ATLASGAL - towards a complete sample of massive star forming clumps

By matching infrared-selected, massive young stellar objects (MYSOs) and compact HII regions in the Red MSX Source survey to massive clumps found in the submillimetre ATLASGAL (APEX Telescope Large Area Survey of the Galaxy) survey, we have identified ~1000 embedded young massive stars between 280 {ring operator} < l < 350 {ring operator} and 10 {ring operator} < l < 60 {ring operator} with | b | < 1 {ring operator} . 5. Combined with an existing sample of radio-selected methanol masers and compact HII regions, the result is a catalogue of ~1700 massive stars embedded within ~1300 clumps located across the inner Galaxy, containing three observationally distinct subsamples, methanol-maser, MYSO and HII-region associations, covering the most important tracers of massive star formation, thought to represent key stages of evolution. We find that massive star formation is strongly correlated with the regions of highest column density in spherical, centrally condensed clumps. We find no significant differences between the three samples in clump structure or the relative location of the embedded stars, which suggests that the structure of a clump is set before the onset of star formation, and changes little as the embedded object evolves towards the main sequence. There is a strong linear correlation between clump mass and bolometric luminosity, with the most massive stars forming in the most massive clumps. We find that the MYSO and HII-region subsamples are likely to cover a similar range of evolutionary stages and that the majority are near the end of their main accretion phase. We find few infrared-bright MYSOs associated with the most massive clumps, probably due to very short pre-main-sequence lifetimes in the most luminous sources. © 2014 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society

ATLASGAL - properties of compact H II regions and their natal clumps

We present a complete sample of molecular clumps containing compact and ultracompact HII (UC HII) regions between ℓ = 10° and 60° and |b| < 1°, identified by combining the APEX Telescope Large Area Survey ofthe Galaxy submm and CORNISH radio continuum surveys with visual examination ofarchival infrared data. Our sample is complete to optically thin, compact and UC HII regions driven by a zero-age main-sequence star of spectral type B0 or earlier embedded within a 1000M clump. In total we identify 213 compact and UC HII regions, associated with 170 clumps. Unambiguous kinematic distances are derived for these clumps and used to estimate their masses and physical sizes, as well as the Lyman continuum fluxes and sizes of their embedded HII regions. We find a clear lower envelope for the surface density of molecular clumps hosting massive star formation of 0.05 g cm, which is consistent with a similar sample of clumps associated with 6.7 GHz masers. The mass of the most massive embedded starsis closely correlated with the mass of their natal clump. Young B stars appearto be significantly more luminous in the ultraviolet than predicted by current stellar atmosphere models. The properties of clumps associated with compact and UC HII regions are very similar to those associated with 6.7 GHz methanol masers and we speculate that there is little evolution in the structure of the molecular clumps between these two phases. Finally, we identifya significant peak in the surface density of compact and UC HII-regions associated with the W49A star-forming complex, noting that this complex is truly one of the most massive and intense regions of star formation in the Galaxy. © 2013 The Authors, Published by Oxford University Press on behalf of the Royal Astronomical Society

Mapping coherence in measurement via full quantum tomography of a hybrid optical detector

Quantum states and measurements exhibit wave-like --- continuous, or particle-like --- discrete, character. Hybrid discrete-continuous photonic systems are key to investigating fundamental quantum phenomena, generating superpositions of macroscopic states, and form essential resources for quantum-enhanced applications, e.g. entanglement distillation and quantum computation, as well as highly efficient optical telecommunications. Realizing the full potential of these hybrid systems requires quantum-optical measurements sensitive to complementary observables such as field quadrature amplitude and photon number. However, a thorough understanding of the practical performance of an optical detector interpolating between these two regions is absent. Here, we report the implementation of full quantum detector tomography, enabling the characterization of the simultaneous wave and photon-number sensitivities of quantum-optical detectors. This yields the largest parametrization to-date in quantum tomography experiments, requiring the development of novel theoretical tools. Our results reveal the role of coherence in quantum measurements and demonstrate the tunability of hybrid quantum-optical detectors.Comment: 7 pages, 3 figure

