Towards Precision Supermassive Black Hole Masses using Megamaser Disks

Megamaser disks provide the most precise and accurate extragalactic supermassive black hole masses. Here we describe a search for megamasers in nearby galaxies using the Green Bank Telescope (GBT). We focus on galaxies where we believe that we can resolve the gravitational sphere of influence of the black hole and derive a stellar or gas dynamical measurement with optical or NIR observations. Since there are only a handful of super massive black holes (SMBH) that have direct black hole mass measurements from more than one method, even a single galaxy with a megamaser disk and a stellar dynamical black hole mass would provide necessary checks on the stellar dynamical methods. We targeted 87 objects from the Hobby-Eberly Telescope Massive Galaxy Survey, and detected no new maser disks. Most of the targeted objects are elliptical galaxies with typical stellar velocity dispersions of 250 km/s and distances within 130 Mpc. We discuss the implications of our non-detections, whether they imply a threshold X-ray luminosity required for masing, or possibly reflect the difficulty of maintaining a masing disk around much more massive (>10^8 Msun) black holes at low Eddington ratio. Given the power of maser disks at probing black hole accretion and demographics, we suggest that future maser searches should endeavour to remove remaining sample biases, in order to sort out the importance of these covariant effects.Comment: 9 pages, 5 figures, Apj, updated to match the accepted versio

What is to blame for postnatal pelvic floor dysfunction in primiparous women — Pre-pregnancy or intrapartum risk factors?

Background: The aetiology of pelvic floor dysfunction (PFD) is still poorly understood. However childbearing is recognized as a major risk factor. Objectives: To elucidate the natural history of PFD by investigating the impact of the mode of delivery on postnatal pelvic floor dysfunction in primiparas, when PFD existing before the first pregnancy is taken into consideration. Study design: 4P-study (Prevalence and Predictors of Pelvic floor dysfunction in Primips) is a prospective cohort study, nested within the Screening for Pregnancy Endpoints (SCOPE) study set in a tertiary referral teaching hospital with 9000 deliveries annually. Established and proposed risk factors for urinary, fecal, prolapse and sexual dysfunction and the severity of symptoms for each of these outcomes were assessed using the Australian Pelvic Floor Questionnaire in 1482 nulliparous women, who each completed the questionnaire in early pregnancy. Of these, 1060 (72%) repeated the questionnaire 12 months postpartum. Outcomes were analyzed using multivariate ordinal logistic regression. Results: Significant (p < 0.05) risk factors for postpartum PFD were pre-pregnancy presence of similar symptoms Odds Ratio (OR) (5.0–30.0), smoking (OR 2.2–4.6), recurrent UTI (OR 2.2–17.3), high hip circumference (OR1.4–1.6), vigorous exercising (OR 3.1–17.9), induction of labor (OR 1.5–2.3), forceps delivery (OR 1.8–8.8), and 3rd degree perineal tear (OR 2.4–2.7). Cesarean section was associated with a lower risk of stress urinary incontinence (OR 0.3–0.5). Other common pre-pregnancy significant (p < 0.05) risk factors for various PFD types prior to the first pregnancy were: diagnosed depression – (OR 1.6–2.1), high BMI (OR 3.1), strenuous exercising (OR 1.3–2.2), recurrent UTI (OR 1.5–2.5) and lower educational achievement (OR 1.5–1.6). Conclusions: Pre-pregnancy PFD was mainly associated with modifiable risk factors such as smoking and exercising. The main risk factor for postpartum PFD was the presence of similar symptoms prior to pregnancy, followed by anthropometric and intrapartum factors. Hip circumference seems to be a better predictor of PFD compared to BMI. When pre-pregnancy PFD was included in the analysis, Cesarean section was protective only for stress urinary incontinence, while delivery by forceps increased the risk of prolapse

Development and Validation of Novel PCR Assays for the Diagnosis of Bovine Stephanofilariasis and Detection of Stephanofilaria sp. Nematodes in Vector Flies

Background: Stephanofilaria spp. nematodes are associated with cutaneous lesions in cattle and other livestock and mammalian wildlife species. In Australia, Haematobia irritans exigua, commonly known as buffalo fly (BF) transmits a well-described but presently unnamed species of Stephanofilaria, which has been speculatively implicated in the aetiology of BF lesions. The sensitivity of current techniques for detecting Stephanofilaria spp. in skin lesions and vector species is low, and there is no genomic sequence for any member of the genus Stephanofilaria currently available in sequence databases. Methods: To develop molecular assays for the detection of the Australian Stephanofilaria sp., skin biopsies were collected from freshly slaughtered cattle with typical lesions near the medial canthus. Adult nematodes and microfilariae were isolated from the biopsies using a saline recovery technique. The nematodes were morphologically identified as Stephanofilaria sp. by scanning electron microscopy. DNA was extracted and the internal transcribed spacer 2 (ITS2) region of rDNA, and the cytochrome c oxidase subunit 1 (cox1) region of mtDNA was amplified and sequenced. Stephanofilaria sp. specific polymerase chain reaction (PCR) and qPCR assays (SYBR Green® and TaqMan™) were developed and optimised from the novel ITS2 sequence obtained. The specificity of each assay was confirmed by testing against nematode species Onchocerca gibsoni and Dirofilaria immitis, as well as host (bovine) and BF DNA. Results: Scanning electron microscopy of the anterior and posterior ends of isolated nematodes confirmed Stephanofilaria sp. A phylogenetic analysis of the cox1 sequence demonstrated that this species is most closely related to Thelazia callipaeda, a parasitic nematode that is a common cause of thelaziasis (or eyeworm infestation) in humans, dogs, and cats. Both conventional and qPCR assays specifically amplified DNA from Stephanofilaria sp. Conventional PCR, TaqMan™, and SYBR Green® assays were shown to detect 1 ng, 1 pg, and 100 fg of Stephanofilaria DNA, respectively. Both qPCR assays detected DNA from single Stephanofilaria microfilaria. Conclusion: Molecular diagnostic assays developed in this study showed high specificity and sensitivity for Stephanofilaria sp. DNA. The availability of an accurate and sensitive PCR assay for Stephanofilaria will assist in determining its role in the pathogenesis of cattle skin lesions, as well as in understanding its epidemiological dynamics. This assay may also have application for use in epidemiological studies with other species of Stephanofilaria, most particularly closely related S. stilesi, but this will require confirmation

