Direct inference and control of genetic population structure from RNA sequencing data.

RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.

The effect of relative air humidity on the evaporation timescales of a human sneeze.

The present paper investigates droplet and aerosol emission from the human respiratory function by numerical and experimental methods, which is analyzed at the worst-case scenario, a violent sneeze without a face covering. The research findings develop the understanding of airborne disease transmission relevant to COVID-19, its recent variants, and other airborne pathogens. A human sneeze is studied using a multiphase Computational Fluid Dynamics (CFD) model using detached eddy simulation coupled to the emission of droplets that break up, evaporate, and disperse. The model provides one of the first experimental benchmarks of CFD predictions of a human sneeze event. The experiments optically capture aerosols and droplets and are processed to provide spatiotemporal data to validate the CFD model. Under the context of large random uncertainty, the studies indicate the reasonable correlation of CFD prediction with experimental measurements using velocity profiles and exposure levels, indicating that the model captures the salient details relevant to pathogen dispersion. Second, the CFD model was extended to study the effect of relative humidity with respect to the Wells curve, providing additional insight into the complexities of evaporation and sedimentation characteristics in the context of turbulent and elevated humidity conditions associated with the sneeze. The CFD results indicated correlation with the Wells curve with additional insight into features, leading to non-conservative aspects associated with increased suspension time. These factors are found to be associated with the combination of evaporation and fluid-structure-induced suspension. This effect is studied for various ambient air humidity levels and peaks for lower humidity levels, indicating that the Wells curve may need a buffer in dry climates. Specifically, we find that the increased risk in dry climates may be up to 50% higher than would be predicted using the underlying assumptions in Wells' model.

Sedimentary metals in developing tropical watersheds in relation to their urbanization intensities.

The spatial distribution of seven metals (Pb, Hg, Cd, Cr, Ni, Cu, and Zn) and As in the surface sediments from three major tributaries of a tropical urbanizing river network (i.e., Chao Phraya River, Thachin River, and Pasak River) was investigated. An obvious metal concentration gradient in response to the intensity of urbanization was found at inter-watershed and intra-watershed scales. Sediment Quality Guidelines (SQGs) exceedances of several metals (Pb, Cr, Ni, Cu, and Zn) and high ecological risk were primarily identified at the down streams of Chao Phraya and Thachin watersheds, where the social-economic center of the country with intensive industries is located. Stepwise multiple linear regression revealed significant correlations between studied metals and catchment land use pattern (with p < 0.0001 except for Ni and Cr). Particularly, urban land use showed remarkable effect on sedimentary Pb, Cd, Cu, and Zn loads with high coefficients over 0.65. The results of cluster analysis and principal component analysis indicated the dominated urban/industrial sources for Pb, Cd, Cu, and Zn, mixed natural and industrial sources for Cr and Ni, and diffuse sources for Hg and As in the watersheds, respectively.

Efficient photocatalytic oxidation of gaseous toluene in a bubbling reactor of water.

Conventional gas-solid photocatalytic oxidation (SPCO) of VOCs has drawbacks such as accumulation of intermediates and catalytic deactivation. In this study, gas-liquid photocatalytic oxidation (LPCO) was exploited to improve the catalytic activity and stability by continuously bubbling VOCs into water. Toluene and commercial TiO2 (P25) were chosen as the representative VOC pollutant and photocatalyst, respectively. Toluene removal efficiency in LPCO was about 6 times of that in conventional SPCO, and no intermediates were detected in the exhaust of LPCO probably due to its high degradation and mineralization rates. However, plentiful intermediates were identified by GC-MS and ITMS both in the gas outlet and on the surface of catalyst in SPCO, which may lead to photocatalytic deactivation. Moreover, LPCO exhibited superior catalytic activity towards typical soluble VOCs such as formaldehyde compared to SPCO. The soluble intermediates formed from toluene degradation can be easily removed by sustaining UV irradiation to avoid water pollution and the water after purification can be reused in LPCO. This study provides a novel gas-liquid photocatalytic oxidation to replace conventional gas-solid photocatalytic oxidation for the sake of better catalytic activity and fewer by-products.

Assessment and Translation of the Antibody-in-Lymphocyte Supernatant (ALS) Assay to Improve the Diagnosis of Enteric Fever in Two Controlled Human Infection Models and an Endemic Area of Nepal.

New diagnostic tests for enteric fever are urgently needed to assist with timely antimicrobial treatment of patients and to measure the efficacy of prevention measures such as vaccination. In a novel translational approach, here we use two recently developed controlled human infection models (CHIM) of enteric fever to evaluate an antibody-in-lymphocyte supernatant (ALS) assay, which can detect recent IgA antibody production by circulating B cells in ex vivo mononuclear cell culture. We calculated the discriminative ability of the ALS assay to distinguish diagnosed cases in the two CHIM studies in Oxford, prior to evaluating blood culture-confirmed diagnoses of patients presenting with fever to hospital in an endemic areas of Kathmandu, Nepal. Antibody responses to membrane preparations and lipopolysaccharide provided good sensitivity (>90%) for diagnosing systemic infection after oral challenge with Salmonella Typhi or S. Paratyphi A. Assay specificity was moderate (~60%) due to imperfect sensitivity of blood culture as the reference standard and likely unrecognized subclinical infection. These findings were augmented through the translation of the assay into the endemic setting in Nepal. Anti-MP IgA responses again exhibited good sensitivity (86%) but poor specificity (51%) for detecting blood culture-confirmed enteric fever cases (ROC AUC 0.79, 95%CI 0.70-0.88). Patients with anti-MP IgA ALS titers in the upper quartile exhibited a clinical syndrome synonymous with enteric fever. While better reference standards are need to assess enteric fever diagnostics, routine use of this ALS assay could be used to rule out infection and has the potential to double the laboratory detection rate of enteric fever in this setting over blood culture alone.

Negative feedback circuit for toll like receptor-8 activation in human embryonic Kidney 293 using outer membrane vesicle delivered bi-specific siRNA.

BACKGROUND: TLR8 assists in antiviral approach by producing Type 1 INF via MyD88 dependent IRF7 pathway. However, over expression of INFα/ß molecule poses threat by developing tolerance in chronic infection cases and enhancing inflammatory response. Here we report a bi-specific siRNA based complex which differentially activates and silences the TLR8 and MYD88 respectively in a negatively regulated fashion. RESULTS: Outer membrane vesicle from Escherichia coli used for siRNA delivery was observed more efficient when attached with invasive protein Ail along with OmpA (P<0.001) in HEK293-TLR8 cell line. siRNA complexed with p19 protein was efficient in activating TLR8, confirmed by the increment of INFß molecules (P<0.001) in HEK293-TLR8 compared to its counterpart. Fusion of lipid bilayer of endosomal compartment was significant at pH 4.5 when fusogenic peptides (diINF-7) were incubated in membrane vesicle, thus facilitating the escape of siRNA complex to the host cytoplasm in order to silence MyD88 transcript (P<0.001). CONCLUSIONS: We investigated the activation of TLR8 by bi-specific si-RNA for the production of INFß. In the same setting we showed that bi-specific si-RNA was able to silence MyD88 transcript in a delayed manner. For the cases of auto immune disease and inflammation where over activation of endosomal TLRs poses serious threat, bi specific siRNA could be used as negative feedback controlled system.

Factors affecting collective action for forest fire management: a comparative study of community forest user groups in central Siwalik, Nepal.

The attributes of social ecological systems affect the management of commons. Strengthening and enhancing social capital and the enforcement of rules and sanctions aid in the collective action of communities in forest fire management. Using a set of variables drawn from previous studies on the management of commons, we conducted a study across 20 community forest user groups in Central Siwalik, Nepal, by dividing the groups into two categories based on the type and level of their forest fire management response. Our study shows that the collective action in forest fire management is consistent with the collective actions in other community development activities. However, the effectiveness of collective action is primarily dependent on the complex interaction of various variables. We found that strong social capital, strong enforcement of rules and sanctions, and users' participation in crafting the rules were the major variables that strengthen collective action in forest fire management. Conversely, users' dependency on a daily wage and a lack of transparency were the variables that weaken collective action. In fire-prone forests such as the Siwalik, our results indicate that strengthening social capital and forming and enforcing forest fire management rules are important variables that encourage people to engage in collective action in fire management.

Management of large medial sphenoid wing meningiomas: a series of 178 cases.

AIM: The aim of this study was to evaluate our treatment and outcome in patients with large medial sphenoid wing meningiomas (SWMs). MATERIAL AND METHODS: Data from 178 patients with large medial SWMs treated was collected and analyzed retrospectively. Most of patients underwent microsurgical resection under electrophysiological monitoring and Doppler probe. Radiation therapy was administered in 64 patients with residual tumor and malignant pathology. RESULTS: Total resection of the tumor was achieved in 118 of 178 cases (66.3%), subtotal in 60 of 178 (33.7%) at the time of initial surgery without serious surgical complications except 2 patients with ptosis. Postoperative vision improved in 84 patients (87.5%), remained unchanged in 8 (8.3%) and deteriorated in 4 (4.2%). The progress free survival (PFS) and Karnofsky performance score (KPS) between patients with gross total resection (GTR) and patients with subtotal resection (STR) followed by radiation therapy (RT) had no significant difference. CONCLUSION: Surgery still remains a principal treatment option for SWMs. Good craniotomy techniques, proper hemostasis and optimal surgery strategy are critical to improve resection rate and elevate prognosis. Likewise, it is expected that STR with adjuvant RT can provide satisfactory results in case of total removal impossible.

Spontaneous chronic subdural hematoma associated with arachnoid cyst in children and young adults.

Arachnoid cysts are clear, colorless fluid-filled cysts that arise during brain and skull development from the splitting of the arachnoid membrane. Chronic subdural hematoma (CSDH) is an encapsulated collection of old blood, mostly or totally liquefied and located between the dura mater and the arachnoid mater. Trauma is an important factor in the development of CSDH. Here, we report four patients, previously asymptomatic, revealing CSDH with AC on computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. All patients underwent craniotomy with evacuation of hematoma and resection of the cystic membrane that was then connected to the basal cistern under the operating microscope. Postoperatively, all patients were symptom-free. Presentation of an AC with chronic subdural hematoma in the absence of preceding head trauma is considered to be rare in children and young adults.

Mild functional ischemic mitral regurgitation following acute coronary syndrome: a retrospective study.

