A forward modeling approach to analyzing galaxy clustering with SimBIG.

We present cosmological constraints from a simulation-based inference (SBI) analysis of galaxy clustering from the SimBIG forward modeling framework. SimBIG leverages the predictive power of high-fidelity simulations and provides an inference framework that can extract cosmological information on small nonlinear scales. In this work, we apply SimBIG to the Baryon Oscillation Spectroscopic Survey (BOSS) CMASS galaxy sample and analyze the power spectrum, [Formula: see text], to [Formula: see text]. We construct 20,000 simulated galaxy samples using our forward model, which is based on 2,000 high-resolution Quijote[Formula: see text]-body simulations and includes detailed survey realism for a more complete treatment of observational systematics. We then conduct SBI by training normalizing flows using the simulated samples and infer the posterior distribution of [Formula: see text]CDM cosmological parameters: [Formula: see text]. We derive significant constraints on [Formula: see text] and [Formula: see text], which are consistent with previous works. Our constraint on [Formula: see text] is 27% more precise than standard [Formula: see text] analyses because we exploit additional cosmological information on nonlinear scales beyond the limit of current analytic models, [Formula: see text]. This improvement is equivalent to the statistical gain expected from a standard [Formula: see text] analysis of galaxy sample [Formula: see text]60% larger than CMASS. While we focus on [Formula: see text] in this work for validation and comparison to the literature, SimBIG provides a framework for analyzing galaxy clustering using any summary statistic. We expect further improvements on cosmological constraints from subsequent SimBIG analyses of summary statistics beyond [Formula: see text].

Neurotoxicity of acrylamide in adult zebrafish following short-term and long-term exposure: evaluation of behavior alterations, oxidative stress markers, expression of antioxidant genes, and histological examination of the brain and eyes.

In the present work, 224 adult female zebrafish (56 fish in each group) were randomly divided into four groups (two control groups and two toxicity groups) as per duration of exposure (7 and 21 days). All fish of the two toxicity groups were exposed to 0.610 mM acrylamide (ACR) concentration for 7 and 21 days. The effects of ACR exposure on behavior, oxidative stress biomarkers, molecular expression of antioxidant genes (sod, cat, and nrf2), and histopathological examination of the brain and eye were examined. Our result shows that ACR exposure for 7 days produced an anxiety-like behavior in zebrafish. Short-term exposure of ACR resulted in alterations of oxidative stress markers (SOD and CAT activity, and the level of GSH and MDA) in the brain and eye of zebrafish. However, the antioxidant defense system of adult female zebrafish could be able to counteract the free radicals generated in long-term ACR exposure as indicated by non-significant difference in oxidative insult following short-term and long-term exposure. ACR exposure downregulated the mRNA expression of the sod, cat, and nrf2 (nuclear factor erythroid 2-related factor 2) genes in the brain and eye without significant difference between the two toxicity groups. Mild histological changes in the dorsal telencephalic area, tectum opticum, medulla, and hypothalamus area of the brain of zebrafish have been observed following short-term and long-term ACR exposure. In the eye, marked histological changes in the retinal pigmented epithelium layer (RPE), structural changes of the photoreceptor layer (PRL) with disorganized layer of rods and cones, and reduction of the relative thickness of the RPE, PRL, outer nuclear layer (ONL), and inner nuclear layer (INL) have been noted following ACR exposure for 21 days as compared to 7 days. ACR produced neurobehavioral aberrations and oxidative stress within 7 days of exposure, while various histological changes in the brain and eyes have been observed following long-term exposure (21 days) to ACR.

Long-term exposure of the binary mixture of cadmium and mercury damages the developed ovary of adult zebrafish.

