Experiences of women who have lost young children to AIDS in KwaZulu-Natal, South Africa: a qualitative study

Background AIDS continues to be the leading cause of death in South Africa. Little is known about the experiences of mothers who have lost a young child to AIDS. The purpose of this qualitative study was to explore the attitudes and experiences of women who had lost a young child to HIV/AIDS in KwaZulu-Natal Province, South Africa. Methods In-depth interviews were conducted with 10 women who had lost a child to AIDS. The average age of the deceased children was six years. Interviews were also conducted with 12 key informants to obtain their perspectives on working with women who had lost a child to AIDS. A thematic analysis of the transcripts was performed. Results In addition to the pain of losing a child, the women in this study had to endure multiple stresses within a harsh and sometimes hostile environment. Confronted with pervasive stigma and extreme poverty, they had few people they could rely on during their child\u27s sickness and death. They were forced to keep their emotions to themselves since they were not likely to obtain much support from family members or people in the community. Throughout the period of caring for a sick child and watching the child die, they were essentially alone. The demands of caring for their child and subsequent grief, together with daily subsistence worries, took its toll. Key informants struggled to address the needs of these women due to several factors, including scarce resources, lack of training around bereavement issues, reluctance by people in the community to seek help with emotional issues, and poverty. Conclusions The present study offers one of the first perspectives on the experiences of mothers who have lost a young child to AIDS. Interventions that are tailored to the local context and address bereavement issues, as well as other issues that affect the daily lives of these mothers, are urgently needed. Further studies are needed to identify factors that promote resilience among these women

Fermi Large Area Telescope observations of PSR J1836+5925

The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8 million years, a spindown luminosity of 1.1$\times10^{34}$ erg s$^{-1}$, and a large off-peak emission component, making it quite unusual among the known gamma-ray pulsar population. We present an analysis of one year of LAT data, including an updated timing solution, detailed spectral results and a long-term light curve showing no indication of variability. No evidence for a surrounding pulsar wind nebula is seen and the spectral characteristics of the off-peak emission indicate it is likely magnetospheric. Analysis of recent XMM observations of the X-ray counterpart yields a detailed characterization of its spectrum, which, like Geminga, is consistent with that of a neutron star showing evidence for both magnetospheric and thermal emission.Comment: Accepted to Astrophysical Journa

Testing the Accuracy of Aerial Surveys for Large Mammals: An Experiment with African Savanna Elephants (Loxodonta africana)

Accurate counts of animals are critical for prioritizing conservation efforts. Past research, however, suggests that observers on aerial surveys may fail to detect all individuals of the target species present in the survey area. Such errors could bias population estimates low and confound trend estimation. We used two approaches to assess the accuracy of aerial surveys for African savanna elephants (Loxodonta africana) in northern Botswana. First, we used double-observer sampling, in which two observers make observations on the same herds, to estimate detectability of elephants and determine what variables affect it. Second, we compared total counts, a complete survey of the entire study area, against sample counts, in which only a portion of the study area is sampled. Total counts are often considered a complete census, so comparing total counts against sample counts can help to determine if sample counts are underestimating elephant numbers. We estimated that observers detected only 76% ± SE of 2% of elephant herds and 87 ± 1% of individual elephants present in survey strips. Detectability increased strongly with elephant herd size. Out of the four observers used in total, one observer had a lower detection probability than the other three, and detectability was higher in the rear row of seats than the front. The habitat immediately adjacent to animals also affected detectability, with detection more likely in more open habitats. Total counts were not statistically distinguishable from sample counts. Because, however, the double-observer samples revealed that observers missed 13% of elephants, we conclude that total counts may be undercounting elephants as well. These results suggest that elephant population estimates from both sample and total counts are biased low. Because factors such as observer and habitat affected detectability of elephants, comparisons of elephant populations across time or space may be confounded. We encourage survey teams to incorporate detectability analysis in all aerial surveys for mammals

Caenorhabditis elegans Myotubularin MTM-1 Negatively Regulates the Engulfment of Apoptotic Cells

During programmed cell death, apoptotic cells are recognized and rapidly engulfed by phagocytes. Although a number of genes have been identified that promote cell corpse engulfment, it is not well understood how phagocytosis of apoptotic cells is negatively regulated. Here we have identified Caenorhabditis elegans myotubularin MTM-1 as a negative regulator of cell corpse engulfment. Myotubularins (MTMs) constitute a large, highly conserved family of lipid phosphatases. MTM gene mutations are associated with various human diseases, but the cellular functions of MTM proteins are not clearly defined. We found that inactivation of MTM-1 caused significant reduction in cell corpses in strong loss-of-function mutants of ced-1, ced-6, ced-7, and ced-2, but not in animals deficient in the ced-5, ced-12, or ced-10 genes. In contrast, overexpression of MTM-1 resulted in accumulation of cell corpses. This effect is dependent on the lipid phosphatase activity of MTM-1. We show that loss of mtm-1 function accelerates the clearance of cell corpses by promoting their internalization. Importantly, the reduction of cell corpses caused by mtm-1 RNAi not only requires the activities of CED-5, CED-12, and CED-10, but also needs the functions of the phosphatidylinositol 3-kinases (PI3Ks) VPS-34 and PIKI-1. We found that MTM-1 localizes to the plasma membrane in several known engulfing cell types and may modulate the level of phosphatidylinositol 3-phosphate (PtdIns(3)P) in vivo. We propose that MTM-1 negatively regulates cell corpse engulfment through the CED-5/CED-12/CED-10 module by dephosphorylating PtdIns(3)P on the plasma membrane

Integrin α PAT-2/CDC-42 Signaling Is Required for Muscle-Mediated Clearance of Apoptotic Cells in Caenorhabditis elegans

Clearance of apoptotic cells by engulfment plays an important role in the homeostasis and development of multicellular organisms. Despite the fact that the recognition of apoptotic cells by engulfment receptors is critical in inducing the engulfment process, the molecular mechanisms are still poorly understood. Here, we characterize a novel cell corpse engulfment pathway mediated by the integrin α subunit PAT-2 in Caenorhabditis elegans and show that it specifically functions in muscle-mediated engulfment during embryogenesis. Inactivation of pat-2 results in a defect in apoptotic cell internalization. The PAT-2 extracellular region binds to the surface of apoptotic cells in vivo, and the intracellular region may mediate signaling for engulfment. We identify essential roles of small GTPase CDC-42 and its activator UIG-1, a guanine-nucleotide exchange factor, in PAT-2–mediated cell corpse removal. PAT-2 and CDC-42 both function in muscle cells for apoptotic cell removal and are co-localized in growing muscle pseudopods around apoptotic cells. Our data suggest that PAT-2 functions through UIG-1 for CDC-42 activation, which in turn leads to cytoskeletal rearrangement and apoptotic cell internalization by muscle cells. Moreover, in contrast to PAT-2, the other integrin α subunit INA-1 and the engulfment receptor CED-1, which signal through the conserved signaling molecules CED-5 (DOCK180)/CED-12 (ELMO) or CED-6 (GULP) respectively, preferentially act in epithelial cells to mediate cell corpse removal during mid-embryogenesis. Our results show that different engulfing cells utilize distinct repertoires of receptors for engulfment at the whole organism level

Astrocytes convert network excitation to tonic inhibition of neurons

<p>Abstract</p> <p>Background</p> <p>Glutamate and γ-aminobutyric acid (GABA) transporters play important roles in balancing excitatory and inhibitory signals in the brain. Increasing evidence suggest that they may act concertedly to regulate extracellular levels of the neurotransmitters.</p> <p>Results</p> <p>Here we present evidence that glutamate uptake-induced release of GABA from astrocytes has a direct impact on the excitability of pyramidal neurons in the hippocampus. We demonstrate that GABA, synthesized from the polyamine putrescine, is released from astrocytes by the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA release can be prevented by blocking glutamate uptake with the non-transportable inhibitor DHK, confirming that it is the glutamate transporter activity that triggers the reversal of GABA transporters, conceivably by elevating the intracellular Na⁺concentration in astrocytes. The released GABA significantly contributes to the tonic inhibition of neurons in a network activity-dependent manner. Blockade of the Glu/GABA exchange mechanism increases the duration of seizure-like events in the low-[Mg²⁺] <it>in vitro </it>model of epilepsy. Under <it>in vivo </it>conditions the increased GABA release modulates the power of gamma range oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is also functioning in the intact hippocampus under physiological conditions.</p> <p>Conclusions</p> <p>The results suggest the existence of a novel molecular mechanism by which astrocytes transform glutamat<it>ergic </it>excitation into GABA<it>ergic </it>inhibition providing an adjustable, <it>in situ </it>negative feedback on the excitability of neurons.</p

Neuron-glial Interactions

Although lagging behind classical computational neuroscience, theoretical and computational approaches are beginning to emerge to characterize different aspects of neuron-glial interactions. This chapter aims to provide essential knowledge on neuron-glial interactions in the mammalian brain, leveraging on computational studies that focus on structure (anatomy) and function (physiology) of such interactions in the healthy brain. Although our understanding of the need of neuron-glial interactions in the brain is still at its infancy, being mostly based on predictions that await for experimental validation, simple general modeling arguments borrowed from control theory are introduced to support the importance of including such interactions in traditional neuron-based modeling paradigms.Junior Leader Fellowship Program by “la Caixa” Banking Foundation (LCF/BQ/LI18/11630006

A randomized, controlled trial of 3.0 mg of liraglutide in weight management

BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P&lt;0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P&lt;0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P&lt;0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)

Colonial America

The first permanent British settlement in what became the United States was established in 1607, nearly 170 years prior to the American declaration of independence. This chapter examines the economic development of the British North American colonies that became the United States. As it describes, abundant natural resources and scarce labor and capital contributed to the remarkable growth in the size of the colonial economy, and allowed the free white colonial population to enjoy a relatively high standard of living. There was not, however, much improvement over time in living standards. Patterns of factor abundance also played an important role in shaping colonial institutions, encouraging reliance on indentured and enslaved labor as well as the development of representative government. For most of the colonial era, the colonists happily accepted their relationship to Britain. After 1763, however, changes in British policies following the end of the Seven Years War created growing tensions with the colonists and ultimately led to the colonies to declare their independence

Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis

Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with HLA region polymorphisms. To determine if associations can be explained by classical HLA determinants we studied Italian 676 cases and 1440 controls with genotyped with dense single nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (p = 1.59 × 10(−11)) was the strongest predisposing allele where as DRB1*11 (p = 1.42 × 10(−10)) was protective. Additionally DRB1*14 and the DPB1 association (DPB1*03:01) (p = 9.18 × 10(−7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC