Allen Telescope Array Multi-Frequency Observations of the Sun

We present the first observations of the Sun with the Allen Telescope Array (ATA). We used up to six frequencies, from 1.43 to 6 GHz, and baselines from 6 to 300 m. To our knowledge, these are the first simultaneous multifrequency full-Sun maps obtained at microwave frequencies without mosaicing. The observations took place when the Sun was relatively quiet, although at least one active region was present each time. We present multi-frequency flux budgets for each sources on the Sun. Outside of active regions, assuming optically thin bremsstrahlung (free--free) coronal emission on top of an optically thick ~10 000 K chromosphere, the multi-frequency information can be condensed into a single, frequency-independent, "coronal bremsstrahlung contribution function" [EM/sqrt(T)] map. This technique allows the separation of the physics of emission as well as a measurement of the density structure of the corona. Deviations from this simple relationship usually indicate the presence of an additional gyroresonance-emission component, as is typical in active regions.Comment: 16 pages, 11 figures. Accepted for publication in Solar Physic

Reactivation of Smac-mediated apoptosis in chronic lymphocytic leukemia cells : mechanistic studies of Smac mimetic

Dysfunctional apoptotic machinery is a hallmark feature of chronic lymphocytic leukemia (CLL). Accordingly, targeting apoptosis regulators has been proven a rational approach for CLL treatment. We show that CLL lymphocytes express high levels of XIAP, cIAP1, and cIAP2 compared to normal lymphocytes. Smac mimetic, Smac066, designed to bind to BIR3-domain of IAPs, induce apoptosis in primary CLL cells (n=71; p<0.0001), irrespective of prognostic markers. Apoptosis was mediated by diminished levels of IAPs (XIAP-p=0.02; cIAP-p<0.0001) and increased activation of caspases-8,-9,-3. The caspase-cleavage was in direct association with the levels of apoptosis (r2=0.8 for caspases-8,-9,-3). Correlative analysis revealed a direct relationship between reduction in IAPs and degree of apoptosis (r2=0.6 (XIAP); 0.5 (cIAP2)). There was a strong association between apoptosis, IAP-degradation, and concurrent caspase-activation. Pan-caspase inhibitor Z-Vad-fmk reversed the degradation of Mcl-1, but not IAPs suggesting that smac066 is selective to IAPs, however, Mcl-1 degradation is through caspase-mediated cleavage. Immunoprecipitation experiments revealed physical interaction between caspase-3 and XIAP that was disrupted by smac066. Importantly, XIAP and cIAP2 were markedly induced in bone-marrow and lymph-node microenvironments, providing a basis for IAP antagonists as anti-tumor agents in CLL. Smac066 synergized with ABT-737, revealing a mechanistic rationale to jointly target BH3 and BIR3 domains

Improving adherence to acute low back pain guideline recommendations with chiropractors and physiotherapists: the ALIGN cluster randomised controlled trial

Background Acute low back pain is a common condition, has high burden, and there are evidence-to-practice gaps in the chiropractic and physiotherapy setting for imaging and giving advice to stay active. The aim of this cluster randomised trial was to estimate the effects of a theory- and evidence-based implementation intervention to increase chiropractors’ and physiotherapists’ adherence to a guideline for acute low back pain compared with the comparator (passive dissemination of the guideline). In particular, the primary aim of the intervention was to reduce inappropriate imaging referral and improve patient low back pain outcomes, and to determine whether this intervention was cost-effective. Methods Physiotherapy and chiropractic practices in the state of Victoria, Australia, comprising at least one practising clinician who provided care to patients with acute low back pain, were invited to participate. Patients attending these practices were included if they had acute non-specific low back pain (duration less than 3 months), were 18 years of age or older, and were able to understand and read English. Practices were randomly assigned either to a tailored, multi-faceted intervention based on the guideline (interactive educational symposium plus academic detailing) or passive dissemination of the guideline (comparator). A statistician independent of the study team undertook stratified randomisation using computer-generated random numbers; four strata were defined by professional group and the rural or metropolitan location of the practice. Investigators not involved in intervention delivery were blinded to allocation. Primary outcomes were X-ray referral self-reported by clinicians using a checklist and patient low back pain-specific disability (at 3 months). Results A total of 104 practices (43 chiropractors, 85 physiotherapists; 755 patients) were assigned to the intervention and 106 practices (45 chiropractors, 97 physiotherapists; 603 patients) to the comparator; 449 patients were available for the patient-level primary outcome. There was no important difference in the odds of patients being referred for X-ray (adjusted (Adj) OR: 1.40; 95% CI 0.51, 3.87; Adj risk difference (RD): 0.01; 95% CI − 0.02, 0.04) or patient low back pain-specific disability (Adj mean difference: 0.37; 95% CI − 0.48, 1.21, scale 0–24). The intervention did lead to improvement for some key secondary outcomes, including giving advice to stay active (Adj OR: 1.96; 95% CI 1.20, 3.22; Adj RD: 0.10; 95% CI 0.01, 0.19) and intending to adhere to the guideline recommendations (e.g. intention to refer for X-ray: Adj OR: 0.27; 95% CI 0.17, 0.44; intention to give advice to stay active: Adj OR: 2.37; 95% CI 1.51, 3.74). Conclusions Intervention group clinicians were more likely to give advice to stay active and to intend to adhere to the guideline recommendations about X-ray referral. The intervention did not change the primary study outcomes, with no important differences in X-ray referral and patient disability between groups, implying that hypothesised reductions in health service utilisation and/or productivity gains are unlikely to offset the direct costs of the intervention. We report these results with the caveat that we enrolled less patients into the trial than our determined sample size. We cannot recommend this intervention as a cost-effective use of resources