The toxicity of the binary mixture of cadmium (Cd) and mercury (Hg) on the ovary of adult zebrafish was evaluated in the present study. Adult female zebrafish were exposed to cadmium chloride (1 mg/L), mercury chloride (30 µg/L), and a binary mixture of both metals for 21 days. The toxic effects of both metals on the ovary were investigated by evaluating the oxidative stress markers and related gene expression in ovarian tissue along with the histopathological examination. The significantly decreased level of GSH and increased level of MDA in ovarian tissue of adult female zebrafish exposed to Cd + Hg indicated that the exposure of binary mixture of Cd and Hg caused more lipid peroxidation in the ovary. The significant changes in expression of mRNA of catalase (CAT) and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) were not observed in the ovary of zebrafish exposed to the binary mixture. Upon histological evaluation, a decreased number of full-growth (mature) oocytes along with degenerative changes due to Cd exposure were noticed, while ovary of zebrafish of the Hg-exposed group had shown a decreased number of pre-and early vitellogenic oocytes along with atretic previtellogenic oocytes compared to the control group. The ovary of zebrafish of the Cd + Hg-exposed group had shown a decreased number of previtellogenic oocytes with marked pathological changes in mature oocytes. Present findings elucidate that simultaneous long-term exposure of Cd and Hg compared to individual exposure significantly damaged the various stages of oocytes of an ovary of adult zebrafish.

Estimating COVID-19 mortality in Italy early in the COVID-19 pandemic.

Estimating rates of COVID-19 infection and associated mortality is challenging due to uncertainties in case ascertainment. We perform a counterfactual time series analysis on overall mortality data from towns in Italy, comparing the population mortality in 2020 with previous years, to estimate mortality from COVID-19. We find that the number of COVID-19 deaths in Italy in 2020 until September 9 was 59,000-62,000, compared to the official number of 36,000. The proportion of the population that died was 0.29% in the most affected region, Lombardia, and 0.57% in the most affected province, Bergamo. Combining reported test positive rates from Italy with estimates of infection fatality rates from the Diamond Princess cruise ship, we estimate the infection rate as 29% (95% confidence interval 15-52%) in Lombardy, and 72% (95% confidence interval 36-100%) in Bergamo.

A Statewide Multi-Institutional Study of Asymptomatic Pretreatment Testing of Radiation Therapy Patients for SARS-CoV-2 in a High-Incidence Region of the United States.

PURPOSE: Our purpose was to establish the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in asymptomatic patients scheduled to receive radiation therapy and its effect on management decisions. METHODS AND MATERIALS: Between April 2020 and July 2020, patients without influenza-like illness symptoms at four radiation oncology departments (two academic university hospitals and two community hospitals) underwent polymerase chain reaction testing for SARS-CoV-2 before the initiation of treatment. Patients were tested either before radiation therapy simulation or after simulation but before treatment initiation. Patients tested for indications of influenza-like illness symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity. RESULTS: Over a 3-month period, a total of 385 tests were performed in 336 asymptomatic patients either before simulation (n = 75), post-simulation, before treatment (n = 230), or on-treatment (n = 49). A total of five patients tested positive for SARS-CoV-2, for a pretreatment prevalence of 1.3% (2.6% in north/central New Jersey and 0.4% in southern New Jersey/southeast Pennsylvania). The median age of positive patients was 58 years (range, 38-78 years). All positive patients were white and were relatively equally distributed with regard to sex (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was five. All five patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of retesting for four patients, and one patient was treated without delay but with additional infectious-disease precautions. CONCLUSIONS: Broad-based pretreatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.

Combining radiation therapy and immunotherapy for lung cancers: a narrative review.

Lung cancer remains the leading cause of cancer morbidity and mortality worldwide among both men and women. While surgical resection remains the standard of care for early stage NSCLC, chemoradiation has been a mainstay of treatment for locally advanced non-small-cell lung cancer (LA-NSCLC) patients for decades. Consolidation immunotherapy has improved survival in this subset of patients after conventional chemoradiation, and has emerged as the new standard. The synergy between immunotherapy and radiation, as well as ongoing research on the effects of radiation on the immune system, allows for the exploration of new avenues in the treatment of LA-NSCLC. In addition to the use of durvalumab as consolidative systemic therapy after concurrent chemoradiotherapy for Stage III NSCLC, other combination regimens have been shown to be effective in various disease stages in preclinical and clinical studies. These regimens include CTLA-4 and PD/PDL-1 checkpoint inhibitors combined with radiation treatment. While these combined regimens have demonstrated efficacy, they are not without toxicity, and require additional evaluation when combined with radiation. In this review, we have summarized the immunostimulatory and immunosuppressive effects of radiation therapy. We also evaluate the current evidence and ongoing research supporting the combination of radiotherapy and immunotherapy across early to LA-NSCLC.

Effect of piperine and quercetin alone or in combination with marbofloxacin on CYP3A37 and MDR1 mRNA expression levels in broiler chickens.

After oral route of administration, drug absorption is unpredictable and is governed by various factors such as multi drug resistance-1 (MDR1) an efflux transporter and drug metabolizing enzymes (like CYP3A4, CYP3A37, CYP2D6) at intestine and liver. Naturally available phyto chemicals like piperine and quercetin as well as some floroquinolones are known to inhibit MDR1 and CYP3A37 activity and increases bioavailability of co-administered drugs. This study was carried out to investigate the effect of piperine and quercetin alone or in combination with marbofloxacin on CYP3A37 and MDR1 mRNA expression levels in liver and intestine of broiler chicken. After oral administration of piperine and quercetin for 3 consecutive days followed by with or without oral administration of marbofloxacin for 5 days, CYP3A37 and MDR1 mRNA expression levels were determined using quantitative real-time PCR. Total of 36 broiler chickens in seven individual groups were treated with different regimen and the mRNA expression levels at duodenum and liver were analyzed with apt statistical tools. After piperine and quercetin combined treatment with marbofloxacin, CYP3A37 mRNA expression levels were significantly down regulated by 20.57 (p = .034) and 25.95 (p = .003) folds; and MDR1 mRNA expression levels were also significantly down regulated by 11.33 (p = .012) and 33.59 (p = .006) folds in liver and duodenum, respectively. Down regulation of CYP3A37 and MDR1 mRNA in liver and duodenum indicate the combined pretreatment of piperine and quercetin may be useful for improving the pharmacokinetics of orally administered drugs which are substrates for CYP3A37 and MDR1.

Radiotherapy for inoperable Merkel cell carcinoma: a systematic review and pooled analysis.

BACKGROUND: Cumulative data on radiation monotherapy for Merkel cell carcinoma (MCC) is lacking. OBJECTIVE: We sought to synthesize all available data on treatment outcomes for radiation monotherapy for inoperable stage I-III MCC. METHODS: We performed a systematic review of the current literature. Articles published in English in the PubMed database up to July 29, 2016, were evaluated. RESULTS: Eight case reports, 4 case series, and 6 retrospective studies, yielding 68 patients, were included in our analysis. Of the 24 stage I/II patients treated with local irradiation, 6 (25%) relapsed and 1 (4%) died from MCC. Of the 24 stage I/II patients treated with local and regional nodal irradiation, 5 (21%) relapsed and 2 (8%) died from MCC. Of the 20 stage III patients treated with local and regional nodal irradiation, 12 (60%) relapsed and 7 (35%) died from MCC. CONCLUSIONS: Radiation monotherapy appears to be a reasonable treatment modality for patients with inoperable stage I-III MCC. Further investigation with prospective studies is needed to draw definitive conclusions.

Low-fidelity simulation to enhance understanding of infection control among undergraduate medical students.

BACKGROUND: Developing economies are stressing institutional care for better health outcomes but its advantages are dampened by healthcare-associated infections (HAIs). Besides other undesired complications, the economic cost of HAIs is enormous. Developing countries have higher HAI rates compared with Europe or the USA. The knowledge and practice of infection control is poor among medical students. Based on introspection of 'Infection Control Module' for undergraduates introduced in 2012, we tested emotional sensitization using low-fidelity techniques to enhance its effectiveness. METHODS: All medical undergraduate students in their second year (n=102) were randomly divided into three groups using balanced randomization (two test and one control). Test groups were made to realize the emotional, social and financial consequences of HAI on patients and their families through low-fidelity simulation in the form of case discussions and video demonstrations. Pre- and postintervention empathy scores were calculated using Toronto empathy questionnaire (TEQ) for all the 102 students. Postintervention, all students were subjected to an infection control module and knowledge test. Perceptions of the intervention groups were recorded. Descriptive statistics and ANOVA were applied for data analysis. RESULTS: Of the 102 students, 93 (91.1%) participated in the study. There was no significant difference in the pre-test TEQ score (p=0.87) but there was a significant difference in the post-test TEQ (p = 0.026) and knowledge test score (p = 0.016) among the groups. Both the simulation exercises were well appreciated by the students. CONCLUSION: Emotional sensitization using low-fidelity simulation served as a catalyst in understanding infection control among medical undergraduate students.

