Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk.

The abundance of Lp(a) protein holds significant implications for the risk of cardiovascular disease (CVD), which is directly impacted by the copy number (CN) of KIV-2, a 5.5 kbp sub-region. KIV-2 is highly polymorphic in the population and accurate analysis is challenging. In this study, we present the DRAGEN KIV-2 CN caller, which utilizes short reads. Data across 166 WGS show that the caller has high accuracy, compared to optical mapping and can further phase ~50% of the samples. We compared KIV-2 CN numbers to 24 previously postulated KIV-2 relevant SNVs, revealing that many are ineffective predictors of KIV-2 copy number. Population studies, including USA-based cohorts, showed distinct KIV-2 CN, distributions for European-, African-, and Hispanic-American populations and further underscored the limitations of SNV predictors. We demonstrate that the CN estimates correlate significantly with the available Lp(a) protein levels and that phasing is highly important.

Aerosols optical depth and Ångström exponent over different regions in Garhwal Himalaya, India.

Aerosol optical depth (AOD) and Ångström exponent (AE) are observed to be important parameters in understanding the status of ambient aerosol concentration over a particular location and depend not only upon the local but also on the large-scale dynamics of the atmosphere. The present article analyses the AOD and AE parameters retrieved with Moderate Resolution Imaging Spectrometer (MODIS) and Multi-angle Imaging Spectro-Radiometer (MISR) instruments onboard satellites, for the upper (Chamoli) and foothill (Dehradun) regions of Garhwal Himalaya in Uttarakhand, India, from 2006 to 2015. Aerosol properties are investigated at monthly, seasonal, and annual scales. The monthly mean values of MODIS-derived AOD and AE were observed to be 0.18 (± 0.14) and 1.05 (± 0.43) respectively over the Dehradun region. The seasonal maximums in AOD with MODIS and MISR were observed as 0.23 ± 0.06 and 0.29 ± 0.07 respectively in the pre-monsoon season, and the minimum values (0.099 ± 0.02) were observed in the post-monsoon season, over the Dehradun region. In contrast, in the Chamoli region, the maximum AOD (MODIS) was 0.21 ± 0.06 observed in the monsoon season and the minimum was 0.036 ± 0.007 in the post-monsoon season. Over a decade, the AE for Chamoli and Dehradun was found to vary from 0.07 to 0.17 and from 0.14 to 0.20 respectively. The median AE for Chamoli and Dehradun was found to be 1.49 and 1.47 respectively, marking the dominance of fine mode particles of anthropogenic origin. Observations show the presence of dust and polluted dust resulting from the long-range transport from the west. The comparison of AOD values from the two sensors shows a significant correlation (0.73) with slightly higher values from MISR over the year. The results obtained are important in understanding the climatic implications due to the atmospheric aerosols over the abovementioned Himalayan region of Uttarakhand, India.

Community sensitization to improve acceptability of indoor residual spraying (IRS) in Mewat district of Haryana, India: A community-based interventional study.

BACKGROUND & OBJECTIVES: Indoor Residual Spraying (IRS) is an important part of malaria prevention and control strategies for villages with annual parasitic incidence (API) of more than 5, or other criteria by National Program of the country. At the time of conception of the study, i.e., in 2012, district Mewat in Haryana state, India was malaria endemic including 35 malaria high risk villages with API more than 5. The current study aimed to improve acceptability of IRS among the residents of Mewat district. METHODS: This was a community based interventional study. Out of the 14 sub-centers, there were 12 sub-centers catering the population of 79 villages, out of which 35 villages had API of more than five, and hence, fulfilled the criteria for regular IRS. Considering sub-center as the unit of randomization, out of all the 12 sub-centers which cater population of villages with API > 5, equal number of the sub-centers matched according to the population size of those villages were assigned to the intervention and non-intervention (control) groups by randomization using lottery technique. The intervention comprised community sensitization through community meetings, wall paintings and distribution of pamphlets. Baseline and post intervention acceptability of IRS was measured and compared. RESULTS: There was 21.7% (95% CI 16.12 to 27.15) increase in intention to accept IRS as per guidelines, and 15.2% (95% CI 9.50 to 20.80) increase in the actual acceptance of IRS in intervention group of villages in Mewat district. INTERPRETATION & CONCLUSION: The intervention can bring about significant increase in the acceptability of IRS which is an important component of malaria control under national programme in district Mewat, Haryana, India.

