Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology

Background: Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the € sensitivity improved two-test' or € SIT²' algorithm. Methods: SIT² involves confirmatory retesting of samples with results falling in a predefined retesting zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT² to single tests and orthogonal testing (OTA) in an Austrian cohort (1117 negative, 64 post-COVID-positive samples) and validated the algorithm in an independent British cohort (976 negatives and 536 positives). Results: The specificity of SIT² was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT² when compared with single tests or OTA. SIT² allowed correct identification of infected individuals even when a live virus neutralisation assay could not detect antibodies. Compared with single testing or OTA, SIT² significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence. Conclusion: For SARS-CoV-2 serology, SIT² proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases

Die liedere van S. le Roux Marais : 'n geannoteerde katalogus

Proefskrif (D. Phil.) -- Universiteit van Stellenbosch, 1992.AFRIKAANSE OPSOMMING: Die besluit om 'n studie van s le Roux Marais te maak is gestimuleer deur die belangstelling en waardering wat gehore in die bui teland vir die komponis se liedere ui tgespreek het. Die hoeveelheid wetenskaplike navorsing wat tot dusver oor sy musiek gedoen is, is beperk en nie vry van vooroordeel nie. Hierdie studie het tot 'n herontdekking van vele van sy liedere gelei en in sekere opsigte ook tot 'n herwaardering van sy kuns. Besonderhede oor Marais se lewensgeskiedenis was tot dusver slegs onvolledig beskikbaar. Om 'n beter begrip van die komponis se musiek te verkry was di t noodsaaklik om eers sy biograf ie op te teken. Hierdie inligting gee insig in sy werksomstandighede as musiekonderwyser en pianis, as orrelis en koorleier, as skilder en komponis - en ook as mens. 'n Volledige lys van sy werke was ook tot dusver nie opgestel nie. Dit word vir die eerste keer in hierdie proefskrif gedoen. Marais was in die eerste plek 'n liederekomponis. Hy het egter ook 'n aansienlike hoeveelheid koormusiek, etlike stukke vir klavier, vir orrel, sowel as drie operettes gekomponeer. Marais se oeuvre hang nou saam met die ontwikkeling van die Afrikaanse taal. Veral aan die begin van sy loopbaan was hy 'n baie aktuele komponis: heelwat van sy toonsettings het kort na die ontstaan van die betrokke gedigte die lig gesien. Op die manier het hy 'n belangrike bydrae tot die Afrikaanse liedereskat en die Afrikaanse kultuur in die algemeen gelewer. Die katalogus in Hoofstuk 5 is as 'n handleiding bedoel vir diegene wat vinnig en doeltreffend informasie oor 'n spesifieke lied wil he. Elke lied is aan die hand van verskillende hoofpunte ontleed, en die inligting word in 'n tienpuntesisteem met 'n beskrywing weergegee. Die opset van elke beskrywing is ui t die aard van die saak by elke lied verskillend. Ter wille van volledigheid is informasie oor Marais se ander werke as Hoofstuk 6 ingesluit. 'n Samevatting van sy komposisiestyl word in Hoofstuk 7 aangebied en sluit die proefskrif af. Marais was geinteresseerd in kuns in die algemeen. Sy eerste groot lief de was die musiek en hy het meer as 150 werke gekomponeer. Sy tweede liefde was die skilderkuns ~n hy het tussen 120 en 130 skilderye, meestal stillewes en blomstudies, gemaak. Marais was 'n instinktiewe komponis. 'n Ontledende aard, formele tegnieke en woordgetroue verklanking is vreemd aan sy styl. Hy gebruik 'n soort neo-romantiese idioom, en die beste eienskap van sy musiek is sy melodiee. Hulle is byna altyd gelaai met gevoel en warmte. aanspreek. Hulle is daarom verstaanbaar en kan 'n wye publiek Onder sy tydgenote wat dieselfde idioom gebruik het, verteenwoordig Marais se musiek 'n hoogtepunt. Marais is reeds dee! van die kultuurgeskiedenis van Suid-Afrika. Van sy bekendste liedere het volksbesit geword. Solank Afrikaans bestaan, sal sy liedere gesing word.ENGLISH ABSTRACT: The decision to embark on a research project on s le Roux Marais was influenced and stimulated by the interest and appreciation expressed by overseas audiences for this particular South African composer's songs. The existing research on his music is very limited and not devoid of prejudice. This study has led to a rediscovery of many of his songs, and to a certain extent, to a new appreciation of his art. In order to gain a deeper understanding of the composer it was necessary to write a more detailed biography than the rather inadequate ones available. This research offers insight into his work as music educator, pianist, organist, choir master, painter and composer - and also about him as a person. For the first time a complete list of his works is given in this dissertation. He was primarily a composer of songs. He did, however, also compose a fair amount of choral music, several pieces for piano, for organ, and three operettas. Marais' works are closely associated with the development of the Afrikaans language. At the beginning of his career it was especially noticeable that he was a very up to date composer: many of his songs appeared shortly after the specific poems were written, and in this respect he made an important contribution to the Afrikaans culture. The catalogue in Chapter 5 is meant to serve as a guide for those who need relevant information about specific songs. The structure of every song is analysed according to specific aspects, and the information is presented according to a ten point system, followed by a discussion, since each song is essentially different. For the sake of completeness information about Marais' other works is included in Chapter 6. Chapter 7 draws conclusions regarding his compositional style and completes the dissertation. Marais was interested in the arts in general. Music was his first big love and he composed more than 150 works. His second love was painting. He painted between 120 and 130 works, mostly still-life presentations and flower studies. Marais composed by instinct rather than by design. An analytical nature, formal techniques, or word-painting are not major elements of his style. His idiom can be described as neo-romantic, and the most outstanding characteristic of his music is his melodies. They are almost always full of feeling and warmth. They are, therefore, easily understandable and readily accessible to a wide public. Marais was foremost among his contemporaries who used the same idiom. Marais is already part of the cultural history of South Africa. So much so that some of his songs have become an integral part of South Africa's national heritage. As long as the Afrikaans language exists, his songs will be sung

