Comparative analysis of chromogenic vs clot based CDC modified, Nijmegen-Bethesda assay for detection of factor viii inhibitor titre

Background:-Inhibitors to infused factor VIII are the most significant complication of hemophilia treatment. These inhibitors are usually IgG antibodies, that react with FVIII in a time and temperature dependent manner. Coagulation factor VIII inhibitors can be detected by Chromogenic, clot based and immunological assays. However, there is lack of consensus as to what constitutes a positive inhibitor, including the appropriate cut-off for inhibitor measurement The main objective of this study is to compare the sensitivity and specificity of chromogenic Nijmegen Bethesda assay (CNBA) with Centre for disease control modified Nijmegen Bethesda (CDC-NBA) assay against the Reference control method (RCM).Materials and Methods: The Coagulometer used for inhibitor titre  quantification is Sysmex CS-5100. APTT reagent used isPathromtin SL supplied by seimensSeimens. All data were expressed as Mean ± SD. Statistical formulae were used for sensitivity and specificity calculations. Unpaired students t test was used whereever necessary and a P value of <0.05 is considered as statistical significanceResults: A total of 150 cases were tested for inhibitor titre using CNBA vs CDC-NBA. For low titre Inhibitor (<2 NBU), CNBA has 92% and 86% and CDC-NBA has 80 and 60% sensitivity and specificity respectively. These results show that CDC-NBA shows false positive results at low inhibitor titre. For High titre Inhibitor ( >2 NBU) CNBA has 88% and 80% and CDC-NBA has 85 and 70 % sensitivity and specificity respectively.Conclusion :- These results shows that CNBA is more sensitive and specific than CDC-NBA at both low and high inhibitor titre. Moreover chromogenic assays can differentiate factor specific inhibitor from nonspecific inhibitors like lupus anticoagulant and unfractionated heparin therapy.Keywords: Hemophilia, Bethesda assay, ELISA, Factor VIII, Inhibitor, Mixing studyAbbrevations: APLA- Antiphospholipid antibody syndrome, CDC:NBA- Centers for Disease Control and Prevention - Nijmegen-BethesdaAssay, CNBA:- chromogenic Nijmegen Bethesda assa

Diarrhea Outbreak Caused by Contaminated Water used for Vegetables Sale

Water has always played a prominent role in human civilization. The water sources used for supplying water were not always clean, and coliforms are the major source of diarrheal infections especially in developing countries and hence contaminated water is the main reason for the spread of these coliforms with in a community by different ways. The contamination of water used in vegetables by pathogens cause diarrheal disease is the most important aspect of vegetables quality. This problem arises as a consequence of contamination of water by faecal matter, particularly human faecal matter, containing pathogenic organisms. Vegetable sellers usually use dirty/contaminated water to shower on vegetables to keep them fresh. This study describes the outbreaks of diarrheal diseases along with the reasons for the outbreaks. In our study we have used Membrane filter technique to test the quality of water used by the vegetable sellers. Purpose of this study is to detect the presence of coliforms which is associated with diarrheal infections due to fecal contamination. We examined the water samples by Membrane filter method in which we use 0.45µm filter paper which was soaked in peptone water and incubated at 37 oC for 24 hours, this peptone water was further streaked on MacConkey and EMB media. Additional identification of microorganisms was done by microscopy and biochemical tests. Observed results revealed that the water is fecally contaminated and the microorganisms isolated were as with described percentages E.coli 12%, Klebsiella 40%, Proteus 44%, Pseudomonas 20%, Shigella 8%, Salmonella 4% and Enterobacter 4% who are the members of coliforms. This study helps in the identification of coliform from different sources which lead to a cause of diarrheal infectio

SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study.