Examining the effects of green revolution led agricultural expansion on net ecosystem service values in India using multiple valuation approaches.

Ecosystem Services (ESs) are bundles of natural processes and functions that are essential for human well-being, subsistence, and livelihoods. The 'Green Revolution' (GR) has substantial impact on the agricultural landscape and ESs in India. However, the effects of GR on ESs have not been adequately documented and analyzed. This leads to the main hypothesis of this work - 'the incremental trend of ESs in India is mainly prompted by GR led agricultural innovations that took place during 1960 - 1970'. The analysis was carried out through five successive steps. First, the spatiotemporal Ecosystem Service Values (ESVs) in Billion US$ for 1985, 1995, and 2005 were estimated using several value transfer approaches. Second, the sensitivity and elasticity of different ESs to land conversion were carried out using coefficient of sensitivity and coefficient of elasticity. Third, the Geographically Weighted Regression model was performed using five explanatory factors, i.e., total crop area, crop production, crop yield, net irrigated area, and cropping intensity, to explore the cumulative and individual effects of these driving factors on ESVs. Fourth, Multi-Layer Perceptron based Artificial Neural Network was employed to estimate the normalized importance of these explanatory factors. Fifth, simple and multiple linear regression modeling was done to assess the linear associations between the driving factors and the ESs. During the observation periods, cropland, forestland and water bodies contributed to 80%-90% of ESVs, followed by grassland, mangrove, wetland and urban built-up. In all three evaluation years, the highest estimated ESVs among the nine ES categories was provided by water regulation, followed by soil formation and soil-water retention, biodiversity maintenance, waste treatment, climate regulation, and greenhouse gas regulation. Among the five explanatory factors, total crop area, crop production, and net irrigated area showed strong positive associations with ESVs, while cropping intensity exhibited a negative association. Therefore, the study reveals a strong association between GR led agricultural expansion and ESVs in India. This study suggests that there should be an urgent need for formulation of rigorous ecosystem management strategies and policies to preserve ecological integrity and flow of uninterrupted ESs and to sustain human well-being.

Urbanization and food consumption in India.

The shift towards urban living is changing food demand. Past studies on India show significant urban-rural differences in food consumption. However, a scientific understanding of the underlying relationships between urbanization and food consumption is limited. This study provides the first detailed analysis of how urbanization influences both quantity and diversity of food consumption in India by harnessing the strength of multiple datasets, including consumer expenditure surveys, satellite imagery, and census data. Our statistical analysis shows three main findings. First, in contrast to existing studies, we find that much of the variation in food consumption quantity is due to income and not urbanization. After controlling for income and state-level differences, our results show that average consumption is higher in urban than rural areas for fewer than 10% of all commodities. That is, there is nearly no difference in average consumption between urban and rural residents. Second, we find the influence of urbanization as a population share on food consumption diversity to be statistically insignificant (p-value > 0.1). Instead, the results show that infrastructure, market access, percentage working women in urban areas, and norms and institutions have a statistically significant influence. Third, all covariates of food consumption diversity we tested were found to be associated with urbanization. This suggests that urbanization influences on food consumption are both indirect and multidimensional. These results show that increases in the urban population size alone do not explain changes in food consumption in India. If we are to understand how food consumption may change in the future due to urbanization, the study points to the need for a more complex and multidimensional understanding of the urbanization process that goes beyond demographic shifts.

Efficacy and Safety of a Novel Broad-Spectrum Anti-MRSA Agent Levonadifloxacin Compared with Linezolid for Acute Bacterial Skin and Skin Structure Infections: A Phase 3, Openlabel, Randomized Study.

