Effects of Hypoxia on Embryonic Development in Two \u3ci\u3eAmbystoma\u3c/i\u3e and Two \u3ci\u3eRana \u3c/i\u3eSpecies

Oxygen available to amphibian embryos fluctuates widely and is often very low. We investigated the effects of oxygen partial pressure (1.3–16.9 kPa) on embryonic development and hatching of two salamander (Ambystoma) and two frog (Rana) species. In Ambystoma, chronic hypoxia resulted in slowed development, delayed hatching, and embryos that were less developed at the time of hatching. Although hypoxia was not lethal to embryos, temporary developmental abnormalities were observed in Ambystoma at oxygen partial pressures of 3.8 kPa and below. Posthatching survival decreased below 3.3 kPa. In Rana, hypoxia did not affect developmental rate, presumably because hatching occurs at a very early stage of development relative to Ambystoma. However, Rana embryos hatched sooner in hypoxia than in normoxia, resulting in less developed embryos at the time of hatching. The results suggest that embryonic hypoxia may negatively affect survival and fitness in these species

Atmospheric oxidation chemistry and ozone production: Results from SHARP 2009 in Houston, Texas

This study considers whether spikes in nitrate in snow sampled at Summit, Greenland, from August 2000 to August 2002 are related to solar proton events. After identifying tropospheric sources of nitrate on the basis of correlations with sulfate, ammonium, sodium, and calcium, we use the three-dimensional global Whole Atmosphere Community Climate Model (WACCM) to examine unaccounted for nitrate spikes. Model calculations confirm that solar proton events significantly impact HOx, NOx, and O3 levels in the mesosphere and stratosphere during the weeks and months following the major 9 November 2000 solar proton event. However, solar proton event (SPE)-enhanced NOy calculated within the atmospheric column is too small to account for the observed nitrate peaks in surface snow. Instead, our WACCM results suggest that nitrate spikes not readily accounted for by measurement correlations are likely of anthropogenic origin. These results, consistent with other recent studies, imply that nitrate spikes in ice cores are not suitable proxies for individual SPEs and motivate the need to identify alternative proxies

Nitrate deposition to surface snow at Summit, Greenland, following the 9 November 2000 solar proton event

Abstract This study considers whether spikes in nitrate in snow sampled at Summit, Greenland, from August 2000 to August 2002 are related to solar proton events. After identifying tropospheric sources of nitrate on the basis of correlations with sulfate, ammonium, sodium, and calcium, we use the three-dimensional global Whole Atmosphere Community Climate Model (WACCM) to examine unaccounted for nitrate spikes. Model calculations confirm that solar proton events significantly impact HOx, NOx, and O3 levels in the mesosphere and stratosphere during the weeks and months following the major 9 November 2000 solar proton event. However, solar proton event (SPE)-enhanced NOy calculated within the atmospheric column is too small to account for the observed nitrate peaks in surface snow. Instead, our WACCM results suggest that nitrate spikes not readily accounted for by measurement correlations are likely of anthropogenic origin. These results, consistent with other recent studies, imply that nitrate spikes in ice cores are not suitable proxies for individual SPEs and motivate the need to identify alternative proxies. Key Points A global model simulates nitrate deposition from solar proton events Soluble ion correlations in Summit snow identify tropospheric sources of nitrate Nitrate ions in snow are found not to be a good proxy for solar proton events

Nitrate Deposition to Surface Snow at Summit, Greenland, Following the 9 November 2000 Solar Proton Event

This study considers whether spurious peaks in nitrate ions in snow sampled at Summit, Greenland from August 2000 to August 2002 are related to solar proton events. After identifying tropospheric sources of nitrate on the basis of correlations with sulfate, ammonium, sodium, and calcium, we use the three-dimensional global Whole Atmosphere Community Climate Model (WACCM) to examine unaccounted for nitrate spikes. Model calculations confirm that solar proton events significantly impact HOx, NOx, and O3 levels in the mesosphere and stratosphere during the weeks and months following the major 9 November 2000 solar proton event. However, SPE-enhanced NOy calculated within the atmospheric column is too small to account for the observed nitrate ion peaks in surface snow. Instead, our WACCM results suggest that nitrate spikes not readily accounted for by measurement correlations are likely of anthropogenic origin. These results, consistent with other recent studies, imply that nitrate spikes in ice cores are not suitable proxies for individual SPEs and motivate the need to identify alternative proxies

Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment. METHODS: We did duplicate searches of databases (from inception to July 27, 2009), searchable websites of major HIV conferences (up to July, 2009), and lay publications and websites (March-July, 2009) to identify randomised trials assessing directly observed therapy to promote adherence to antiretroviral therapy in adults. Our primary outcome was virological suppression at study completion. We calculated relative risks (95% CIs), and pooled estimates using a random-effects method. FINDINGS: 12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n=1862 participants); we calculated a pooled relative risk of 1.04 (95% CI 0.91-1.20, p=0.55), and noted moderate heterogeneity between the studies (I(2)= 53.8%, 95% CI 0-75.7, p=0.0247) for directly observed versus self-administered treatment. INTERPRETATION: Directly observed antiretroviral therapy seems to offer no benefit over self-administered treatment, which calls into question the use of such an approach to support adherence in the general patient population. FUNDING: None

A retrospective review of α-gal syndrome complicating the management of suspected pancreatic exocrine insufficiency in one gastroenterology clinic in central Virginia

The galactose-α-1,3-galactose (α-gal) mammalian meat allergy, α-gal syndrome, often includes diarrhea, abdominal pain, and other gastrointestinal (GI) symptoms. Pancreatic exocrine insufficiency causes similar symptoms. The pancreatic replacement enzymes, referred to here as pancreatic enzymes, used to treat pancreatic insufficiency are porcine products and contain α-gal. Patients with pancreatic insufficiency who also have α-gal syndrome may be intolerant of mammalian products in their diet and of α-gal in pancreatic enzymes. In this article, we describe 40 patients from one GI clinic in central Virginia with suspected pancreatic insufficiency and increased α-gal immunoglobulin E (IgE) levels. Over 50% of these patients had some clinical improvement when mammalian products were removed from the diet. Most patients could tolerate pancreatic enzymes; 10% could not tolerate them due to suspected allergy symptoms, but none developed anaphylaxis. Understanding that α-gal syndrome can be superimposed on pancreatic exocrine insufficiency and exacerbate symptoms, and that treatment with pancreatic enzymes may increase GI and/or allergy symptoms in this group, will lead to improved medical management of this complex patient population

Density of Healthcare Providers and Patient Outcomes: Evidence from a Nationally Representative Multi-Site HIV Treatment Program in Uganda

This study examined the association between density of healthcare providers and patient outcomes using a large nationally representative cohort of patients receiving combination antiretroviral therapy (cART) in Uganda.Objective: We examined the association between density of healthcare providers and patient outcomes using a large nationally representative cohort of patients receiving combination antiretroviral therapy (cART) in Uganda. Design: We obtained data from The AIDS Support Organization (TASO) in Uganda. Patients 18 years of age and older who initiated cART at TASO between 2004 and 2008 contributed to this analysis. The number of healthcare providers per 100 patients, the number of patients lost to follow-up per 100 person years and number of deaths per 100 person years were calculated. Spearman correlation was used to identify associations between patient loss to follow-up and mortality with the healthcare provider-patient ratios. Results: We found no significant associations between the number of patients lost to follow-up and physicians (p = 0.45), nurses (p = 0.93), clinical officers (p = 0.80), field officers (p = 0.56), and healthcare providers overall (p = 0.83). Similarly, no significant associations were observed between mortality and physicians (p = 0.65), nurses (p = 0.49), clinical officers (p = 0.73), field officers (p = 0.78), and healthcare providers overall (p = 0.73). Conclusions: Patient outcomes, as measured by loss to follow-up and mortality, were not significantly associated with the number of doctors, nurses, clinical officers, field officers, or healthcare providers overall. This may suggest that that other factors, such as the presence of volunteer patient supporters or broader political or socioeconomic influences, may be more closely associated with outcomes of care among patients on cART in Uganda

Enhancing the efficacy of glycolytic blockade in cancer cells via RAD51 inhibition.

Targeting the early steps of the glycolysis pathway in cancers is a well-established therapeutic strategy; however, the doses required to elicit a therapeutic effect on the cancer can be toxic to the patient. Consequently, numerous preclinical and clinical studies have combined glycolytic blockade with other therapies. However, most of these other therapies do not specifically target cancer cells, and thus adversely affect normal tissue. Here we first show that a diverse number of cancer models - spontaneous, patient-derived xenografted tumor samples, and xenografted human cancer cells - can be efficiently targeted by 2-deoxy-D-Glucose (2DG), a well-known glycolytic inhibitor. Next, we tested the cancer-cell specificity of a therapeutic compound using the MEC1 cell line, a chronic lymphocytic leukemia (CLL) cell line that expresses activation induced cytidine deaminase (AID). We show that MEC1 cells, are susceptible to 4,4\u27-Diisothiocyano-2,2\u27-stilbenedisulfonic acid (DIDS), a specific RAD51 inhibitor. We then combine 2DG and DIDS, each at a lower dose and demonstrate that this combination is more efficacious than fludarabine, the current standard- of- care treatment for CLL. This suggests that the therapeutic blockade of glycolysis together with the therapeutic inhibition of RAD51-dependent homologous recombination can be a potentially beneficial combination for targeting AID positive cancer cells with minimal adverse effects on normal tissue. IMPLICATIONS: Combination therapy targeting glycolysis and specific RAD51 function shows increased efficacy as compared to standard of care treatments in leukemias

Two-loop corrections to the decay rate of parapositronium

Order $\alpha^2$ corrections to the decay rate of parapositronium are calculated. A QED scattering calculation of the amplitude for electron-positron annihilation into two photons at threshold is combined with the technique of effective field theory to determine an NRQED Hamiltonian, which is then used in a bound state calculation to determine the decay rate. Our result for the two-loop correction is $5.1243(33)$ in units of $(\alpha/\pi)^2$ times the lowest order rate. This is consistent with but more precise than the result $5.1(3)$ of a previous calculation.Comment: 26 pages, 7 figure

Uptake of home-based voluntary HIV testing in sub-Saharan Africa: a systematic review and meta-analysis

Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here