGFR) signaling in angiogenesis and tumorigenesis of Cr(VI)-transformed cells. Our preliminary studies have shown that EGFR is constitutively activated in Cr(VI)-transformed cells, in lung tissue from Cr(VI)-exposed animals, and in lung tumor tissue from a non-smoking worker occupationally exposed to Cr(VI) for 19 years. Using in vitro and in vivo models, the present study has investigated the role of EGFR in angiogenesis of Cr(VI)-transformed cells. The results show that Cr(VI)-transformed cells are angiogenic. Hypoxia inducible factor (HIF) 1α, proangiogenic protein matrix metalloproteinase-1 (MMP-1), and vascular endothelial growth factor (VEGF) are all highly expressed in Cr(VI)-transformed cells, in lung tissue from animals exposed to Cr(VI), and in lung tumor tissue from a non-smoking worker occupationally exposed to Cr(VI) for 19 years. p38 MAPK was also activated in Cr(VI)-transformed cells and in the human lung tumor tissue. Inhibition of EGFR reduces p38 MAPK, resulting in decreased expressions of HIF-1α, MMP-1, and VEGF, leading to suppressions of angiogenesis and tumorigenesis. Overall, the present study has demonstrated that EGFR plays an important role in angiogenesis and tumorigenesis of Cr(VI)-transformed cells.

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Examining the pathways for young people with drug and alcohol dependence: a mixed-method design to examine the role of a treatment programme

Introduction

Young people with drug and alcohol problems are likely to have poorer health and other psychosocial outcomes than other young people. Residential treatment programmes have been shown to lead to improved health and related outcomes for young people in the short term. There is very little robust research showing longer term outcomes or benefits of such programmes. This paper describes an innovative protocol to examine the longer term outcomes and experiences of young people referred to a residential life management and treatment programme in Australia designed to address alcohol and drug issues in a holistic manner.

Methods and analysis

This is a mixed-methods study that will retrospectively and prospectively examine young people's pathways into and out of a residential life management programme. The study involves 3 components: (1) retrospective data linkage of programme data to health and criminal justice administrative data sets, (2) prospective cohort (using existing programme baseline data and a follow-up survey) and (3) qualitative in-depth interviews with a subsample of the prospective cohort. The study will compare findings among young people who are referred and (a) stay 30 days or more in the programme (including those who go on to continuing care and those who do not); (b) start, but stay fewer than 30 days in the programme; (c) are assessed, but do not start the programme.

Ethics and dissemination

Ethics approval has been sought from several ethics committees including a university ethics committee, state health departments and an Aboriginal-specific ethics committee. The results of the study will be published in peer-reviewed journals, presented at research conferences, disseminated via a report for the general public and through Facebook communications. The study will inform the field more broadly about the value of different methods in evaluating programmes and examining the pathways and trajectories of vulnerable young people.



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Reactions and coping strategies in lay rescuers who have provided CPR to out-of-hospital cardiac arrest victims: a qualitative study

Objective

Cardiopulmonary resuscitation (CPR) provided by community citizens is of paramount importance for out-of-hospital cardiac arrest (OHCA) victims' survival. Fortunately, CPR rates by community citizens seem to be rising. However, the experience of providing CPR is rarely investigated. The aim of this study was to explore reactions and coping strategies in lay rescuers who have provided CPR to OHCA victims.

Methods, participants

This is a qualitative study of 20 lay rescuers who have provided CPR to 18 OHCA victims. We used a semistructured interview guide focusing on their experiences after providing CPR.

Setting

The study was conducted in the Stavanger region of Norway, an area with very high bystander CPR rates.

Results

Three themes emerged from the interview analysis: concern, uncertainty and coping strategies. Providing CPR had been emotionally challenging for all lay rescuers and, for some, had consequences in terms of family and work life. Several lay rescuers experienced persistent mental recurrences of the OHCA incident and had concerns about the outcome for the cardiac arrest victim. Unknown or fatal outcomes often caused feelings of guilt and were particularly difficult to handle. Several reported the need to be acknowledged for their CPR attempts. Health-educated lay rescuers seemed to be less affected than others. A common coping strategy was confiding in close relations, preferably the health educated. However, some required professional help to cope with the OHCA incident.

Conclusions

Lay rescuers experience emotional and social challenges, and some struggle to cope in life after providing CPR in OHCA incidents. Experiencing a positive patient outcome and being a health-educated lay rescuer seem to mitigate concerns. Common coping strategies are attempts to reduce uncertainty towards patient outcome and own CPR quality. Further studies are needed to determine whether an organised professional follow-up can mitigate the concerns and uncertainty of lay rescuers.



