Optical detection of the structural properties of tumor tissue generated by xenografting of drug-sensitive and drug-resistant cancer cells using partial wave spectroscopy (PWS)

mesoscopic physics-based optical imaging technique, partial wave spectroscopy (PWS), has been used for the detection of cancer by probing nanoscale structural alterations in cells/tissue. The development of drug-resistant cancer cells/tissues during chemotherapy is a major challenge in cancer treatment. In this paper, using a mouse model and PWS, the structural properties of tumor tissue grown in 3D structures by xenografting drug-resistant and drug-sensitive human prostate cancer cells having 2D structures, are studied. The results show that the 3D xenografted tissues maintain a similar hierarchy of the degree of structural disorder properties as that of the 2D original drug-sensitive and drug-resistant cells

Speciated online PM1 from South Asian combustion sources-Part 1: Fuel-based emission factors and size distributions

Combustion of biomass, garbage, and fossil fuels in South Asia has led to poor air quality in the region and has uncertain climate forcing impacts. Online measurements of submicron aerosol (PM1) emissions were conducted as part of the Nepal Ambient Monitoring and Source Testing Experiment (NAMaSTE) to investigate and report emission factors (EFs) and vacuum aerodynamic diameter (dva) size distributions from prevalent but poorly characterized combustion sources. The online aerosol instrumentation included a qmini aerosol mass spectrometer (mAMS) and a dual-spot eight-channel aethalometer (AE33). The mAMS measured non-refractory PM1 mass, composition, and size. The AE33-measured black carbon (BC) mass and estimated light absorption at 370 nm due to organic aerosol or brown carbon. Complementary gas-phase measurements of carbon dioxide (CO2), carbon monoxide (CO), and methane (CH4) were collected using a Picarro Inc. cavity ring-down spectrometer (CRDS) to calculate fuel-based EFs using the carbon mass balance approach. The investigated emission sources include open garbage burning, diesel-powered irrigation pumps, idling motorcycles, traditional cookstoves fueled with dung and wood, agricultural residue fires, and coal-fired brick-making kilns, all of which were tested in the field. Open-garbage-burning emissions, which included mixed refuse and segregated plastics, were found to have some of the largest PM1 EFs (3.77-19.8 g k-1) and the highest variability of the investigated emission sources. Non-refractory organic aerosol (OA) size distributions measured by the mAMS from garbage-burning emissions were observed to have lognormal mode dva values ranging from 145 to 380 nm. Particle-phase hydrogen chloride (HCl) was observed from open garbage burning and was attributed to the burning of chlorinated plastics. Emissions from two diesel-powered irrigation pumps with different operational ages were tested during NAMaSTE. Organic aerosol and BC were the primary components of the emissions and the OA size distributions were centered at ∼ 80 nm dva. The older pump was observed to have significantly larger EFOA than the newer pump (5.18 g k-1 compared to 0.45 g k-1) and similar EFBC. Emissions from two distinct types of coal-fired brick-making kilns were investigated. The less advanced, intermittently fired clamp kiln was observed to have relatively large EFs of inorganic aerosol, including sulfate (0.48 g k-1) and ammonium (0.17 g k-1), compared to the other investigated emission sources. The clamp kiln was also observed to have the largest absorption Ångström exponent (AAE Combining double low line 4) and organic carbon (OC) to BC ratio (OC: BC Combining double low line 52). The continuously fired zigzag kiln was observed to have the largest fraction of sulfate emissions with an EFSO4 of 0.96 g k-1. Non-refractory aerosol size distributions for the brick kilns were centered at ∼ 400 nm dva. The biomass burning samples were all observed to have significant fractions of OA and non-refractory chloride; based on the size distribution results, the chloride was mostly externally mixed from the OA. The dung-fueled traditional cookstoves were observed to emit ammonium, suggesting that the chloride emissions were partially neutralized. In addition to reporting EFs and size distributions, aerosol optical properties and mass ratios of OC to BC were investigated to make comparisons with other NAMaSTE results (i.e., online photoacoustic extinctiometer (PAX) and off-line filter based) and the existing literature. This work provides critical field measurements of aerosol emissions from important yet under-characterized combustion sources common to South Asia and the developing world

Nepal Ambient Monitoring and Source Testing Experiment (NAMaSTE): Emissions of trace gases and light-absorbing carbon from wood and dung cooking fires, garbage and crop residue burning, brick kilns, and other sources

The Nepal Ambient Monitoring and Source Testing Experiment (NAMaSTE) campaign took place in and around the Kathmandu Valley and in the Indo-Gangetic Plain (IGP) of southern Nepal during April 2015. The source characterization phase targeted numerous important but undersampled (and often inefficient) combustion sources that are widespread in the developing world such as cooking with a variety of stoves and solid fuels, brick kilns, open burning of municipal solid waste (a.k.a. trash or garbage burning), crop residue burning, generators, irrigation pumps, and motorcycles. NAMaSTE produced the first, or rare, measurements of aerosol optical properties, aerosol mass, and detailed trace gas chemistry for the emissions from many of the sources. This paper reports the trace gas and aerosol measurements obtained by Fourier transform infrared (FTIR) spectroscopy, whole-air sampling (WAS), and photoacoustic extinctiometers (PAX; 405 and 870nm) based on field work with a moveable lab sampling authentic sources. The primary aerosol optical properties reported include emission factors (EFs) for scattering and absorption coefficients (EF Bscat, EF Babs, inm2kg-1 fuel burned), single scattering albedos (SSAs), and absorption Ångström exponents (AAEs). From these data we estimate black and brown carbon (BC, BrC) emission factors (gkg-1 fuel burned). The trace gas measurements provide EFs (gkg-1) for CO2, CO, CH4, selected non-methane hydrocarbons up to C10, a large suite of oxygenated organic compounds, NH3, HCN, NOx, SO2, HCl, HF, etc. (up to ∼ 80 gases in all). The emissions varied significantly by source, and light absorption by both BrC and BC was important for many sources. The AAE for dung-fuel cooking fires (4.63±0.68) was significantly higher than for wood-fuel cooking fires (3.01±0.10). Dung-fuel cooking fires also emitted high levels of NH3 (3.00±1.33gkg-1), organic acids (7.66±6.90gkg-1), and HCN (2.01±1.25gkg-1), where the latter could contribute to satellite observations of high levels of HCN in the lower stratosphere above the Asian monsoon. HCN was also emitted in significant quantities by several non-biomass burning sources. BTEX compounds (benzene, toluene, ethylbenzene, xylenes) were major emissions from both dung- (∼4.5gkg-1) and wood-fuel (∼1.5gkg-1) cooking fires, and a simple method to estimate indoor exposure to the many measured important air toxics is described. Biogas emerged as the cleanest cooking technology of approximately a dozen stove-fuel combinations measured. Crop residue burning produced relatively high emissions of oxygenated organic compounds (∼12gkg-1) and SO2 (2.54±1.09gkg-1). Two brick kilns co-firing different amounts of biomass with coal as the primary fuel produced contrasting results. A zigzag kiln burning mostly coal at high efficiency produced larger amounts of BC, HF, HCl, and NOx, with the halogenated emissions likely coming from the clay. The clamp kiln (with relatively more biomass fuel) produced much greater quantities of most individual organic gases, about twice as much BrC, and significantly more known and likely organic aerosol precursors. Both kilns were significant SO2 sources with their emission factors averaging 12.8±0.2gkg-1. Mixed-garbage burning produced significantly more BC (3.3±3.88gkg-1) and BTEX (∼4.5gkg-1) emissions than in previous measurements. For all fossil fuel sources, diesel burned more efficiently than gasoline but produced larger NOx and aerosol emission factors. Among the least efficient sources sampled were gasoline-fueled motorcycles during start-up and idling for which the CO EF was on the order of ∼700gkg-1 - or about 10 times that of a typical biomass fire. Minor motorcycle servicing led to minimal if any reduction in gaseous pollutants but reduced particulate emissions, as detailed in a companion paper (Jayarathne et al., 2016). A small gasoline-powered generator and an insect repellent fire were also among the sources with the highest emission factors for pollutants. These measurements begin to address the critical data gap for these important, undersampled sources, but due to their diversity and abundance, more work is needed

Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis

Background The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse. Methods A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to 50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose. Results In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to 25% drop in haemoglobin to <70 g/L. Conclusions Primaquine treatment led to a marked decrease in P. vivax recurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events. PROSPERO registration number CRD42022313730

RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Pneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries.</p> <p>Methods</p> <p>From July 2004 to June 2007, we examined nasopharyngeal aspirates (NPA) from 2,230 cases of pneumonia (World Health Organization criteria) in children 2 to 35 months old recruited in a randomized trial of zinc supplementation at a field clinic in Bhaktapur, Nepal. The specimens were examined for respiratory syncytial virus (RSV), influenza virus type A (InfA) and B (InfB), parainfluenza virus types 1, 2 and 3 (PIV1, PIV2, and PIV3), and human metapneumovirus (hMPV) using a multiplex reverse transcriptase polymerase chain reaction (PCR) assay.</p> <p>Results</p> <p>We identified 919 virus isolates in 887 (40.0%) of the 2,219 NPA specimens with a valid PCR result, of which 334 (15.1%) yielded RSV, 164 (7.4%) InfA, 129 (5.8%) PIV3, 98 (4.4%) PIV1, 93 (4.2%) hMPV, 84 (3.8%) InfB, and 17 (0.8%) PIV2. CAP occurred in an epidemic pattern with substantial temporal variation during the three years of study. The largest peaks of pneumonia occurrence coincided with peaks of RSV infection, which occurred in epidemics during the rainy season and in winter. The monthly number of RSV infections was positively correlated with relative humidity (<it>r</it>_{<it>s </it>}= 0.40, <it>P </it>= 0.01), but not with temperature or rainfall. An hMPV epidemic occurred during one of the three winter seasons and the monthly number of hMPV cases was also associated with relative humidity (<it>r</it>_{<it>s </it>}= 0.55, <it>P </it>= 0.0005).</p> <p>Conclusion</p> <p>Respiratory RNA viruses were detected from NPA in 40% of CAP cases in our study. The most commonly isolated viruses were RSV, InfA, and PIV3. RSV infections contributed substantially to the observed CAP epidemics. The occurrence of viral CAP in this community seemed to reflect more or less overlapping micro-epidemics with several respiratory viruses, highlighting the challenges of developing and implementing effective public health control measures.</p

