On the concept of virtual states

The technique of the decomposed Feynman propagator is used to establish the equivalence between the Feynman and field theoretic formalisms. It is shown that for an nth order process, each of the 2n−1 decomposed Feynman diagrams is equivalent to a certain group in the n! field theoretic diagrams. This is demonstrated for the fourth order Compton scattering of an electron by identifying the energy denominators in the two formalisms

On the decomposition of the Feynman propagator

The Feynman propagator, in momentum representation, is a four-dimensional transform over space and time variables. If the space and time integrations are performed separately, the propagator can be decomposed into two parts, one corresponding to positive and the other to negative energy intermediate state. By the use of this decomposed propagator, the relative contributions of the positive and negative energy intermediate states to the matrix element can be estimated. For example in Compton scattering it leads to the apparently paradoxical result that in the "non-relativistic approximation" it is only the negative energy intermediate state that contributes to the matrix element

Diverse Clinical Isolates of Mycobacterium tuberculosis Develop Macrophage-Induced Rifampin Tolerance.

The Mycobacterium tuberculosis lineage 4 strains CDC1551 and H37Rv develop tolerance to multiple antibiotics upon macrophage residence. To determine whether macrophage-induced tolerance is a general feature of clinical M. tuberculosis isolates, we assessed macrophage-induced drug tolerance in strains from lineages 1-3, representing the other predominant M. tuberculosis strains responsible for tuberculosis globally. All 3 lineages developed isoniazid tolerance. While lineage 1, 3, and 4 strains developed rifampin tolerance, lineage 2 Beijing strains did not. Their failure to develop tolerance may be explained by their harboring of a loss-of-function mutation in the Rv1258c efflux pump that is linked to macrophage-induced rifampicin tolerance

The impact of different fertiliser management options and cultivars on nitrogen use efficiency and yield for rice cropping in the Indo-Gangetic Plain: two seasons of methane, nitrous oxide and ammonia emissions

This study presents detailed crop and gas flux data from two years of rice production at the experimental farm of the ICAR-Indian Agricultural Research Institute, New Delhi, India. In comparing 4 nitrogen (N) fertiliser regimes across 4 rice cultivars (CRD 310, IR-64, MTU 1010, P-44), we have added to growing evidence of the environmental costs of rice production in the region. The study shows that rice cultivar can impact yields of both grain, and total biomass produced in given circumstances, with the CRD 310 cultivar showing consistently high nitrogen use efficiency (NUE) for total biomass compared with other tested varieties, but not necessarily with the highest grain yield, which was P-44 in this experiment. While NUE of the rice did vary depending on experimental treatments (ranging from 41% to 73%), 73%), this did not translate directly into the reduction of emissions of ammonia (NH3) and nitrous oxide (N2O). Emissions were relatively similar across the different rice cultivars regardless of NUE. Conversely, agronomic practices that reduced total N losses were associated with higher yield. In terms of fertiliser application, the outstanding impact was of the very high methane (CH4) emissions as a result of incorporating farmyard manure (FYM) into rice paddies, which dominated the overall effect on global warming potential. While the use of nitrification and urease inhibiting substances decreased N2O emissions overall, NH3 emissions were relatively unaffected (or slightly higher). Overall, the greatest reduction in greenhouse gas (GHG) emissions came from reducing irrigation water added to the fields, resulting in higher N2O, but significantly less CH4 emissions, reducing net GHG emission compared with continuous flooding. Overall, genetic differences generated more variation in yield and NUE than agronomic management (excluding controls), whereas agronomy generated larger differences than genetics concerning gaseous losses. This study suggests that a mixed approach needs to be applied when attempting to reduce pollution and global warming potential from rice production and potential pollution swapping and synergies need to be considered. Finding the right balance of rice cultivar, irrigation technique and fertiliser type could significantly reduce emissions, while getting it wrong can result in considerably poorer yields and higher pollution

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D

Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis

A recent Genome-wide Association Study (GWAS) identified association with variants in X-linked CLDN2 and MORC4 and PRSS1-PRSS2 loci with Chronic Pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10-09; rs12008279—OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10-09; rs6622126—OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Correlation problems in evolutionary stochastic processess

In a previous contribution to these Proceedings (Ramakrishnan(1)) the concept of product density was introduced to describe the statistical distribution of a discrete number of particles in a continuous space E, corresponding to a single point t, where t is the parameter with respect to which the stochastic process evolves. This is extended to densities corresponding to n points on the t axis and correlation problems associated with these density functions are studied with particular reference to electron-photon cascades

Klinefelter syndrome and its association with male infertility

Klinefelter's syndrome is the most common genetic disorder in which there is at least one extra X chromosome. Males normally have an X chromosome and a Y chromosome (XY). But males who have Klinefelter syndrome have an extra X chromosome (XXY), giving them a total of 47 instead of the normal 46 chromosomes. Sex chromosome abnormalities are more frequently associated with male infertility. The prevalence of XXYs has risen from 1.09 to 1.72 per 1 000 male births. A patient attended to fertility and genetic clinic, during the clinical diagnosis we found the following complaints of loss of secondary sexual characteristics and infertility. Physical examination revealed breast development, thin built, small size testes, and absence of beard and pubic hairs. Karyotype and biochemical analysis were performed to detect chromosomal abnormality as well as hormonal level to confirm the diagnosis of Klinefelter's syndrome. Chromosomal analysis of the peripheral blood lymphocytes demonstrated the constitutional karyotype of 47, XXY. Using karyotype the presence of extra X chromosome was confirmed, supporting the cytogenetic finding. The 47, XXY syndrome is relatively uncommon and can be missed clinically because of its variable clinical presentations. Accurate diagnosis of this constitutional karyotype provides a valuable aid in the counselling and early management of the patients who undertake fertility evaluation