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.

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.

Collective synchrony increases prosociality towards non-performers and out-group members

Previous research has found that behavioural synchrony between people leads to greater prosocial tendencies towards co-performers. In this study we investigated the scope of this prosocial effect: does it extend beyond the performance group to an extended in-group (extended parochial prosociality) or even to other people in general (generalized prosociality)? Participants performed a simple rhythmic movement either in time (synchrony condition) or out of time (asynchrony condition) with each other. Before and during the rhythmic movement, participants were exposed to a prime that made salient an extended in-group identity. After the task, half the participants had the opportunity to help an extended in-group member; the other half had the opportunity to help an out-group member. We found a main effect of our synchrony manipulation across both help targets suggesting that the prosocial effects of synchrony extend to non-performers. Furthermore, there was a significantly higher proportion of participants willing to help an out-group member after moving collectively in synchrony. This study shows that under certain intergroup contexts synchrony can lead to generalized prosociality with performers displaying greater prosociality even towards out-group members.