23 research outputs found
Magnetic field induced Fabry-P\'erot resonances in helical edge states
We study electronic transport across a helical edge state exposed to a
uniform magnetic ({}) field over a finite length. We show that this
system exhibits Fabry-P\'erot type resonances in electronic transport. The
intrinsic spin anisotropy of the helical edge states allows us to tune these
resonances by changing the direction of the {} field while keeping its
magnitude constant. This is in sharp contrast to the case of non-helical one
dimensional electron gases with a parabolic dispersion, where similar
resonances do appear in individual spin channels ( and )
separately which, however, cannot be tuned by merely changing the direction of
the {} field. These resonances provide a unique way to probe the
helical nature of the theory.Comment: v1: 5 pages, 5 figure
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Impact of admixture and ancestry on eQTL analysis and GWAS colocalization in GTEx
Background
Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings. The Genotype-Tissue Expression (GTEx) project largely contains individuals of European ancestry, but the v8 release also includes up to 15% of individuals of non-European ancestry. Assessing ancestry-based adjustments in GTEx improves portability of this research across populations and further characterizes the impact of population structure on GWAS colocalization.
Results
Here, we identify a subset of 117 individuals in GTEx (v8) with a high degree of population admixture and estimate genome-wide local ancestry. We perform genome-wide cis-eQTL mapping using admixed samples in seven tissues, adjusted by either global or local ancestry. Consistent with previous work, we observe improved power with local ancestry adjustment. At loci where the two adjustments produce different lead variants, we observe 31 loci (0.02%) where a significant colocalization is called only with one eQTL ancestry adjustment method. Notably, both adjustments produce similar numbers of significant colocalizations within each of two different colocalization methods, COLOC and FINEMAP. Finally, we identify a small subset of eQTL-associated variants highly correlated with local ancestry, providing a resource to enhance functional follow-up.
Conclusions
We provide a local ancestry map for admixed individuals in the GTEx v8 release and describe the impact of ancestry and admixture on gene expression, eQTLs, and GWAS colocalization. While the majority of the results are concordant between local and global ancestry-based adjustments, we identify distinct advantages and disadvantages to each approach
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Exploiting the GTEx resources to decipher the mechanisms at GWAS loci.
The resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of the biology of human diseases. Here, we present an in-depth examination of the phenotypic consequences of transcriptome regulation and a blueprint for the functional interpretation of genome-wide association study-discovered loci. Across a broad set of complex traits and diseases, we demonstrate widespread dose-dependent effects of RNA expression and splicing. We develop a data-driven framework to benchmark methods that prioritize causal genes and find no single approach outperforms the combination of multiple approaches. Using colocalization and association approaches that take into account the observed allelic heterogeneity of gene expression, we propose potential target genes for 47% (2519 out of 5385) of the GWAS loci examined
A genome-wide association study in a large community-based cohort identifies multiple loci associated with susceptibility to bacterial and viral infections
There is limited data on host-specific genetic determinants of susceptibility to bacterial and viral infections. Genome-wide association studies using large population cohorts can be a first step towards identifying patients prone to infectious diseases and targets for new therapies. Genetic variants associated with clinically relevant entities of bacterial and viral infections (e.g., abdominal infections, respiratory infections, and sepsis) in 337,484 participants of the UK Biobank cohort were explored by genome-wide association analyses. Cases (n = 81,179) were identified based on ICD-10 diagnosis codes of hospital inpatient and death registries. Functional annotation was performed using gene expression (eQTL) data. Fifty-seven unique genome-wide significant loci were found, many of which are novel in the context of infectious diseases. Some of the detected genetic variants were previously reported associated with infectious, inflammatory, autoimmune, and malignant diseases or key components of the immune system (e.g., white blood cells, cytokines). Fine mapping of the HLA region revealed significant associations with HLA-DQA1, HLA-DRB1, and HLA-DRB4 locus alleles. PPP1R14A showed strong colocalization with abdominal infections and gene expression in sigmoid and transverse colon, suggesting causality. Shared significant loci across infections and non-infectious phenotypes in the UK Biobank cohort were found, suggesting associations for example between SNPs identified for abdominal infections and CRP, rheumatoid arthritis, and diabetes mellitus. We report multiple loci associated with bacterial and viral infections. A better understanding of the genetic determinants of bacterial and viral infections can be useful to identify patients at risk and in the development of new drugs
Management and Elimination of mother-to-child transmission of hepatitis B virus: A therapeutical Approach
A major worldwide health issue is the persistent transmission of the chronic form of the hepatitis B virus (HBV) from mothers to their unborn children (MTCT) during the perinatal period. In endemic areas, HBV infection occurs mainly during infancy and early childhood, with MTCT accounting for approximately half of the transmission routes of chronic HBV infections. Prevention of MTCT is an important step in reducing the global burden of chronic HBV. In addition to such considerations regarding the transmission of HBV to the child, the combination of HBV infection and pregnancy raises several unique management issues. Up to 9% of newborns still acquire HBV infection, especially from mothers who have the hepatitis B e antigen (HBeAg), despite routine passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and the hepatitis B vaccine. The failure of passive-active immunoprophylaxis in newborns, the impact and requirement of routine hepatitis B immunoglobulin (HBIG) injections to mothers, the safety of antiviral prophylaxis, and the safety of nursing are some of the complications associated with managing HBV infection throughout pregnancy. Chronic HBV infection during pregnancy is usually but may flare after delivery. These unresolved issues are highlighted in this review and we aim to an optimal approach to the management of preventing MTCT of HBV infection.