Chronic lymphocytic leukaemia: the role of T cells in a B cell disease

Chronic lymphocytic leukaemia (CLL) has long been thought to be an immunosuppressive disease and abnormalities in T‐cell subset distribution and function have been observed in many studies. However, the role of T cells (if any) in disease progression remains unclear and has not been directly studied. This has changed with the advent of new therapies, such as chimeric antigen receptor‐T cells, which actively use retargeted patient‐derived T cells as “living drugs” for CLL. However complete responses are relatively low (~26%) and recent studies have suggested the differentiation status of patient T cells before therapy may influence efficacy. Non‐chemotherapeutic drugs, such as idelalisib and ibrutinib, also have an impact on T cell populations in CLL patients. This review will highlight what is known about T cells in CLL during disease progression and after treatment, and discuss the prospects of using T cells as predictive biomarkers for immune status and response to therapy

Methods of a national colorectal cancer cohort study: the PIPER Project

A national study looking at bowel cancer in New Zealand has previously been completed (the PIPER Project). The study included 5,610 patients and collected medical information about how each person was found to have bowel cancer and the treatment they received. This paper reports how the study was carried out. The information collected in the study will be used to look at the quality of care being provided to New Zealand patients with bowel cancer, and to find out if differences in care occur based on where people live, their ethnicity and their socioeconomic status

Socioeconomic disparities in physical health among Aboriginal and Torres Strait Islander children in Western Australia

Objective. Few empirical studies have specifically examined the relationship between socio-economic status (SES) and health in Indigenous populations of Australia. We sought to provide insights into the nature of this relationship by examining socio-economic disparities in physical health outcomes among Aboriginal and Torres Strait Islander children in Western Australia. Design. We used a diverse set of health and SES indicators from a representative survey conducted in 20002002 on the health and development of 5289 Indigenous children aged 017 years in Western Australia. Analysis was conducted using multivariate logistic regression within a multilevel framework. Results. After controlling for age and sex, we found statistically significant socio- economic disparities in health in almost half of the associations that were investigated, although the direction, shape and magnitude of associations differed. For ear infections, recurring chest infections and sensory function problems, the patterns were generally consistent with a positive socio-economic gradient where better health was associated with higher SES. The reverse pattern was found for asthma, accidents and injuries, and oral health problems, although this was primarily observed for area-level SES indicators. Conclusion. Conventional notions of social position and class have some influence on the physical health of Indigenous children, although the diversity of results implies that there are other ways of conceptualising and measuring SES that are important for Indigenous populations. We need to consider factors that relate specifically to Indigenous circumstances and culture in the past and present day, and give more thought to how we measure social position in the Indigenous community, to gain a better understanding of the pathways from SES to Indigenous child health

Mudança de paradigma no ensino da Bioquímica na licenciatura em Ciências da Nutrição na Universidade do Porto

No primeiro ano da licenciatura em Ciências da Nutrição, na Faculdade de Ciências da Nutriçãoe Alimentação, da Universidade do Porto, existem duas Unidades Curriculares que introduzem aBioquímica aos estudantes [Química Orgânica e Bioquímica I (no 1º e 2º semestres,respetivamente)] e cujos programas e modalidades pedagógicas estão inter-relacionados,confrontando o estudante, progressivamente ao longo do ano letivo, com oportunidades deaprendizagem ativa.A divulgação de descobertas científicas e o envolvimento dos estudantes em projetos deinvestigação científica melhoram a aprendizagem e a retenção de conhecimentos, assim comooperacionalizam a sua aplicabilidade prática, ao mesmo tempo que desenvolvem um efeitopositivo no interesse pela investigação científica.Com o objetivo de melhorar não só a aquisição de conhecimentos, mas também a compreensão e aplicabilidade dos mesmos, assim como o desenvolvimento de competências e de raciocíniohipotético-dedutivo pelos estudantes, o ensino da Bioquímica "tradicional/clássico/base" foimodificado de modo a: 1) introduzir a discussão de artigos científicos relevantes (nas sessõesteóricas e/ou práticas); 2) possibilitar o contacto com a investigação científica feita pelosdocentes (nas sessões teóricas) e 3) possibilitar a realização de pequenos projetos deinvestigação científica (nas sessões práticas). Nestas 3 modalidades pedagógicas estãosubjacentes temas bioquímicos que integram o programa "clássico/base" das referidas UnidadesCurriculares. Adicionalmente, ao estudante são divulgados, nas 3 modalidades pedagógicasacima referidas, temas atuais da Bioquímica Nutricional ao mesmo tempo que contacta comtodas as fases da metodologia de aquisição de conhecimentos, de raciocínio e de investigaçãousadas na área da Nutrição