BCL-W has a fundamental role in B cell survival and lymphomagenesis.

Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types. Here, however, we have exposed a critical role for BCL-W in B cell survival and lymphomagenesis. Loss of Bcl-w conferred sensitivity to growth factor deprivation-induced B cell apoptosis. Moreover, Bcl-w loss profoundly delayed MYC-mediated B cell lymphoma development due to increased MYC-induced B cell apoptosis. We also determined that MYC regulates BCL-W expression through its transcriptional regulation of specific miR. BCL-W expression was highly selected for in patient samples of Burkitt lymphoma (BL), with 88.5% expressing BCL-W. BCL-W knockdown in BL cell lines induced apoptosis, and its overexpression conferred resistance to BCL-2 family-targeting BH3 mimetics. Additionally, BCL-W was overexpressed in diffuse large B cell lymphoma and correlated with decreased patient survival. Collectively, our results reveal that BCL-W profoundly contributes to B cell lymphoma, and its expression could serve as a biomarker for diagnosis and aid in the development of better targeted therapies

A Synthetic 21-cm Galactic Plane Survey of an SPH Galaxy Simulation

We have created synthetic neutral hydrogen (HI) Galactic Plane Survey data cubes covering 90 degrees < l < 180 degrees, using a model spiral galaxy from SPH simulations and the radiative transfer code TORUS. The density, temperature and other physical parameters are fed from the SPH simulation into TORUS, where the HI emissivity and opacity are calculated before the 21-cm line emission profile is determined. Our main focus is the observation of Outer Galaxy `Perseus Arm' HI, with a view to tracing atomic gas as it encounters shock motions as it enters a spiral arm interface, an early step in the formation of molecular clouds. The observation of HI self-absorption features at these shock sites (in both real observations and our synthetic data) allows us to investigate further the connection between cold atomic gas and the onset of molecular cloud formation.Comment: MNRAS accepted; 11 pages, 12 figure

The structure of HI in galactic disks: Simulations vs observations

We generate synthetic HI Galactic plane surveys from spiral galaxy simulations which include stellar feedback processes. Compared to a model without feedback we find an increased scale height of HI emission (in better agreement with observations) and more realistic spatial structure (including supernova blown bubbles). The synthetic data show HI self-absorption with a morphology similar to that seen in observations. The density and temperature of the material responsible for HI self-absorption is consistent with observationally determined values, and is found to be only weakly dependent on absorption strength and star formation efficiency.Comment: 12 pages, 7 figures. Accepted for publication in MNRA

Inheritance of resistance to common bacterial blight in four selected common bean (\u3ci\u3ePhaseolus vulgaris\u3c/i\u3e L.) genotypes

Common bacterial blight (CBB) is the most serious bacterial disease of common bean in Uganda. It causes severe yield losses of up to 62%. Genetic resistance is the most effective option for controlling CBB in smallholder common bean production systems. This study was carried out to determine the inheritance pattern of CBB resistance in leaf and pod of four new resistance sources. The four resistant and four susceptible genotypes were crossed in a half-diallel mating design. F1 individuals were advanced to F2 and evaluated with the parents, in a randomized complete block design replicated twice. Combining ability analysis was performed according to Griffing\u27s (1956) method IV and model 1 using Genstat 12th. General combining ability effects were significant whereas specific combining ability was not suggesting that resistance to CBB in leaf and pod was primarily controlled by additive genes effects. The estimated narrow sense coefficient of genetic determination was moderately high (0.65) for the resistance in leaf and high (0.83) for resistance in pod suggesting that early-generation selection would be effective. Baker’s ratio estimates were relatively high for resistance in leaf (0.79) and pod (0.9) suggesting that hybrids’ performance can be predicted based on the parents’ general combining ability (GCA) effects

Social skill and social cognition in adolescents at genetic risk for psychosis

Adolescents at genetic high risk (GHR) for schizophrenia have shown social skill impairments and there is some evidence to suggest they have Theory of Mind (ToM) deficits; however no research has used a standardized, performance-based behavioral measure to assess social functioning in this population nor evaluated ToM with a well-validated measure. We evaluated the psychometric properties of a new, theoretically-derived assessment of social functioning in GHR adolescents: the &quot;High-Risk Social Challenge&quot; task (HiSoC). The second aim was to explore whether GHR adolescents would show social skill and ToM deficits as compared to a nonpsychiatric control (NPC) group. The present study evaluated social functioning with the HiSoC and ToM with the Eyes Test in 23 GHR adolescents and 31 NPCs. The HiSoC demonstrated high levels of reliability and validity. The GHR adolescents showed social skill impairments, but not ToM deficits. The results suggest that the HiSoC is a potentially useful new measure of social functioning in GHR adolescents. Furthermore, the findings add to the current body of literature that indicates that social skill impairments are related to schizophrenia vulnerability

