Fine mapping of variants associated with endometriosis in the WNT4 region on chromosome 1p36

Genome-wide association studies show strong evidence of association with endometriosis for markers on chromosome 1p36 spanning the potential candidate genes WNT4, CDC42 and LINC00339. WNT4 is involved in development of the uterus, and the expression of CDC42 and LINC00339 are altered in women with endometriosis. We conducted fine mapping to examine the role of coding variants in WNT4 and CDC42 and determine the key SNPs with strongest evidence of association in this region. We identified rare coding variants in WNT4 and CDC42 present only in endometriosis cases. The frequencies were low and cannot account for the common signal associated with increased risk of endometriosis. Genotypes for five common SNPs in the region of chromosome 1p36 show stronger association signals when compared with rs7521902 reported in published genome scans. Of these, three SNPs rs12404660, rs3820282, and rs55938609 were located in DNA sequences with potential functional roles including overlap with transcription factor binding sites for FOXA1, FOXA2, ESR1, and ESR2. Functional studies will be required to identify the gene or genes implicated in endometriosis risk

Suboptimal Exposure to Anti-TB Drugs in a TBM/HIV+ Population is not Related to Anti-retroviral Therapy.

A placebo-controlled trial that compares the outcomes of immediate versus deferred initiation of antiretroviral therapy in HIV+ve Tuberculous Meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of Rifampicin, Isoniazid, Pyrazinamide and Ethambutol were investigated in the presence and absence of anti-HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact upon the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low CSF and systemic exposures to rifampicin compared to previously reported HIV –ve cohorts. Elevated CSF concentrations of pyrazinamide on the other hand were strongly and independently correlated with increased mortality and neurological toxicity. The findings suggest that the current standard dosing regimens may put the patient at risk of treatment failure from suboptimal rifampicin exposure, and potentially increasing the risk of adverse CNS events which are independently correlated with pyrazinamide CSF exposure

Polarimetry and Unification of Low-Redshift Radio Galaxies

We have made high-quality measurements of the polarization spectra of 13 FR II radio galaxies and taken polarization images for 11 of these with the Keck telescopes. Seven of the eight narrow-line radio galaxies (NLRG) are polarized, and six of the seven show prominent broad Balmer lines in polarized light. The broad lines are also weakly visible in total flux. Some of the NLRG show bipolar regions with roughly circumferential polarization vectors, revealing a large reflection nebula illuminated by a central source. Our observations powerfully support the hidden quasar hypothesis for some NLRG. Classification as NLRG, broad-line radio galaxy (BLRG), or quasar therefore depends on orientation. However, not all objects fit into this unification scheme. Our sample is biased towards objects known in advance to be polarized, but the combination of our results with those of Hill, Goodrich and DePoy (1996) show that at least 6 out of a complete, volume and flux-limited sample of 9 FR II NLRG have broad lines, seen either in polarization or P_alpha.Comment: To appear in November 1999 Astronomical Journal. 49 pages, 13 figure

The Unified Model & Evolution of Active Galaxies: Implications from a Spectropolarimetric Study

We extend the analysis presented in Tran (2001) of a spectropolarimetric survey of the CfA and 12micron samples of Seyfert 2 galaxies (S2s). We confirm that S2s with hidden broad line regions (HBLRs) tend to have hotter circumnuclear dust temperatures, show mid-IR spectra more characteristic of S1 galaxies, and are intrinsically more luminous than non-HBLR S2s. The level of obscuration and circumnuclear star formation, however, appear to be similar between HBLR and non-HBLR S2 galaxies, based on an examination of various observational indicators. HBLR S2s, on average, share many similar large-scale, presumably isotropic, characteristics with Seyfert 1 galaxies (S1s), as would be expected if the unified model is correct, while non-HBLR S2s generally do not. The active nuclear engines of non-HBLR S2s then, appear to be truly weaker than HBLR S2s, which in turn, are fully consistent with being S1s viewed from another direction. There is also evidence that the fraction of detected HBLR increases with radio power of the AGN. Thus, not all Seyfert 2 galaxies may be intrinsically similar in nature, and we speculate that evolutionary processes may be at work.Comment: 15 pages with embedded figs, ApJ in press, vol. 583, 2003 Feb. 1. v2: minor corrections to text, some typos removed; updated reference list: some added, some remove

Advanced Camera for Surveys Observations of Young Star Clusters in the Interacting Galaxy UGC 10214

We present the first Advanced Camera for Surveys (ACS) observations of young star clusters in the colliding/merging galaxy UGC 10214. The observations were made as part of the Early Release Observation (ERO) program for the newly installed ACS during service mission SM3B for the Hubble Space Telescope (HST). Many young star clusters can be identified in the tails of UGC 10214, with ages ranging from ~3 Myr to 10 Myr. The extreme blue V-I (F606W-F814W) colors of the star clusters found in the tail of UGC 10214 can only be explained if strong emission lines are included with a young stellar population. This has been confirmed by our Keck spectroscopy of some of these bright blue stellar knots. The most luminous and largest of these blue knots has an absolute magnitude of M_V = -14.45, with a half-light radius of 161 pc, and if it is a single star cluster, would qualify as a super star cluster (SSC). Alternatively, it could be a superposition of multiple scaled OB associations or clusters. With an estimated age of ~ 4-5 Myr, its derived mass is < 1.3 x 10^6 solar masses. Thus the young stellar knot is unbound and will not evolve into a normal globular cluster. The bright blue clusters and associations are much younger than the dynamical age of the tail, providing strong evidence that star formation occurs in the tail long after it was ejected. UGC 10214 provides a nearby example of processes that contributed to the formation of halos and intra-cluster media in the distant and younger Universe.Comment: 6 pages with embedded figures, ApJ in pres

