National Self-Harm Registry Ireland annual report 2017.

This is the sixteenth annual report from the National Self-Harm Registry Ireland. It is based on data collected on persons presenting to hospital emergency departments following self-harm in 2017 in the Republic of Ireland. The Registry had near complete coverage of the country’s hospitals for the period 2002-2005 and, since 2006, all general hospital and paediatric hospital emergency departments in the Republic of Ireland have contributed data to the Registry. Role of alcohol in self-harm: Alcohol was involved in 31% of all cases. Alcohol was significantly more often involved in male episodes of self-harm than female episodes (33% and 29%, respectively). In line with previous years, misuse or abuse of alcohol is one of the factors associated with the higher rate of self-harm presentations on Sundays, Mondays and public holidays, around the hours of midnight. Recent publications from the Registry data have highlighted the role of alcohol in selfharm. Such complex presentations indicate the need for active consultation and collaboration between the mental health services and addiction treatment services for patients who present with dual diagnoses. In addition, alcohol involvement has been shown to be strongly associated with self-harm presentations out-of-hours, at weekends and on public holidays. The Registry findings related to alcohol provide further support for the full implementation of the Public Health (Alcohol) Bill, which would introduce evidence-based policies to reduce the burden of alcohol harm on our society by improving health, safety and wellbeing. Restricting access to means: …In line with previous years, drug overdose was the most common method of self-harm recorded. Over the years, the Registry has identified the drug types most frequently involved in intentional overdoses. New research has classified the range of drugs recorded by the Registry according to the World Health Organisation’s (WHO) Anatomical Therapeutic Chemical (ATC) classification system. This work has systematically classified the wide range of drugs involved in intentional overdoses, and will be instrumental in facilitating comparative work in this area. This system has allowed for examination of trends in specific drug types, with a recent publication highlighting the increasing involvement of gabapentinoids (prescription-only neuropathic pain medication). Despite a decrease in their involvement in intentional overdose in 2017, minor tranquillisers have been the most frequently used type of drug involved in intentional overdoses. Reducing access to frequently used drugs should be an ongoing priority

The toll of stalking: the relationship between features of stalking and psychopathology of victims.

Information on the psychological consequences of stalking on victims is scarce. The present study aimed to investigate whether stalking victims have a heightened prevalence of psychopathology and the extent to which symptom levels are associated with stalking features. Stalking victims (N = 241) completed the General Health Questionnaire and provided information on specific features of their stalking experiences. High levels of psychopathology were found among stalking victims. Symptom levels were comparable with those of psychiatric outpatients. The frequency, pervasiveness, duration, and cessation of stalking were associated with symptom levels but explained only 9% of the variance of the level of distress. It is concluded that stalking victims generally have many symptoms of psychopathology. The symptoms are largely independent of features of their stalking experience. These findings indicate that better therapy outcomes can be expected from therapies focusing on boosting general coping skills and on decreasing general vulnerability than from therapies focusing on specifically dealing with the stalking situation

WNT7B mediates autocrine Wnt/β-catenin signaling and anchorage-independent growth in pancreatic adenocarcinoma

Developmental and cancer models show Wnt/β-catenin-dependent signaling mediates diverse phenotypic outcomes in the pancreas that are dictated by context, duration and strength of activation. While generally assumed to be pro-tumorigenic, it is unclear to what extent dysregulation of Wnt/β-catenin signaling impacts tumor progression in pancreatic adenocarcinoma (PDAC). In the present study, Wnt/β-catenin activity was characterized across a spectrum of PDAC cell lines and primary tumors. Reporter and gene expression based assays revealed wide heterogeneity in Wnt/β-catenin transcriptional activity across PDAC cell lines and patient tumors, as well as variable responsiveness to exogenous Wnt ligand stimulation. An experimentally-generated, pancreas-specific gene expression signature of Wnt/β-catenin transcriptional activation was used to stratify pathway activation across a cohort of resected, early stage PDAC tumors (N=41). In this cohort, higher Wnt/β-catenin activation was found to significantly correlate with lymphvascular invasion and worse disease specific survival (median survival time 20.3 versus 43.9 months, log rank P=0.03). Supporting the importance of Wnt ligand in mediating autocrine Wnt signaling, Wnt/β-catenin activity was significantly inhibited in PDAC cell lines by WLS gene silencing and the small molecule inhibitor IWP-2, both of which functionally block Wnt ligand processing and secretion. Transcriptional profiling revealed elevated expression of WNT7B occurred in PDAC cell lines with high levels of cell autonomous Wnt/β-catenin activity. Gene knockdown studies in AsPC-1 and HPAF-2 cell lines confirmed WNT7B mediated cell autonomous Wnt/β-catenin activation, as well as an anchorage-independent growth phenotype. Our findings indicate WNT7B can serve as a primary determinant of differential Wnt/β-catenin activation in PDAC. Disrupting the interaction between Wnt ligands and their receptors may be a particularly suitable approach for therapeutic modulation of Wnt/β-catenin signaling in PDAC and other cancer contexts where Wnt activation is mediated by ligand expression rather than mutations in canonical pathway members

