Measuring changes in Schlemm’s canal and trabecular meshwork in different accommodation states in myopia children: an observational study

Abstract Purpose: Studies were designed to evaluate changes in the size of the Schlemm's Canal (SC) and trabecular meshwork(TM) during accommodation stimuli and cycloplegia states in myopic children. Methods: 34 children were enrolled. A -6D accommodation stimulus was achieved by looking at an optotype through a mirror. Cycloplegia state was induced with 1% tropicamide. Two states were confirmed by measuring the central lens thickness（CLT）, the anterior chamber depth and the pupil diameter. The size of the Schlemm's Canal (SC) and Trabecular Meshwork(TM) was measured using swept-source optical coherence tomography. And the associations between the change of the SC and the CLT were analyzed. Results: When compared with the relaxation state, under -6D accommodation stimuli, the size of SC increased significantly: the SC area (SCA) amplified from 6371±2517μm2 to 7824±2727 μm2; the SC length (SCL) from 249±10 μm to 295±12 μm, and SC width (SCW) from 27±9 μm to 31±8 μm. Under cycloplegia state, the SCA reduced to 5009±2028 μm2; the SCL to 212±μm and the SCW to 22±5 μm. In addition, the changed areas of SCA (r=0. 35; P=0.0007), SCL (r=0. 251; P=0.0172), and SCW (r=0. 253; P=0.016) were significantly correlated with the change in CLT. However, the size of TM did not change substantially when compared with the relaxation state. Only the TM length (TML) increased from 562±45μm to 587±47μm after -6D accommodation stimulus. Conclusion: SC size enlarges after -6D accommodation stimuli and shrinks under cycloplegia. However, for TM, only the TM length increase under accommodation stimulus state. KEYWORDS: Schlemm’s Canal, Trabecular Meshwork, accommodatio

Venetoclax–Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia

Background: Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. Methods: In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax–rituximab group) or bendamustine plus rituximab for 6 months (bendamustine–rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine–rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival. Results: After a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax–rituximab group (32 events of progression or death in 194 patients) than in the bendamustine–rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax–rituximab group versus 27.8% in the bendamustine–rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax–rituximab group than in the bendamustine–rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax–rituximab group was 3.1% (6 of 194 patients). Conclusions: Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab. (Funded by Genentech and AbbVie; ClinicalTrials.gov number, NCT02005471.

Biophysical interactions in tropical agroforestry systems

sequential systems, simultaneous systems Abstract. The rate and extent to which biophysical resources are captured and utilized by the components of an agroforestry system are determined by the nature and intensity of interac-tions between the components. The net effect of these interactions is often determined by the influence of the tree component on the other component(s) and/or on the overall system, and is expressed in terms of such quantifiable responses as soil fertility changes, microclimate modification, resource (water, nutrients, and light) availability and utilization, pest and disease incidence, and allelopathy. The paper reviews such manifestations of biophysical interactions in major simultaneous (e.g., hedgerow intercropping and trees on croplands) and sequential (e.g., planted tree fallows) agroforestry systems. In hedgerow intercropping (HI), the hedge/crop interactions are dominated by soil fertility improvement and competition for growth resources. Higher crop yields in HI than in sole cropping are noted mostly in inherently fertile soils in humid and subhumid tropics, and are caused by large fertility improvement relative to the effects of competition. But, yield increases are rare in semiarid tropics and infertile acid soils because fertility improvement does not offse

Treatment of anorexia nervosa:A multimethod investigation translating experimental neuroscience into clinical practice

Background Anorexia nervosa (AN) is a severe psychiatric condition and evidence on how to best treat it is limited. Objectives This programme consists of seven integrated work packages (WPs) and aims to develop and test disseminable and cost-effective treatments to optimise management for people with AN across all stages of illness. Methods WP1a used surveys, focus groups and a pre–post trial to develop and evaluate a training programme for school staff on eating disorders (EDs). WP1b used a randomised controlled trial (RCT) [International Standard Randomised Controlled Trial Number (ISRCTN) 42594993] to evaluate a prevention programme for EDs in schools. WP2a evaluated an inpatient treatment for AN using case reports, interviews and a quasi-experimental trial. WP2b used a RCT (ISRCTN67720902) to evaluate two outpatient psychological therapies for AN. WP3 used a RCT (ISRCTN06149665) to evaluate an intervention for carers of inpatients with AN. WP4 used actimetry, self-report and endocrine assessment to examine physical activity (PA) in AN. WP5 conducted a RCT (ISRCTN18274621) of an e-mail-guided relapse prevention programme for inpatients with AN. WP6 analysed cohort data to examine the effects of maternal EDs on fertility and their children’s diet and growth. WP7a examined clinical case notes to explore how access to specialist ED services affects care pathways and user experiences. Finally, WP7b used data from this programme and the British Cohort Study (1970) to identify the costs of services used by people with AN and to estimate annual costs of AN for England. Results WP1a: a brief training programme improved knowledge, attitudes and confidence of school staff in managing EDs in school. WP1b: a teacher-delivered intervention was feasible and improved risk factors for EDs in adolescent girls. WP2a: both psychological therapies improved outcomes in outpatients with AN similarly, but patients preferred one of the treatments. WP2b: the inpatient treatment (Cognitive Remediation and Emotional Skills Training) was acceptable with perceived benefits by patients, but showed no benefits compared with treatment as usual (TAU). WP3: compared with TAU, the carer intervention improved a range of patient and carer outcomes, including carer burden and patient ED symptomatology. WP4: drive to exercise is tied to ED pathology and a desire to improve mood in AN patients. PA was not increased in these patients. WP5: compared with TAU, the e-mail-guided relapse prevention programme resulted in higher body mass index and lower distress in patients at 12 months after discharge. WP6: women with an ED had impaired fertility and their children had altered dietary and growth patterns compared with the children of women without an ED. WP7a: direct access to specialist ED services was associated with higher referral rates, lower admission rates, greater consistency of care and user satisfaction. WP7b: the annual costs of AN in England are estimated at between £45M and £230M for 2011. Conclusions This programme has produced evidence to inform future intervention development and has developed interventions that can be disseminated to improve outcomes for individuals with AN. Directions for future research include RCTs with longer-term outcomes and sufficient power to examine mediators and moderators of change. Trial registration Current Controlled Trials ISRCTN42594993, ISRCTN67720902, ISRCTN06149665 and ISRCTN18274621