“I h 8 u”: Findings from a five-year study of text and e-mail bullying

Copyright @ 2010 British Educational Research Association. The final version of this article is available at the link below.This study charts reports of nasty or threatening text and e-mail messages received by students in academic years 7 and 8 (11-13 years of age) attending 13 secondary schools in the North of England between 2002-2006. Annual surveys were undertaken on behalf of the local education authority (LEA) to monitor bullying. Results indicated that, over five years, the number of pupils receiving one or more nasty or threatening text messages or e-mails increased significantly, particularly among girls. However, receipt of frequent nasty or threatening text and e-mail messages remained relatively stable. For boys, being a victim of direct-physical bullying was associated with receiving nasty or threatening text and e-mail messages; for girls it was being unpopular among peers. Boys received more hate-related messages and girls were primarily the victims of name-calling, Findings are discussed with respect to theoretical and policy developments, and recommendations for future research are offered

Knotting and unknotting of a protein in single molecule experiments.

Spontaneous folding of a polypeptide chain into a knotted structure remains one of the most puzzling and fascinating features of protein folding. The folding of knotted proteins is on the timescale of minutes and thus hard to reproduce with atomistic simulations that have been able to reproduce features of ultrafast folding in great detail. Furthermore, it is generally not possible to control the topology of the unfolded state. Single-molecule force spectroscopy is an ideal tool for overcoming this problem: by variation of pulling directions, we controlled the knotting topology of the unfolded state of the 52-knotted protein ubiquitin C-terminal hydrolase isoenzyme L1 (UCH-L1) and have therefore been able to quantify the influence of knotting on its folding rate. Here, we provide direct evidence that a threading event associated with formation of either a 31 or 52 knot, or a step closely associated with it, significantly slows down the folding of UCH-L1. The results of the optical tweezers experiments highlight the complex nature of the folding pathway, many additional intermediate structures being detected that cannot be resolved by intrinsic fluorescence. Mechanical stretching of knotted proteins is also of importance for understanding the possible implications of knots in proteins for cellular degradation. Compared with a simple 31 knot, we measure a significantly larger size for the 52 knot in the unfolded state that can be further tightened with higher forces. Our results highlight the potential difficulties in degrading a 52 knot compared with a 31 knot.N.C.H.L. is supported by a UBD Chancellor’s Scholarship from the Brunei Government. W.N. was supported by the Ministry of Education (MoE) Singapore. S.S.M acknowledges funding from the Alexander von Humboldt Foundation. This work was supported by an SFB 863 A2 grant of Deutsche Forschungsgemeinschaft to M.R

Functional illness in primary care: dysfunction versus disease

<p>Abstract</p> <p>Background</p> <p>The Biopsychosocial Model aims to integrate the biological, psychological and social components of illness, but integration is difficult in practice, particularly when patients consult with medically unexplained physical symptoms or functional illness.</p> <p>Discussion</p> <p>This Biopsychosocial Model was developed from General Systems Theory, which describes nature as a dynamic order of interacting parts and processes, from molecular to societal. Despite such conceptual progress, the biological, psychological, social and spiritual components of illness are seldom managed as an integrated whole in conventional medical practice. This is because the biomedical model can be easier to use, clinicians often have difficulty relinquishing a disease-centred approach to diagnosis, and either dismiss illness when pathology has been excluded, or explain all undifferentiated illness in terms of psychosocial factors. By contrast, traditional and complementary treatment systems describe reversible functional disturbances, and appear better at integrating the different components of illness. Conventional medicine retains the advantage of scientific method and an expanding evidence base, but needs to more effectively integrate psychosocial factors into assessment and management, notably of 'functional' illness. As an aid to integration, pathology characterised by structural change in tissues and organs is contrasted with dysfunction arising from disordered physiology or psychology that may occur independent of pathological change.</p> <p>Summary</p> <p>We propose a classification of illness that includes orthogonal dimensions of pathology and dysfunction to support a broadly based clinical approach to patients; adoption of which may lead to fewer inappropriate investigations and secondary care referrals and greater use of cognitive behavioural techniques, particularly when managing functional illness.</p

