Life expectancy among HIV-positive patients in Rwanda: a retrospective observational cohort study

Background Rwanda has achieved substantial progress in scaling up of antiretroviral therapy. We aimed to assess the eff ect of increased access to antiretroviral therapy on life expectancy among HIV-positive patients in two distinct periods of lower and higher antiretroviral therapy coverage (1997–2007 and 2008–11). Methods In a retrospective observational cohort study, we collected clinical and demographic data for all HIV-positive patients enrolled in care at 110 health facilities across all fi ve provinces of Rwanda. We included patients aged 15 years or older with a known enrolment date between 1997 and 2014. We constructed abridged life tables from age-specifi c mortality rates and life expectancy stratifi ed by sex, CD4 cell count, and WHO disease stage at enrolment in care and initiation of antiretroviral therapy. Findings We included 72 061 patients in this study, contributing 213 983 person-years of follow-up. The crude mortality rate was 33·4 deaths per 1000 person-years (95% CI 32·7–34·2). Life expectancy for the overall cohort was 25·6 additional years (95% CI 25·1–26·1) at 20 years of age and 23·3 additional years (95% CI 22·9–23·7) at 35 years of age. Life expectancy at 20 years of age in the period of 1997–2007 was 20·4 additional years (95% CI 19·5–21·3); for the period of 2008–11, life expectancy had increased to 25·6 additional years (95% CI 24·8–26·4). Individuals enrolling in care with CD4 cell counts of 500 cells per μL or more, and with WHO disease stage I, had the highest life expectancies. Interpretation This study adds to the growing body of evidence showing the benefi t to HIV-positive patients of early enrolment in care and initiation of antiretroviral therapy

The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition

Novel targets of the oncogenic miR-17-92 cluster have been identified and the mechanism of regulation of proliferation at the G1/S phase cell cycle transition via the miR-17-5p microRNA has been elucidated

A Fibreoptic Endoscopic Study of Upper Gastrointestinal Bleeding at Bugando Medical Centre in Northwestern Tanzania: a Retrospective Review of 240 Cases.

Upper gastrointestinal (GI) bleeding is recognized as a common and potentially life-threatening abdominal emergency that needs a prompt assessment and aggressive emergency treatment. A retrospective study was undertaken at Bugando Medical Centre in northwestern Tanzania between March 2010 and September 2011 to describe our own experiences with fibreoptic upper GI endoscopy in the management of patients with upper gastrointestinal bleeding in our setting and compare our results with those from other centers in the world. A total of 240 patients representing 18.7% of all patients (i.e. 1292) who had fibreoptic upper GI endoscopy during the study period were studied. Males outnumbered female by a ratio of 2.1:1. Their median age was 37 years and most of patients (60.0%) were aged 40 years and below. The vast majority of the patients (80.4%) presented with haematemesis alone followed by malaena alone in 9.2% of cases. The use of non-steroidal anti-inflammatory drugs, alcohol and smoking prior to the onset of bleeding was recorded in 7.9%, 51.7% and 38.3% of cases respectively. Previous history of peptic ulcer disease was reported in 22(9.2%) patients. Nine (3.8%) patients were HIV positive. The source of bleeding was accurately identified in 97.7% of patients. Diagnostic accuracy was greater within the first 24 h of the bleeding onset, and in the presence of haematemesis. Oesophageal varices were the most frequent cause of upper GI bleeding (51.3%) followed by peptic ulcers in 25.0% of cases. The majority of patients (60.8%) were treated conservatively. Endoscopic and surgical treatments were performed in 30.8% and 5.8% of cases respectively. 140 (58.3%) patients received blood transfusion. The median length of hospitalization was 8 days and it was significantly longer in patients who underwent surgical treatment and those with higher Rockall scores (P < 0.001). Rebleeding was reported in 3.3% of the patients. The overall mortality rate of 11.7% was significantly higher in patients with variceal bleeding, shock, hepatic decompensation, HIV infection, comorbidities, malignancy, age > 60 years and in patients with higher Rockall scores and those who underwent surgery (P < 0.001). Oesophageal varices are the commonest cause of upper gastrointestinal bleeding in our environment and it is associated with high morbidity and mortality. The diagnostic accuracy of fibreoptic endoscopy was related to the time interval between the onset of bleeding and endoscopy. Therefore, it is recommended that early endoscopy should be performed within 24 h of the onset of bleeding

Hα star formation main sequence in cluster and field galaxies at z ∼ 1.6

We calculate Hα-based star formation rates and determine the star formation rate–stellar mass relation for members of three Spitzer Adaptation of the Red-Sequence Cluster Survey (SpARCS) clusters at z ∼ 1.6 and serendipitously identified field galaxies at similar redshifts to the clusters. We find similar star formation rates in cluster and field galaxies throughout our range of stellar masses. The results are comparable to those seen in other clusters at similar redshifts, and consistent with our previous photometric evidence for little quenching activity in clusters. One possible explanation for our results is that galaxies in our z ∼ 1.6 clusters have been accreted too recently to show signs of environmental quenching. It is also possible that the clusters are not yet dynamically mature enough to produce important environmental quenching effects shown to be important at low redshift, such as ram-pressure stripping or harassment

A highly selective, label-free, homogenous luminescent switch-on probe for the detection of nanomolar transcription factor NF-kappaB

Transcription factors are involved in a number of important cellular processes. The transcription factor NF-κB has been linked with a number of cancers, autoimmune and inflammatory diseases. As a result, monitoring transcription factors potentially represents a means for the early detection and prevention of diseases. Most methods for transcription factor detection tend to be tedious and laborious and involve complicated sample preparation, and are not practical for routine detection. We describe herein the first label-free luminescence switch-on detection method for transcription factor activity using Exonuclease III and a luminescent ruthenium complex, [Ru(phen)2(dppz)]2+. As a proof of concept for this novel assay, we have designed a double-stranded DNA sequence bearing two NF-κB binding sites. The results show that the luminescence response was proportional to the concentration of the NF-κB subunit p50 present in the sample within a wide concentration range, with a nanomolar detection limit. In the presence of a known NF-κB inhibitor, oridonin, a reduction in the luminescence response of the ruthenium complex was observed. The reduced luminescence response of the ruthenium complex in the presence of small molecule inhibitors allows the assay to be applied to the high-throughput screening of chemical libraries to identify new antagonists of transcription factor DNA binding activity. This will allow the rapid and low cost identification and development of novel scaffolds for the treatment of diseases caused by the deregulation of transcription factor activity

The GOGREEN survey: The environmental dependence of the star-forming galaxy main sequence at 1.0<z<1.51.0<z<1.5

We present results on the environmental dependence of the star-forming galaxy main sequence in 11 galaxy cluster fields at $1.0 < z < 1.5$ from the Gemini Observations of Galaxies in Rich Early Environments Survey (GOGREEN) survey. We use a homogeneously selected sample of field and cluster galaxies whose membership is derived from dynamical analysis. Using [OII]-derived star formation rates (SFRs), we find that cluster galaxies have suppressed SFRs at fixed stellar mass in comparison to their field counterparts by a factor of 1.4 $\pm$ 0.1 ($\sim3.3\sigma$) across the stellar mass range: $9.0 < \log(M_{*} /M_{\odot}) < 11.2$. We also find that this modest suppression in the cluster galaxy star-forming main sequence is mass and redshift dependent: the difference between cluster and field increases towards lower stellar masses and lower redshift. When comparing the distribution of cluster and field galaxy SFRs to the star-forming main sequence, we find an overall shift towards lower SFRs in the cluster population, and note the absence of a tail of high SFR galaxies as seen in the field. Given this observed suppression in the cluster galaxy star-forming main sequence, we explore the implications for several scenarios such as formation time differences between cluster and field galaxies, and environmentally-induced star formation quenching and associated timescales

Amphiphilic block copolymers from a renewable Ɛ-decalactone monomer: prediction and characterization of micellar core effects on drug encapsulation and release

Here we describe a methoxy poly(ethyleneglycol)-b-poly(ε-decalactone) (mPEG-b-PεDL) copolymer and investigate the potential of the copolymer as a vehicle for solubilisation and sustained release of indomethacin (IND). The indomethacin loading and release from mPEG-b-PεDL micelles (amorphous cores) was compared against methoxy poly(ethyleneglycol)-b-poly(ε-caprolactone)(mPEG-b-PCL) micelles (semicrystalline cores). The drug–polymer compatibility was determined through a theoretical approach to predict drug incorporation into hydrated micelles. Polymer micelles were prepared by solvent evaporation and characterised for size, morphology, indomethacin loading and release. All the formulations generated spherical micelles but significantly larger mPEG-b-PεDL micelles were observed compared to mPEG-b-PCL micelles. A higher compatibility of the drug was predicted for PCL cores based on Flory–Huggins interaction parameters (χsp) using the Hansen solubility parameter (HSP) approach, but higher measured drug loadings were found in micelles with PεDL cores compared to PCL cores. This we attribute to the higher amorphous content in the PεDL-rich regions which generated higher micellar core volumes. Drug release studies showed that the semicrystalline PCL core was able to release IND over a longer period (80% drug release in 110 h) compared to PεDL core micelles (80% drug release in 72 h)

Targeting Primitive Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1BCR-ABL-JAK2 Complex

This is a pre-copyedited, author-produced version of an article accepted for publication in JNCI: Journal of the National Cancer Institute following peer review. The version of record Chen, M., et al. (2013). "Targeting Primitive Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1–BCR-ABL–JAK2 Complex." JNCI: Journal of the National Cancer Institute 105(6): 405-423. is available online at: https://doi.org/10.1093/jnci/djt006This work was funded by the Canadian Cancer Society (grant 700289), in part by the Canadian Institutes of Health Research, the Leukemia & Lymphoma Society of Canada, and the Cancer Research Society (XJ), the Canadian Cancer Society Research Institute (AE, XJ, CE), Cancer Research UK Programme grant C11074/A11008 (TLH), the Glasgow Experimental Cancer Medicine Centre, which is funded by Cancer Research UK and by the Chief Scientist’s Office (Scotland), and Cancer Research UK grant C973/A9894 (JP, JS). M. Chen was supported by a fellowship from Lymphoma Foundation Canada, and P. Gallipoli was supported by Medical Research Council grant G1000288. X. Jiang was a Michael Smith Foundation for Health Research Scholar

The carrier of the "30" micron emission feature in evolved stars. A simple model using magnesium sulfide

We present 2-45 micron spectra of a large sample of carbon-rich evolved stars in order to study the ``30'' micron feature. We find the ``30'' micron feature in sources in a wide range of sources: low mass loss carbon stars, extreme carbon-stars, post-AGB objects and planetary nebulae. We extract the profiles from the sources by using a simple systematic approach to model the continuum. We find large variations in the wavelength and width of the extracted profiles of the ``30'' micron feature. We modelled the whole range of profiles in a simple way by using magnesium sulfide (MgS) dust grains with a MgS grain temperature different from the continuum temperature. The systematic change in peak positions can be explained by cooling of MgS grains as the star evolves off the AGB. In several sources we find that a residual emission excess at ~26 micron can also be fitted using MgS grains but with a different grains shape distribution. The profiles of the ``30'' micron feature in planetary nebulae are narrower than our simple MgS model predicts. We discuss the possible reasons for this difference. We find a sample of warm carbon-stars with very cold MgS grains. We discuss possible causes for this phenomenon. We find no evidence for rapid destruction of MgS during the planetary nebula phase and conclude that the MgS may survive to be incorporated in the ISM.Comment: 31 pages, accepted for publication in Astronomy and Astrophysics. Full resolution version can be obtained by contacting [email protected]