BACKGROUND: Ischemic mitral regurgitation is a frequent complication of acute coronary syndrome. It primarily occurs in patients with a prior myocardial infarction but also may be seen with acute ischemia, a setting in which the MR typically resolves after the ischemia resolves. The vast majority of patients have "functional" ischemic MR. In these individuals, the papillary muscles, chordae, and valve leaflets are normal. However, the leaflets do not coapt and restricted leaflet motion is frequently noted on echocardiography. Ischemic mitral regurgitation indicates a poor prognosis after acute myocardial infarction. This study addresses the clinical characteristics of patients of acute coronary syndrome with mild functional ischemic mitral regurgitation and its impact on immediate in-hospital cardiovascular outcomes and death. PATIENTS AND METHODS: From March 2006 through May 2007, patients who underwent 2-dimensional (2D) color doppler echocardiographic quantification of ischemic mitral regurgitation within 10 days of admission for acute coronary syndrome (ACS) in Manipal Teaching Hospital, a tertiary hospital in the western region of Nepal were noted. The demographic details, conventional risk factors of coronary artery disease, clinical and laboratory findings, treatment course and in-hospital outcomes of all the patients with mild functional ischemic MR following ACS in that time duration were recorded in a designated Performa. A total of 94 patients enrolled in the study were divided into two groups: Group I with mild functional ischemic MR and Group II without MR on 2D echocardigraphic assessment. Patient characteristics, risk factors, ejection fraction, and cardiovascular outcome and death among the two groups were compared and analyzed using software package SPSS 17.0 version. RESULTS: Group I constituted 64.89% of the study population and Group II comprised of 35.11%. The patients in Group I was more likely to be elderly diabetic (P<0.05), and smokers with hypertension (P < 0.05). Mild functional ischemic MR was more common in patients with STEMI as compared to those with unstable angina and NSTEMI (55.7%, 36.1%, and 8.2%; P < 0.05).The mean ejection fraction in the first group was 54.84% in contrast to 58.92% observed in group II (P < 0.05).The type of wall involvement inferred from EKG analysis was homogeneously distributed in both the groups. Finally, there was no difference in immediate in-hospital (within 10 days) mortality or cardiovascular outcomes (heart failure, ventricular tachycardia/fibrillation, hypotension, and cardiogenic shock) between these two groups. CONCLUSION: Ischemic mitral regurgitation following acute coronary syndromeare more likely in elderly diabetics and hypertensive smokers. It is a more common finding in STEMI. Although mild MR following ACS does reduce ejection fraction, the immediate (within 10 days) in-hospital mortality and cardiovascular outcomes are not significantly altered.

Removal of trichloroethylene (TCE) contaminated soil using a two-stage anaerobic-aerobic composting technique.

The effect of organic carbon addition on remediation of trichloroethylene (TCE) contaminated clay soil was investigated using a two stage anaerobic-aerobic composting system. TCE removal rate and processes involved were determined. Uncontaminated clay soil was treated with composting materials (dried cow manure, rice husk and cane molasses) to represent carbon based treatments (5%, 10% and 20% OC). All treatments were spiked with TCE at 1,000 mg TCE/kg DW and incubated under anaerobic and mesophillic condition (35 degrees C) for 8 weeks followed by continuous aerobic condition for another 6 weeks. TCE dissipation, its metabolites and biogas composition were measured throughout the experimental period. Results show that TCE degradation depended upon the amount of organic carbon (OC) contained within the composting treatments/matrices. The highest TCE removal percentage (97%) and rate (75.06 micro Mole/kg DW/day) were obtained from a treatment of 10% OC composting matrices as compared to 87% and 27.75 micro Mole/kg DW/day for 20% OC, and 83% and 38.08 micro Mole/kg DW/day for soil control treatment. TCE removal rate was first order reaction kinetics. Highest degradation rate constant (k(1) = 0.035 day(- 1)) was also obtained from the 10% OC treatment, followed by 20% OC (k(1) = 0.026 day(- 1)) and 5% OC or soil control treatment (k(1) = 0.023 day(- 1)). The half-life was 20, 27 and 30 days, respectively. The overall results suggest that sequential two stages anaerobic-aerobic composting technique has potential for remediation of TCE in heavy texture soil, providing that easily biodegradable source of organic carbon is present.

Knowledge attitude and practice (KAP) study regarding facts for life.

This knowledge attitude and practice (KAP) study was done in the married women of age 18-38 years in Jorpati and Gokarna village development committees of Katmandu district to evaluate the knowledge of "Facts for Life". There were 510 married women involved in this study. Altogether 28 questions were asked to each of them regarding the "Facts for Life". It includes the following five subjects: Safe motherhood, Childhood Immunization, Childhood diarrhea, Acute Respiratory Infection (ARI) in childhood and hygiene. There was a significant increase in knowledge about hygiene and knowledge regarding childhood immunization than diarrhea, ARI and Safe motherhood. Results showed that the overall knowledge was at 62.8%. This shows that still more attention is needed to Nepalese women.