Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings

There is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody testing technologies and their potential use as diagnostic tools. Highly specific in-house ELISAs were developed for the detection of anti-spike (S), -receptor binding domain (RBD) and -nucleocapsid (N) antibodies and used for the cross-comparison of ten commercial serological assays-a chemiluminescence-based platform, two ELISAs and seven colloidal gold lateral flow immunoassays (LFIAs)-on an identical panel of 110 SARS-CoV-2-positive samples and 50 pre-pandemic negatives. There was a wide variation in the performance of the different platforms, with specificity ranging from 82% to 100%, and overall sensitivity from 60.9% to 87.3%. However, the head-to-head comparison of multiple sero-diagnostic assays on identical sample sets revealed that performance is highly dependent on the time of sampling, with sensitivities of over 95% seen in several tests when assessing samples from more than 20 days post onset of symptoms. Furthermore, these analyses identified clear outlying samples that were negative in all tests, but were later shown to be from individuals with mildest disease presentation. Rigorous comparison of antibody testing platforms will inform the deployment of point-of-care technologies in healthcare settings and their use in the monitoring of SARS-CoV-2 infections

Protection from the 2009 H1N1 Pandemic Influenza by an Antibody from Combinatorial Survivor-Based Libraries

Influenza viruses elude immune responses and antiviral chemotherapeutics through genetic drift and reassortment. As a result, the development of new strategies that attack a highly conserved viral function to prevent and/or treat influenza infection is being pursued. Such novel broadly acting antiviral therapies would be less susceptible to virus escape and provide a long lasting solution to the evolving virus challenge. Here we report the in vitro and in vivo activity of a human monoclonal antibody (A06) against two isolates of the 2009 H1N1 pandemic influenza virus. This antibody, which was obtained from a combinatorial library derived from a survivor of highly pathogenic H5N1 infection, neutralizes H5N1, seasonal H1N1 and 2009 “Swine” H1N1 pandemic influenza in vitro with similar potency and is capable of preventing and treating 2009 H1N1 influenza infection in murine models of disease. These results demonstrate broad activity of the A06 antibody and its utility as an anti-influenza treatment option, even against newly evolved influenza strains to which there is limited immunity in the general population

Sex impacts Th1 cells, Tregs, and DCs in both intestinal and systemic immunity in a mouse strain and location-dependent manner

Background: Males and females have a different predisposition for the development of intestinal disorders, like inflammatory bowel disease (IBD). We hypothesized that sex specific differences in intestinal immune responses may underlie this bias. To test this hypothesis, we studied sex differences in immune cell populations in the Peyer's patches (PP). For comparison with systemic immunity, we studied spleen cells. Methods: Two mouse strains with different susceptibility for developing colitis (BALB/c and C57Bl/6) were used. Using flow cytometry, we measured the percentage of T cells, Th1, Th17, and Treg cells in the PP and spleen. In addition, we measured the percentages of NK cells, macrophages, myeloid, and lymphoid dendritic cells (DCs) and their expression of CD80 and CD103. Moreover, we measured percentages of monocyte subsets in the peripheral circulation. Results were tested using two-way ANOVA, p <0.05. Results: Males had a lower percentage of T cells in both PP and spleen (PP BALB/c 22.1 %, B6 13.6 %; spleen BALB/c 4.7 %, B6 19.9 %) but a higher percentage of Th1 cell in both tissues (PP BALB/c 350 %, B6 109.5 %; spleen BALB/c 48.7 %, B6 41.9 %) than females. They also had a higher percentage of Tregs in the spleen than females (BALB/c 20.5 %, B6 4.5 %). Furthermore, males had a higher percentage of CD80(+) DCs in both the PP and spleen (lymphoid DCs in PP BALB/c 104.7 %, B6 29.6 %; spleen BALB/c 72.2 %, B6 44.2 %; myeloid DCs in PP BALB/c 80.5 %, B6 93.3 %; spleen BALB/c 88.5 %, B6 50.8 %) and a higher percentage of lymphoid CD103(+) DCs in the spleen than females (BALB/c 41.5 %, B6 28.3 %). The percentage of NK cells was decreased in the spleen (BALB/c 12.5 %, B6 25.1 %) but increased in the PP (BALB/c 75.7 %, B6 78.6 %) of males as compared with females. Strain differences were also found in the PP; BALB/c mice had a higher percentage of T cells (males 58.1 %, females 75.5 %), a higher Th/Tc ratio (males 81.0 %, females 134.2 %), less FoxP3(+)CD25(-) T cells (males 14.6 %, females 30.0 %), more DCs (males 14.8 %, females 15.7 %) and macrophages (males 67.9 %, females 141.2 %), and more NK cells (males 160 %, females 164.3 %) than BALB/c mice. Conclusions: In this study, we show sex differences in intestinal and peripheral immune populations. These differences may underlie sex differences in intestinal disorders like IBD, and this information may be an important knowledge for the treatment of intestinal-related diseases