Good adherence to HAART and improved survival in a community HIV/AIDS treatment and care programme: the experience of The AIDS Support Organization (TASO), Kampala, Uganda

BACKGROUND: Poor adherence to highly active antiretroviral therapy (HAART) may result in treatment failure and death. Most reports of the effect of adherence to HAART on mortality come from studies where special efforts are made to provide HAART under ideal conditions. However, there are few reports of the impact of non-adherence to HAART on mortality from community HIV/AIDS treatment and care programmes in developing countries. We therefore conducted a study to assess the effect of adherence to HAART on survival in The AIDS Support Organization (TASO) community HAART programme in Kampala, Uganda. METHODS: The study was a retrospective cohort of 897 patients who initiated HAART at TASO clinic, Kampala, between May 2004 and December 2006. A total of 7,856 adherence assessments were performed on the data. Adherence was assessed using a combination of self-report and pill count methods. Patients who took 95%. The crude death rate was 12.2 deaths per 100 patient-years, with a rate of 42.5 deaths per 100 patient-years for non-adherent patients and 6.1 deaths per 100 patient-years for adherent patients. Non-adherence to ART was significantly associated with mortality. Patients with a CD4 count of less than 50 cells/mm3 had a higher mortality (HR = 4.3; 95% CI: 2.22-5.56) compared to patients with a CD4 count equal to or greater than 50 cells/mm3 (HR = 2.4; 95% CI: 1.79-2.38). CONCLUSION: Our study showed that good adherence and improved survival are feasible in community HIV/AIDS programmes such as that of TASO, Uganda. However, there is need to support community HAART programmes to overcome the challenges of funding to provide sustainable supplies particularly of antiretroviral drugs; provision of high quality clinical and laboratory support; and achieving a balance between expansion and quality of services. Measures for the early identification and treatment of HIV infected people including home-based VCT and HAART should be strengthened

Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection.

BACKGROUND: Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm). RESULTS: At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, -0.4 percentage points; 95% confidence interval [CI], -2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, -3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, -10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48. CONCLUSIONS: Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir-abacavir-lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.)

Experimental quantum-enhanced estimation of a lossy phase shift

When standard light sources are employed, the precision of the phase determination is limited by the shot noise. Quantum entanglement provides means to exceed this limit with the celebrated example of N00N states that saturate the ultimate Heisenberg limit on precision, but at the same time are extremely fragile to losses. In contrast, we provide experimental evidence that appropriately engineered quantum states outperform both standard and N00N states in the precision of phase estimation when losses are present.Comment: 5 page

Risk factors for adverse perinatal outcomes in imprisoned pregnant women: a systematic review

BACKGROUND: Imprisoned pregnant women constitute an important obstetric group about whom relatively little is known. This systematic review was conducted to identify the risk factors associated with adverse pregnancy outcome present in this group of women. METHODS: The review was conducted according to a prespecified protocol. Studies of any design were included if they described information on any of the pre-specified risk factors. We calculated the results as summary percentages or odds ratios where data was available on both cases and population controls. RESULTS: The search strategy identified 27 relevant papers of which 13 met the inclusion criteria, involving 1504 imprisoned pregnant women and 4571 population control women. Imprisoned women are more likely to be single, from an ethnic minority, and not to have completed high school. They are more likely to have a medical problem which could affect the pregnancy outcome and yet less likely to receive adequate antenatal care. They are also more likely to smoke, drink alcohol to excess and take illegal drugs. CONCLUSION: Imprisoned women are clearly a high risk obstetric group. These findings have important implications for the provision of care to this important group of women

Analyses of HIV-1 integrase sequences prior to South African national HIV-treatment program and available of integrase inhibitors in Cape Town, South Africa

HIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatmentnaive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2.85% (9/314) in database derived sequences. RAMs were present at IN-positions 66, 92, 143, 147 and 148, all of which may confer resistance to Raltegravir (RAL) and Elvitegravir (EVG), but are unlikely to affect second-generation Dolutegravir (DTG), except mutations in the Q148 pathway. Furthermore, protein modeling showed, naturally occurring polymorphisms impact the stability of the intasome-complex and therefore may contribute to an overall potency against InSTIs. Our data suggest the prevalence of InSTI RAMs, against InSTIs, is low in South Africa, but natural polymorphisms and subtype-specific differences may influence the effect of individual treatment regimens

