Randomized Bendamustine-Rituximab(R) + Bortezomib Induction and R + Lenalidomide Maintenance for Mantle Cell Lymphoma.

While initial therapy of mantle cell lymphoma (MCL) is not standardized, bendamustine-rituximab (BR) is commonly used in older patients. Rituximab (R) maintenance following induction is often utilized. Thus, the open-label, randomized phase II ECOG-ACRIN Cancer Research Group E1411 trial was designed to test two questions: 1) Does addition of bortezomib to BR induction (BVR) and/or 2) addition of lenalidomide to rituximab (LR) maintenance improve progression-free survival (PFS) in patients with treatment-naïve MCL? From 2012-2016, 373 previously untreated patients, 87% ≥ 60 years old, were enrolled in this trial. At a median follow up of 7.5 years, there is no difference in the median PFS of BR compared to BVR (5.5 yrs vs. 6.4 yrs, HR 0.90, 90% CI 0.70, 1.16). There were no unexpected additional toxicities with BVR treatment compared to BR, with no impact on total dose/duration of treatment received. Independent of the induction treatment, addition of lenalidomide to rituximab did not significantly improve PFS, with median PFS in R vs LR (5.9 yrs vs 7.2 yrs, HR 0.84 90% CI 0.62, 1.15). The majority of patients completed the planned 24 cycles of LR at the scheduled dose. In summary, adding bortezomib to BR induction does not prolong PFS in treatment-naïve MCL, and LR maintenance was not associated with longer PFS compared with rituximab alone following BR. Nonetheless, the > 5 year median PFS outcomes in this prospective cooperative group trial indicate the efficacy of BR followed by rituximab maintenance as highly effective initial therapy for older MCL patients. (NCT01415752).

Lessons Learned from a Citywide Abandoned Housing Experiment.

Problem research strategy and findings: The negative impact of vacant and abandoned housing in city neighborhoods is extreme, affecting health and quality of life, promoting violence, and leading to further abandonment. One approach to addressing abandoned housing is to intervene with low-cost interventions that provide a visual sense of ownership. We tested whether a low-cost remediation of abandoned and vacant houses or a trash cleanup intervention would make a noticeable difference in the levels of nearby disrepair, disorder, and public safety. The abandoned housing remediation and trash cleanup interventions were a test of compliance with municipal ordinances. We used an experimental design to test the causal effects of the ordinances, and because the scale of abandonment was too large to provide treatment to all abandoned houses in the city. We used systematic social observation methods to rate changes in disrepair, disorder, and litter at housing sites and on the city blocks they were located, and police reported data on gun violence and illegal substance uses. Our experimental design allowed us to see if observed disrepair, disorder, and public safety improved after working windows and doors were installed on abandoned houses compared with a trash cleanup around properties or a no-intervention control condition. Our results showed significant changes in observed disrepair, disorder, and gun violence and illustrate the benefits of experimental evaluations of place-based changes to the built environment. Takeaway for practice: Improving compliance with ordinances to remediate abandoned housing can make a noticeable difference in disrepair in neighborhoods and contribute improved public safety. We illustrate how planners can use field experiments in partnership with city agencies, nonprofit community groups, and local universities to discover novel approaches to advance place-based changes to the built environment that can help economically disadvantaged communities abate problems of physical disorder.

'Fragmented care': Asylum seekers' experience of accessing health care in NSW.

Medicare is central to accessing health care in Australia, yet many asylum seekers are ineligible for this scheme. In NSW, Medicare ineligible asylum seekers have some access to public health care under the Medicare Ineligible Asylum Seekers - Provision of Specified Public Health Services policy. This policy was updated in November 2020 to clarify services where a fee waiver applies for asylum seekers without Medicare. We examined the experiences of Medicare ineligible asylum seekers in accessing health care in New South Wales (NSW) in light of the revised policy. Employing qualitative methods, we conducted semi-structured interviews with asylum seekers (n = 7) and service providers (n = 6) in South Western Sydney. The interviews were analysed using thematic analysis and the socio-ecological model was used to interpret the data. Participants identified that chronic and mental health conditions are the main health issues for asylum seekers. Factors across the four levels of the socio-ecological model were identified as influencing the health care of asylum seekers, including a lack of awareness about health care rights at the individual level, support from relatives and friends at the interpersonal level, providers' lack of awareness of fee waivers at the organizational level and limited access to primary health care at the policy level. The results imply that Medicare ineligible asylum seekers in NSW do not have optimal access to health care which may worsen existing health disparities. Educational initiatives that improve service providers' and asylum seekers' awareness of the revised policy are needed to improve asylum seeker health equity in NSW.

Development of Shortened miR-506-3p Mimics Exhibiting Strong Differentiation-Inducing Activity in Neuroblastoma Cells.

microRNA mimics are synthetic RNA molecules that imitate the mature miRNA duplexes and their functions. These mimics have shown promise in treating cancers. Nucleotide chemical modifications of microRNA mimics have been investigated and have improved the stability of miRNA mimics. However, the potential therapeutic benefit of mimic analogs based on sequence modifications has not been explored. miR-506-3p was identified as a differentiation-inducing microRNA in neuroblastoma cells, suggesting the potential of applying the miR-506-3p mimic in neuroblastoma differentiation therapy. In this study, we explored the possibility of developing shortened miR-506-3p analogs that can maintain differentiation-inducing activities comparable to the wild-type miR-506-3p mimic. We found that deleting up to two nucleotides at either the 3' end or within the middle region of the miR-506-3p sequence fully maintained the differentiation-inducing activity when compared to the wild-type mimic. Deleting up to four nucleotides from the 3' end or deleting three nucleotides in the middle positions diminished the differentiation-inducing activity, but the analogs still maintained differentiation-inducing activities that were significantly higher than the negative control oligo. The shortened analog designs potentially benefit patients from two perspectives: (1) the reduced cost of manufacturing shortened analogs, and (2) the reduced non-specific toxicity due to their smaller molecular sizes.

Twelve tips for engaging students and community partners in medical education.

There is increasing evidence on the positive outcomes of engaging students and community partners in medical education, especially in achieving social accountability. However, less is known about the steps through which these engagements are established. This paper outlines twelve tips on establishing a robust and enduring partnership with students and community partners in medical education, using examples from the Western Sydney University School of Medicine. While context is paramount in any engagement program, these tips are formulated to be transferable to medical education settings in different countries, education systems, and the broader context of health professional education.

Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity.

A 15-step chemoenzymatic total synthesis of C-1 methoxycarbonyl narciclasine (10) was accomplished. The synthesis began with the toluene dioxygenase-mediated dihydroxylation of ortho-dibromobenzene to provide the corresponding cis-dihydrodiol (12) as a single enantiomer. Further key steps included a nitroso Diels-Alder reaction and an intramolecular Heck cyclization. The C-1 homolog 10 was tested and evaluated for antiproliferative activity against natural narciclasine (1) as the positive control. Experimental and spectral data are reported for all novel compounds.

Conversion of Natural Narciclasine to Its C-1 and C-6 Derivatives and Their Antitumor Activity Evaluation: Some Unusual Chemistry of Narciclasine.

During the search for a general, efficient route toward the synthesis of C-1 analogues of narciclasine, natural narciclasine was protected and converted to its C-1 enol derivative using a novel semi-synthetic route. Attempted conversion of this material to its triflate in order to conduct cross-coupling at C-1 resulted in a triflate at C-6 that was successfully coupled with several functionalities. Four novel compounds were fully deprotected after seven steps and subjected to evaluation for cytotoxic activity against three cancer cell lines. Only one derivative showed moderate activity compared to that of narciclasine. Spectral and physical data are provided for all new compounds.

OPTIMISE: a pragmatic stepped wedge cluster randomised trial of an intervention to improve primary care for refugees in Australia.