BACKGROUND: Levonadifloxacin is a novel broad-spectrum anti-MRSA agents belonging to the benzoquinolizine subclass of quinolone. It is developed for oral or intravenous administration for the treatment of infections caused by Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA). OBJECTIVES: To establish the non-inferiority of levonadifloxacin compared with linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and to compare the safety of the two antimicrobials. SUBJECTS AND METHODS: This was a Phase 3, multicentre, randomized, open-label, active- comparator study with 500 subjects. Oral levonadifloxacin 1000 mg was compared with oral linezolid 600 mg whereas IV levonadifloxacin 800mg was compared with IV linezolid 600 mg, each treatment was administered twice daily for 7-10 days. Non-inferiority was evaluated by comparing oral levonadifloxacin to oral linezolid and IV levonadifloxacin to IV linezolid for overall clinical response at TOC (Test of Cure) Visit. RESULTS: The clinical cure rates observed at the TOC in the mITT (modified Intent to treat) populations for levonadifloxacin was numerically higher compared to linezolid in the IV sub-group [(91.0% verses 87.8%); treatment difference of 3.2% (95%CI, -4.5 to 10.9)] and in the oral sub-group (95.2% versus 93.6%); treatment difference of 1.6 % [95%CI, -4.2 to 7.3]). As the lowerbound of the 95% CI around the treatment difference was greater than -15% for both subgroups, the primary objective of the study was met. Therefore, both IV levonadifloxacin and oral levonadifloxacin were non-inferior to IV linezolid and oral linezolid, respectively. The majority of subjects in the micro-ITT population had a baseline infection caused by S. aureus with approximately 30% of subjects having MRSA. Levonadifloxacin (IV and oral) had a higher clinical cure rate at TOC for MRSA patients compared with linezolid (IV and oral), (95.0% vs. 89.3% respectively). Levonadifloxacin showed evidence of favourable clinical and microbiological efficacy in subjects with concurrent bacteraemia as well as in subjects with diabetes including diabetic foot infections caused by Gram-positive pathogens including MRSA. Pharmacokinetic analysis showed that bioavailability of oral levonadifloxacin was 90% and similar pharmacokinetic profile of levonadifloxacin by both routes provide an option for IV to oral switch for the treatment of subjects. Incidences of treatment-emergent adverse events (TEAEs) were similar between treatment groups and between IV (20.8% vs. 22.4%, for levonadifloxacin and linezolid, respectively) and oral therapy (16.0% vs. 13.5%, respectively), There were no SAEs or deaths related to study drug and the majority of the AEs observed were mild in nature. Overall, the administration of both IV and oral levonadifloxacin was well-tolerated in subjects with ABSSSI. CONCLUSIONS: The results demonstrate that IV and oral levonadifloxacin therapy has excellent clinical activity against MRSA and offers advantage compared to other quinolones which generally lack MRSA coverage. Levonadifloxacin is safe and well tolerated in the treatment of ABSSSI caused by Gram -positive pathogens including MRSA as well as non-inferior to IV and oral linezolid, respectively. Similar pharmacokinetic profile of IV and oral levonadifloxacin provides an option for IV to oral switch for the treatment of subjects. Both oral and IV levonadifloxacin have recently been granted approval in India for the treatment of ABSSSI including diabetic foot infections and concurrent bacteraemia in adults (18 years of age or older). ClinicalTrials.gov Registration: NCT03405064. CTRI No.: CTRI/2017/06/008843.

Examining the glacial lake dynamics in a warming climate and GLOF modelling in parts of Chandra basin, Himachal Pradesh, India.

The presented study reports applicability of Lake Detection Algorithm (LDA) for an automated extraction of glacial lakes over a large geographical region and dynamics of Samudra Tapu and Gepang Gath glacial lakes. The areal extent of lake boundary extracted through LDA and areal extent of manually interpreted lake boundary exhibit a remarkable agreement (R2~0.99). Glacial lake dynamics is assessed in terms of areal and volumetric expansion for two selected glacial lakes from 1979 to 2017, i.e. Samudra Tapu (0.95 km2), and Gepang Gath (0.67 km2). They show volumetric expansion from 8.52 × 106 m3 (1979) to 80.34 × 106 m3 (2017) and 2.04 × 106 m3 (1979) to 32.44 × 106 m3 (2017) respectively. Statistical analysis (Mann-Kendall and Sen's slope) of climate data indicates rise in mean annual temperature (0.021 °C yr-1; 1961-2015) and fall in annual precipitation (-2.74 mm yr-1; 1951-2015) at different confidence intervals. Further Glacial Lake Outburst Flood (GLOF) is modelled using empirical relationship and Simplified Dam Breach Model (SMPDBK). The SMPDBK demonstrates discharge of 3866.52 and 2100.90 m3 s-1 reaching Chhatru and Sissu village posing threat to life and property. The study also exhibits that glacial shrinkage under the influence of climate change causes expansion of glacial lakes. This expansion is expected to intensify catastrophic GLOF and resultant fatalities and destruction in the downstream region.