Social validity of randomised controlled trials in health services research and intellectual disabilities: a qualitative exploration of stakeholder views

<p>Abstract</p> <p>Background</p> <p>Randomised controlled trials (RCTs) are the gold standard of evidence-based practice in medicine but they have had limited influence in the field of intellectual disabilities. Previous literature suggests that participants and professionals have limited tolerance for this type of research methodology. However, it is not known how well service users, carers and other health professionals understand and accept the need for RCTs, and why it is important for individuals with intellectual disabilities to be included in this kind of research.</p> <p>Methods</p> <p>We examined individual perceptions of RCTs in 51 participants (18 carers, 6 service users and 27 professionals) using semi-structured interviews. A framework approach was adopted in the analysis of data.</p> <p>Results</p> <p>We found that participants had concerns about capacity and resource allocation but held positive views towards this type of research methodology. Understanding of the principles behind RCTs was poor amongst service users and a minority of carers, but mediated by previous exposure to research for professionals.</p> <p>Conclusions</p> <p>The social validity of RCTs in intellectual disabilities may be compromised by lack of understanding of the design and the on-going concerns about obtaining informed consent especially in incapacitated adults. However, the overall finding that the need for this form of research was seen in a positive light suggests that there is a turning point in the perceptions of stakeholders working in intellectual disabilities services. We recommend that researchers include on-going education on RCT design during trials, tailoring it to all stakeholders with emphasis on strong service user and care involvement. This could be a pivotal element in improving acceptability of, and recruitment to RCTs.</p

Hypoxia-Inducible Factor 1α Determines Gastric Cancer Chemosensitivity via Modulation of p53 and NF-κB

BACKGROUND: Reduced chemosensitivity of solid cancer cells represents a pivotal obstacle in clinical oncology. Hence, the molecular characterization of pathways regulating chemosensitivity is a central prerequisite to improve cancer therapy. The hypoxia-inducible factor HIF-1alpha has been linked to chemosensitivity while the underlying molecular mechanisms remain largely elusive. Therefore, we comprehensively analysed HIF-1alpha's role in determining chemosensitivity focussing on responsible molecular pathways. METHODOLOGY AND PRINCIPAL FINDINGS: RNA interference was applied to inactivate HIF-1alpha or p53 in the human gastric cancer cell lines AGS and MKN28. The chemotherapeutic agents 5-fluorouracil and cisplatin were used and chemosensitivity was assessed by cell proliferation assays as well as determination of cell cycle distribution and apoptosis. Expression of p53 and p53 target proteins was analyzed by western blot. NF-kappaB activity was characterized by means of electrophoretic mobility shift assay. Inactivation of HIF-1alpha in gastric cancer cells resulted in robust elevation of chemosensitivity. Accordingly, HIF-1alpha-competent cells displayed a significant reduction of chemotherapy-induced senescence and apoptosis. Remarkably, this phenotype was completely absent in p53 mutant cells while inactivation of p53 per se did not affect chemosensitivity. HIF-1alpha markedly suppressed chemotherapy-induced activation of p53 and p21 as well as the retinoblastoma protein, eventually resulting in cell cycle arrest. Reduced formation of reactive oxygen species in HIF-1alpha-competent cells was identified as the molecular mechanism of HIF-1alpha-mediated inhibition of p53. Furthermore, loss of HIF-1alpha abrogated, in a p53-dependent manner, chemotherapy-induced DNA-binding of NF-kappaB and expression of anti-apoptotic NF-kappaB target genes. Accordingly, reconstitution of the NF-kappaB subunit p65 reversed the increased chemosensitivity of HIF-1alpha-deficient cells. CONCLUSION AND SIGNIFICANCE: In summary, we identified HIF-1alpha as a potent regulator of p53 and NF-kappaB activity under conditions of genotoxic stress. We conclude that p53 mutations in human tumors hold the potential to confound the efficacy of HIF-1-inhibitors in cancer therapy