9 research outputs found
Development of fully intuitionistic fuzzy data envelopment analysis model with missing data: an application to Indian police sector
Data Envelopment Analysis (DEA) is a technique used to measure the efficiency
of decision-making units (DMUs). In order to measure the efficiency of DMUs,
the essential requirement is input-output data. Data is usually collected by
humans, machines, or both. Due to human/machine errors, there are chances of
having some missing values or inaccuracy, such as
vagueness/uncertainty/hesitation in the collected data. In this situation, it
will be difficult to measure the efficiencies of DMUs accurately. To overcome
these shortcomings, a method is presented that can deal with missing values and
inaccuracy in the data. To measure the performance efficiencies of DMUs, an
input minimization BCC (IMBCC) model in a fully intuitionistic fuzzy (IF)
environment is proposed. To validate the efficacy of the proposed fully
intuitionistic fuzzy input minimization BCC (FIFIMBCC) model and the technique
to deal with missing values in the data, a real-life application to measure the
performance efficiencies of Indian police stations is presented
Translation rescue by targeting Ppp1r15a upstream open reading frame in vivo
The eIF2 initiation complex is central to maintaining a functional translation machinery. Extreme stress such as life-threatening sepsis exposes vulnerabilities in this tightly regulated system, resulting in an imbalance between the opposing actions of kinases and phosphatases on the main regulatory subunit eIF2α. Here, we report that translation shutdown is a hallmark of established sepsis-induced kidney injury brought about by excessive eIF2α phosphorylation and sustained by blunted expression of the counterregulatory phosphatase subunit Ppp1r15a. We determined that the blunted Ppp1r15a expression persists because of the presence of an upstream open reading frame (uORF). Overcoming this barrier with genetic approaches enabled the derepression of Ppp1r15a, salvaged translation and improved kidney function in an endotoxemia model. We also found that the loss of this uORF has broad effects on the composition and phosphorylation status of the immunopeptidome that extended beyond the eIF2α axis. Collectively, our findings define the breath and potency of the highly conserved Ppp1r15a uORF and provide a paradigm for the design of uORF-based translation rheostat strategies. The ability to accurately control the dynamics of translation during sepsis will open new paths for the development of therapies at codon level precision
A Two-stage Network Data Envelopment Analysis: An Education Sector Application
Data envelopment analysis (DEA) works like a black box that does not provide
any adequate detail to identify the specific reason for inefficiency in
decision-making units (DMUs). The motivation of this study is to analyze the
cause of the inefficiency of DMUs in a decision process with the help of a
two-stage relational network DEA model. In the current study, a two-stage
relational network DEA model is applied to measure the performance of DMUs for
the whole process and each stage independently. In general, past studies used
conventional DEA models in education sectors to analyze the performances of
educational institutions. In the current study, by considering quantitative
attributes to measure the performance of Indian institutes of management (IIMs)
by using network DEA, we develop a procedure that captures both quality and
quantity
Epidemiological Evaluation and Causes of delayed presentation of Orthopaedic polytrauma patients to Emergency Department - A Tertiary Care Centre Experience
Introduction: Polytrauma is a leading cause of death and disability with high financial burden. The study was done with an aim to delineate specific epidemiological characteristics as well as to determine specific causes of delays of polytrauma patients in reaching emergency departments (ED). Materials and Methods: All patients with Orthopaedic polytrauma fulfilling the inclusion criteria, within a six month period were included in our study. Epidemiological data and causes of delay were tabulated and appropriate statistical analysis was done. Results: 60 patients who fulfilled the inclusion criteria were included in our study. 71.67% were male. The mean age in our series was 35.2 ± 8.34 years. Mode of trauma as per our study was 65% following road traffic accidents. 36.67% of patients were under influence of alcohol at time of injury. Patients who arrived in hospital by hired/ self-owned vehicle constituted 41.66% and rest of patients were found to arrive in Govt. run ambulance. Only 18 patients (30%) could reach the hospital in the golden hour (<1 hr.). 55% of patients sustained an injury during day time (9.00AM- 9.00PM) and 45% were injured during the night. 18.33% of patients reached the hospital late due to distance of accident from the hospital. Other major causes of late presentation included lack of finance, and traffic related delay constituting 16.67% each. Conclusion: Less than one-third of the patients presented to the emergency within 1 hour of the time of injury which stresses the need to improve prehospital care and transport in our country
L-Asparaginase of Leishmania donovani: Metabolic target and its role in Amphotericin B resistance
Emergence of Amphotericin B (AmB) resistant Leishmania donovani has posed major therapeutic challenge against the parasite. Consequently, combination therapy aimed at multiple molecular targets, based on proteome wise network analysis has been recommended. In this regard we had earlier identified and proposed L-asparaginase of Leishmania donovani (LdAI) as a crucial metabolic target. Here we report that both LdAI overexpressing axenic amastigote and promastigote forms of L. donovani survives better when challenged with AmB as compared to wild type strain. Conversely, qRT-PCR analysis showed an upregulation of LdAI in both forms upon AmB treatment. Our data demonstrates the importance of LdAI in imparting immediate protective response to the parasite upon AmB treatment. In the absence of structural and functional information, we modeled LdAI and validated its solution structure through small angle X-ray scattering (SAXS) analysis. We identified its specific inhibitors through ligand and structure-based approach and characterized their effects on enzymatic properties (Km, Vmax, Kcat) of LdAI. We show that in presence of two of the inhibitors L1 and L2, the survival of L. donovani is compromised whereas overexpression of LdAI in these cells restores viability. Taken together, our results conclusively prove that LdAI is a crucial metabolic enzyme conferring early counter measure against AmB treatment by Leishmania. Keywords: Leishmania donovani, L-asparaginase, Amphotericin B resistance, Metabolic targe
The Gelsolin Pathogenic D187N Mutant Exhibits Altered Conformational Stability and Forms Amyloidogenic Oligomers
Gelsolin
is an actin-severing protein that attains an open functional
conformation in the presence of Ca<sup>2+</sup> or low pH. Mutations
(D187N/Y) in the second domain of gelsolin trigger the proteolytic
pathway producing amyloidogenic fragments that form the pathological
hallmark of gelsolin amyloidosis and lattice corneal dystrophy type
2 (LCD2). Here, we show that the D187N mutant gelsolin in a Ca<sup>2+</sup> depleted, low pH-activated, open conformation could assemble
into amyloidogenic oligomers without necessarily undergoing the specific
proteolytic step. Although both wild-type (WT) and mutant proteins
exhibit closely overlapping globular shapes at physiological conditions,
the latter exhibits subjugated actin depolymerization, loss of thermodynamic
stability, and folding cooperativity. Mutant gelsolin displayed aberrant
conformational unwinding and formed structural conformers with high
associative properties at low pH conditions. A SAXS intensity profile
and Guinier analysis of these conformers showed the formation of unusual,
higher order aggregates. Extended incubation at low pH resulted in
the formation of thioflavin T and Congo red positive, ÎČ-sheet
rich aggregates with a fibrillar, amyloid-like morphology visible
under electron and atomic force microscopy. Mass spectrometric analysis
of disaggregated end-stage fibrils displayed peptide fragments encompassing
the entire protein sequence, indicating the involvement of full length
mutant gelsolin in fibril formation. Atomistic and REMD simulations
indicated a larger increase in solvent accessibility and loss of fold
architecture in mutant gelsolin at low pH as compared to WT gelsolin.
Our findings support the existence of a secondary oligomerization-dependent
aggregation pathway associated with gelsolin amyloidosis and can pave
the way for better therapeutic strategies
Abstracts of National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020
This book presents the abstracts of the papers presented to the Online National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020 (RDMPMC-2020) held on 26th and 27th August 2020 organized by the Department of Metallurgical and Materials Science in Association with the Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, India.
Conference Title: National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020Conference Acronym: RDMPMC-2020Conference Date: 26â27 August 2020Conference Location:Â Online (Virtual Mode)Conference Organizer: Department of Metallurgical and Materials Engineering, National Institute of Technology JamshedpurCo-organizer: Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, IndiaConference Sponsor: TEQIP-
Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries
Background
Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks.
Methods
The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned.
Results
A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31).
Conclusion
Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)