Nonclinical safety assessment of PF614: A novel TAAP prodrug of oxycodone for chronic pain indication.

PF614, a novel trypsin activated abuse protection (TAAP) prodrug of oxycodone, is being studied as chronic pain analgesic with extended release and abuse resistant properties. A series of nonclinical safety studies were conducted to support PF614 introduction to clinical trials. Ames assays (PF614 and its metabolites), comet assay (PF614 ≤ 50 mg/kg/day oral gavage in rats) and micronucleus assay (PF614 ≤ 175 mg/kg/day oral gavage in rats) were negative. hERG assay IC50 for PF614 was ≥300 µM. PF614 (0.1 and 10 µM) showed a low permeability in Caco-2 cells (≤1.17 x 10-6 cm/s) and was not a P-gp or BCRP substrate or inhibitor. The mean percent unbound PF614 among all concentrations in plasma ranged from 91.2 to 98.4, 79.4 to 100, and 52.9-79.9% in rat, dog, and human, respectively. Also, PF614 was metabolically stable in rat, dog, and human hepatocytes with no metabolites identified. Safety pharmacology study in dog indicated moderately lower heart rate at ≥ 2 mg/kg oral gavage doses. Toxicity studies of PF614 in rat and dog with daily oral doses of 25 and 18 mg/kg, respectively, for 14 Days were well tolerated with favorable safety profile supporting its further clinical evaluation.

Comprehensive case management of malaria: Operational research informing policy.

In 2013, the Odisha state Vector Borne Disease Control Programme led a five year operational research project, under programmatic conditions, in close collaboration with several partners. This Comprehensive Case Management Project covered a population of 900,000 across paired control and intervention blocks in four districts, each with different transmission intensities. Key gaps in access to malaria services were identified through household surveys and a detailed situation analysis. The interventions included ensuring adequate stocks of rapid diagnostic tests and antimalarial drugs at the village level, the capacity building of health workers and ASHAs, setting up microscopy centres at the primary health care level, and conducting mass screening and treatment in poorly accessible areas. The programme strengthened the routine health system, and improved malaria surveillance as well as the access to and quality of care. Initially, the programme led to increased case reporting due to improved detection, followed by a decline in malaria incidence. Lessons from the project were then scaled up statewide in the form of a new initiative-Durgama Anchalare Malaria Nirakaran (DAMaN).

Experimental Evidence for Transverse Wobbling in

New rotational bands built on the ν(h_{11/2}) configuration have been identified in ^{105}Pd. Two bands built on this configuration show the characteristics of transverse wobbling: the ΔI=1 transitions between them have a predominant E2 component and the wobbling energy decreases with increasing spin. The properties of the observed wobbling bands are in good agreement with theoretical results obtained using constrained triaxial covariant density functional theory and quantum particle rotor model calculations. This provides the first experimental evidence for transverse wobbling bands based on a one-neutron configuration, and also represents the first observation of wobbling motion in the A∼100 mass region.

Metal complexes driven from Schiff bases and semicarbazones for biomedical and allied applications: a review.

Schiff bases are versatile organic compounds which are widely used and synthesized by condensation reaction of different amino compound with aldehydes or ketones known as imine. Schiff base ligands are considered as privileged ligands as they are simply synthesized by condensation. They show broad range of application in medicine, pharmacy, coordination chemistry, biological activities, industries, food packages, dyes, and polymer and also used as an O2 detector. Semicarbazone is an imine derivative which is derived from condensation of semicarbazide and suitable aldehyde and ketone. Imine ligand-containing transition metal complexes such as copper, zinc, and cadmium have shown to be excellent precursors for synthesis of metal or metal chalcogenide nanoparticles. In recent years, the researchers have attracted enormous attention toward Schiff bases, semicarbazones, thiosemicarbazones, and their metal complexes owing to numerous applications in pharmacology such as antiviral, antifungal, antimicrobial, antimalarial, antituberculosis, anticancer, anti-HIV, catalytic application in oxidation of organic compounds, and nanotechnology. In this review, we summarize the synthesis, structural, biological, and catalytic application of Schiff bases as well as their metal complexes.