BACKGROUND: SARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. METHODS: We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. FINDINGS: Sequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086). INTERPRETATION: In common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.This report was produced by members of the COG-UK-HOCI Variant substudy consortium. COG-UK-HOCI is part of COG-UK. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Comparaison de matériaux pour la fabrication d'un plan en réhabilation fonctionnelle

One of the “never thought of before” developments is the current advancement in the field of biotechnology. The revolutionary Brain Computer Interface (BCI) has paved the way for scientific researchers everywhere to help fight birth defects, traumatic loss of a limb, and/or motor function of a specific area. This Ph.D. manuscript presents the work done with the target of fabricating full diamond implants. At first, conventional materials were used (as both conductive and non-conductive or passivation layers) to fabricate electrode samples to understand and study the behavior of traditional matter in an electrochemical environment. This study paved the way for fabricating electrodes of similar shapes and sizes, but with different materials to optimize performance, and ensure longevity while managing overall production costs, etc. Later, different shapes and structures for different materials were also employed to ameliorate and enhance the performance of the electrode, resulting in the implants. Another part of this thesis was to prove the superiority of diamond over conventional materials not only in terms of performance, thinness, and hermeticity but also in its ability to withstand the hostile environment of the human body. A longevity test setup was also installed and improved step by step to demonstrate the lasting performance of the full diamond samples. The global idea of the project NEURODIAM is fabricating the first-ever full diamond implants and this thesis provided important R&D work for this project. Going forward, this thesis demonstrates the bottom-up approach to characterizing a specific metal from laboratory to in-vitro tests and with the possibility to incorporate that technology for application in-vivo, and later animal testing, which is some of the steps of fabricating bio-implants. The thesis gives context and chronological description of the fabrication and characterization procedures of the different types of electrodes to understand the different parts of the samples (conducting and non-conducting parts) using conventional materials, eg: Gold and SU8. After the samples were adopted with the project-specific material, i.e., diamond along with proper modification and addition. TiN was used in the structure to reduce the serial resistance of the full Diamond samples and nanostructured TiN was used and characterized and explored for further use. Electrochemical characterization processes (eg: Bio-impedance Spectroscopy, Cyclic Voltammetry, Nyquist Analysis) were employed to understand the performance of the samples and upon characterization the drawbacks were modified, corrected and the performance was optimized. Finally, the chronic test setup was established to predict the performance of the samples in the long run compared to conventional material. This setup uses “Analog Discovery 2” to measure and collect the data of the samples automatically and save those in real time. The primary result of the said setup is favorable toward diamond and is added to the manuscriptLes progrès actuels dans le domaine de la biotechnologie constituent l'un des développements "jamais imaginés auparavant". L'interface cerveau-ordinateur révolutionnaire a ouvert la voie aux chercheurs scientifiques du monde entier pour les aider à lutter contre les malformations congénitales, la perte traumatique d'un membre et/ou la fonction motrice d'une zone spécifique. Ce manuscrit de doctorat présente les travaux réalisés dans le but de fabriquer des implants entièrement en diamant. Dans un premier temps, des matériaux conventionnels ont été utilisés (en tant que couches conductrices et non conductrices ou de passivation) pour fabriquer des échantillons d'électrodes afin de comprendre et d'étudier le comportement de la matière traditionnelle dans un environnement électrochimique. Cette étude a ouvert la voie à la fabrication d'électrodes de formes et de tailles similaires, mais avec des matériaux différents pour optimiser les performances et assurer la longévité tout en gérant les coûts de production globaux, etc. Par la suite, différentes formes et structures pour différents matériaux ont également été utilisées pour améliorer et renforcer les performances de l'électrode, ce qui a donné naissance aux implants. Une autre partie de cette thèse consistait à prouver la supériorité du diamant sur les matériaux conventionnels, non seulement en termes de performances, de finesse et d'herméticité, mais aussi de capacité à résister à l'environnement hostile du corps humain. Un dispositif de test de longévité a également été installé et amélioré étape par étape pour démontrer la performance durable des échantillons de diamant complets. L'idée générale du projet NEURODIAM est de fabriquer les tout premiers implants en diamant intégral et cette thèse a fourni un important travail de R&D pour ce projet. Cette thèse démontre l'approche ascendante de la caractérisation d'un métal spécifique, du laboratoire aux tests in-vitro, avec la possibilité d'incorporer cette technologie pour une application in-vivo, et plus tard pour des tests sur les animaux, ce qui constitue certaines des étapes de la fabrication de bio-implants. La thèse présente le contexte et la description chronologique des procédures de fabrication et de caractérisation des différents types d'électrodes afin de comprendre les différentes parties des échantillons (parties conductrices et non conductrices) en utilisant des matériaux conventionnels, par exemple l'or et le SU8 : Or et SU8. Ensuite, les échantillons ont été adoptés avec le matériau spécifique au projet, c'est-à-dire le diamant, avec les modifications et les ajouts appropriés. Le TiN a été utilisé dans la structure pour réduire la résistance série des échantillons de diamant et le TiN nanostructuré a été utilisé, caractérisé et exploré en vue d'une utilisation ultérieure. Des processus de caractérisation électrochimique (par exemple : spectroscopie de bio-impédance, voltampérométrie cyclique, analyse de Nyquist) ont été utilisés pour comprendre les performances des échantillons et, après caractérisation, les inconvénients ont été modifiés, corrigés et les performances ont été optimisées. Enfin, le dispositif d'essai chronique a été mis en place pour prédire les performances des échantillons à long terme par rapport aux matériaux conventionnels. Cette installation utilise "Analog Discovery 2" pour mesurer et collecter les données des échantillons automatiquement et les enregistrer en temps réel. Le résultat principal de cette configuration est favorable à l'utilisation d'un matériau de bas