OBJECTIVES: To examine whether primary care outreach facilitation improves the quality of care for general practice patients from refugee backgrounds. DESIGN: Pragmatic, cluster randomised controlled trial, with stepped wedge allocation to early or late intervention groups. SETTING, PARTICIPANTS: 31 general practices in three metropolitan areas of Sydney and Melbourne with high levels of refugee resettlement, November 2017 - August 2019. INTERVENTION: Trained facilitators made three visits to practices over six months, using structured action plans to help practice teams optimise routines of refugee care. MAJOR OUTCOME MEASURE: Change in proportion of patients from refugee backgrounds with documented health assessments (Medicare billing). Secondary outcomes were refugee status recording, interpreter use, and clinician-perceived difficulty in referring patients to appropriate dental, social, settlement, and mental health services. RESULTS: Our sample comprised 14 633 patients. The intervention was associated with an increase in the proportion of patients with Medicare-billed health assessments during the preceding six months, from 19.1% (95% CI, 18.6-19.5%) to 27.3% (95% CI, 26.7-27.9%; odds ratio, 1.88; 95% CI, 1.42-2.50). The impact of the intervention was greater in smaller practices, practices with larger proportions of patients from refugee backgrounds, recent training in refugee health care, or higher baseline provision of health assessments for such patients. There was no impact on refugee status recording, interpreter use increased modestly, and reported difficulties in refugee-specific referrals to social, settlement and dental services were reduced. CONCLUSIONS: Low intensity practice facilitation may improve some aspects of primary care for people from refugee backgrounds. Facilitators employed by local health services could support integrated approaches to enhancing the quality of primary care for this vulnerable population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618001970235 (retrospective).

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.

BACKGROUND: In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. METHODS: In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. RESULTS: Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response. CONCLUSIONS: In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .).

Factors Associated with Exposure to Trihalomethanes, NHANES 2001-2012.

Disinfection is critical for maintaining a safe water supply, but the use of chlorine or chloramine leads to exposure to disinfection byproducts (DBPs), including trihalomethanes (THMs), which have been associated with adverse reproductive outcomes and bladder cancer. The U.S. Environmental Protection Agency revised the DBP regulations starting in 1998 to further limit levels of THMs in household water. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) collected between 2001 and 2012 (with 2 years per cycle) using models with and without water-related predictors to examine the utility of including these measures. Median blood chloroform levels (25th-75th percentiles) were 16.2 (9.13-31.2) ng/L in 2001-2002 and 5.97 (2.92-12.3) ng/L in 2011-2012. Median blood bromodichloromethane (BDCM) levels (25th-75th percentiles) were 2.22 (1.06-4.61) ng/L in 2001-2002 and 1.18 (

Early Generated B-1-Derived B Cells Have the Capacity To Progress To Become Mantle Cell Lymphoma-like Neoplasia in Aged Mice.

In mice, fetal/neonatal B-1 cell development generates murine CD5+ B cells (B1a) with autoreactivity. We analyzed B1a cells at the neonatal stage in a VH11/D/JH knock-in mouse line (VH11t) that generates an autoreactive antiphosphatidylcholine BCR. Our study revealed that antiphosphatidylcholine B1a cells develop in liver, mature in spleen, and distribute in intestine/colon, mesenteric lymph node (mLN), and body cavity as the outcome of B-1 cell development before B-2 cell development. Throughout life, self-renewing B-1 B1a cells circulate through intestine, mesenteric vessel, and blood. The body cavity-deposited B1a cells also remigrate. In old age, some B1a cells proceed to monoclonal B cell lymphocytosis. When neonatal B-1 B1a cells express an antithymocyte/Thy-1 autoreactivity (ATA) BCR transgene in the C.B17 mouse background, ATA B cells increase in PBL and strongly develop lymphomas in aging mice that feature splenomegaly and mLN hyperplasia with heightened expression of CD11b, IL-10, and activated Stat3. At the adult stage, ATA B cells were normally present in the mantle zone area, including in intestine. Furthermore, frequent association with mLN hyperplasia suggests the influence by intestinal microenvironment on lymphoma development. When cyclin D1 was overexpressed by the Eµ-cyclin D1 transgene, ATA B cells progressed to further diffused lymphoma in aged mice, including in various lymph nodes with accumulation of IgMhiIgDloCD5+CD23-CD43+ cells, resembling aggressive human mantle cell lymphoma. Thus, our findings reveal that early generated B cells, as an outcome of B-1 cell development, can progress to become lymphocytosis, lymphoma, and mantle cell lymphoma-like neoplasia in aged mice.

Improving the mental wellbeing of Arabic speaking refugees: an evaluation of a mental health promotion program.

BACKGROUND: Refugee populations have particularly high rates of mental health problems, including Posttraumatic Stress Disorder (PTSD) and depression. However, uptake of mental health care may be low even when severe depression and PTSD symptoms are present in individuals following resettlement. This is likely due, at least in part, to cultural influences on refugees' knowledge and beliefs about mental health problems and their treatment. We sought to provide preliminary evidence for the effectiveness of a culturally tailored mental health promotion program for Arabic-speaking refugees. METHODS: A total of 33 Arabic-speaking refugees resettled in South Western Sydney were recruited and completed intervention which consisted of weekly three-hour sessions for 4 weeks delivered in Arabic. Key aspects of mental health literacy, help-seeking intentions and levels of general psychological distress were assessed, by means of a self-report survey, pre-intervention, (immediately) post-intervention and 3 months following intervention. RESULTS: Of the 33 participants that completed the intervention, 31 completed the immediate post-intervention survey and 29 completed the 3 months follow-up survey. Improvements in most aspects of mental health literacy assessed were found immediately post-intervention and at follow-up, although only changes relating to stigmatising attitudes were statistically significant. Additionally, a statistically significant decrease in participants' levels of general psychological distress was observed immediately following the intervention, and this decrease was sustained at follow-up. CONCLUSION: While further research employing a more rigorous study design and larger sample size will be needed, results of this initial trial suggest that a culturally tailored mental health promotion program targeting key aspects of mental health literacy can improve the mental health of Arabic-speaking refugees resettled in a Western nation.

Understanding the presence of mental fatigue in English academy soccer players.

Research has demonstrated that induced mental fatigue impairs soccer-specific technical, tactical and physical performance in soccer players. The findings are limited by the lack of elite players and low ecological validity of the tasks used to induce mental fatigue, which do not resemble the cognitive demands of soccer. The current study collected survey data from English academy soccer players (n = 256; age groups - U14 - U23), with questions comprising of five themes (descriptors of physical and mental fatigue, travel, education, match-play and fixture congestion). The survey consisted of multiple choice responses, checkboxes and blinded/unblinded (for duration based questions) 0-100 arbitrary unit (AU) slider scales. Listening to music (81.6% of players), using social media (58.3%) and watching videos (34.3%) were the most common pre-match activities. Pre-match subjective mental fatigue was low (18.7±18.8 AU), and most frequently reported at the end of a match (47±26 AU) and remained elevated 24-hours post-match (36±27 AU). Travel (29±24 AU), fixture congestion (44±25 AU) and education (30±26 AU) demonstrated a low to moderate presence of subjective mental fatigue. These findings provide an overview of activities performed by English academy soccer players pre-match, and demonstrate that mental fatigue is experienced as a result of match-play.

Dribble Deficit quantifies dribbling speed independently of sprinting speed and differentiates between age categories in pre-adolescent basketball players.

The aims of this study were to a) quantify the relationships between sprinting and dribbling speed measured using dribble time and Dribble Deficit and b) assess the difference between age categories in sprinting and dribbling speed in pre-adolescent basketball players. Pre-adolescent, male basketball players (Total, N = 81; Under-10, n = 32, Under-9, n = 49) completed two trials of different tasks including 20-m linear sprints without dribbling, 20-m linear sprints dribbling with dominant and non-dominant hands, and change-of-direction (COD) sprints with and without dribbling. Sprinting time, dribbling time and Dribble Deficit were then calculated for each trial. Spearman rank correlations were used to assess the relationships between outcome measures for Under-9 and Under-10 players separately and combined. The Mann-Whitney U test with effect sizes (ES) was used to assess differences in outcome measures between Under-9 and Under-10 players. Moderate-to-very large significant relationships (p <0.05) between linear and COD sprinting time and dribbling time using dominant and non-dominant hands were found in Under-9, Under-10 and all players combined. Trivial-to-moderate relationships were found between sprinting time and Dribble Deficit in all age categories across linear and COD paths. Quicker performance times (p <0.05) were found for Under-10 compared to Under-9 players in all outcome measures (ES: small-to-moderate), except for COD sprinting time (p >0.05; ES: small). Dribble Deficit measures dribbling speed independently of sprinting speed across linear and COD paths in pre-adolescent basketball players and differentiates between age categories.

Neuronal connections of direct and indirect pathways for stable value memory in caudal basal ganglia.

Direct and indirect pathways in the basal ganglia work together for controlling behavior. However, it is still a controversial topic whether these pathways are segregated or merged with each other. To address this issue, we studied the connections of these two pathways in the caudal parts of the basal ganglia of rhesus monkeys using anatomical tracers. Our previous studies showed that the caudal basal ganglia control saccades by conveying long-term values (stable values) of many visual objects toward the superior colliculus. In experiment 1, we injected a tracer in the caudate tail (CDt), and found local dense plexuses of axon terminals in the caudal-dorsal-lateral part of substantia nigra pars reticulata (cdlSNr) and the caudal-ventral part of globus pallidus externus (cvGPe). These anterograde projections may correspond to the direct and indirect pathways, respectively. To verify this in experiment 2, we injected different tracers into cdlSNr and cvGPe, and found many retrogradely labeled neurons in CDt and, in addition, the caudal-ventral part of the putamen (cvPut). These cdlSNr-projecting and cvGPe-projecting neurons were found intermingled in both CDt and cvPut (which we call "striatum tail"). A small but significant proportion of neurons (<15%) were double-labeled, indicating that they projected to both cdlSNr and cvGPe. These anatomical results suggest that stable value signals (good vs. bad) are sent from the striatum tail to cdlSNr and cvGPe in a biased (but not exclusive) manner. These connections may play an important role in biasing saccades toward higher valued objects and away from lower valued objects.

An open-label phase 2 trial of entospletinib in indolent non-Hodgkin lymphoma and mantle cell lymphoma.

Spleen tyrosine kinase (Syk) mediates B-cell receptor signalling in normal and malignant B cells. Entospletinib is an oral, selective Syk inhibitor. Entospletinib monotherapy was evaluated in a multicentre, phase 2 study of patients with relapsed or refractory indolent non-Hodgkin lymphoma or mantle cell lymphoma (MCL). Subjects received 800 mg entospletinib twice daily. Forty-one follicular lymphoma (FL), 17 lymphoplasmacytoid lymphoma/Waldenström macroglobulinaemia (LPL/WM), 17 marginal zone lymphoma (MZL) and 39 MCL patients were evaluated. The primary endpoint was a progression-free survival (PFS) rate (defined as not experiencing progression or death) at 16 weeks for patients with MCL and at 24 weeks for patients with FL, LPL/WM and MZL. The most common treatment-emergent adverse events were fatigue, nausea, diarrhoea, vomiting, headache and cough. Common laboratory abnormalities were anaemia, neutropenia and thrombocytopenia; aspartate transaminase, alanine transaminase, total bilirubin and serum creatinine were all increased. PFS at 16 weeks in the MCL cohort was 63·9% [95% confidence interval (CI) 45-77·8%]; PFS at 24 weeks in the FL, LPL/WM, MCL and MZL cohorts was 51·5% (95% CI 32·8-67·4%), 69·8% (95% CI 31·8-89·4%), 56·6% (95% CI 37·5-71·8%) and 46·2% (95% CI 18·5-70·2%), respectively. Entospletinib had limited single-agent activity with manageable toxicity in these patient populations.

Nitromethane Exposure from Tobacco Smoke and Diet in the U.S. Population: NHANES, 2007-2012.

Nitromethane is a known toxicant and suspected human carcinogen. Exposure to nitromethane in a representative sample of the civilian, noninstitutionalized population in the United States ≥12 years old was assessed using 2007-2012 National Health and Nutritional Examination Survey (NHANES) data. Nitromethane was detected in all 8000 human blood samples collected, of which 6730 were used for analyses reported here. Sample-weighted median blood nitromethane was higher among exclusive combusted tobacco users (exclusive smokers; 774 ng/L) than nonusers of tobacco products (625 ng/L). In stratified sample-weighted regression analysis, smoking 0.5 pack of cigarettes per day was associated with a statistically significant increase in blood nitromethane by 150 ng/L, and secondhand smoke exposure (serum cotinine >0.05 ng/mL and <10 ng/mL) was statistically significant with a 31.1 ng/L increase in blood nitromethane. Certain dietary sources were associated with small but statistically significant increases in blood nitromethane. At median consumption levels, blood nitromethane was associated with an increase of 7.55 ng/L (meat/poultry), 9.32 ng/L (grain products), and 14.5 ng/L (vegetables). This is the first assessment of the magnitude and relative source apportionment of nitromethane exposure in the U.S. population.