Farmer typology to understand differentiated climate change adaptation in Himalaya.

Smallholder farmers' responses to the climate-induced agricultural changes are not uniform but rather diverse, as response adaptation strategies are embedded in the heterogonous agronomic, social, economic, and institutional conditions. There is an urgent need to understand the diversity within the farming households, identify the main drivers and understand its relationship with household adaptation strategies. Typology construction provides an efficient method to understand farmer diversity by delineating groups with common characteristics. In the present study, based in the Uttarakhand state of Indian Western Himalayas, five farmer types were identified on the basis of resource endowment and agriculture orientation characteristics. Factor analysis followed by sequential agglomerative hierarchial and K-means clustering was use to delineate farmer types. Examination of adaptation strategies across the identified farmer types revealed that mostly contrasting and type-specific bundle of strategies are adopted by farmers to ensure livelihood security. Our findings show that strategies that incurred high investment, such as infrastructural development, are limited to high resource-endowed farmers. In contrast, the low resourced farmers reported being progressively disengaging with farming as a livelihood option. Our results suggest that the proponents of effective adaptation policies in the Himalayan region need to be cognizant of the nuances within the farming communities to capture the diverse and multiple adaptation needs and constraints of the farming households.

Severe Sub-Acromial Bursitis with Rice Bodies in a Patient with Rheumatoid Arthritis: A Case Report and Review of Literature.

Multiple rice body formation is a rare presentation of chronic sub-acromial bursitis secondary to extensive underlying rheumatoid arthritis, sero-negative inflammatory arthritis or tuberculous joints. Although there is usually an accompanying inflammatory arthropathy, it can occur in the absence of any underlying systemic disorder. We report a case of five years old neglected rice body deposition in shoulder in a 54-years old lady diagnosed to be having rheumatoid arthritis. After initial investigations, arthroscopic removal of rice bodies with bursa excision relieved the symptoms. The underlying rheumatic condition continued its course, generally sparing the involved shoulder joint. We suggest thorough examination for systemic rheumatologic disease in patients diagnosed with such lesions.

Estimation of air-to-grass mass interception factors for iodine.

Air-to-grass mass interception factors for radionuclide are important basic input parameter for the estimation of radiation dose to the public around a nuclear power plant. In this paper, we present the determination of air-to- grass mass interception factors for iodine using a 2 m × 2 m × 2 m (l × b × h) size environmental chamber. The temperature, humidity, and rainfall inside the environmental chamber was controlled to required values to simulate different environmental conditions. Grass (Pennisetum purpureum, Schum), grown in pots, was kept inside the environmental chamber and stable iodine in elemental form was sublimed quickly inside the chamber to simulate an accidental release of iodine to the environment. The concentration of iodine in the air was measured periodically by drawing air through a bubbling setup, containing 1% sodium carbonate solution. The mass interception factor for dry deposition varied in the range of 0.25-7.7 m2 kg-1 with mean value of 2.2 m2 kg-1 with respect to fresh weight of grass, and that due to wet deposition varied in the range of 0.6-4.8 m2 kg-1 with mean value of 2.3 m2 kg-1. The mass interception factor was inversely correlated with the total iodine deposited through dry deposition as well as with the rainfall.

Chitosan: A macromolecule as green corrosion inhibitor for mild steel in sulfamic acid useful for sugar industry.

The present investigation aims at investigation of low cost nontoxic carbohydrate biopolymer chitosan as corrosion inhibitor alone and in combination with KI for mild steel in 1M sulfamic acid medium using gravimetric, electrochemical and surface analysis techniques. It is found that chitosan alone exhibits inhibition efficiency of 73.8% at 200ppm concentration. However, in combination with KI (5ppm), it gave more than 90% inhibition efficiency. The significant increase in the inhibition performance of chitosan has been explained by the synergistic mechanism. The results of Potentiodynamic polarization study shows that chitosan and its blend with KI decreases both anodic and cathodic reactions occurring at mild steel surface in 1M sulfamic acid medium by blocking active sites of the metal and acts as mixed type inhibitor. EIS study reveals that the polarization resistance increases with increase in the concentration of inhibitors which increases charge transfer resistance across the metal/solution interface. The adsorption of chitosan followed the Langmuir adsorption isotherm. The formation of inhibitor film on metal surface was supported by scanning electron microscopy (SEM) and atomic force microscopy (AFM) surface studies.

