ABT-199: Taking Dead Aim at BCL-2

ABT-199 is a new selective small molecule inhibitor of BCL-2 that appears to spare platelets while achieving potent antitumor activity. Assays that can predict the efficacy of ABT-199 in individual tumors will be critical in determining how best to incorporate this promising agent into the armamentarium of cancer therapies

EFFECTS OF ATTENTIONAL STRATEGIES, TASK EXPERTISE AND ANXIETY ON COORDINATION OF A DISCRETE MULTI-ARTICULAR ACTION

The purpose of this study was to determine whether anxiety effects on performance of a discrete multi-articular action could be alleviated by attentional strategies and task expertise. 10 expert and 9 novice male basketball players performed 30 freethrows under both control and anxiety conditions. The dependent variables of interest included shooting performance, reaction time, joint amplitude of the wrist, elbow and shoulder, and coordination variability of the shooting arm using the normalised root mean squared difference technique. A significant main effect for condition was observed for reaction time, indicating the implementation of attentional strategies in both groups. In relation to this observation, no significant main effects for condition were found for shooting performance or any of the kinematic variables. Under conditions of elevated emotions, the allocation of additional attention to the primary shooting task seemed to attenuate the effects of anxiety, regardless of expertise. The findings are harmonious with existing data on attention and anxiety effects on coordination of rhythmical actions. They specifically demonstrated how participants, differing in expertise, used attentional strategies to stabilise performance of a discrete multi-articular action against emotional fluctuations

Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States.

BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is \u3e 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites. Patients with CLL were enrolled within 2 months of initiating first line of therapy (LOT1) or a subsequent LOT (LOT ≥ 2). Kaplan-Meier methods were used to evaluate overall survival. CLL- and infection-related mortality were assessed using cumulative incidence functions (CIF) and cause-specific hazards. Logistic regression was used to develop a classification model. RESULTS: A total of 455 E-CLL patients were enrolled; 259 were enrolled in LOT1 and 196 in LOT ≥ 2. E-CLL patients were more likely to receive rituximab monotherapy (19.3 vs. 8.6%; p \u3c 0.0001) and chemotherapy-alone regimens (p \u3c 0.0001) than younger patients. Overall and complete responses were lower in E-CLL patients than younger patients when given similar regimens. With a median follow-up of 3 years, CLL-related deaths were higher in E-CLL patients than younger patients in LOT1 (12.6 vs. 5.1% p = 0.0005) and LOT ≥ 2 (31.3 vs. 21.5%; p = 0.0277). Infection-related deaths were also higher in E-CLL patients than younger patients in LOT1 (7.4 vs. 2.7%; p = 0.0033) and in LOT ≥ 2 (16.2 vs. 11.2%; p = 0.0786). A prognostic score for E-CLL patients was developed: time from diagnosis to treatment \u3c 3 months, enrollment therapy other than bendamustine/rituximab, and anemia, identified patients at higher risk of inferior survival. Furthermore, higher-risk patients experienced an increased risk of CLL- or infection-related death (30.6 vs 10.3%; p = 0.0006). CONCLUSION: CLL- and infection-related mortality are higher in CLL patients aged ≥ 75 years than younger patients, underscoring the urgent need for alternative treatment strategies for these understudied patients. TRIAL REGISTRATION: The Connect CLL registry was registered at clinicaltrials.gov: NCT01081015 on March 4, 2010

Metropolitan quantum key distribution with silicon photonics

Photonic integrated circuits (PICs) provide a compact and stable platform for quantum photonics. Here we demonstrate a silicon photonics quantum key distribution (QKD) transmitter in the first high-speed polarization-based QKD field tests. The systems reach composable secret key rates of 950 kbps in a local test (on a 103.6-m fiber with a total emulated loss of 9.2 dB) and 106 kbps in an intercity metropolitan test (on a 43-km fiber with 16.4 dB loss). Our results represent the highest secret key generation rate for polarization-based QKD experiments at a standard telecom wavelength and demonstrate PICs as a promising, scalable resource for future formation of metropolitan quantum-secure communications networks

Coach to learn and learn to coach: synergising performance and development in the athlete-coach-environment learning system

While high-performance sport traditionally highlights a dualist perspective on distinct pathways of development and performance coaching, an ecological dynamics rationale recognises the deeply entwined relations between development and performance. Acknowledging an athlete-environment-centred approach, an increasingly relevant topic concerns “coach learning”, supporting the idea that theories of athlete development present useful insights for understanding coach development. In this position paper, it is argued that athlete and coach learning are not independent from one another, thus forming part of an athlete-coach-environment learning system. This first of two insights papers discusses the contiguity between athlete development and performance and coach learning. It seeks to highlight a dual coach learning pathway towards “coaching to learn” (infused by knowledge of the environment) and “learning to coach” (supported by knowledge about the environment). To underline the interconnectedness of athlete/coach learning, two examples are discussed from: I) the 2021 Wheelchair Rugby League World Cup; and II), high-performance workshops for Olympic sport coaches