Longitudinal study of adolescent tobacco use and tobacco control policies in India

Abstract Background This project will use a multilevel longitudinal cohort study design to assess whether changes in Community Tobacco Environmental (CTE) factors, measured as community compliance with tobacco control policies and community density of tobacco vendors and tobacco advertisements, are associated with adolescent tobacco use in urban India. India’s tobacco control policies regulate secondhand smoke exposure, access to tobacco products and exposure to tobacco marketing. Research data about the association between community level compliance with tobacco control policies and youth tobacco use are largely unavailable, and are needed to inform policy enforcement, implementation and development. Methods The geographic scope will include Mumbai and Kolkata, India. The study protocol calls for an annual comprehensive longitudinal population-based tobacco use risk and protective factors survey in a cohort of 1820 adolescents ages 12–14 years (and their parent) from baseline (Wave 1) to 36-month follow-up (Wave 4). Geographic Information Systems data collection will be used to map tobacco vendors, tobacco advertisements, availability of e-cigarettes, COTPA defined public places, and compliance with tobacco sale, point-of-sale and smoke-free laws. Finally, we will estimate the longitudinal associations between CTE factors and adolescent tobacco use, and assess whether the associations are moderated by family level factors, and mediated by individual level factors. Discussion India experiences a high burden of disease and mortality from tobacco use. To address this burden, significant long-term prevention and control activities need to include the joint impact of policy, community and family factors on adolescent tobacco use onset. The findings from this study can be used to guide the development and implementation of future tobacco control policy designed to minimize adolescent tobacco use.https://deepblue.lib.umich.edu/bitstream/2027.42/144539/1/12889_2018_Article_5727.pd

Phylogenetic Distribution and Evolutionary History of Bacterial DEAD-Box Proteins

DEAD-box proteins are found in all domains of life and participate in almost all cellular processes that involve RNA. The presence of DEAD and Helicase_C conserved domains distinguish these proteins. DEAD-box proteins exhibit RNA-dependent ATPase activity in vitro, and several also show RNA helicase activity. In this study, we analyzed the distribution and architecture of DEAD-box proteins among bacterial genomes to gain insight into the evolutionary pathways that have shaped their history. We identified 1,848 unique DEAD-box proteins from 563 bacterial genomes. Bacterial genomes can possess a single copy DEAD-box gene, or up to 12 copies of the gene, such as in Shewanella. The alignment of 1,208 sequences allowed us to perform a robust analysis of the hallmark motifs of DEAD-box proteins and determine the residues that occur at high frequency, some of which were previously overlooked. Bacterial DEAD-box proteins do not generally contain a conserved C-terminal domain, with the exception of some members that possess a DbpA RNA-binding domain (RBD). Phylogenetic analysis showed a separation of DbpA-RBD-containing and DbpA-RBD-lacking sequences and revealed a group of DEAD-box protein genes that expanded mainly in the Proteobacteria. Analysis of DEAD-box proteins from Firmicutes and γ-Proteobacteria, was used to deduce orthologous relationships of the well-studied DEAD-box proteins from Escherichia coli and Bacillus subtilis. These analyses suggest that DbpA-RBD is an ancestral domain that most likely emerged as a specialized domain of the RNA-dependent ATPases. Moreover, these data revealed numerous events of gene family expansion and reduction following speciation

Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma. In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017. Methods Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex. Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases. We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs. Findings In 2017, 544.9 million people (95% uncertainty interval [UI] 506.9- 584.8) worldwide had a chronic respiratory disease, representing an increase of 39.8% compared with 1990. Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia. The age-sex- specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically. Chronic respiratory diseases were the third leading cause of death in 2017 (7.0% [95% UI 6.8-7 .2] of all deaths), behind cardiovascular diseases and neoplasms. Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18.0% since 1990, while total DALYs increased by 13.3%. However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14.3% decrease), agestandardised death rates (42.6%), and age-standardised DALY rates (38.2%). In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD. In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes. Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world. Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions. Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men. Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region. Interpretation Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990. Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis

Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: A systematic analysis for the global burden of disease study 2017

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma. In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex. Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases. We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs. Findings: In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9–584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990. Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia. The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically. Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8–7·2] of all deaths), behind cardiovascular diseases and neoplasms. Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578–4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%. However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%). In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD. In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes. Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world. Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions. Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men. Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region. Interpretation: Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990. Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis. Funding: Bill & Melinda Gates Foundation

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks