Duration-dependent effects of the BDNF Val66Met polymorphism on anodal tDCS induced motor cortex plasticity in older adults: a group and individual perspective

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations.

Beyond Criminal Justice: An anthology of abolitionist papers presented to conferences of the European Group for the Study of Deviance and Social Control over the past decade

Beyond Criminal Justice presents a vision of a future without brutal, authoritarian and repressive penal regimes. Many of the papers brought together here have been unavailable for more than two decades. Their republication indicates not only their continuing theoretical importance to abolitionist studies but also how they provide important insights into the nature and legitimacy of criminal processes in the here and now. Contributors highlight the human consequences of the harms of imprisonment, evidencing the hurt, injury and damage of penal incarceration across a number of different countries in Europe. Focusing on penal power and prisoner contestation to such power, the moral and political crises of imprisonment are laid bare. The contributors to Beyond Criminal Justice explore the urgent need for a coherent, rational and morally and politically sophisticated theoretical basis for penal abolitionism. Advocating a utopian imagination and at the same time practical solutions already implemented in countries around Europe - alongside grappling with controversial debates such as abolitionist responses to rape and sexual violence - the book steps outside of common sense assumptions regarding 'crime', punishment and 'criminal justice'. Beyond Criminal Justice will be of interest to students of criminology, zemiology, sociology, penology and critical legal studies as well as anyone interested in rethinking the problem of 'crime' and challenging the logic of the penal rationale.

Efficient Processing of Spatial Group Keyword Queries

With the proliferation of geo-positioning and geo-tagging techniques, spatio-textual objects that possess both a geographical location and a textual description are gaining in prevalence, and spatial keyword queries that exploit both location and textual description are gaining in prominence. However, the queries studied so far generally focus on finding individual objects that each satisfy a query rather than finding groups of objects where the objects in a group together satisfy a query.

We define the problem of retrieving a group of spatio-textual objects such that the group's keywords cover the query's keywords and such that the objects are nearest to the query location and have the smallest inter-object distances. Specifically, we study three instantiations of this problem, all of which are NP-hard. We devise exact solutions as well as approximate solutions with provable approximation bounds to the problems. In addition, we solve the problems of retrieving top-k groups of three instantiations, and study a weighted version of the problem that incorporates object weights. We present empirical studies that offer insight into the efficiency of the solutions, as well as the accuracy of the approximate solutions.

A review of excision repair cross-complementation group 1 in colorectal cancer

Oxaliplatin-based chemotherapy is the standard of care in patients with high-risk stage II and stage III colorectal cancer as well as in patients with advanced disease. Unfortunately, a large proportion of patients offered oxaliplatin fail to benefit from it. In the era of personalized treatment, there are strong efforts to identify biomarkers that will predict efficacy to oxaliplatin-based treatments. Excision repair cross-complementation group 1 (ERCC1) is a key element in the nucleotide excision repair (NER) pathway, which is responsible for repairing DNA adducts induced by platinum compounds. ERCC1 has recently been shown to be closely associated with outcome in patients with non-small-cell lung cancer (NSCLC): both high ERCC1 protein and gene expression are associated with resistance to cisplatin-based chemotherapy and better outcome without treatment. Therefore, ERCC1 has the potential to be used as a strong candidate biomarker, both predictive and prognostic, for colorectal cancer. This review will focus on the preclinical and clinical evidences supporting ERCC1 as a major molecule in oxaliplatin resistance. In addition, the important technologies used to assess ERCC1 gene and protein expression will be highlighted.

Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.

Attitudes of physicians, patients, and village health workers toward glaucoma and diabetic retinopathy in rural China:A focus group study

Objective: To understand the knowledge and attitudes of rural Chinese physicians, patients, and village health workers (VHWs) toward diabetic eye disease and glaucoma. Methods: Focus groups for each of the 3 stakeholders were conducted in 3 counties (9 groups). The focus groups were recorded, transcribed, and coded using specialized software. Responses to questions about barriers to compliance and interventions to remove these barriers were also ranked and scored. Results: Among 22 physicians, 23 patients, and 25 VHWs, knowledge about diabetic eye disease was generally good, but physicians and patients understood glaucoma only as an acutely symptomatic disease of relatively low prevalence. Physicians did not favor routine pupillary dilation to detect asymptomatic disease, expressing concerns about workflow and danger and inconvenience to patients. Providers believed that cost was the main barrier to patient compliance, whereas patients ranked poorly trained physicians as more important. All 3 stakeholder groups ranked financial interventions to improve compliance (eg, direct payment, lotteries, and contracts) low and preferred patient education and telephone contact by nurses. All the groups somewhat doubted the ability of VHWs to screen for eye disease accurately, but patients were generally willing to pay for VHW screening. The VHWs were uncertain about the value of eye care training but might accept it if accompanied by equipment. They did not rank payment for screening services as important. Conclusions: Misconceptions about glaucoma's asymptomatic nature and an unwillingness to routinely examine asymptomatic patients must be addressed in training programs. Home contact by nurses and patient education may be the most appropriate interventions to improve compliance.

A closer look at Carver and White's BIS/BAS scales: Factor analysis and age group differences

The Behavioural Inhibition and Behavioural Activation System (BIS/BAS) scales were developed by Carver and White (1994) and comprise four scales which measure individual differences in personality (Gray 1982, 1991). More recent modifications, namely the five-factor model derived from Gray and McNaughton's (2000) revised Reward Sensitivity Theory (RST) suggests that Anxiety and Fear are separable components of inhibition. This study employed exploratory and confirmatory factor analyses on the scales in order to test whether the four or five-factor model was the better fit in a sample of 994 participants aged 11–30 years. Consistent with RST, superior model fit was shown for the five-factor model with all variables correlated. Significant age effects were observed for BIS Fear and BIS Anxiety, with scores peaking in middle and late adolescence respectively. The BAS subscales showed differential effects of age group. Significantly increasing scores from early to mid and from mid to late adolescence were found for Drive, but the effect of age on Fun Seeking and Reward Responsiveness was not significant.

Nurturing attachments in looked after children: a feasibility study of a group-based programme for carers

Introduction: The attachment related difficulties of Looked after Children are well recognised in literature with difficulties linked to early experiences hypothesised to be perpetuated by experiences of the care system itself. Recent policy guidelines have emphasised the importance of relationships for children in care, one of the most important being with their primary carer. Golding (2014) published a group format training resource entitled ‘Nurturing Attachments’ which aims to promote ‘therapeutic parenting’; however there is limited knowledge on the feasibility of this intensive approach.
Aims: To assess the feasibility of Nurturing Attachments through exploring (i.) recruitment, retention and attrition, (ii.) initial outcomes, (iii.) acceptability and (iv.) ability of the programme to be delivered in line with the manual content and structure.
Method Two Health and Social Care Trusts in NI participated in the study by facilitating a Nurturing Attachments group in each site with adoptive parents, foster carers and kinship carers (N = 26). Carers completed pre and post measures to explore initial outcome, completing an evaluation questionnaire to explore acceptability. Acceptability was also explored with Trust stakeholders and group facilitators through focus group and interview. To explore if the manual can be delivered as intended, each group completed debrief tools.
Results: The overall response rate for uptake was 13.9%, which impacted on engagement for a ‘treatment as usual’ group. Once engaged in the programme, attrition was low and attendance was high. Initial outcomes have shown positive effects for both young person and carers. Feedback suggests a positive response regarding acceptability with limited expressed concern. The manual can be delivered in a standardised way; however can be flexible enough to allow for group processes.
Conclusions: Further research is needed to continue to explore efficacy, however the current study has provided supporting evidence that Nurturing Attachments as an intervention has positively impacted on many levels of the LAAC system.

Beyond managerial talent: ‘key group’ identification and differential compensation practices in multinational companies

With the maturation of strategic human resource management scholarship, there appears to be a greater call to move from monolithic workforce management to a more strategic and differentiated emphasis on employees with the greatest capacity to enhance competitive advantage. There has been little consideration in the literature as to whether organizations formally identify key groups of employees based on their impact on organizational learning and core competences. Using survey evidence from 260 multinational companies (MNCs), this paper explores the extent to which key groups of employees are formally recognized and whether they are subject to differential compensation practices. The results demonstrate that just in excess of half of these MNCs identify a key group. There was considerable differentiation in the compensation practices between these key groups, managers and the largest occupational group in the workforce. The results give rise to questions worthy of future investigation, namely whether the differentiated approaches used lead to improved performance outcomes.

Confidence in Contact: A New Perspective on Promoting Cross-Group Friendship Among Children and Adolescents

Intergroup contact theory proposes that positive interactions between members of different social groups can improve intergroup relations. Contact should be especially effective in schools, where opportunities may exist to engage cooperatively with peers from different backgrounds and develop cross-group friendships. In turn, these friendships have numerous benefits for intergroup relations. However, there is evidence that children do not always engage in cross-group friendships, often choosing to spend time with same-group peers, even in diverse settings. We argue that in order to capitalize on the potential impact of contact in schools for promoting harmonious intergroup relations, a new model is needed that places confidence in contact at its heart. We present an empirically driven theoretical model of intergroup contact that outlines the conditions that help to make young people contact ready, preparing them for successful, sustained intergroup relationships by giving them the confidence that they can engage in contact successfully. After evaluating the traditional approach to intergroup contact in schools, we present our theoretical model which outlines predictors of cross-group friendships that enhance confidence in and readiness for contact. We then discuss theory-driven, empirically tested interventions that could potentially promote confidence in contact. Finally, we make specific recommendations for practitioners and policy makers striving to promote harmonious intergroup relations in the classroom.