Photo-reverberation mapping of a protoplanetary accretion disk around a T Tauri star

This is the final version. Available from the American Astronomical Society via the DOI in this recordTheoretical models and spectroscopic observations of newborn stars suggest that protoplantary disks have an inner "wall" at a distance set by the disk interaction with the star. Around T Tauri stars, the size of this disk hole is expected to be on a 0.1 au scale that is unresolved by current adaptive optics imaging, though some model-dependent constraints have been obtained by near-infrared interferometry. Here we report the first measurement of the inner disk wall around a solar-mass young stellar object, YLW 16B in the ρ Ophiuchi star-forming region, by detecting the light-travel time of the variable radiation from the stellar surface to the disk. Consistent time lags were detected on two nights, when the time series in H (1.6 μm) and K (2.2 μm) bands were synchronized while the 4.5 μm emission lagged by 74.5 ± 3.2 s. Considering the nearly edge-on geometry of the disk, the inner rim should be 0.084 au from the protostar on average, with an error of order 0.01 au. This size is likely larger than the range of magnetospheric truncations and consistent with an optically and geometrically thick disk front at the dust sublimation radius at ∼1500 K. The widths of the cross-correlation functions between the data in different wavebands place possible new constraints on the geometry of the disk.National Science Foundation (NSF

Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments

Background: The accuracy of prostate-specific antigen (PSA) testing in prostate cancer detection is constrained by low sensitivity and specificity. Dysregulated expression of minichromosome maintenance (Mcm) 2–7 proteins is an early event in epithelial multistep carcinogenesis and thus MCM proteins represent powerful cancer diagnostic markers. In this study we investigate Mcm5 as a urinary biomarker for prostate cancer detection. Methods: Urine was obtained from 88 men with prostate cancer and from two control groups negative for malignancy. A strictly normal cohort included 28 men with complete, normal investigations, no urinary calculi and serum PSA <2 ng ml–1. An expanded control cohort comprised 331 men with a benign final diagnosis, regardless of PSA level. Urine was collected before and after prostate massage in the cancer patient cohort. An immunofluorometric assay was used to measure Mcm5 levels in urine sediments. Results: The Mcm5 test detected prostate cancer with 82% sensitivity (confidence interval (CI)= 72–89%) and with a specificity ranging from 73 (CI=68–78%) to 93% (CI=76–99%). Prostate massage led to increased Mcm5 signals compared with pre-massage samples (median 3440 (interquartile range (IQR) 2280 to 5220) vs 2360 (IQR <1800 to 4360); P=0.009), and was associated with significantly increased diagnostic sensitivity (82 vs 60%; P=0.012). Conclusions: Urinary Mcm5 detection seems to be a simple, accurate and noninvasive method for identifying patients with prostate cancer. Large-scale prospective trials are now required to evaluate this test in diagnosis and screening

Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas

Proteins necessary for the normal regulation of the cell cycle include minichromosome maintenance protein 2 (Mcm2) and geminin. These are overexpressed in several premalignant and malignant tumours. The Mcm2/Ki67 ratio can be used to estimate the population of cells that are in early G1 (licensed to proliferate), and the geminin/Ki67 ratio can determine the relative length of G1. A high ratio indicates a short G1 and a high rate of cell proliferation. Mcm2 and geminin have been scarcely explored in oral epithelial dysplasia (OED) and oral squamous-cell carcinoma (OSCC). The purpose of this study was to identify the expression pattern of Mcm2, Ki67 and geminin in normal oral mucosa (NOM), OED and their subsequent OSCC, to determine if expression could help predict the prognosis of OED. Paraffin sections of 41 OED cases that progressed to carcinoma, 40 OED without malignant progression, 38 OSCC and 15 NOM were immunostained with antibodies against Mcm2, geminin and Ki67. Labelling indices (LIs) increased progressively from NOM, OED and OSCC (Mcm2, Po0.001; geminin, Po0.001 and Ki67, Po0.001). In all the OED cases (n ¼ 81) the levels of expression of Mcm2 (LI, 73.6), geminin (LI, 24.4) and Ki67 (LI, 44.5) were elevated indicating a constant cellcycle re-entry. When the OED groups were compared, Mcm2 protein expression was higher in the OED with malignant progression (P ¼ 0.04), likewise there was a significant increase in the Mcm2/Ki67 and geminin/Ki67 ratios (P ¼ 0.04 and 0.02 respectively). Mcm2 and geminin proteins seem to be novel biomarkers of growth and may be useful prognostic tools for OED

Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review

<p>Abstract</p> <p>Background</p> <p>Diarrhea is recognized as a leading cause of morbidity and mortality among children under 5 years of age in low- and middle-income countries yet updated estimates of diarrhea incidence by age for these countries are greatly needed. We conducted a systematic literature review to identify cohort studies that sought to quantify diarrhea incidence among any age group of children 0-59 mo of age.</p> <p>Methods</p> <p>We used the Expectation-Maximization algorithm as a part of a two-stage regression model to handle diverse age data and overall incidence rate variation by study to generate country specific incidence rates for low- and middle-income countries for 1990 and 2010. We then calculated regional incidence rates and uncertainty ranges using the bootstrap method, and estimated the total number of episodes for children 0-59 mo of age in 1990 and 2010.</p> <p>Results</p> <p>We estimate that incidence has declined from 3.4 episodes/child year in 1990 to 2.9 episodes/child year in 2010. As was the case previously, incidence rates are highest among infants 6-11 mo of age; 4.5 episodes/child year in 2010. Among these 139 countries there were nearly 1.9 billion episodes of childhood diarrhea in 1990 and nearly 1.7 billion episodes in 2010.</p> <p>Conclusions</p> <p>Although our results indicate that diarrhea incidence rates may be declining slightly, the total burden on the health of each child due to multiple episodes per year is tremendous and additional funds are needed to improve both prevention and treatment practices in low- and middle-income countries.</p

Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

Non-healing chronic ulcers are a serious complication of diabetes and are a major healthcare problem. While a host of treatments have been explored to heal or prevent these ulcers from forming, these treatments have not been found to be consistently effective in clinical trials. An understanding of the changes in gene expression in the skin of diabetic patients may provide insight into the processes and mechanisms that precede the formation of non-healing ulcers. In this study, we investigated genome wide changes in gene expression in skin between patients with type 2 diabetes and non-diabetic patients using next generation sequencing. We compared the gene expression in skin samples taken from 27 patients (13 with type 2 diabetes and 14 non-diabetic). This information may be useful in identifying the causal factors and potential therapeutic targets for the prevention and treatment of diabetic related diseases

Circumstellar discs: What will be next?

This prospective chapter gives our view on the evolution of the study of circumstellar discs within the next 20 years from both observational and theoretical sides. We first present the expected improvements in our knowledge of protoplanetary discs as for their masses, sizes, chemistry, the presence of planets as well as the evolutionary processes shaping these discs. We then explore the older debris disc stage and explain what will be learnt concerning their birth, the intrinsic links between these discs and planets, the hot dust and the gas detected around main sequence stars as well as discs around white dwarfs.Comment: invited review; comments welcome (32 pages

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

High-throughput Screening and Sensitized Bacteria Identify an M. tuberculosis Dihydrofolate Reductase Inhibitor with Whole Cell Activity

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a bacterial pathogen that claims roughly 1.4 million lives every year. Current drug regimens are inefficient at clearing infection, requiring at least 6 months of chemotherapy, and resistance to existing agents is rising. There is an urgent need for new drugs that are more effective and faster acting. The folate pathway has been successfully targeted in other pathogens and diseases, but has not yielded a lead drug against tuberculosis. We developed a high-throughput screening assay against Mtb dihydrofolate reductase (DHFR), a critical enzyme in the folate pathway, and screened a library consisting of 32,000 synthetic and natural product-derived compounds. One potent inhibitor containing a quinazoline ring was identified. This compound was active against the wild-type laboratory strain H37Rv (MIC99 = 207 µM). In addition, an Mtb strain with artificially lowered DHFR levels showed increased sensitivity to this compound (MIC99 = 70.7 µM), supporting that the inhibition was target-specific. Our results demonstrate the potential to identify Mtb DHFR inhibitors with activity against whole cells, and indicate the power of using a recombinant strain of Mtb expressing lower levels of DHFR to facilitate the discovery of antimycobacterial agents. With these new tools, we highlight the folate pathway as a potential target for new drugs to combat the tuberculosis epidemic