Learning to coach: an ecological dynamics perspective

A constraints-led approach (CLA), based on an ecological dynamics rationale for athlete learning and development has been applied to analyses of individual and team sports. To date, such an approach has yet to be applied to the learning of coaches. Here, we propose how applying a CLA in education and professional development programmes can shape emerging behaviours of coaches as they interact with constraints of representative environments to adapt their practice. A core concept within ecological dynamics for coach education is the conceptual differentiation between knowledge of (direct perception) and knowledge about (indirect perception) the environment. Current coach education and development practices focus primarily on the acquisition and transmission of knowledge about, which over-relies on provision of (abstract) verbal and visual augmented corrective information found in manuals. Reconsidering coaches’ behaviours as emerging under constraints provides a coach developer opportunities to identify and manipulate key individual, environmental and task constraints. This approach guides attention to relevant and alternative affordances (opportunities for action) when coaching, and promotes continuous self-regulation of coach learning, supported by an experienced mentor. Learning to coach through a CLA could result in an extensive appreciation of multiple sources of knowledge, resulting in a continuously deepening fit between the coach and their performance environment. An ecological perspective of a coach learning to adapt to the constraints of a performance environment offers an alternative to current formalised coach development practice

The impact of solar ultraviolet radiation on human health in sub-Saharan Africa

Photoprotection messages and ‘SunSmart’ programmes exist mainly to prevent skin cancers and, more recently, to encourage adequate personal sun exposure to elicit a vitamin D response for healthy bone and immune systems. Several developed countries maintain intensive research networks and monitor solar UV radiation to support awareness campaigns and intervention development. The situation is different in sub-Saharan Africa. Adequate empirical evidence of the impact of solar UV radiation on human health, even for melanomas and cataracts, is lacking, and is overshadowed by other factors such as communicable diseases, especially HIV, AIDS and tuberculosis. In addition, the established photoprotection messages used in developed countries have been adopted and implemented in a limited number of sub-Saharan countries but with minimal understanding of local conditions and behaviours. In this review, we consider the current evidence for sun-related effects on human health in sub-Saharan Africa, summarise published research and identify key issues. Data on the prevalence of human diseases affected by solar UV radiation in all subpopulations are not generally available, financial support is insufficient and the infrastructure to address these and other related topics is inadequate. Despite these limitations, considerable progress may be made regarding the management of solar UV radiation related health outcomes in sub-Saharan Africa, provided researchers collaborate and resources are allocated appropriately

The phase III DUO trial of PI3K inhibitor duvelisib versus ofatumumab in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: final analysis including overall survival

Not available

Assessment of foot alignment and function for ambulatory children with cerebral palsy: Results of a modified Delphi technique consensus study

PURPOSE The purpose of this study was to establish consensus for the assessment of foot alignment and function in ambulatory children with cerebral palsy, using expert surgeon's opinion through a modified Delphi technique. METHODS The panel used a five-level Likert-type scale to record agreement or disagreement with 33 statements regarding the assessment of foot alignment and function. Consensus was defined as at least 80% of responses being in the highest or lowest of two of the five Likert-type ratings. General agreement was defined as 60%-79% falling into the highest or lowest two ratings. There was no agreement if neither threshold was reached. RESULTS Consensus was achieved for 25 (76%) statements, general agreement for 4 (12%) statements, and lack of consensus for 4 (12%) of the statements. There was consensus that the functional anatomy of the foot is best understood by dividing the foot into three segments and two columns. Consensus was achieved concerning descriptors of foot segmental alignment for both static and dynamic assessment. There was consensus that radiographs of the foot should be weight-bearing. There was general agreement that foot deformity in children with cerebral palsy can be classified into three levels based on soft tissue imbalance and skeletal malalignment. CONCLUSION The practices identified in this study can be used to establish best care guidelines, and the format used will be a template for future Delphi technique studies on clinical decision-making for the management of specific foot segmental malalignment patterns commonly seen in children with cerebral palsy. LEVEL OF EVIDENCE V

Distal femoral extension osteotomy and patellar tendon advancement or shortening in ambulatory children with cerebral palsy: A modified Delphi consensus study and literature review

PURPOSE In children with cerebral palsy, flexion deformities of the knee can be treated with a distal femoral extension osteotomy combined with either patellar tendon advancement or patellar tendon shortening. The purpose of this study was to establish a consensus through expert orthopedic opinion, using a modified Delphi process to describe the surgical indications for distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening. A literature review was also conducted to summarize the recent literature on distal femoral extension osteotomy and patellar tendon shortening/patellar tendon advancement. METHOD A group of 16 pediatric orthopedic surgeons, with more than 10 years of experience in the surgical management of children with cerebral palsy, was established. The group used a 5-level Likert-type scale to record agreement or disagreement with statements regarding distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening. Consensus for the surgical indications for distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening was achieved through a modified Delphi process. The literature review, summarized studies of clinical outcomes of distal femoral extension osteotomy/patellar tendon shortening/patellar tendon advancement, published between 2008 and 2022. RESULTS There was a high level of agreement with consensus for 31 out of 44 (70%) statements on distal femoral extension osteotomy. Agreement was lower for patellar tendon advancement/patellar tendon shortening with consensus reached for 8 of 21 (38%) of statements. The literature review included 25 studies which revealed variation in operative technique for distal femoral extension osteotomy, patellar tendon advancement, and patellar tendon shortening. Distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening were generally effective in correcting knee flexion deformities and extensor lag, but there was marked variation in outcomes and complication rates. CONCLUSION The results from this study will provide guidelines for surgeons who care for children with cerebral palsy and point to unresolved questions for further research. LEVEL OF EVIDENCE level V