Prenatal screening of cytogenetic anomalies - a Western Indian experience.

BACKGROUND: Children born with congenital anomalies present a very high rate of perinatal death and neonatal mortality. Cytogenetic analysis is a convincing investigation along with clinical suspicion and biochemical screening tests. The current study was designed to characterize the prevalence and types of chromosomal abnormalities in high risk prenatal samples using different cytogenetic techniques. METHODS: This study was conducted on a total of 1,728 prenatal samples (1,324 amniotic fluids, 366 chorionic villi and 38 cord blood samples) from 1994 to 2014 at Institute of Human Genetics, Ahmedabad, India. Conventional karyotyping was conducted with GTG-banding. Molecular approaches were used (fluorescence in situ hybridization = FISH and/ or array-comparative genomic hybridization = aCGH) when indicated to detect karyotypic abnormalities. RESULTS: Abnormal karyotypes were detected in 125/1,728 (7.2%) cases. Trisomy 21 was the most common abnormality detected in 46 (2.7%) followed by trisomy 18 in 11 (0.6%) and trisomy 13 in 2 (0.1%) samples. Besides, structural abnormalities such as reciprocal and Robertsonian translocation were detected in 20 [1.2%] cases. Turner syndrome was diagnosed in seven (0.4%) cases; in six (0.34%) cases there was an inversion in the Y-chromosome. Heteromorphic variants were diagnosed in 22 (1.3%) cases. Finally, small supernumerary marker chromosomes (sSMC) were found in six (0.34%) cases. CONCLUSION: Conventional GTG-banding along with molecular cytogenetic techniques is useful in detecting genomic alterations and rearrangements. Comprehensive characterization of chromosomal rearrangements like sSMC has the potential to save potentially healthy fetuses from being terminated.

A comprehensive review on pharmacotherapeutics of herbal bioenhancers.

In India, Ayurveda has made a major contribution to the drug discovery process with new means of identifying active compounds. Recent advancement in bioavailability enhancement of drugs by compounds of herbal origin has produced a revolutionary shift in the way of therapeutics. Thus, bibliographic investigation was carried out by analyzing classical text books and peer-reviewed papers, consulting worldwide-accepted scientific databases from last 30 years. Herbal bioenhancers have been shown to enhance bioavailability and bioefficacy of different classes of drugs, such as antibiotics, antituberculosis, antiviral, antifungal, and anticancerous drugs at low doses. They have also improved oral absorption of nutraceuticals like vitamins, minerals, amino acids, and certain herbal compounds. Their mechanism of action is mainly through absorption process, drug metabolism, and action on drug target. This paper clearly indicates that scientific researchers and pharmaceutical industries have to give emphasis on experimental studies to find out novel active principles from such a vast array of unexploited plants having a role as a bioavailability and bioefficacy enhancer. Also, the mechanisms of action by which bioenhancer compounds exert bioenhancing effects remain to be explored.

Delayed-onset heparin-induced thrombocytopenia type-2 during fondiparinux (Arixtra) therapy.

Heparin is the most commonly used anticoagulant drug for prevention and treatment of thromboembolic diseases. Heparin-induced thrombocytopenia (HIT) is a well-known and potentially fatal side-effect of heparin therapy. HIT type 1 (HIT-1) is transient and relatively common; it usually develops within 1-7 days of initial heparin exposure. Type 2 HIT (HIT-2) is more severe and is associated with thrombocytopenia and thrombosis. HIT-2 usually develops 5 or more days after initial heparin exposure. It is an immune-mediated disorder that is presumably caused by development of platelet activating antibody against platelet factor 4 (PF4)/heparin complex. Fondaparinux (Arixtra) is a fast-acting selective inhibitor of factor Xa believed to be non-reactive to HIT sera and therefore may be used as prophylaxis for thrombosis in patients with a history of HIT-1 or HIT-2. Development of HIT-2 in patients currently taking fondaparinux prophylaxis is rare. Here we present a fatal case of delayed-onset HIT-2 (1 year after heparin exposure) manifesting while on fondaparinux prophylaxis.