The OPTIMISE project: protocol for a mixed methods, pragmatic, quasi-experimental trial to improve primary care delivery to refugees in Australia.

BACKGROUND: Australia is one of many nations struggling with the challenges of delivering quality primary health care (PHC) to increasing numbers of refugees. The OPTIMISE project represents a collaboration between 12 organisations to generate a model of integrated refugee PHC suitable for uptake throughout Australia. This paper describes the methodology of one component; an outreach practice facilitation intervention, directed towards improving the quality of PHC received by refugees in Australian general practices. METHODS: Our mixed methods study will use a cluster stepped wedge randomised controlled trial design set in 3 urban regions of high refugee resettlement in Australia. The intervention was build upon regional partnerships of policy advisors, clinicians, academics and health service managers. Following a regional needs assessment, the partnerships reached consensus on four core areas for intervention in general practice (GP): recording of refugee status; using interpreters; conducting comprehensive health assessments; and referring to refugee specialised services. Refugee health staff trained in outreach practice facilitation techniques will work with GP clinics to modify practice routines relating to the four core areas. 36 general practice clinics with no prior involvement in a refugee health focused practice facilitation will be randomly allocated into early and late intervention groups. The primary outcome will be changes in number of claims for Medical Benefit Service reimbursed comprehensive health assessments among patients identified as being from a refugee background. Changes in practice performance for this and 3 secondary outcomes will be evaluated using multilevel mixed effects models. Baseline data collection will comprise (i) pre-intervention provider survey; (ii) two surveys documenting each practices' structure and approaches to delivery of care to refugees. De-identified medical record data will be collected at baseline, at the end of the intervention and 6 and 12 months following completion. DISCUSSION: OPTIMISE will test whether a regionally oriented practice facilitation initiative can improve the quality of PHC delivered to refugees. Findings have the potential to influence policy and practice in broader primary care settings. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618001970235 , 05/12/2018, Retrospectively registered. Protocol Version 1, 21/08/2017.

Reliability, usefulness and construct validity of the Combined Basketball Skill Test (CBST).

This study aimed to assess the reliability, usefulness and construct validity of the newly developed Combined Basketball Skill Test (CBST). Fifteen recreational (age = 22.8 ± 4.2 y, stature = 184.8 ± 6.5 cm, body mass = 81.6 ± 9.6 kg, training experience = 9.8 ± 5.3 y) and fifteen semiprofessional (age = 18.9 ± 3.3 y, stature = 190.5 ± 8.1 cm, body mass = 84.2 ± 11.2 kg, training experience = 11.1 ± 3.5 y) players volunteered to participate in this study. Test-retest reliability and usefulness were examined for recreational players, while construct validity was evaluated comparing the two player groups. The CBST is composed of 12 trials and its outcome measures include: completion time (sum of the 12 trial times); penalty time (sum of the times from the 12 trials); performance time (completion time + penalty time) and total number of errors. Relative reliability analysis showed acceptable ICC values (i.e. ≥0.70) in all the studied variables. Absolute reliability analysis showed a CV < 5% for completion (1.6%) and performance (2.0%) time, while a CV >5% is reported for the remaining variables. The usefulness of the test was considered "Marginal" and "Good" when comparing TE values with SWC02 and SWC05, respectively for all the studied variables. Likely and very likely differences were shown between recreational and semiprofessional players in all investigated variables. Results showed that the CBST is reliable, useful to detect moderate changes and valid to assess basketball skills.

Ibrutinib: a force with a dark side?

In this issue of Blood, Martin et al report poor outcomes for ibrutinib-refractory patients with mantle cell lymphoma (MCL). MCL, an uncommon B-cell lymphoma driven by dysregulated cyclin D1, responds well to initial therapy but is destined to relapse. Subsequent single-agent treatments had modest response rates and duration until the advent of ibrutinib. These data are important, given that ibrutinib is not curative, so clinicians will increasingly encounter patients with MCL who require therapy after ibrutinib.