Development and characterisation of a decellularised bovine osteochondral biomaterial for cartilage repair.

It is proposed that an acellular natural osteochondral scaffold will provide a successful repair material for the early intervention treatment of cartilage lesions, to prevent or slow the progression of cartilage deterioration to osteoarthritis. Here, we investigated the efficacy of methods for the decellularisation of bovine osteochondral plugs. The plugs were subject to four freeze/thaw cycles followed by two cycles of washes in hypotonic solution and low concentration (0.1 % w/v) sodium dodecyl sulphate with protease inhibitors. Plugs were treated with nuclease (DNase and RNase) treatment followed by sterilization in peracetic acid. Full tissue decellularisation was achieved as confirmed by histological analysis and DNA quantification, however the resultant acellular matrix had reduced glycosaminoglycan content which led to an increased percent deformation of cartilage. Furthermore, the acellular scaffold was not reproducibly biocompatible. Additional terminal washes were included in the process to improve biocompatibility, however, this led to visible structural damage to the cartilage. This damage was found to be minimised by reducing the cut edge to cartilage area ratio through decellularisation of larger cuts of osteochondral tissue

Health Behavior Change Interventions for Teenage and Young Adult Cancer Survivors: A Systematic Review

PURPOSE: It is important that teenage and young adult (TYA) cancer survivors adopt a healthy lifestyle, since health vulnerabilities associated with their diagnosis and treatment may be exacerbated by poor health behaviors. This review aims to synthesize the current literature on health behavior change interventions created specifically for TYA-aged cancer survivors. METHOD: MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched for studies investigating interventions targeting one or more health behaviors, including: physical activity, diet, smoking cessation, and alcohol consumption. Studies were eligible for review if the study population were defined as TYA cancer survivors and the mean age of the sample was younger than 30 years of age. RESULTS: Twelve studies were identified, of which nine were randomized controlled trials. Physical activity was the most commonly targeted health behavior. Six of the 12 interventions included within this review were successful in changing health behavior. Due to the heterogeneity of intervention characteristics, the relationship between intervention efficacy or outcome and intervention content, delivery mode, or theoretical framework was not discernible. Nevertheless, trends emerged relating to the delivery and content of health behavior interventions designed specifically for TYA cancer survivors. CONCLUSION: More research is required to identify the most effective means of promoting health behavior change among the TYA cancer survivor population. Specifically, future research should focus on providing evidence of the efficiency and feasibility of interventions that use online technologies to facilitate remote intervention delivery and peer support

Childhood maltreatment and the medical morbidity in bipolar disorder: a case-control study.

BACKGROUND: Childhood maltreatment (abuse and neglect) can have long-term deleterious consequences, including increased risk for medical and psychiatric illnesses, such as bipolar disorder in adulthood. Emerging evidence suggests that a history of childhood maltreatment is linked to the comorbidity between medical illnesses and mood disorders. However, existing studies on bipolar disorder have not yet explored the specific influence of child neglect and have not included comparisons with individuals without mood disorders (controls). This study aimed to extend the existing literature by examining the differential influence of child abuse and child neglect on medical morbidity in a sample of bipolar cases and controls. METHODS: The study included 72 participants with bipolar disorder and 354 psychiatrically healthy controls (average age of both groups was 48 years), who completed the Childhood Trauma Questionnaire, and were interviewed regarding various medical disorders. RESULTS: A history of any type of childhood maltreatment was significantly associated with a diagnosis of any medical illness (adjusted OR = 6.28, 95% confidence intervals 1.70-23.12, p = 0.006) and an increased number of medical illnesses (adjusted OR = 3.77, 95% confidence intervals 1.34-10.57, p = 0.012) among adults with bipolar disorder. Exposure to child abuse was more strongly associated with medical disorders than child neglect. No association between childhood maltreatment and medical morbidity was detected among controls. CONCLUSIONS: To summarise, individuals with bipolar disorder who reported experiencing maltreatment during childhood, especially abuse, were at increased risk of suffering from medical illnesses and warrant greater clinical attention.The bipolar case–control genetic association study was funded by an unrestricted grant from GlaxoSmithKline Research and Development. Funding for the depression case–control study was provided by the UK Medical Research Council (MRC; G0701420). The BADGE study was supported by an Interdisciplinary Ph.D. studentship from the UK Economic Social Research Council (ESRC) and MRC to Dr. Hosang. Prof. Uher is supported by the Canada Research Chairs program (http://www.chairs-chaires.gc.ca/him) and Dr. Fisher is supported by an MQ Fellows Award (MQ14F40). The sources of funding had no involvement in the study design, data collection or decision to submit for publication

Compact Labelings For Efficient First-Order Model-Checking

We consider graph properties that can be checked from labels, i.e., bit sequences, of logarithmic length attached to vertices. We prove that there exists such a labeling for checking a first-order formula with free set variables in the graphs of every class that is \emph{nicely locally cwd-decomposable}. This notion generalizes that of a \emph{nicely locally tree-decomposable} class. The graphs of such classes can be covered by graphs of bounded \emph{clique-width} with limited overlaps. We also consider such labelings for \emph{bounded} first-order formulas on graph classes of \emph{bounded expansion}. Some of these results are extended to counting queries

Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool

Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants

Childhood maltreatment and adult medical morbidity in mood disorders: comparison of unipolar depression with bipolar disorder.

BACKGROUND: The medical burden in mood disorders is high; various factors are thought to drive this pattern. Little research has examined the role of childhood maltreatment and its effects on medical morbidity in adulthood among people with unipolar depression and bipolar disorder.AimsThis is the first study to explore the association between childhood maltreatment and medical morbidity in bipolar disorder and in unipolar depression, and examine whether the impact of abuse and neglect are distinct or combined. METHOD: The participants consisted of 354 psychiatrically healthy controls, 248 participants with recurrent unipolar depression and 72 with bipolar disorder. Participants completed the Childhood Trauma Questionnaire and received a validated medical history interview. RESULTS: Any type of childhood maltreatment, child abuse and child neglect were significantly associated with the medical burden in bipolar disorder, but not unipolar depression or for controls. These associations worked in a dose-response fashion where participants with bipolar disorder with a history of two or more types of childhood maltreatment had the highest odds of having a medical illness relative to those without such history or those who reported one form. No such significant dose-response patterns were detected for participants with unipolar depression or controls. CONCLUSIONS: These findings suggest that childhood maltreatment may play a stronger role in the development of medical illnesses in individuals with bipolar disorder relative to those with unipolar depression. Individuals who had been maltreated with a mood disorder, especially bipolar disorder may benefit most from prevention and intervention efforts surrounding physical health.Declaration of interestNone.GlaxoSmithKline Research and Development funded BaCCs. The UK Medical Research Council (MRC; G0701420) funded DeCC. The BADGE study was supported by an Interdisciplinary PhD studentship from the UK Economic Social Research Council and MRC to G.M.H. H.L.F. is supported by an MQ Fellows Award (MQ14F40). K.H. is supported by the National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The sources of funding had no involvement in the study design, data collection or decision to submit for publication

Predicting onset of early- and late-treatment resistance in first-episode schizophrenia patients using advanced shrinkage statistical methods in a small sample

Evidence suggests there are two treatment-resistant schizophrenia subtypes (i.e. early treatment resistant (E-TR) and late-treatment resistant (L-TR)). We aimed to develop prediction models for estimating individual risk for these outcomes by employing advanced statistical shrinkage methods. 239 first-episode schizophrenia (FES) patients were followed-up for approximately 5 years after first presentation to psychiatric services; of these, n=56 (25.2%) were defined as E-TR and n=24 (12.6%) were defined as L-TR. Using known risk factors for poor schizophrenia outcomes, we developed prediction models for E-TR and L-TR using LASSO and RIDGE logistic regression models. Models’ internal validation was performed employing Harrell's optimism-correction with repeated cross-validation; their predictive accuracy was assessed through discrimination and calibration. Both LASSO and RIDGE models had high discrimination, good calibration. While LASSO had moderate sensitivity for estimating an individual risk for E-TR and L-TR, sensitivity estimated for RIDGE model for these outcomes was extremely low, which was due to having a very large estimated optimism. Although it was possible to discriminate with sufficient accuracy who would meet criteria for E-TR and L-TR during the 5-year follow-up after first contact with mental health services for schizophrenia, further work is necessary to improve sensitivity for these models

Inconsistent findings for the eyes closed effect in children: the implications for interviewing child witnesses

A child who alleges that they have been the victim of a crime will be interviewed by police officers. During a police interview it is important that the interviewer obtains the most accurate testimony possible from the child. Previous studies have shown that if children have their eyes closed during an interview they sometimes report more correct information. This paper includes two studies. In Experiment 1 156 children experienced an event and were then questioned about it. Half the children answered with their eyes open and half with their eyes closed. The participants with eyes closed provided more correct information. In Experiment 2 152 children answered questions in different conditions including eyes open and eyes closed conditions. In contrast to Experiment 1 there was no beneficial effect for the eyes closed condition. These inconsistent results are discussed with reference to actual police interviews. It is suggested that until there has been more research into eyes closed procedures caution should be taken in recommending such procedures for police interviews with children

Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults

Background: Dysfunctional neutrophils with advanced age are a hallmark of immunesenescence. Reduced migration and bactericidal activity increase the risk of infection. It remains unclear why neutrophil dysfunction occurs with age. Physical activity and structured exercise have been suggested to improve immune function in the elderly. The aim of this study was to assess a comprehensive range of neutrophil functions and determine their association with habitual physical activity. Method: Physical activity levels were determined in 211 elderly (67 ± 5 years) individuals by 7-days of accelerometry wear. Twenty of the most physically active men and women were matched for age and gender to twenty of the least physically active individuals. Groups were compared for neutrophil migration, phagocytosis, oxidative burst, cell surface receptor expression, metabolic health parameters and systemic inflammation. Groups were also compared against ten young participants (23 ± 4 years). Results: The most active group completed over twice as many steps/day as the least active group (p0.05). These differences remained after adjusting for BMI, body fat and plasma metabolic markers which were different between groups. Correlations revealed that steps/day, higher adiponectin and lower insulin were positively associated with migratory ability (p0.05 for both). CD11b was higher in the most active group compared to the least active (p=0.048). No differences between activity groups or young controls were observed for neutrophil phagocytosis or oxidative 2  burst in response to E.coli (p>0.05). The young group had lower concentrations of IL- 6, IL-8, MCP-1, CRP, IL-10 and IL-13 (p<0.05 for all) with no differences between the two older groups. Conclusion: These data suggest that impaired neutrophil migration, but not bactericidal function, in older adults may be, in part, the result of reduced physical activity. A 2-fold difference in physical activity is associated with better preserved neutrophil migratory dynamics in healthy older people. As a consequence increasing habitual physical activity may be beneficial for neutrophil mediated immunity