Atypical hemolytic uremic syndrome in the postpartum period: a case series

Background: Atypical hemolytic uremic syndrome (aHUS) may present in either the antepartum or postpartum period and is often indistinguishable from other pregnancy-associated diseases. Timely recognition and appropriate treatment can greatly reduce maternal morbidity and mortality. Cases: This case series describes two cases of aHUS in the post-partum period, the difficulty in distinguishing the diagnosis, and the implementation of appropriate treatment with eculizumab, a terminal complement inhibitor. Conclusion: As a terminal complement inhibitor, eculizumab, has been shown to significantly improve clinical and long term renal outcomes, early diagnosis of aHUS is increasingly important. These two cases of aHUS demonstrate the path of accurate diagnosis and timely initiation of therapy to maximize the possibility of patient recovery

The Diverse Infrared Properties of a Complete Sample of Star-Forming Dwarf Galaxies

We present mid-infrared Spitzer Space Telescope observations of a complete sample of star-forming dwarf galaxies selected from the KPNO International Spectroscopic Survey. The galaxies span a wide range in mid-infrared properties. Contrary to expectations, some of the galaxies emit strongly at 8 micron indicating the presence of hot dust and/or PAHs. The ratio of this mid-infrared dust emission to the stellar emission is compared with the galaxies' luminosity, star-formation rate, metallicity, and optical reddening. We find that the strength of the 8.0 micron dust emission to the stellar emission ratio is more strongly correlated with the star-formation rate than it is with the metallicity or the optical reddening in these systems. Nonetheless, there is a correlation between the 8.0 micron luminosity and metallicity. The slope of this luminosity-metallicity correlation is shallower than corresponding ones in the B-band and 3.6 micron. The precise nature of the 8.0 micron emission seen in these galaxies (i.e., PAH versus hot dust or some combination of the two) will require future study, including deep mid-IR spectroscopy.Comment: 14 pages, accepted Ap

Rescuing high-scale leptogenesis using primordial black holes

We explore the interplay between light primordial black holes (PBH) and high-scale baryogenesis, with a particular emphasis on leptogenesis. We first review a generic baryogenesis scenario where a heavy particle, X, with mass, MX, produced solely from PBH evaporation decays to generate a baryon asymmetry. We show that the viable parameter space is bounded from above by MX≲1017GeV and increases with decreasing MX. We demonstrate that regions of the leptogenesis parameter space, where the lightest right-handed neutrino (RHN) mass MN1≳1015GeV and neutrino mass scale mν≳0.1eV, excluded in standard cosmology due to ΔL=2 washout processes, become viable with the assistance of light PBHs. This scenario of PBH-assisted leptogenesis occurs because the PBHs radiate RHNs via Hawking evaporation late in the Universe’s evolution when the temperature of the thermal plasma is low relative to the RHN mass. Subsequently, these RHNs can decay and produce a lepton asymmetry while the washout processes are suppressed

Mediation analysis for a survival outcome with time-varying exposures, mediators, and confounders

We propose an approach to conduct mediation analysis for survival data with time-varying exposures, mediators, and confounders. We identify certain interventional direct and indirect effects through a survival mediational g-formula and describe the required assumptions. We also provide a feasible parametric approach along with an algorithm and software to estimate these effects. We apply this method to analyze the Framingham Heart Study data to investigate the causal mechanism of smoking on mortality through coronary artery disease. The risk ratio of smoking 30 cigarettes per day for ten years compared with no smoking on mortality is 2.34 (95 % CI = (1.44, 3.70)). Of the overall effect, 7.91% (95% CI: = 1.36%, 19.32%) is mediated by coronary artery disease. The survival mediational g-formula constitutes a powerful tool for conducting mediation analysis with longitudinal data

Principles of Anti-infective Dosing in Pregnancy

AbstractPurposeAnti-infectives are among the most commonly prescribed medications in pregnancy. However, detailed information on the pharmacokinetics and pharmacodynamics of these medications in pregnancy is limited, leading to uncertainty among clinicians regarding the tolerability and efficacy of treatments. The purposes of this review were to highlight key physiologic changes during pregnancy that influence drug behavior, and to discuss areas of active research related to anti-infective drugs in pregnancy.MethodsA review of literature in PubMed was performed for topics related to physiologic changes of pregnancy, postcesarean surgical site infections, vaccines in pregnancy, and intrauterine infections. The literature was reviewed and pertinent sources were utilized for this article.FindingsPhysiologic changes during pregnancy may impact drug disposition and efficacy. Cefazolin regimens are the current prophylactic treatment of choice for postcesarean surgical site infections. Vaccines are provided in pregnancy for both maternal and neonatal benefit. Broad-spectrum antibiotics continue to be used as first-line therapy for intrauterine infections.ImplicationsContinued efforts to broaden the knowledge base on anti-infective drug behavior in pregnancy will result in increased therapeutic options for this population

MLGuard: Defend Your Machine Learning Model!

Machine Learning (ML) is used in critical highly regulated and high-stakes fields such as finance, medicine, and transportation. The correctness of these ML applications is important for human safety and economic benefit. Progress has been made on improving ML testing and monitoring of ML. However, these approaches do not provide i) pre/post conditions to handle uncertainty, ii) defining corrective actions based on probabilistic outcomes, or iii) continual verification during system operation. In this paper, we propose MLGuard, a new approach to specify contracts for ML applications. Our approach consists of a) an ML contract specification defining pre/post conditions, invariants, and altering behaviours, b) generated validation models to determine the probability of contract violation, and c) an ML wrapper generator to enforce the contract and respond to violations. Our work is intended to provide the overarching framework required for building ML applications and monitoring their safety.Comment: Accepted in SE4SafeML'2

Minority stress, resilience, and health in Italian and Taiwanese LGB+ people : a cross-cultural comparison

The present study, using a moderated mediational model, explored levels of distal/proximal stressors, rumination, resilience, and health in a group of Italian and Taiwanese LGB+ people. The study also examined the role of internalized sexual stigma (ISS) and rumination as mediators between discrimination and health, and resilience as a moderator of the relationship between discrimination and ISS, rumination, and health, respectively. An online survey was administered to 508 LGB+ participants (270 Italian and 238 Taiwanese) whose age ranged from 18 to 70 years (M = 37.93, SD = 13.53). The moderated mediation model was tested through a series of path analyses stratified by group nationality. Italian participants reported higher discrimination and resilience, but lower ISS, rumination, and health problems compared to their Taiwanese counterparts. The only common path between groups was the direct effect of discrimination on health problems. The mediating role of ISS and rumination in the relationship between discrimination and health, as well as the moderating role of resilience, were partly significant only for the Italian group. Conclusions: The findings suggest that mediators and moderators used to evaluate the effects of minority stress on health may differ between groups; further culturally sensitive research in the field of LGB+ health is needed

Autonomic Nerve Activity and Blood Pressure in Ambulatory Dogs

Background The relationship between cardiac autonomic nerve activity and blood pressure (BP) changes in ambulatory dogs is unclear. Objective To test the hypotheses that simultaneous termination of stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA) predisposes to spontaneous orthostatic hypotension and that specific β2 adrenoceptor blockade prevents the hypotensive episodes. Methods We used a radiotransmitter to record SGNA, VNA and blood pressure (BP) in 8 ambulatory dogs. Video imaging was used to document postural changes. Results Out of these 8 dogs, 5 showed simultaneous sympathovagal discharges in which the minute by minute integrated SGNA correlated with integrated VNA in a linear pattern (“Group 1”). In these dogs abrupt termination of simultaneous SGNA-VNA at the time of postural changes (as documented by video imaging) was followed by abrupt (>20 mmHg over 4 beats) drops in BP. Dogs without simultaneous on/off firing (“Group 2”) did not have drastic drops in pressure. ICI 118,551 (ICI, a specific β2-blocker) infused at 3.1 µg/kg/hr for 7 days significantly increased BP from 126 (95% confidence interval, CI: 118 to 133) mmHg to 133 (95% CI 125 to141) mmHg (p=0.0001). The duration of hypotension (mean systolic BP < 100 mmHg) during baseline accounted for 7.1% of the recording. The percentage was reduced by ICI to 1.3% (p = 0.01). Conclusions Abrupt simultaneous termination of SGNA-VNA was observed at the time of orthostatic hypotension in ambulatory dogs. Selective β2 adrenoceptor blockade increased BP and reduced the duration of hypotension in this model

The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer

Ovarian cancer is the 5th leading cause of cancer death among women in the United States. The mevalonate pathway is thought to be a potential oncogenic pathway in the pathogenesis of ovarian cancer. Simvastatin, a 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) inhibitor, is a widely used drug for inhibiting the synthesis of cholesterol and may also have anti-tumorigenic activity. Our goal was to evaluate the effects of simvastatin on ovarian cancer cell lines, primary cultures of ovarian cancer cells and in an orthotopic ovarian cancer mouse model. Simvastatin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, and caused cellular stress via reduction in the enzymatic activity of HMGCR and inhibition of the MAPK and mTOR pathways in ovarian cancer cells. Furthermore, simvastatin induced DNA damage and reduced cell adhesion and invasion. Simvastatin also exerted anti-proliferative effects on primary cell cultures of ovarian cancer. Treatment with simvastatin in an orthotopic mouse model reduced ovarian tumor growth, coincident with decreased Ki-67, HMGCR, phosphorylated-Akt and phosphorylated-p42/44 protein expression. Our findings demonstrate that simvastatin may have therapeutic benefit for ovarian cancer treatment and be worthy of further exploration in clinical trials

Rats can predict aversiveness of Active Pharmaceutical Ingredients.

Taste is crucial for patient acceptability and compliance with prescribed medicines, in particular with pediatric patients. Evaluating the taste of new active pharmaceutical ingredients (APIs) is therefore essential to put in place adequate taste-masking techniques, if needed, which will lead to acceptable palatable formulations. Thus, there is an urgent need to develop and optimize taste assessment methods that could be used at different stages of the drug development process. The aim of this study was to investigate the suitability of the rat brief-access taste aversion (BATA) model as a screening tool for assessment of APIs aversiveness that could predict human taste responses. Presently, the taste intensity of nine marketed APIs known to have different levels of bitter intensity (quinine hydrochloride dihydrate, 6-n-propylthiouracil, sildenafil citrate, diclofenac sodium, ranitidine hydrochloride, caffeine citrate, isoniazid, telbivudine and paracetamol) was investigated at different overlapping concentrations with two in vivo taste assessment methods: the rat BATA model and human taste panels with the intention of determining the drugs' concentrations to produce half of the maximal rating. Overall there was a strong correlation (R2?=?0.896) between rats IC50 and humans EC50 values. This correlation verifies the BATA model as a rapid and reliable tool for quantitative assessment of API aversiveness. A comparable ranking order was obtained mainly for high and medium aversive compounds, whereas it was less aligned for weakly aversive compounds. It was nonetheless possible to propose a classification of poor taste intensity determined in rats that would predict human taste tolerability