Walk-ins seeking treatment at an emergency department or general practitioner out-of-hours service: a cross-sectional comparison

Background Emergency Departments (ED) in Switzerland are faced with increasing numbers of patients seeking non-urgent treatment. The high rate of walks-ins with conditions that may be treated in primary care has led to suggestions that those patients would best cared for in a community setting rather than in a hospital. Efficient reorganisation of emergency care tailored to patients needs requires information on the patient populations using the various emergency services currently available. The aim of this study is to evaluate the differences between the characteristics of walk-in patients seeking treatment at an ED and those of patients who use traditional out-of-hours GP (General Practitioner) services provided by a GP-Cooperative (GP-C). Methods In 2007 and 2009 data was collected covering all consecutive patient-doctor encounters at the ED of a hospital and all those occurring as a result of contacting a GP-C over two evaluation periods of one month each. Comparison was made between a GP-C and the ED of the Waid City Hospital in Zurich. Patient characteristics, time and source of referral, diagnostic interventions and mode of discharge were evaluated. Medical problems were classified according to the International Classification of Primary Care (ICPC-2). Patient characteristics were compared using non-parametric tests and multiple logistic regression analysis was applied to investigate independent determinants for contacting a GP-C or an ED. Results Overall a total of 2974 patient encounters were recorded. 1901 encounters were walk-ins and underwent further analysis (ED 1133, GP-C 768). Patients consulting the GP-C were significantly older (58.9 vs. 43.8 years), more often female (63.5 vs. 46.9%) and presented with non-injury related medical problems (93 vs. 55.6%) in comparison with patients at the ED. Independent determining factors for ED consultation were injury, male gender and younger age. Walk-in distribution in both settings was equal over a period of 24 hours and most common during daytime hours (65%). Outpatient care was predominant in both settings but significantly more so at the GP-C (79.9 vs. 85.7%). Conclusions We observed substantial differences between the two emergency settings in a non gate-keeping health care system. Knowledge of the distribution of diagnoses, their therapy, of diagnostic measures and of the factors which determine the patients' choice of the ED or the GP-C is essential for the efficient allocation of resources and the reduction of costs

Estimates of probable dementia prevalence from population-based surveys compared with dementia prevalence estimates based on meta-analyses

<p>Abstract</p> <p>Background</p> <p>National data on dementia prevalence are not always available, yet it may be possible to obtain estimates from large surveys that include dementia screening instruments. In Australia, many of the dementia prevalence estimates are based on European data collected between 15 and 50 years ago. We derived population-based estimates of probable dementia and possible cognitive impairment in Australian studies using the Mini-Mental State Examination (MMSE), and compared these to estimates of dementia prevalence from meta-analyses of European studies.</p> <p>Methods</p> <p>Data sources included a pooled dataset of Australian longitudinal studies (DYNOPTA), and two Australian Bureau of Statistics National Surveys of Mental Health and Wellbeing. National rates of probable dementia (MMSE < 24) and possible cognitive impairment (24-26) were estimated using combined sample weights.</p> <p>Results</p> <p>Estimates of probable dementia were higher in surveys than in meta-analyses for ages 65-84, but were similar at ages 85 and older. Surveys used weights to account for sample bias, but no adjustments were made in meta-analyses. Results from DYNOPTA and meta-analyses had a very similar pattern of increase with age. Contrary to trends from some meta-analyses, rates of probable dementia were not higher among women in the Australian surveys. Lower education was associated with higher prevalence of probable dementia. Data from investigator-led longitudinal studies designed to assess cognitive decline appeared more reliable than government health surveys.</p> <p>Conclusions</p> <p>This study shows that estimates of probable dementia based on MMSE in studies where cognitive decline and dementia are a focus, are a useful adjunct to clinical studies of dementia prevalence. Such information and may be used to inform projections of dementia prevalence and the concomitant burden of disease.</p

Exploiting Clinical Trial Data Drastically Narrows the Window of Possible Solutions to the Problem of Clinical Adaptation of a Multiscale Cancer Model

The development of computational models for simulating tumor growth and response to treatment has gained significant momentum during the last few decades. At the dawn of the era of personalized medicine, providing insight into complex mechanisms involved in cancer and contributing to patient-specific therapy optimization constitute particularly inspiring pursuits. The in silico oncology community is facing the great challenge of effectively translating simulation models into clinical practice, which presupposes a thorough sensitivity analysis, adaptation and validation process based on real clinical data. In this paper, the behavior of a clinically-oriented, multiscale model of solid tumor response to chemotherapy is investigated, using the paradigm of nephroblastoma response to preoperative chemotherapy in the context of the SIOP/GPOH clinical trial. A sorting of the model's parameters according to the magnitude of their effect on the output has unveiled the relative importance of the corresponding biological mechanisms; major impact on the result of therapy is credited to the oxygenation and nutrient availability status of the tumor and the balance between the symmetric and asymmetric modes of stem cell division. The effect of a number of parameter combinations on the extent of chemotherapy-induced tumor shrinkage and on the tumor's growth rate are discussed. A real clinical case of nephroblastoma has served as a proof of principle study case, demonstrating the basics of an ongoing clinical adaptation and validation process. By using clinical data in conjunction with plausible values of model parameters, an excellent fit of the model to the available medical data of the selected nephroblastoma case has been achieved, in terms of both volume reduction and histological constitution of the tumor. In this context, the exploitation of multiscale clinical data drastically narrows the window of possible solutions to the clinical adaptation problem