Comparaison de matériaux pour la fabrication d'un plan en réhabilation fonctionnelle

Les progrès actuels dans le domaine de la biotechnologie constituent l'un des développements "jamais imaginés auparavant". L'interface cerveau-ordinateur révolutionnaire a ouvert la voie aux chercheurs scientifiques du monde entier pour les aider à lutter contre les malformations congénitales, la perte traumatique d'un membre et/ou la fonction motrice d'une zone spécifique. Ce manuscrit de doctorat présente les travaux réalisés dans le but de fabriquer des implants entièrement en diamant. Dans un premier temps, des matériaux conventionnels ont été utilisés (en tant que couches conductrices et non conductrices ou de passivation) pour fabriquer des échantillons d'électrodes afin de comprendre et d'étudier le comportement de la matière traditionnelle dans un environnement électrochimique. Cette étude a ouvert la voie à la fabrication d'électrodes de formes et de tailles similaires, mais avec des matériaux différents pour optimiser les performances et assurer la longévité tout en gérant les coûts de production globaux, etc. Par la suite, différentes formes et structures pour différents matériaux ont également été utilisées pour améliorer et renforcer les performances de l'électrode, ce qui a donné naissance aux implants. Une autre partie de cette thèse consistait à prouver la supériorité du diamant sur les matériaux conventionnels, non seulement en termes de performances, de finesse et d'herméticité, mais aussi de capacité à résister à l'environnement hostile du corps humain. Un dispositif de test de longévité a également été installé et amélioré étape par étape pour démontrer la performance durable des échantillons de diamant complets. L'idée générale du projet NEURODIAM est de fabriquer les tout premiers implants en diamant intégral et cette thèse a fourni un important travail de R&D pour ce projet. Cette thèse démontre l'approche ascendante de la caractérisation d'un métal spécifique, du laboratoire aux tests in-vitro, avec la possibilité d'incorporer cette technologie pour une application in-vivo, et plus tard pour des tests sur les animaux, ce qui constitue certaines des étapes de la fabrication de bio-implants. La thèse présente le contexte et la description chronologique des procédures de fabrication et de caractérisation des différents types d'électrodes afin de comprendre les différentes parties des échantillons (parties conductrices et non conductrices) en utilisant des matériaux conventionnels, par exemple l'or et le SU8 : Or et SU8. Ensuite, les échantillons ont été adoptés avec le matériau spécifique au projet, c'est-à-dire le diamant, avec les modifications et les ajouts appropriés. Le TiN a été utilisé dans la structure pour réduire la résistance série des échantillons de diamant et le TiN nanostructuré a été utilisé, caractérisé et exploré en vue d'une utilisation ultérieure. Des processus de caractérisation électrochimique (par exemple : spectroscopie de bio-impédance, voltampérométrie cyclique, analyse de Nyquist) ont été utilisés pour comprendre les performances des échantillons et, après caractérisation, les inconvénients ont été modifiés, corrigés et les performances ont été optimisées. Enfin, le dispositif d'essai chronique a été mis en place pour prédire les performances des échantillons à long terme par rapport aux matériaux conventionnels. Cette installation utilise "Analog Discovery 2" pour mesurer et collecter les données des échantillons automatiquement et les enregistrer en temps réel. Le résultat principal de cette configuration est favorable à l'utilisation d'un matériau de baseOne of the “never thought of before” developments is the current advancement in the field of biotechnology. The revolutionary Brain Computer Interface (BCI) has paved the way for scientific researchers everywhere to help fight birth defects, traumatic loss of a limb, and/or motor function of a specific area. This Ph.D. manuscript presents the work done with the target of fabricating full diamond implants. At first, conventional materials were used (as both conductive and non-conductive or passivation layers) to fabricate electrode samples to understand and study the behavior of traditional matter in an electrochemical environment. This study paved the way for fabricating electrodes of similar shapes and sizes, but with different materials to optimize performance, and ensure longevity while managing overall production costs, etc. Later, different shapes and structures for different materials were also employed to ameliorate and enhance the performance of the electrode, resulting in the implants. Another part of this thesis was to prove the superiority of diamond over conventional materials not only in terms of performance, thinness, and hermeticity but also in its ability to withstand the hostile environment of the human body. A longevity test setup was also installed and improved step by step to demonstrate the lasting performance of the full diamond samples. The global idea of the project NEURODIAM is fabricating the first-ever full diamond implants and this thesis provided important R&D work for this project. Going forward, this thesis demonstrates the bottom-up approach to characterizing a specific metal from laboratory to in-vitro tests and with the possibility to incorporate that technology for application in-vivo, and later animal testing, which is some of the steps of fabricating bio-implants. The thesis gives context and chronological description of the fabrication and characterization procedures of the different types of electrodes to understand the different parts of the samples (conducting and non-conducting parts) using conventional materials, eg: Gold and SU8. After the samples were adopted with the project-specific material, i.e., diamond along with proper modification and addition. TiN was used in the structure to reduce the serial resistance of the full Diamond samples and nanostructured TiN was used and characterized and explored for further use. Electrochemical characterization processes (eg: Bio-impedance Spectroscopy, Cyclic Voltammetry, Nyquist Analysis) were employed to understand the performance of the samples and upon characterization the drawbacks were modified, corrected and the performance was optimized. Finally, the chronic test setup was established to predict the performance of the samples in the long run compared to conventional material. This setup uses “Analog Discovery 2” to measure and collect the data of the samples automatically and save those in real time. The primary result of the said setup is favorable toward diamond and is added to the manuscrip

Managing Access to Confidential Documents: A Case Study of an Email Security Tool

User adoption and usage of end-to-end encryption tools is an ongoing research topic. A subset of such tools allows users to encrypt confidential emails, as well as manage their access control using features such as the expiration time, disabling forwarding, persistent protection, and watermarking. Previous studies have suggested that protective attitudes and behaviors could improve the adoption of new security technologies. Therefore, we conducted a user study on 19 participants to understand their perceptions of an email security tool and how they use it to manage access control to confidential information such as medical, tax, and employee information if sent via email. Our results showed that the participants’ first impression upon receiving an end-to-end encrypted email was that it looked suspicious, especially when received from an unknown person. After the participants were informed about the importance of the investigated tool, they were comfortable sharing medical, tax, and employee information via this tool. Regarding access control management of the three types of confidential information, the expiration time and disabling forwarding were most useful for the participants in preventing unauthorized and continued access. While the participants did not understand how the persistent protection feature worked, many still chose to use it, assuming it provided some extra layer of protection to confidential information and prevented unauthorized access. Watermarking was the least useful feature for the participants, as many were unsure of its usage. Our participants were concerned about data leaks from recipients’ devices if they set a longer expiration date, such as a year. We provide the practical implications of our findings