Latent provisions for building information modeling (BIM) contracts: a social network analysis approach

The effective adoption and use of Building Information Modeling (BIM) require appropriate contract design to fairly allocate the contracting parties’ rights and responsibilities. Several standards for BIM protocols and contracts have been developed for the industry. However, the awareness and the use of these are rather limited, leading to unclear provisions in BIM contracts. Therefore, the research aims to identify the influential legal aspects that serve as the latent contract provisions in BIM contracts. A questionnaire survey was conducted to survey experts and active BIM users in construction projects. The data were analyzed using social network analysis (SNA) by assuming interdependent relationships among various the legal aspects in BIM contacts. The key legal aspects associated with BIM contracts pertain to the roles and responsibilities of the project participants. The results also reveal that data security is the center of all latent legal aspects in the contracts. The study provides significant new insights into clarifying the required contract provisions in BIM contracts

Efficacy of dose-escalated chemoradiation on complete tumour response in patients with locally advanced rectal cancer (RECTAL-BOOST); a phase 2 randomised controlled trial

Purpose Pathological complete tumour response following chemoradiation in patients with locally advanced rectal cancer (LARC) is associated with favourable prognosis and allows organ-sparing treatment strategies. We aimed to investigate the effect of an external radiation boost to the tumour prior to chemoradiation on pathological or sustained clinical complete tumour response in LARC. Methods and materials This multicentre, non-blinded, phase 2, randomised controlled trial followed the trials within cohorts-design, which is a pragmatic trial design allowing cohort participants to be randomized for an experimental intervention. Patients in the intervention group are offered the intervention (and can accept or refuse this), whereas patients in the control group are not notified about the randomisation. Participants of a colorectal cancer cohort referred for chemoradiation of LARC to either of two radiotherapy centres were eligible. Patients were randomised to no boost or an external radiation boost (5 x 3 Gy) without concurrent chemotherapy directly followed by standard pelvic chemoradiation (25 x 2 Gy with concurrent capecitabine). The primary outcome was pathological complete response (pCR, i.e. ypT0N0) in patients with planned surgery at 12 weeks or, as surrogate for pCR, a 2-year sustained clinical complete response for patients treated with an organ preservation strategy. Analyses were intention to treat. The study was registered with ClinicalTrials.gov, number NCTXXXXXX. Results Between Sept 2014 and July 2018, 128 patients were randomised. Fifty-one of the 64 (79.7%) patients in the intervention group accepted and received a boost. Compared with the control group, fewer patients in the intervention group had a cT4-stage and a low rectal tumour (31.3% versus 17.2% and 56.3% versus 45.3% respectively), and more patients had a cN2-stage (59.4% versus 70.3% respectively). Rate of pathological or sustained clinical complete tumour response was similar between the groups: 23 of 64 (35.9%, 95%CI 24.3-48.9) in the intervention group versus 24 of 64 (37.5%, 95%CI 25.7-50.5) in the control group (OR=0.94 95%CI 0.46-1.92). Near-complete or complete tumour regression was more common in the intervention group: 34 of 49 (69.4%) versus 24 of 53 (45.3%) in the control group (OR=2.74, 95%CI 1.21-6.18). Grade >3 acute toxicity was comparable: 6 of 64 (9.4%) in the intervention group versus 5 of 64 (7.8%) in the control group (OR=1.22 95%CI 0.35-4.22). Conclusion Dose escalation with an external radiotherapy boost to the tumour prior to neoadjuvant chemoradiation did not increase the pathological or sustained clinical complete tumour response rate in LARC