Keywords: Hepatitis B, perinatal period transmission, immunoprophylaxis, breastfeeding, viremia
Randomized routing and sorting on fixed-connection networks
This paper presents a general paradigm for the design of packet routing algorithms for fixed-connection networks. Its basis is a randomized on-line algorithm for scheduling any set of N packets whose paths have congestion c on any bounded-degree leveled network with depth L in O(c + L + log N) steps, using constant-size queues. In this paradigm, the design of a routing algorithm is broken into three parts: (1) showing that the underlying network can emulate a leveled network, (2) designing a path selection strategy for the leveled network, and (3) applying the scheduling algorithm. This strategy yields randomized algorithms for routing and sorting in time proportional to the diameter for meshes, butterflies, shuffle-exchange graphs, multidimensional arrays, and hypercubes. It also leads to the construction of an area-universal network: an N-node network with area Θ(N) that can simulate any other network of area O(N) with slowdown O(log N)
Topical corticosteroids: Abuse and Misuse
Background: The Topical Corticosteroids are among the most commonly prescribed medication in an out-patient dermatology setting since they were first introduced in early 1950s. Probably no other group of drugs has had such a profound impact on the specialty as Topical Corticosteroid. They provide rapid symptomatic relief in almost all inflammatory dermatoses, especially in the short term. Multiple pathways including rebound vasodilatation and proinflammatory cytokine release have been proposed as the mechanism for such reactions.
Aim: To study various adverse effects of topical corticosteroids misuse over face.
Materials and Methods: 130 patients with a history of topical corticosteroid use on face for minimum 1 month duration were included in this study.
Results: Majority of patients were between age group of 21 to 30 (65.4%). Female sex preponderance over male sex with 67.8%. Majority of patients were House wives (49%) followed by Employees (23%). Duration of application of TC was 3-6 months (77%) in majority of cases. Most commonly abused TC was Betamethasone Valerate (79.2%).
Conclusion: Topical Corticosteroid should not be used on the face unless it is under strict dermatological supervision
Pulmonary tuberculosis in an adult presenting with severe hyponatremia: A case report and review of literature
Key Clinical Message Identifying pulmonary pathology while evaluating electrolyte disorders is crucial for optimal patient management. Physicians working in endemic regions of tuberculosis should consider this pathology as a differential for electrolyte imbalances. Abstract Hyponatremia, a common electrolyte imbalance, can arise from various underlying etiologies such as diuretics, diarrhea, vomiting, congestive heart failure, and liver and renal disease. We present a case report of a 74‐year‐old man highlighting the association between pulmonary tuberculosis (TB) and the development of hyponatremia. GeneXpert assay of the patient's sputum sample led to the identification of underlying active pulmonary TB as the cause of hyponatremia. The patient was started on anti‐TB therapy, and concurrent fluid restriction and sodium supplementation were initiated to correct the electrolyte imbalance. Over the next 3 days, the patient demonstrated clinical improvement with the resolution of hyponatremia. This case also highlights the importance of considering TB as a potential etiology in patients presenting with hyponatremia, especially in endemic areas. Further research is warranted to explore the mechanistic pathways linking pulmonary TB and hyponatremia, aiding in the development of targeted therapeutic interventions