Molecular data suggest population expansion and high level of gene flow in the Plain Tiger (Danaus chrysippus; Nymphalidae: Danainae).

In the present study, we sequenced the individuals of the Danaus chrysippus from the different altitudinal ranges in the western Himalayan state of Uttarakhand, India and compared with other global published data across its distribution range using the cytochrome oxidase c subunit-I (COI). Among the sequences generated in this study, we observed total six haplotypes with intra-species sequence divergence of 0.001-0.009. Whereas the combined data generated a total of 24 haplotypes. The genetic diversity and neutrality test indices suggested overall population expansion of the species. This has also been supported by the MJ Network as it shows the star-like topology and formation of one core haplotype with maximum frequency distribution to the multiple locations. Whereas, the phylogenetic tree shows mixing of the haplotype from the different locations to the same clade. Haplotype arrangement in both phylogenetic tree and MJ Network is not clustered as per their geographic affinity, which suggests incomplete lineage shorting and recent population expansion or colonizations to the new area.

Imaging out-of-plane polarized emission patterns on gap mode SERS substrates: from high molecular coverage to the single molecule regime.

Gap mode surface-enhanced Raman scattering (SERS) substrates are created when a single nanoparticle is deposited on a thin metal film, creating a region of significant electromagnetic field enhancement in the gap between the nanoparticle and the film due to excitation of a vertically-oriented, out-of-plane dipole plasmon mode, e.g. the gap plasmon. When molecules are located in the gap and couple to the gap plasmon mode, the resulting emission is polarized perpendicular to the thin film, generating SERS emission patterns that have a characteristic donut shape. We analyze these SERS emission patterns using a dipole emission model and extract out-of-plane and in-plane emission angles associated with the gap plasmon mode. Fluctuations in both of these angles reveal dynamic heterogeneity due to molecular motion within the hot spot that changes as a function of molecular coverage. We also reveal static heterogeneity associated with structural defects in the thin film component of the gap mode substrates, indicating that even nanometer-scale surface roughness can impact the quality of gap mode emission.

Prescriber and dispenser perceptions about antibiotic use in acute uncomplicated childhood diarrhea and upper respiratory tract infection in New Delhi: Qualitative study.

OBJECTIVE: The objective of the study was to explore the prescribing practices, knowledge, and attitudes of primary care doctors and community pharmacists, regarding antibiotic use in acute upper respiratory tract infections (URTI) and diarrhea in children to better understand causes of misuse and identify provider suggestions to change such behavior. MATERIALS AND METHODS: Two focus group discussions (FGDs) each were conducted with primary care government doctors (GDs), private general practitioners (GPs), pediatricians, and community pharmacists in Delhi. Each FGD had 8-12 participants and lasted 2 h. Furthermore, 22 individual face-to-face semi-structured interviews were conducted with providers of varying type and experience at their workplaces. Thematic and summative qualitative content analysis was done. RESULTS: All groups admitted to overusing antibiotics, GPs appearing to use more antibiotics than GDs and pediatricians for URTI and diarrhea in children. Pharmacists copy the prescribing of neighborhood doctors. Antimicrobial resistance (AMR) knowledge was poor for all stakeholders except pediatricians. Causes for prescribing antibiotics were patient pressure, profit motive, lack of follow-up and in addition for GDs, workload, no diagnostic facility, and pressure to use near-expiry medicines. Knowledge was gained through self-experience, copying others, information from pharmaceutical companies, and for some, training, continuous medical education/conferences. All groups blamed other professional groups/quacks for antibiotic overuse. Interventions suggested were sensitizing and empowering prescribers through training of providers and the public about the appropriate antibiotic use and AMR and implementing stricter regulations. CONCLUSIONS: A package of interventions targeting providers and consumers is urgently needed for awareness and change in behavior to reduce inappropriate community antibiotic use.