The host galaxies and explosion sites of long-duration gamma-ray bursts: Hubble Space Telescope near-infrared imaging

We present the results of a Hubble Space Telescope WFC3/F160WSnapshot survey of the host galaxies of 39 long-duration gamma-ray bursts (LGRBs) at z < 3. We have non-detections of hosts at the locations of four bursts. Sufficient accuracy to astrometrically align optical afterglowimages and determine the location of the LGRB within its hostwas possible for 31/35 detected hosts. In agreement with other work, we find the luminosity distribution of LGRB hosts is significantly fainter than that of a star formation rate-weighted field galaxy sample over the same redshift range, indicating LGRBs are not unbiasedly tracing the star formation rate. Morphologically, the sample of LGRB hosts is dominated by spiral-like or irregular galaxies. We find evidence for evolution of the population of LGRB hosts towards lower luminosity, higher concentrated hosts at lower redshifts. Their half-light radii are consistent with other LGRB host samples where measurements were made on rest-frame UV observations. In agreement with recent work, we find their 80 per cent enclosed flux radii distribution to be more extended than previously thought, making them intermediate between core-collapse supernova (CCSN) and superluminous supernova (SLSN) hosts. The galactocentric projectedoffset distribution confirms LGRBs as centrally concentrated, much more so than CCSNe and similar to SLSNe. LGRBs are strongly biased towards the brighter regions in their host light distributions, regardless of their offset. We find a correlation between the luminosity of the LGRB explosion site and the intrinsic column density, NH, towards the burst. © 2017 The Authors

TGF-b2 induction regulates invasiveness of theileria-transformed leukocytes and disease susceptibility

Theileria parasites invade and transform bovine leukocytes causing either East Coast fever (T. parva), or tropical theileriosis (T. annulata). Susceptible animals usually die within weeks of infection, but indigenous infected cattle show markedly reduced pathology, suggesting that host genetic factors may cause disease susceptibility. Attenuated live vaccines are widely used to control tropical theileriosis and attenuation is associated with reduced invasiveness of infected macrophages in vitro. Disease pathogenesis is therefore linked to aggressive invasiveness, rather than uncontrolled proliferation of Theileria-infected leukocytes. We show that the invasive potential of Theileria-transformed leukocytes involves TGF-b signalling. Attenuated live vaccine lines express reduced TGF-b2 and their invasiveness can be rescued with exogenous TGF-b. Importantly, infected macrophages from disease susceptible Holstein-Friesian (HF) cows express more TGF-b2 and traverse Matrigel with great efficiency compared to those from disease-resistant Sahiwal cattle. Thus, TGF-b2 levels correlate with disease susceptibility. Using fluorescence and time-lapse video microscopy we show that Theileria-infected, disease-susceptible HF macrophages exhibit increased actin dynamics in their lamellipodia and podosomal adhesion structures and develop more membrane blebs. TGF-b2-associated invasiveness in HF macrophages has a transcription-independent element that relies on cytoskeleton remodelling via activation of Rho kinase (ROCK). We propose that a TGF-b autocrine loop confers an amoeboid-like motility on Theileria-infected leukocytes, which combines with MMP-dependent motility to drive invasiveness and virulence

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

Maintenance treatment with interferon for advanced ovarian cancer: results of the Northern and Yorkshire gynaecology group randomised phase III study

A randomised phase III trial was conducted to assess the role of interferon-alpha (INFα) 2a as maintenance therapy following surgery and/or chemotherapy in patients with epithelial ovarian carcinoma. Patients were randomised following initial surgery/chemotherapy to interferon-alpha 2a as 4.5 mega-units subcutaneously 3 days per week or to no further treatment. A total of 300 patients were randomised within the study between February 1990 and July 1997. No benefit for interferon maintenance was seen in terms of either overall or clinical event-free survival. We conclude that INF-α is not effective as a maintenance therapy in the management of women with ovarian cancer. The need for novel therapeutics or strategies to prevent the almost inevitable relapse of patients despite increasingly effective surgery and chemotherapy remains

Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

A tiered-layered-staged model for informed consent in personal genome testing

In recent years, developments in genomics technologies have led to the rise of commercial personal genome testing (PGT): broad genome-wide testing for multiple diseases simultaneously. While some commercial providers require physicians to order a personal genome test, others can be accessed directly. All providers advertise directly to consumers and offer genetic risk information about dozens of diseases in one single purchase. The quantity and the complexity of risk information pose challenges to adequate pre-test and post-test information provision and informed consent. There are currently no guidelines for what should constitute informed consent in PGT or how adequate informed consent can be achieved. In this paper, we propose a tiered-layered-staged model for informed consent. First, the proposed model is tiered as it offers choices between categories of diseases that are associated with distinct ethical, personal or societal issues. Second, the model distinguishes layers of information with a first layer offering minimal, indispensable information that is material to all consumers, and additional layers offering more detailed information made available upon request. Finally, the model stages informed consent as a process by feeding information to consumers in each subsequent stage of the process of undergoing a test, and by accommodating renewed consent for test result updates, resulting from the ongoing development of the science underlying PGT. A tiered-layered-staged model for informed consent with a focus on the consumer perspective can help overcome the ethical problems of information provision and informed consent in direct-to-consumer PGT.European Journal of Human Genetics advance online publication, 21 November 2012; doi:10.1038/ejhg.2012.237

Short and long term retention in antiretroviral care in health facilities in rural Malawi and Zimbabwe.

Despite the successful scale-up of ART services over the past years, long term retention in ART care remains a major challenge, especially in high HIV prevalence and resource-limited settings. This study analysed the short (<12 months) and long (>12 months) term retention on ART in two ART programmes in Malawi (Thyolo district) and Zimbabwe (Buhera district)

Reliability and validity of the modified child and adolescent physical activity and nutrition survey (CAPANS-C) questionnaire examining potential correlates of physical activity participation among Chinese-Australian youth

BACKGROUND: To date, few questionnaires examining psychosocial influences of physical activity (PA) participation have been psychometrically tested among Culturally and Linguistically Diverse (CALD) youth. An understanding of these influences may help explain the observed differences in PA among CALD youth. Therefore, this study examined the reliability and predictive validity of a brief self-report questionnaire examining potential psychological and social correlates of physical activity among a sample of Chinese-Australian youth. METHODS: Two Chinese-weekend cultural schools from eastern metropolitan Melbourne consented to participate in this study. In total, 505 students aged 11 to 16 years were eligible for inclusion in the present study, and of these, 106 students agreed to participate (21% response rate). Participants completed at 37-item self-report questionnaire examining perceived psychological and social influences on physical activity participation twice, with a test–retest interval of 7 days. Predictive validity, internal consistency and test–retest reliability were evaluated using exploratory factor analyses, Cronbach’s α coefficient, and the intraclass correlation coefficient (ICC) respectively. Predictive validity was assessed by correlating responses against duration spent in self-reported moderate-to-vigorous physical activity (MVPA). RESULTS: The exploratory factor analysis revealed a nine factor structure, with the majority of factors exhibiting high internal consistency (α ≥ 0.6). In addition, four of the nine factors had an ICC ≥ 0.6. Spearman rank-order correlations coefficients between the nine factors and self-reported minutes spent in MVPA ranged from -0.5 to 0.3 for all participants. CONCLUSION: This is the first study to examine the psychometric properties of a potential psychological and social correlates questionnaire among Chinese-Australian youth. The questionnaire was found to provide reliable estimates on a range of psychological and social influences on physical activity and evidence of predictive validity on a limited number of factors. More research is required to improve the reliability and validity of the questionnaire

Enhancing the sensitivity of magnetic sensors by 3D metamaterial shells

Magnetic sensors are key elements in our interconnected smart society. Their sensitivity becomes essential for many applications in fields such as biomedicine, computer memories, geophysics, or space exploration. Here we present a universal way of increasing the sensitivity of magnetic sensors by surrounding them with a spherical metamaterial shell with specially designed anisotropic magnetic properties. We analytically demonstrate that the magnetic field in the sensing area is enhanced by our metamaterial shell by a known factor that depends on the shell radii ratio. When the applied field is non-uniform, as for dipolar magnetic field sources, field gradient is increased as well. A proof-of-concept experimental realization confirms the theoretical predictions. The metamaterial shell is also shown to concentrate time-dependent magnetic fields upto frequencies of 100 kHz