Observable Social Cognition – A Rating Scale: an interview-based assessment for schizophrenia

Individuals with schizophrenia consistently show impairments in social cognition (SC). SC has become a potential treatment target due to its association with functional outcomes. An alternative method of assessment is to administer an observer-based scale incorporating an informant’s “first hand” impressions in ratings

The Role of Human-Automation Consensus in Multiple Unmanned Vehicle Scheduling

Objective: This study examined the impact of increasing automation replanning rates on operator performance and workload when supervising a decentralized network of heterogeneous unmanned vehicles. Background: Futuristic unmanned vehicles systems will invert the operator-to-vehicle ratio so that one operator can control multiple dissimilar vehicles connected through a decentralized network. Significant human-automation collaboration will be needed because of automation brittleness, but such collaboration could cause high workload. Method: Three increasing levels of replanning were tested on an existing multiple unmanned vehicle simulation environment that leverages decentralized algorithms for vehicle routing and task allocation in conjunction with human supervision. Results: Rapid replanning can cause high operator workload, ultimately resulting in poorer overall system performance. Poor performance was associated with a lack of operator consensus for when to accept the automation’s suggested prompts for new plan consideration as well as negative attitudes toward unmanned aerial vehicles in general. Participants with video game experience tended to collaborate more with the automation, which resulted in better performance. Conclusion: In decentralized unmanned vehicle networks, operators who ignore the automation’s requests for new plan consideration and impose rapid replans both increase their own workload and reduce the ability of the vehicle network to operate at its maximum capacity. Application: These findings have implications for personnel selection and training for futuristic systems involving human collaboration with decentralized algorithms embedded in networks of autonomous systems.Aurora Flight Sciences Corp.United States. Office of Naval Researc

Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study

OBJECTIVES: To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020. DESIGN: National retrospective cohort study. SETTING: Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records. PARTICIPANTS: 273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years. MAIN OUTCOME MEASURES: Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016–2019. RESULTS: The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016–2019. CONCLUSIONS: National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm

The prevalence of suicidal ideation identified by the Edinburgh Postnatal Depression Scale in postpartum women in primary care: findings from the RESPOND trial

<p>1 Abstract</p> <p>1.1 Background</p> <p>Suicide is a leading cause of perinatal maternal deaths in industrialised countries but there has been little research to investigate prevalence or correlates of postpartum suicidality. The Edinburgh Postnatal Depression Scale is widely used in primary and maternity services to screen for perinatal depressive disorders, and includes a question on suicidal ideation (question 10). We aimed to investigate the prevalence, persistence and correlates of suicidal thoughts in postpartum women in the context of a randomised controlled trial of treatments for postnatal depression.</p> <p>1.2 Methods</p> <p>Women in primary care were sent postal questionnaires at 6 weeks postpartum to screen for postnatal depression before recruitment into an RCT. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for postnatal depression and in those with high levels of symptoms, a home visit with a standardised psychiatric interview was carried out using the Clinical Interview Schedule-Revised version (CIS-R). Other socio-demographic and clinical variables were measured, including functioning (SF12) and quality of the marital relationship (GRIMS). Women who entered the trial were followed up for 18 weeks.</p> <p>1.3 Results</p> <p>9% of 4,150 women who completed the EPDS question relating to suicidal ideation reported some suicidal ideation (including hardly ever); 4% reported that the thought of harming themselves had occurred to them sometimes or quite often. In women who entered the randomised trial and completed the EPDS question relating to suicidal ideation (n = 253), suicidal ideation was associated with younger age, higher parity and higher levels of depressive symptoms in the multivariate analysis. Endorsement of 'yes, quite often' to question 10 on the EPDS was associated with affirming at least two CIS-R items on suicidality. We found no association between suicidal ideation and SF-12 physical or mental health or the EPDS total score at 18 weeks.</p> <p>1.4 Conclusions</p> <p>Healthcare professionals using the EPDS should be aware of the significant suicidality that is likely to be present in women endorsing 'yes, quite often' to question 10 of the EPDS. However, suicidal ideation does not appear to predict poor outcomes in women being treated for postnatal depression.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN16479417">ISRCTN16479417</a>.</p