Signed zeros of Gaussian vector fields-density, correlation functions and curvature

We calculate correlation functions of the (signed) density of zeros of Gaussian distributed vector fields. We are able to express correlation functions of arbitrary order through the curvature tensor of a certain abstract Riemann-Cartan or Riemannian manifold. As an application, we discuss one- and two-point functions. The zeros of a two-dimensional Gaussian vector field model the distribution of topological defects in the high-temperature phase of two-dimensional systems with orientational degrees of freedom, such as superfluid films, thin superconductors and liquid crystals.Comment: 14 pages, 1 figure, uses iopart.cls, improved presentation, to appear in J. Phys.

Usefulness of the Twinkling Artifact in Identifying Implanted Mesh After Inguinal Hernia Repair

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135644/1/jum20113081059.pd

A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes

Securin inhibits the protease separase and must be removed before anaphase to ensure timely chromosome segregation. Here, the authors define a mechanism of securin destruction in prometaphase I in mouse oocytes and demonstrate its importance for successful meiotic progression

Inhaled PGE1 in neonates with hypoxemic respiratory failure: two pilot feasibility randomized clinical trials.

BackgroundInhaled nitric oxide (INO), a selective pulmonary vasodilator, has revolutionized the treatment of neonatal hypoxemic respiratory failure (NHRF). However, there is lack of sustained improvement in 30 to 46% of infants. Aerosolized prostaglandins I2 (PGI2) and E1 (PGE1) have been reported to be effective selective pulmonary vasodilators. The objective of this study was to evaluate the feasibility of a randomized controlled trial (RCT) of inhaled PGE1 (IPGE1) in NHRF.MethodsTwo pilot multicenter phase II RCTs are included in this report. In the first pilot, late preterm and term neonates with NHRF, who had an oxygenation index (OI) of ≥15 and <25 on two arterial blood gases and had not previously received INO, were randomly assigned to receive two doses of IPGE1 (300 and 150 ng/kg/min) or placebo. The primary outcome was the enrollment of 50 infants in six to nine months at 10 sites. The first pilot was halted after four months for failure to enroll a single infant. The most common cause for non-enrollment was prior initiation of INO. In a re-designed second pilot, co-administration of IPGE1 and INO was permitted. Infants with suboptimal response to INO received either aerosolized saline or IPGE1 at a low (150 ng/kg/min) or high dose (300 ng/kg/min) for a maximum duration of 72 hours. The primary outcome was the recruitment of an adequate number of patients (n = 50) in a nine-month-period, with fewer than 20% protocol violations.ResultsNo infants were enrolled in the first pilot. Seven patients were enrolled in the second pilot; three in the control, two in the low-dose IPGE1, and two in the high-dose IPGE1 groups. The study was halted for recruitment futility after approximately six months as enrollment targets were not met. No serious adverse events, one minor protocol deviation and one pharmacy protocol violation were reported.ConclusionsThese two pilot RCTs failed to recruit adequate eligible newborns with NHRF. Complex management RCTs of novel therapies for persistent pulmonary hypertension of the newborn (PPHN) may require novel study designs and a longer period of time from study approval to commencement of enrollment.Trial registrationCLINICALTRIALS.GOV: Pilot one: NCT number: 00598429 registered on 10 January 2008. Last updated: 3 February 2011. Pilot two: NCT number: 01467076 17 October 2011. Last updated: 13 February 2013

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Discovery of the Largest Orbweaving Spider Species: The Evolution of Gigantism in Nephila

More than 41,000 spider species are known with about 400-500 added each year, but for some well-known groups, such as the giant golden orbweavers, Nephila, the last valid described species dates from the 19(th) century. Nephila are renowned for being the largest web-spinning spiders, making the largest orb webs, and are model organisms for the study of extreme sexual size dimorphism (SSD) and sexual biology. Here, we report on the discovery of a new, giant Nephila species from Africa and Madagascar, and review size evolution and SSD in Nephilidae.We formally describe N. komaci sp. nov., the largest web spinning species known, and place the species in phylogenetic context to reconstruct the evolution of mean size (via squared change parsimony). We then test female and male mean size correlation using phylogenetically independent contrasts, and simulate nephilid body size evolution using Monte Carlo statistics.Nephila females increased in size almost monotonically to establish a mostly African clade of true giants. In contrast, Nephila male size is effectively decoupled and hovers around values roughly one fifth of female size. Although N. komaci females are the largest Nephila yet discovered, the males are also large and thus their SSD is not exceptional

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Development and validation of a Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN‐HN) in a scarce resource setting: Response to the COVID‐19 pandemic

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163412/2/cncr33114_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163412/1/cncr33114.pd

Gabapentin for the hemodynamic response to intubation: systematic review and meta-analysis

Purpose Endotracheal intubation is the gold standard for securing the airway before surgery. Nevertheless, this procedure can produce an activation of the sympathetic nervous system and result in a hemodynamic response which, in high-risk patients, may lead to cardiovascular instability and myocardial ischemia. The aim of this review was to evaluate whether gabapentin can attenuate this response and whether such an attenuation could translate into reduced myocardial ischemia and mortality. Source We searched MEDLINE®, EMBASE™, CINAHL, AMED, and unpublished clinical trial databases for randomized-controlled trials that compared gabapentin with control, fentanyl, clonidine, or beta blockers for attenuating the hemodynamic response to intubation. Primary outcomes were mortality, myocardial infarction, and myocardial ischemia. Secondary outcomes were hemodynamic changes following intubation. Principal findings We included 29 randomized trials with only two studies at low risk of bias. No data were provided for the primary outcomes and no studies included high-risk patients. The use of gabapentin resulted in attenuation in the rise in mean arterial blood pressure [mean difference (MD), −12 mmHg; 95% confidence interval (CI), −17 to −8] and heart rate (MD, −8 beats·min−1; 95% CI, −11 to −5) one minute after intubation. Gabapentin also reduced the risk of hypertension or tachycardia requiring treatment (risk ratio, 0.15; 95% CI, 0.05 to 0.48). Data were limited on adverse hemodynamic events such as bradycardia and hypotension. Conclusion It remains unknown whether gabapentin improves clinically relevant outcomes such as death and myocardial infarction since studies failed to report on these. Nevertheless, gabapentin attenuated increases in heart rate and blood pressure following intubation when compared with the control group. Even so, the studies included in this review were at potential risk of bias. Moreover, they did not include high-risk patients or report adverse hemodynamic outcomes. Future studies are required to address these limitations