The first ultracompact Roche lobe-filling hot subdwarf binary

We report the discovery of the first short period binary in which a hot subdwarf star (sdOB) fills its Roche lobe and started mass transfer to its companion. The object was discovered as part of a dedicated high-cadence survey of the Galactic Plane named the Zwicky Transient Facility and exhibits a period of Porb=39.3401(1) min, making it the most compact hot subdwarf binary currently known. Spectroscopic observations are consistent with an intermediate He-sdOB star with an effective temperature of Teff=42,400±300 K and a surface gravity of log(g)=5.77±0.05. A high-signal-to noise GTC+HiPERCAM light curve is dominated by the ellipsoidal deformation of the sdOB star and an eclipse of the sdOB by an accretion disk. We infer a low-mass hot subdwarf donor with a mass MsdOB=0.337±0.015 M⊙ and a white dwarf accretor with a mass MWD=0.545±0.020 M⊙. Theoretical binary modeling indicates the hot subdwarf formed during a common envelope phase when a 2.5−2.8 M⊙ star lost its envelope when crossing the Hertzsprung Gap. To match its current Porb, Teff, log(g), and masses, we estimate a post-common envelope period of Porb≈150 min, and find the sdOB star is currently undergoing hydrogen shell burning. We estimate that the hot subdwarf will become a white dwarf with a thick helium layer of ≈0.1 M⊙ and will merge with its carbon/oxygen white dwarf companion after ≈17 Myr and presumably explode as a thermonuclear supernova or form an R CrB star

Emerging role of insulin with incretin therapies for management of type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a progressive disease warranting intensification of treatment, as beta-cell function declines over time. Current treatment algorithms recommend metformin as the first-line agent, while advocating the addition of either basal-bolus or premixed insulin as the final level of intervention. Incretin therapy, including incretin mimetics or enhancers, are the latest group of drugs available for treatment of T2DM. These agents act through the incretin axis, are currently recommended as add-on agents either as second-or third-line treatment, without concurrent use of insulin. Given the novel role of incretin therapy in terms of reducing postprandial hyperglycemia, and favorable effects on weight with reduced incidence of hypoglycemia, we explore alternative options for incretin therapy in T2DM management. Furthermore, as some evidence alludes to incretins potentially increasing betacell mass and altering disease progression, we propose introducing these agents earlier in the treatment algorithm. In addition, we suggest the concurrent use of incretins with insulin, given the favorable effects especially in relation to weight gain

Enhanced glycemic control with combination therapy for type 2 diabetes in primary care

Type 2 diabetes mellitus is an increasingly common medical problem for primary care clinicians to address. Treatment of diabetes has evolved from simple replacement of insulin (directly or through insulin secretagogs) through capture of mechanisms such as insulin sensitizers, alpha-glucosidase inhibitors, and incretins. Only very recently has recognition of the critical role of the gastrointestinal system as a major culprit in glucose dysregulation been established. Since glycated hemoglobin A1c reductions provide meaningful risk reduction as well as improved quality of life, it is worthwhile to explore evolving paths for more efficient use of the currently available pharmacotherapies. Because diabetes is a progressive disease, even transiently successful treatment will likely require augmentation as the disorder progresses. Pharmacotherapies with complementary mechanisms of action will be necessary to achieve glycemic goals. Hence, clinicians need to be well informed about the various noninsulin alternatives that have been shown to be successful in glycemic goal attainment. This article reviews the benefits of glucose control, the current status of diabetes control, pertinent pathophysiology, available pharmacological classes for combination, limitations of current therapies, and suggestions for appropriate combination therapies, including specific suggestions for thresholds at which different strategies might be most effectively utilized by primary care clinicians

A dense 0.1-solar-mass star in a 51-minute-orbital-period eclipsing binary

Of more than a thousand known cataclysmic variables (CVs), where a white dwarf is accreting from a hydrogen-rich star, only a dozen have orbital periods below 75 minutes1,2,3,4,5,6,7,8,9. One way to achieve these short periods requires the donor star to have undergone substantial nuclear evolution before interacting with the white dwarf10,11,12,13,14, and it is expected that these objects will transition to helium accretion. These transitional CVs have been proposed as progenitors of helium CVs13,14,15,16,17,18. However, no known transitional CV is expected to reach an orbital period short enough to account for most of the helium CV population, leaving the role of this evolutionary pathway unclear. Here we report observations of ZTF J1813+4251, a 51-minute-orbital-period, fully eclipsing binary system consisting of a star with a temperature comparable to that of the Sun but a density 100 times greater owing to its helium-rich composition, accreting onto a white dwarf. Phase-resolved spectra, multi-band light curves and the broadband spectral energy distribution allow us to obtain precise and robust constraints on the masses, radii and temperatures of both components. Evolutionary modelling shows that ZTF J1813+4251 is destined to become a helium CV binary, reaching an orbital period under 20 minutes, rendering ZTF J1813+4251 a previously missing link between helium CV binaries and hydrogen-rich CVs

Burden of diarrhea in the eastern mediterranean region, 1990-2013: Findings from the global burden of disease study 2013

Diarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6 of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low-and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95 uncertainty interval UI = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden. Copyright © 2016 by The American Society of Tropical Medicine and Hygiene

Purification and characterization of 2 ' aminobiphenyl-2,3-diol 1,2-dioxygenase from Pseudomonas sp LD2

Carbazole is a nitrogen-containing heteroaromatic compound that occurs as a widespread and mutagenic environmental pollutant. The 2¿aminobiphenyl-2,3-diol 1,2-dioxygenase involved in carbazole degradation was purified to near electrophoretic homogeneity from Pseudomonas sp. LD2 by a combination of ion-exchange chromatography, ammonium sulfate precipitation, and hydrophobic interaction chromatography. This purification was challenging due to the great instability of the enzyme under many standard conditions. The enzyme was also purified to electrophoretic homogeneity from recombinant Escherichia coli expressing the 2¿aminobiphenyl-2,3-diol 1,2-dioxygenase-encoding gene cloned from Pseudomonas sp. LD2. The molecular mass of the native enzyme was determined by gel filtration to be 70 kDa. The subunit molecular masses were determined to be 25 and 8 kDa by sodium dodecyl sulfate¿polyacrylamide gel electrophoresis, indicating that the dioxygenase is an [¿2ß2] heterotetramer. The optimal temperature and pH for the enzymatic production of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) from 2,3-dihydroxybiphenyl were determined to be 40 °C and 8.0, respectively. The maximum observed specific activity on 2,3-dihydroxybiphenyl was 48.1 mmol HOPDA min¿1 mg¿1. This indicated a maximum observed turnover rate of 360,000 molecules HOPDA enz¿1 s¿1. The K¿m, inhibition constant Ks, and Vmax on 2,3 dihydroxybiphenyl were determined to be 5 ¿M, 37 ¿M, and 44 mmolmin¿1 mg¿1, respectively. These results show that 2¿aminobiphenyl-2,3-diol 1,2-dioxygenase is a meta-cleavage enzyme related to the 4,5-protocatechuate dioxygenase family, with comparable purification challenges posed by intrinsic enzyme instability

Phylogeographic information systems: putting the geography into phylogeography

Phylogeography is concerned with the observation, description and analysis of the spatial distribution of genotypes and the inference of historical scenarios. In the past, the discipline has concentrated on the historical 'phylo-' component through the utilization of phylogenetic analyses. In contrast, the spatial '-geographic' component is not a prominent feature of many existing phylogenetic approaches and has often been dealt with in a relatively naive fashion. Recently, there has been a resurgence of interest in the importance of geography in evolutionary biology. Thus, we believe that it is time to assess how geographic information is currently handled and incorporated into phylogeographical analysis. Geographical information systems (GISs) are computer systems that facilitate the integration and interrelation of different geographically referenced data sets; however, so far they have been little utilized by the phylogeographical community to manage, analyse and disseminate phylogeographical data. However, the growth in individual studies and the resurgence of interest in the geographical components of genetic pattern and biodiversity should stimulate further uptake. Some advantages of GIS are the integration of disparate data sets via georeferencing, dynamic data base design and update, visualization tools and data mining. An important step in linking GIS to existing phylogeographical and historical biogeographical analysis software and the dissemination of spatial phylogenies will be the establishment of 'GeoPhylo' data standards. We hope that this paper will further stimulate the resurgence of geography as an equal partner in the symbiosis that is phylogeography as well as advertise some benefits that can be obtained from the application of GIS practices and technologies.</p