Scattered Radiation from Obscured Quasars in Distant Radio Galaxies

We present optical spectropolarimetric and imaging polarimetric observations of four high-redshift radio galaxies (HzRGs) obtained with the 10-m Keck I telescope. A broad Mg II emission line is detected in the total and polarized flux spectra of 3C 265 and 3C 277.2. The fractional polarization is high, and both it and the position angle are constant with wavelength after accounting for dilution by unpolarized starlight of the host galaxy, which can contribute substantially. An extended unpolarized continuum similar to that observed in other AGNs is also detected. Imaging polarimetry reveals a rough double-fan morphology of the polarized light coincident with the extended aligned emission regions, with the position angle essentially perpendicular to the radial structure of the extended UV/optical emission, and with the degree of polarization increasing with radius away from the nucleus. The radio jets lie inside the extended emission regions and, like every radius, are roughly perpendicular to the polarization PA. These results strengthen the view that powerful radio galaxies would be called quasars if viewed from a proper direction. Based on the polarimetric data presented in this paper and in previous studies, scattering of radiation from an obscured quasar source appears to be the preferred interpretation over jet-induced star formation for explaining the alignment effect in HzRGs. Both electrons and dust can play a major role in the scattering process. However, the lack of strong direct evidence for either case, and our ignorance of the properties and distribution of the scatterers in these galaxies make it very difficult to discriminate between the two. Our data reveal a chance alignment of 3C 343.1 with a foreground galaxy, which dominates the observed optical flux from the system.Comment: 36 pages, 12 figures, 2 tables, Astrophysical Journal, accepted Dec. 21, 199

The clinical implications of thrombocytopenia in adults with severe falciparum malaria: a retrospective analysis

BackgroundThrombocytopenia is a common finding in adults with severe falciparum malaria, but its clinical and prognostic utility is incompletely defined.MethodsClinical and laboratory data from 647 adults with severe falciparum malaria were analysed retrospectively to determine the relationship between a patient&rsquo;s platelet count on admission to hospital and their subsequent clinical course.ResultsOn admission, 614 patients (94.9%) were thrombocytopenic (platelet count &lt;150&thinsp;&times;&thinsp;109/L) and 328 (50.7%) had a platelet count &lt;50&thinsp;&times;&thinsp;109/L. The admission platelet count was inversely correlated with parasite biomass (estimated from plasma PfHRP2 concentrations, rs&thinsp;=&thinsp;&minus;0.28, P&thinsp;=&thinsp;0.003), the degree of microvascular sequestration (measured with orthogonal polarizing spectral imaging, rs&thinsp;=&thinsp;&minus;0.31, P&thinsp;=&thinsp;0.001) and disease severity (the number of World Health Organization severity criteria satisfied by the patient, rs&thinsp;=&thinsp;&minus;0.21, P &lt;0.001). Platelet counts were lower on admission in the patients who died (median: 30 (interquartile range 22 to 52)&thinsp;&times;&thinsp;109/L versus 50 (34 to 78)&thinsp;&times;&thinsp;109/L in survivors; P &lt;0.001), but did not predict outcome independently from other established laboratory and clinical prognostic indices. The 39 patients (6%) with profound thrombocytopenia (platelet count &lt;20&thinsp;&times;&thinsp;109/L) were more likely to die (odds ratio: 5.00, 95% confidence interval: 2.56 to 9.75) than patients with higher platelet counts, but these high-risk patients could be identified more rapidly with simple bedside clinical assessment. The admission platelet count did not reliably identify the 50 patients (7.7%) with major bleeding during the study.ConclusionsThrombocytopenia is a marker of disease severity in adults with falciparum malaria, but has limited utility in prognostication, triage and management

Impact of Education and Network for Avian Influenza H5N1 in Human: Knowledge, Clinical Practice, and Motivation on Medical Providers in Vietnam

BACKGROUND: Knowledge, clinical practice, and professional motivation of medical providers relating to H5N1 infection have an important influence on care for H5N1 patients who require early diagnosis and early medical intervention. METHODS/PRINCIPAL FINDINGS: Novel educational programs including training and workshops for medical providers relating to H5N1 infection in Vietnam were originally created and implemented in 18 provincial hospitals in northern Vietnam between 2008 and 2010. A self-administered, structured questionnaire survey was conducted in 8 provincial hospitals where both educational training and workshops were previously provided. A total of 326 medical providers, including physicians, nurses, and laboratory technicians who attended or did not attend original programs were enrolled in the survey. Knowledge, clinical attitudes and practice (KAP), including motivation surrounding caring for H5N1 patients, were evaluated. The study indicated a high level of knowledge and motivation in all professional groups, with especially high levels in laboratory technicians. Conferences and educational programs were evaluated to be the main scientific information resources for physicians, along with information from colleagues. The chest radiographs and the initiation of antiviral treatment in the absence of RT-PCR result were identified as gaps in education. Factors possibly influencing professional motivation for caring for H5N1 patients included healthcare profession, the hospital where the respondents worked, age group, attendance at original educational programs and at educational programs which were conducted by international health-related organizations. CONCLUSIONS: Educational programs provide high knowledge and motivation for medical providers in Vietnam caring for H5N1 patients. Additional educational programs related to chest radiographs and an initiation of treatment in the absence of RT-PCR are needed. Networking is also necessary for sharing updated scientific information and practical experiences. These enhanced KAPs by educational programs and integrated systems among hospitals should result in appropriate care for H5N1 patients and may reduce morbidity and mortality