B-cell translocation gene 2 is over-expressed in peri-infarct neurons after ischaemic stroke

[Objectives]: Recovery from stroke is dependent on the survival of neurons in the dynamic peri-infarcted region. Although several markers of neuronal injury and apoptotic cell death have been described, administration of neuroprotective drugs directed at specific molecules has had limited success. A complete understanding of deregulated genes associated with neuronal death would be beneficial. Our previous microarray studies identified increased expression of a novel protein, the B-cell translocation gene 2 (BTG2), in infarcted regions.[Methods]: We have used immunohistochemistry and Western blotting to examine the expression and localization of BTG2 in stroked brain tissue and immunofluorescent staining of human fetal brain neurons to determine if oxygen-glucose deprivation affected its expression.[Results]: We show that BTG2 is strongly expressed in peri-infarcted and infarcted regions of brain tissue, localizing in neuronal nuclei and cytoplasm, whilst being absent or very weakly expressed in normal looking contralateral tissue. Exposure of human fetal brain neurons to oxygen-glucose deprivation also induced BTG2 expression in the cytoplasm and perinuclear regions of cells staining positive for propidium iodide (a marker of nuclear damage).[Conclusions]: BTG2 may be a modulator of cell survival and differentiation and could help to protect against cell death by inhibition of necrosis and/or apoptotic signalling pathways.We would like to thank the Fundacion BBVA for the generous support of Prof. Mark Slevin through the award of the BBVA Chair in Clinical Biomedicine at the ICCC, St Pau Hospital, Barcelona, Spain.Peer reviewe

Direct and indirect impacts of climate change on wheat yield in the Indo-Gangetic plain in India

The Indo-Gangetic Plain (IGP) is one of the main wheat-production regions in India and the world. With climate change, wheat yields in this region will be affected through changes in temperature and precipitation and decreased water availability for irrigation, raising major concerns for national and international food security. Here we use a regional climate model and a crop model to better understand the direct (via changes in temperature and precipitation) and indirect (via a decrease in irrigation availability) impacts of climate change on wheat yields at four sites spread across different states of the IGP: Punjab, Haryana, Uttar Pradesh and Bihar. The results show an increase in mean temperature and precipitation as well as maximum temperature during the growing season or Rabi season (November–April). The direct impact of climate change, via changes in temperature and precipitation, leads to wheat yield losses between −1% and −8% depending on the site examined. Then, the indirect impact of climate change is examined, considering the impact of climate change on water availability leading to a decrease in irrigation. In this case, the yield losses become significant and much higher, reaching −4% to −36% depending on the site examined and the irrigation regime chosen (6, 5, 3 or 1 irrigations). This work shows that the indirect impacts of climate change may be more detrimental than the direct climatic effects for the future wheat yields in the IGP. It also emphasizes the complexity of climatic risk and the necessity of integrating indirect impacts of climate change to fully assess how it affects agriculture and choose the adequate adaptation response

Direct and indirect impacts of climate change on wheat yield in the Indo-Gangetic plain in India

The Indo-Gangetic Plain (IGP) is one of the main wheat-production regions in India and the world. With climate change, wheat yields in this region will be affected through changes in temperature and precipitation and decreased water availability for irrigation, raising major concerns for national and international food security. Here we use a regional climate model and a crop model to better understand the direct (via changes in temperature and precipitation) and indirect (via a decrease in irrigation availability) impacts of climate change on wheat yields at four sites spread across different states of the IGP: Punjab, Haryana, Uttar Pradesh and Bihar. The results show an increase in mean temperature and precipitation as well as maximum temperature during the growing season or Rabi season (November–April). The direct impact of climate change, via changes in temperature and precipitation, leads to wheat yield losses between −1% and −8% depending on the site examined. Then, the indirect impact of climate change is examined, considering the impact of climate change on water availability leading to a decrease in irrigation. In this case, the yield losses become significant and much higher, reaching −4% to −36% depending on the site examined and the irrigation regime chosen (6, 5, 3 or 1 irrigations). This work shows that the indirect impacts of climate change may be more detrimental than the direct climatic effects for the future wheat yields in the IGP. It also emphasizes the complexity of climatic risk and the necessity of integrating indirect impacts of climate change to fully assess how it affects agriculture and choose the adequate adaptation response

Hydrocortisone dosing in children with classic congenital adrenal hyperplasia: results of the German/Austrian registry

Objective: Treatment of classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH but recommendations regarding dosage/administration are inconsistent. The aim of this study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicenter CAH registry. Design: The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included. Methods: A custom-made electronic health record software is used at the participating centers. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4. Results: We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean (lower-upper quartiles) daily HC dose (mg/m(2) body surface area) was 19.4 (18.9-19.8) for patients = 3-12 months (n = 463), 14.0 (13.7-14.3) for age 1-5.9 years (n = 745), 14.2 (14.0-14.5) for age 6 years to puberty entry (n = 669), and 14.9 (14.6-15.2) during puberty to 18 years (n = 801). Fludrocortisone was administered in 74.1% of patients with a median daily dosage of 88.8 mu g. Conclusion: Our analyses showed that still a high proportion of children are treated with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily pra ctice