On the effect specificity of accessory gland products transferred by the love-dart of land snails

Background: Sexual selection favours the evolution of male bioactive substances transferred during mating to enhance male reproductive success by affecting female physiology. These effects are mainly well documented for separate-sexed species. In simultaneous hermaphrodites, one of the most peculiar examples of transfer of such substances is via stabbing a so-called love-dart in land snails. This calcareous stylet delivers mucous products produced by accessory glands into the mate's haemolymph. In Cornu aspersum, this mucus temporarily causes two changes in the recipient. First, the spermatophore uptake into the spermatophore-receiving organ, called diverticulum, is probably favoured by contractions of this organ. Second, the amount of stored sperm increases by contractions of the copulatory canal, which close off the tract leading to the sperm digesting organ. However, it has yet to be determined whether these effects are similar across species, which would imply a common strategy of the dart in increasing male reproductive success. Results: We performed a cross-reactivity test to compare the in vitro response of the diverticulum and copulatory canal of C. aspersum (Helicidae) to its own and other species' mucus (seven helicids and one bradybaenid). We found that the contractions in the diverticulum were only induced by dart mucus of certain species, while the copulatory canal responded equally to all but one species' mucus tested. In addition, we report a newly-discovered effect causing the shortening of the diverticulum, which is also only caused by dart mucus of certain species. The advantage seems to be a distance reduction to the sperm storage organ. Conclusions: All these findings are the first to shed light on the evolution of the different functions of accessory gland products in dart-bearing species. These functions may be achieved via common physiological changes caused by the substances contained in the dart mucus, since the responses evoked were similar across species' mucus. Moreover, while these substances can act similarly in separate-sexed species as in simultaneous hermaphrodites, differences may occur in their evolution between the two sexual systems

Bias of health estimates obtained from chronic disease and risk factor surveillance systems using telephone population surveys in Australia: Results from a representative face-to-face survey in Australia from 2010 to 2013

Background: Emerging communication technologies have had an impact on population-based telephone surveys worldwide. Our objective was to examine the potential biases of health estimates in South Australia, a state of Australia, obtained via current landline telephone survey methodologies and to report on the impact of mobile-only household on household surveys. Methods: Data from an annual multi-stage, systematic, clustered area, face-to-face population survey, Health Omnibus Survey (approximately 3000 interviews annually), included questions about telephone ownership to assess the population that were non-contactable by current telephone sampling methods (2006 to 2013). Univariable analyses (2010 to 2013) and trend analyses were conducted for sociodemographic and health indicator variables in relation to telephone status. Relative coverage biases (RCB) of two hypothetical telephone samples was undertaken by examining the prevalence estimates of health status and health risk behaviours (2010 to 2013): directory-listed numbers, consisting mainly of landline telephone numbers and a small proportion of mobile telephone numbers; and a random digit dialling (RDD) sample of landline telephone numbers which excludes mobile-only households. Results: Telephone (landline and mobile) coverage in South Australia is very high (97 %). Mobile telephone ownership increased slightly (7.4 %), rising from 89.7 % in 2006 to 96.3 % in 2013; mobile-only households increased by 431 % over the eight year period from 5.2 % in 2006 to 27.6 % in 2013. Only half of the households have either a mobile or landline number listed in the telephone directory. There were small differences in the prevalence estimates for current asthma, arthritis, diabetes and obesity between the hypothetical telephone samples and the overall sample. However, prevalence estimate for diabetes was slightly underestimated (RCB value of -0.077) in 2013. Mixed RCB results were found for having a mental health condition for both telephone samples. Current smoking prevalence was lower for both hypothetical telephone samples in absolute differences and RCB values: -0.136 to -0.191 for RDD landline samples and -0.129 to -0.313 for directory-listed samples. Conclusion: These findings suggest landline-based sampling frames used in Australia, when appropriately weighted, produce reliable representative estimates for some health indicators but not for all. Researchers need to be aware of their limitations and potential biased estimates.Emerging communication technologies have had an impact on population-based telephone surveys worldwide. Our objective was to examine the potential biases of health estimates in South Australia, a state of Australia, obtained via current landline telephone survey methodologies and to report on the impact of mobile-only household on household surveys