Efficacy and cost-effectiveness of two online interventions for children and adolescents at risk for depression (E.motion trial): study protocol for a randomized controlled trial within the ProHEAD consortium

Background: Depression is a serious mental health problem and is common in children and adolescents. Online interventions are promising in overcoming the widespread undertreatment of depression and in improving the help-seeking behavior in children and adolescents. Methods: The multicentre, randomized controlled E.motion trial is part of the German ProHEAD consortium (Promoting Help-seeking using E-technology for ADolescents). The objective of the trial is to investigate the efficacy and cost-effectiveness of two online interventions to reduce depressive symptomatology in high-risk children and adolescents with subsyndromal symptoms of depression in comparison to an active control group. Participants will be randomized to one of three conditions: (1) Intervention 1, a clinician-guided self-management program (iFightDepression®); (2) Intervention 2, a clinician-guided group chat intervention; and (3) Control intervention, a psycho-educational website on depressive symptoms. Interventions last six weeks. In total, N = 363 children and adolescents aged ≥ 12 years with Patient Health Questionnaire-9 modified for Adolescents (PHQ-A) scores in the range of 5–9 will be recruited at five study sites across Germany. Online questionnaires will be administered before onset of the intervention, at the end of the intervention, and at the six-month follow-up. Further, children and adolescents will participate in the baseline screening and the one- and two-year school-based follow-up assessments integrated in the ProHEAD consortium. The primary endpoint is depression symptomatology at the end of intervention as measured by the PHQ-A score. Secondary outcomes include depression symptomatology at all follow-ups, help-seeking attitudes, and actual face-to-face help-seeking, adherence to and satisfaction with the interventions, depression stigma, and utilization and cost of interventions. Discussion: This study represents the first randomized controlled trial (RCT) investigating efficacy and cost-effectiveness of two online interventions in children and adolescents aged ≥ 12 years at risk for depression. It aims to provide a better understanding of the help-seeking behavior of children and adolescents, potential benefits of E-mental health interventions for this age group, and new insights into so far understudied aspects of E-mental health programs, such as potential negative effects of online interventions. This knowledge will be used to tailor and improve future help offers and programs for children and adolescents and ways of treatment allocation. Trial registration: German Register for Clinical Trials (DRKS), DRKS00014668. Registered on 4 May 2018. International trial registration took place through the “international clinical trials registry platform” with the secondary ID S-086/2018

Does local ownership bring about effectiveness? The case of a transnational advocacy network

In international development, shared ownership is assumed to be a condition for effectiveness. Academic studies question this relation, claiming shared ownership can instead lead to ineffectiveness. This study analysed the interplay between ownership and effectiveness in a transnational advocacy network for conflict prevention observed 2012–2015. Building on recent discussions about balancing unity and diversity in networks, this article unpacks the ownership/effectiveness relationship into three dimensions: collective identity, accountability processes and a shared advocacy message. We find that the question is not about more or less effectiveness, but about the processes shaping the meaning of effectiveness in particular institutional constellations

National Self-Harm Registry Ireland annual report 2014.

This is the thirteenth annual report from the National Self-Harm Registry Ireland. It is based on data collected on persons presenting to hospital emergency departments as a result of self-harm in 2014 in the Republic of Ireland. In 2014, the Registry recorded 11,126 presentations to hospital due to self-harm nationally, involving 8,708 individuals. Taking the population into account, the age-standardised rate of individuals presenting to hospital following self-harm in 2014 was 200 per 100,000. Thus, the self-harm rate was essentially unchanged from 2013. This levelling-off follows three successive decreases in the rate of persons presenting to hospital following self-harm in Ireland from 2011 to 2013. However, the rate in 2014 was still significantly higher (+6%) than the pre-recession rate in 2007 (188 per 100,000). Within the calendar year 2014, at least five self-harm presentations were made by 138 individuals, accounting for just 2% of all self-harm patients in the year but 10% of all self-harm presentations recorded. As in previous years, self-cutting was associated with an increased level of repetition. Almost one in five (17.6%) of those who used cutting as their main method of self-harm in their index act made at least one subsequent self-harm presentation in the calendar year compared to over one in ten (13.7%) of those who took an intentional drug overdose. Risk of repetition was greatest in the days and weeks following a self-harm presentation to hospital and the risk increased markedly with each subsequent presentation