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Efficacy of an internet-based self-help intervention to reduce co-occurring alcohol misuse and depression symptoms in adults: study protocol of a three-arm randomised controlled trial

Introduction

In the general population, alcohol use disorder and depression more often occur together than any other combination of a mental illness with a substance use disorder. It is important to have a cost-effective intervention that is able to reach at-risk individuals in the early stages of developing alcohol use disorders and depression disorders.

Methods and analysis

This paper presents the protocol for a 3-arm multicentre randomised controlled trial (RCT) to test the efficacy and cost-effectiveness of the combined internet-based self-help intervention Take Care of You (TCOY) to reduce alcohol misuse and depression symptoms in comparison with a waiting list control group and a comparable intervention focusing on problematic alcohol use only. The active interventions consist of modules designed to reduce alcohol use, based on the principles of motivational interviewing and methods of cognitive behavioural therapy, together with additional modules in the combined study arm to reduce symptoms of depression. Data will be collected at baseline, as well as at 3 and 6 months postrandomisation. The primary outcome is the quantity of alcohol used in the past 7 days. A number of secondary outcome measures will be studied. These include the Centre of Epidemiologic Studies of Depression Scale (CES-D) and a combined measure with the criteria of values below the cut-off for severe alcohol use disorder and for CES-D. Data analysis will follow the intention-to-treat principle using (generalised) linear mixed models. In order to investigate the interventions’ cost-utility and cost-effectiveness, a full economic evaluation will be performed.

Ethics and dissemination

This RCT will be executed in compliance with the Helsinki Declaration and has been approved by 2 local Ethics Committees. Results will be reported at conferences and in peer-reviewed publications. Participant-friendly summaries of trial findings will be published on the TCOY websites.

Trial registration number

ISRCTN10323951.



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Development of a brief assessment and algorithm for ascertaining dementia in low-income and middle-income countries: the 10/66 short dementia diagnostic schedule

Objectives

To develop and evaluate a short version of the 10/66 dementia diagnostic schedule for use in low-income and middle-income countries.

Design

Split-half analysis for algorithm development and testing; cross-evaluation of short-schedule and standard-schedule algorithms in 12 community surveys.

Settings

(1) The 10/66 pilot sample data set of people aged 60 years and over in 25 international centres each recruiting the following samples: (a) dementia; (b) depression, no dementia; (c) no dementia, high education and (d) no dementia, low education. (2) Cross-sectional surveys of people aged 65 years or more from 12 urban and rural sites in 8 countries (Cuba, Dominican Republic, Peru, Mexico, Venezuela, India, China and Puerto Rico).

Participants

In the 10/66 pilot samples, the algorithm for the short schedule was developed in 1218 participants and tested in 1211 randomly selected participants; it was evaluated against the algorithm for the standard 10/66 schedule in 16 536 survey participants.

Outcome measures

The short diagnostic schedule was derived from the Community Screening Instrument for Dementia, the CERAD 10-word list recall task and the Euro-D depression screen; it was evaluated against clinically assigned groups in the pilot data and against the standard schedule (using the Geriatric Mental State (GMS) rather than Euro-D) in the surveys.

Results

In the pilot test sample, the short-schedule algorithm ascertained dementia with 94.2% sensitivity. Specificities were 80.2% in depression, 96.6% in the high-education group and 92.7% in the low-education group. In survey samples, it coincided with standard algorithm dementia classifications with over 95% accuracy in most sites. Estimated dementia prevalences in the survey samples were not consistently higher or lower using the short compared to standard schedule.

Conclusions

For epidemiological studies of dementia in low-income and middle-income settings where the GMS interview (and/or interviewer training required) is not feasible, the short 10/66 schedule and algorithm provide an alternative with acceptable levels of performance.



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Elder mistreatment in a community dwelling population: the Malaysian Elder Mistreatment Project (MAESTRO) cohort study protocol

Introduction

Despite being now recognised as a global health concern, there is still an inadequate amount of research into elder mistreatment, especially in low and middle-income regions. The purpose of this paper is to report on the design and methodology of a population-based cohort study on elder mistreatment among the older Malaysian population. The study aims at gathering data and evidence to estimate the prevalence and incidence of elder mistreatment, identify its individual, familial and social determinants, and quantify its health consequences.

Methods and analysis

This is a community-based prospective cohort study using randomly selected households from the national census. A multistage sampling method was employed to obtain a total of 2496 older adults living in the rural Kuala Pilah district. The study is divided into two phases: cross-sectional study (baseline), and a longitudinal follow-up study at the third and fifth years. Elder mistreatment was measured using instrument derived from the previous literature and modified Conflict Tactic Scales. Outcomes of elder mistreatment include mortality, physical function, mental health, quality of life and health utilisation. Logistic regression models are used to examine the relationship between risk factors and abuse estimates. Cox proportional hazard regression will be used to estimate risk of mortality associated with abuse. Associated annual rate of hospitalisation and health visit frequency, and reporting of abuse, will be estimated using Poisson regression.