An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease

Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD risk and related endophenotypes in females carrying the Apolipoprotein E (APOE)-ε4 genotype; the association is stronger in Chinese than in European-descent populations. Human and mouse transcriptome and immunohistochemical studies showed that rs1921622/sST2 regulates amyloid-beta (Aβ) pathology through the modulation of microglial activation and Aβ clearance. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD

A pragmatic randomised controlled trial of the Welsh National Exercise Referral Scheme: protocol for trial and integrated economic and process evaluation

Background: The benefits to health of a physically active lifestyle are well established and there is evidence that a sedentary lifestyle plays a significant role in the onset and progression of chronic disease. Despite a recognised need for effective public health interventions encouraging sedentary people with a medical condition to become more active, there are few rigorous evaluations of their effectiveness. Following NICE guidance, the Welsh national exercise referral scheme was implemented within the context of a pragmatic randomised controlled trial. Methods/Design: The randomised controlled trial, with nested economic and process evaluations, recruited 2,104 inactive men and women aged 16+ with coronary heart disease (CHD) risk factors and/or mild to moderate depression, anxiety or stress. Participants were recruited from 12 local health boards in Wales and referred directly by health professionals working in a range of health care settings. Consenting participants were randomised to either a 16 week tailored exercise programme run by qualified exercise professionals at community sports centres (intervention), or received an information booklet on physical activity (control). A range of validated measures assessing physical activity, mental health, psycho-social processes and health economics were administered at 6 and 12 months, with the primary 12 month outcome measure being 7 day Physical Activity Recall. The process evaluation explored factors determining the effectiveness or otherwise of the scheme, whilst the economic evaluation determined the relative cost-effectiveness of the scheme in terms of public spending. Discussion: Evaluation of such a large scale national public health intervention presents methodological challenges in terms of trial design and implementation. This study was facilitated by early collaboration with social research and policy colleagues to develop a rigorous design which included an innovative approach to patient referral and trial recruitment, a comprehensive process evaluation examining intervention delivery and an integrated economic evaluation. This will allow a unique insight into the feasibility, effectiveness and cost effectiveness of a national exercise referral scheme for participants with CHD risk factors or mild to moderate anxiety, depression, or stress and provides a potential model for future policy evaluations. Trial registration: Current Controlled Trials ISRCTN4768044

Managing multimorbidity in primary care in patients with chronic respiratory conditions

The term multimorbidity is usually defined as the coexistence of two or more chronic conditions within an individual, whereas the term comorbidity traditionally describes patients with an index condition and one or more additional conditions. Multimorbidity of chronic conditions markedly worsens outcomes in patients, increases treatment burden and increases health service costs. Although patients with chronic respiratory disease often have physical comorbidities, they also commonly experience psychological problems such as depression and anxiety. Multimorbidity is associated with increased health-care utilisation and specifically with an increased number of prescription drugs in individuals with multiple chronic conditions such as chronic obstructive pulmonary disease. This npj Primary Care Respiratory Medicine Education Section case study involves a patient in a primary care consultation presenting several common diseases prevalent in people of this age. The patient takes nine different drugs at this moment, one or more pills for each condition, which amounts to polypharmacy. The problems related with polypharmacy recommend that a routine medication review by primary care physicians be performed to reduce the risk of adverse effects of polypharmacy among those with multiple chronic conditions. The primary care physician has the challenging role of integrating all of the clinical problems affecting the patient and reviewing all medicaments (including over-the-counter medications) taken by the patient at any point in time, and has the has the key to prevent the unwanted consequences of polypharmacy. Multimorbid chronic disease management can be achieved with the use of care planning, unified disease templates, use of information technology with appointment reminders and with the help of the wider primary care and community teams