Efficacy, safety, and dose of Pafuramidine, a new oral drug for treatment of first stage sleeping sickness, in a phase 2a clinical study and phase 2b randomized clinical studies

Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.; The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.; Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3

Pancreatic Fistula Following Pancreaticoduodenectomy: Clinical Predictors and Patient Outcomes

Pancreatic fistula continues to be a common complication following PD. This study seeks to identify clinical factors which may predict pancreatic fistula (PF) and evaluate the effect of PF on outcomes following pancreaticoduodenectomy (PD). We performed a retrospective analysis of a clinical database at an academic tertiary care hospital with a high volume of pancreatic surgery. Five hundred ten consecutive patients underwent PD, and PF occurred in 46 patients (9%). Perioperative mortality of patients with PF was 0%. Forty-five of 46 PF (98%) closed without reoperation with a mean time to closure of 34 days. Patients who developed PF showed a higher incidence of wound infection, intra-abdominal abscess, need for reoperation, and hospital length of stay. Multivariate analysis demonstrated an invaginated pancreatic anastomosis and closed suction intraperitoneal drainage were associated with PF whereas a diagnosis of chronic pancreatitis and endoscopic stenting conferred protection. Development of PF following PD in this series was predicted by gender, preoperative stenting, pancreatic anastomotic technique, and pancreas pathology. Outcomes in patients with PF are remarkable for a higher rate of septic complications, longer hospital stays, but in this study, no increased mortality

Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis

Nanostructured, Alkaline Titanate‐Converted, and Heat‐Treated Ti6Al4V Microspheres via Wet‐Chemical Alkaline Modification and their ORR Electrocatalytic Response

This study describes the chemical conversion and heat treatment of Ti6Al4V microspheres (Ti6_MS), and the resulting effects on their electrocatalytic properties. The wet‐chemical conversion (5.0 m NaOH, 60 °C, 24 h; Sample label: Ti6_TC) converts the top surface of the Ti6_MS powder into an ≈820 nm thick sodium titanate surface. Heat‐treatment (Ti6_TC_HT) at 450 °C increases the stability of the surface, through partial titanate crystallization, while mitigating excess rutile formation. All samples are analyzed chemically (XPS, EDX, Raman, EELS), structurally (XRD and TEM), and morphologically (SEM, TEM), demonstrating the characteristic formation of sodium titanate dendritic structures, with minimal chemical, structural, and morphological differences due to the 450 °C heat‐treatment. The effect of the preparation methodology on oxygen reduction reaction (ORR) electrocatalytic performance is also tested. The introduction of the sodium titanate layer changes the mechanism of the ORR, from a mixed 4 electron/2 electron pathway to a predominantly 2‐electron pathway. By maintaining the microspherical nature of the material while also tuning the surface of the material toward different reaction mechanisms, a design strategy for new electrocatalyst materials is explored

Nanostructured, Alkaline Titanate‐Converted, and Heat‐Treated Ti6Al4V Microspheres via Wet‐Chemical Alkaline Modification and their ORR Electrocatalytic Response

This study describes the chemical conversion and heat treatment of Ti6Al4V microspheres (Ti6_MS), and the resulting effects on their electrocatalytic properties. The wet-chemical conversion (5.0m NaOH, 60°C, 24h; Sample label: Ti6_TC) converts the top surface of the Ti6_MS powder into an ≈820nm thick sodium titanate surface. Heat-treatment (Ti6_TC_HT) at 450°C increases the stability of the surface, through partial titanate crystallization, while mitigating excess rutile formation. All samples are analyzed chemically (XPS, EDX, Raman, EELS), structurally (XRD and TEM), and morphologically (SEM, TEM), demonstrating the characteristic formation of sodium titanate dendritic structures, with minimal chemical, structural, and morphological differences due to the 450°C heat-treatment. The effect of the preparation methodology on oxygen reduction reaction (ORR) electrocatalytic performance is also tested. The introduction of the sodium titanate layer changes the mechanism of the ORR, from a mixed 4 electron/2 electron pathway to a predominantly 2-electron pathway. By maintaining the microspherical nature of the material while also tuning the surface of the material toward different reaction mechanisms, a design strategy for new electrocatalyst materials is explored

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy