Study protocol for economic evaluation of probiotic intervention for prevention of neonatal sepsis in 0-2-month old low-birth weight infants in India: the ProSPoNS trial

Introduction: The ProSPoNS trial is a multicentre, double-blind, placebo-controlled trial to evaluate the role of probiotics in prevention of neonatal sepsis. The present protocol describes the data and methodology for the cost utility of the probiotic intervention alongside the controlled trial. Methods and analysis: A societal perspective will be adopted in the economic evaluation. Direct medical and non-medical costs associated with neonatal sepsis and its treatment would be ascertained in both the intervention and the control arm. Intervention costs will be facilitated through primary data collection and programme budgetary records. Treatment cost for neonatal sepsis and associated conditions will be accessed from Indian national costing database estimating healthcare system costs. A cost–utility design will be employed with outcome as incremental cost per disability-adjusted life year averted. Considering a time-horizon of 6 months, trial estimates will be extrapolated to model the cost and consequences among high-risk neonatal population in India. A discount rate of 3% will be used. Impact of uncertainties present in analysis will be addressed through both deterministic and probabilistic sensitivity analysis. Ethics and dissemination: Has been obtained from EC of the six participating sites (MGIMS Wardha, KEM Pune, JIPMER Puducherry, AIPH, Bhubaneswar, LHMC New Delhi, SMC Meerut) as well as from the ERC of LSTM, UK. A peer-reviewed article will be published after completion of the study. Findings will be disseminated to the community of the study sites, with academic bodies and policymakers. Registration: The protocol has been approved by the regulatory authority (Central Drugs Standards Control Organisation; CDSCO) in India (CT-NOC No. CT/NOC/17/2019 dated 1 March 2019). The ProSPoNS trial is registered at the Clinical Trial Registry of India (CTRI). Registered on 16 May 2019. Trial registration number: CTRI/2019/05/019197; Clinical Trial Registry

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Optimization of friction STIR welded AA6061 + SiCp metal matrix composite to increase joint tensile strength and reduce defects

Friction stir welding has been used in automobiles, locomotive, and aircraft structures. This metal joining process exhibits defects like kissing bonds, micropores, and tunnels. Factors like the joining material, joint thickness, tool geometry, and operating parameters control the defects in friction stir welding. The parameters like tool rotation, tool pass speed, and tool force have a greater influence on the joint quality. In this study, these parameters are considered to augment the strength of the joint and minimize defects. The metal matrix composite consisting of AA6061 matrix and 10 wt. % SiCp reinforcement is joined used FSW. The weld parameters were varied between 731 and 1068 rpm tool rotation speed, 0.33 and 1.17 mm/s tool pass speed, and 11 and 28 MPa tool force. The joint strength varied from 165 MPa to 244 MPa. The numerical analysis using ANOVA revealed that compared between the three parameters, the tool force had greater control over the tensile strength of the joint. After optimization, the joint was made at a tool rotation speed of 910 rpm, tool pass speed of 0.77 mm/s, and tool force of 22.33 MPa. The tensile strength increased to 249 MPa after using the optimized weld parameters. The number of defects in the joint was reduced after using the optimized weld parameters

Lumbar Intraspinal Osteolipoma Presenting as Cauda Equina Syndrome: A Case Report and Review of Literature

Introduction. Osteolipomas are uncommon variants of lipoma. These lesions have been usually reported to arise from the oral cavity, brain, and neck and scarcely from the knee and thigh. Intraspinal osteolipomas are rare. A single case of intraspinal osteolipoma has been reported in the cervical and thoracic spine in the literature. To our knowledge, there is no report of osteolipomas in the lumbar spine. Case Presentation. We report a very rare case of a solitary lumbar intraspinal osteolipoma, presenting as a cauda equina syndrome. The intraspinal osteolipoma was excised en bloc and fusion was performed as it required partial resection of the facet joint within 24 hours of presentation. He has since then improved neurologically, and there has been no recurrence of the lesion so far. The clinical presentation, radiological characteristics, treatment course, and histopathological features of this lesion along with the clinical outcomes and a pertinent literature review were done and have been discussed. Discussion. The heterogeneous signal intensity of the lesion in MRI differentiates it from other dural-based lesions, and this should raise suspicion of an osteolipoma, which warrants a CT. Although intraspinal osteolipomas are benign lesions and generally have good prognosis, they need to be removed en bloc as they may result in rapid neurological deterioration

The Effectiveness of Noninvasive Positive Pressure Ventilation in Subarachnoid Pleural Fistula: A Case Report and Literature Review

Subarachnoid pleural fistula (SPF) is an aberrant communication between the pleural cavity and subarachnoid space, resulting in uncontrolled cerebrospinal fluid drainage. The negative pressure of the pleural cavity creates a continuous suctioning effect, thereby impeding the spontaneous closure of these fistulas. Dural tears or punctures in cardiothoracic procedures, spinal operations, and trauma are known to cause such abnormal communications. Failure to recognize this entity may result in sudden neurological or respiratory complications. Hence, a high index of suspicion is required for early diagnosis and prompt management. Noninvasive positive pressure ventilation has been described to be effective in managing such fistulas, thus mitigating the high morbidity associated with exploratory surgery for primary repair. Herein, we describe the typical presentation of SPF and the clinical course, treatment, and follow-up of a patient who sustained SPF following anterior thoracic spinal surgery

Characterization of a pathogen induced thaumatin-like protein gene AdTLP from Arachis diogoi, a wild peanut.

Peanut (Arachis hypogaea L) is one of the widely cultivated and leading oilseed crops of the world and its yields are greatly affected by various biotic and abiotic stresses. Arachis diogoi, a wild relative of peanut, is an important source of genes for resistance against various stresses that affect peanut. In our previous study a thaumatin-like protein gene was found to be upregulated in a differential expression reverse transcription PCR (DDRT-PCR) study using the conidial spray of the late leaf spot pathogen, Phaeoisariopsis personata. In the present study, the corresponding full length cDNA was cloned using RACE-PCR and has been designated as AdTLP. It carried an open reading frame of 726 bp potentially capable of encoding a polypeptide of 241 amino acids with 16 conserved cysteine residues. The semi-quantitative RT-PCR analysis showed that the transcript level of AdTLP increased upon treatment with the late leaf spot pathogen of peanut, P. personata and various hormone treatments indicating its involvement in both, biotic and abiotic stresses. The antifungal activity of the purified recombinant protein was checked against different fungal pathogens, which showed enhanced anti-fungal activity compared to many other reported TLP proteins. The recombinant AdTLP-GFP fusion protein was found to be predominantly localized to extracellular spaces. Transgenic tobacco plants ectopically expressing AdTLP showed enhanced resistance to fungal pathogen, Rhizoctonia solani. The seedling assays showed enhanced tolerance of AdTLP transgenic plants against salt and oxidative stress. The transcript analysis of various defense related genes highlighted constitutively higher level expression of PR1a, PI-I and PI-II genes in transgenic plants. These results suggest that the AdTLP is a good candidate gene for enhancing stress resistance in crop plants