Ethics and dissemination

The study has been approved by the Medical Ethics Committee of the University of Malaya Medical Center (MEC Ref 902.2) and the Malaysian National Medical Research Register (NMRR-12-1444-11726). Written consent was obtained from all respondents prior to baseline assessment and subsequent follow-up. Findings will be disseminated to local stakeholders via forums with community leaders, and health and social welfare departments, and published in appropriate scientific journals and presented at conferences.



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Treatment goal setting for complex patients: protocol for a scoping review

Introduction

An increasing number of people are living longer with multiple health and social care needs, and may rely heavily on health system resources. When dealing with multiple conditions, patients, caregivers and healthcare providers (HCPs) often experience high treatment burden due to unclear care trajectories, a myriad of treatment decisions and few guidelines on how to manage care needs. By understanding patient and caregiver priorities, and setting treatment goals, HCPs may help improve patient outcomes and experiences. This study aims to examine the extent and nature of the literature on treatment goal setting in complex patients, identify gaps in evidence and areas for further inquiry and guide a research programme to develop definitions, measures and recommendations for treatment goal setting.

Methods and analysis

This study protocol outlines a scoping review of the peer reviewed and the grey literature, using established scoping review methodology. Literature will be identified using a multidatabase and grey literature search strategy developed by two librarians. Papers and reports on the topic of goal setting that address complexity or complex patients will be included. Results of the search will be screened independently by two reviewers and included studies will be abstracted and charted in duplicate.

Ethics and dissemination

Ethics approval is not required for this scoping review. Working with the knowledge users on the team, we will prepare educational materials and presentations to disseminate study findings to HCPs, caregivers and patients, and at relevant national and international conferences. Results will also be published in a peer-reviewed journal.



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Correction: Protocol for a randomised controlled trial of standard wound management versus negative pressure wound therapy in the treatment of adult patients with an open fracture of the lower limb: UK Wound management of Open Lower Limb Fractures (UK WOLFF)

Achten J, Parsons NR, Bruce J, et al. Protocol for a randomised controlled trial of standard wound management versus negative pressure wound therapy in the treatment of adult patients with an open fracture of the lower limb: UK Wound management of Open Lower Limb Fractures (UK WOLFF). BMJ Open 2015;5: e009087. The acronym of the study in the title is incorrect. The correct expansion is: Wound management of Lower Limb Fractures (WOLLF). The corrected title of the article is: Protocol for a randomised controlled trial of standard wound management versus negative pressure wound therapy in the treatment of adult patients with an open fracture of the lower limb: UK Wound management of Lower Limb Fractures (UK WOLLF).



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Correction

Proaño A, Bravard MA, Tracey BH, et al. Protocol for studying cough frequency in people with pulmonary tuberculosis. BMJ Open 2016;6:e010365. The segmentation of the tenth author's name is incorrect: his first name is Jose, middle name is Luis and last name is Cabrera, and he should be cited as Cabrera JL.



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Trends in vital signs and routine biomarkers in patients with sepsis during resuscitation in the emergency department: a prospective observational pilot study

Objectives

Sepsis lacks a reliable and readily available measure of disease activity. Thereby, it remains unclear how to monitor response to treatment. Research on numerous (new) biomarkers associated with sepsis provided disappointing results and little is known about changes in vital signs during sepsis resuscitation. We hypothesised that trends in vital signs together with routine biomarker levels during resuscitation might provide information about the response to treatment at a very early stage of sepsis in the emergency department (ED). We therefore explore trends in vital signs and routine biomarker levels during sepsis resuscitation in the ED.

Design

Prospective observational pilot study.

Setting

ED of a tertiary care teaching hospital.

Participants

99 Adult non-trauma patients with suspected infection and 2 or more systemic inflammatory response syndrome criteria admitted to the ED.

Primary and secondary outcome measures

Vital signs and biomarker levels at admittance (T0) and after 3 h in the ED (T1).

Results

In total, data of 99 patients were analysed. Of these patients, 63 presented with sepsis, 30 with severe sepsis and 6 with septic shock. All vital signs decreased, except for peripheral oxygen saturation which increased. Almost all routine biomarker levels decreased during resuscitation, except for C reactive protein, bands, potassium, troponin T and direct bilirubin which remained stable. Sodium, chloride and N-terminal prohormone of brain natriuretic peptide increased slightly.

Conclusions

Vital signs and biomarker levels showed descending trends during resuscitation, except for parameters directly affected by treatment modalities. Despite these trends, most patients improved clinically. Trends in vital signs and routine biomarkers might be helpful in predicting clinical course and response to treatment in patients with sepsis during early resuscitation.



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