Norwich COVID-19 testing initiative pilot: evaluating the feasibility of asymptomatic testing on a university campus.

BACKGROUND: There is a high prevalence of COVID-19 in university-age students, who are returning to campuses. There is little evidence regarding the feasibility of universal, asymptomatic testing to help control outbreaks in this population. This study aimed to pilot mass COVID-19 testing on a university research park, to assess the feasibility and acceptability of scaling up testing to all staff and students. METHODS: This was a cross-sectional feasibility study on a university research park in the East of England. All staff and students (5625) were eligible to participate. All participants were offered four PCR swabs, which they self-administered over two weeks. Outcome measures included uptake, drop-out rate, positivity rates, participant acceptability measures, laboratory processing measures, data collection and management measures. RESULTS: 798 (76%) of 1053 who registered provided at least one swab; 687 (86%) provided all four; 792 (99%) of 798 who submitted at least one swab had all negative results and 6 participants had one inconclusive result. There were no positive results. 458 (57%) of 798 participants responded to a post-testing survey, demonstrating a mean acceptability score of 4.51/5, with five being the most positive. CONCLUSIONS: Repeated self-testing for COVID-19 using PCR is feasible and acceptable to a university population.

The time lag prior to the rise in glucose requirements to maintain stable glycaemia during moderate exercise in a fasted insulinaemic state is of short duration and unaffected by the level at which glycaemia is maintained in Type 1 diabetes.

AIMS: To determine the duration of the low hypoglycaemia risk period after the start of moderate-intensity exercise performed under basal insulinaemic conditions and whether this period is affected by the level at which glycaemia is maintained under these conditions. METHODS: This was a prospective, randomized counterbalanced study. Eight participants with Type 1 diabetes (mean ± sd age 21.5 ± 4.0 years) underwent either a euglycaemic (5-6 mmol/l) or hyperglycaemic clamp (9-10 mmol/l) on separate days and were infused with insulin at basal rates and [6,6-2 H]glucose while cycling for 40 min at 50% maximum oxygen consumption rate. The main outcome measures were the glucose infusion rates required to maintain stable glycaemia and glucoregulatory hormone levels, and rates of glucose appearance and disappearance. RESULTS: During the first 20 min of exercise, the glucose infusion rate did not increase significantly, irrespective of the level at which glycaemia was maintained, but increased acutely between 20 and 25 min under both conditions. Maintaining higher glycaemia resulted in higher glucose infusion rate during, but not early post-exercise. With the exception of epinephrine, the glucoregulatory hormone levels and rates of glucose appearance and disappearance were similar between conditions. CONCLUSION: Irrespective of the levels at which glycaemia is maintained, there is a 20-min low exogenous glucose demand period during which the exogenous glucose requirements to maintain stable glycaemia do not increase during moderate exercise performed at basal insulin level.

A 10-second sprint does not blunt hormonal counter-regulation to subsequent hypoglycaemia.

AIM: To investigate whether a 10-second (s) sprint impairs the counter-regulatory response to subsequent hypoglycaemia. METHODS: Nine people (five male, four female) with Type 1 diabetes, aged 21.1 ± 4.5 years, performed a 10-s rest or a 10-s maximum-effort sprint in random order on different days, while subjected to an euinsulinaemic-euglycaemic clamp. This was followed by a hyperinsulinaemic-hypoglycaemic glucose clamp 2.5 h later to induce hypoglycaemia for 40 min. At timed intervals, the counter-regulatory hormonal responses to hypoglycaemia were measured. Blood pressure, heart rate and hypoglycaemic symptoms were also assessed. RESULTS: During the hypoglycaemic clamp, epinephrine, norepinephrine, growth hormone and cortisol levels increased significantly from baseline, and their responses were similar after both rest and sprint conditions. In particular, plasma epinephrine rose eightfold, from 197 ± 103 pmol/l to 1582 ± 1118 pmol/l after the rest condition, and from 219 ± 119 pmol/l to 1900 ± 898 pmol/l after the sprint condition. CONCLUSION: A 10-s sprint is unlikely to blunt the subsequent hormonal counter-regulation to hypoglycaemia in individuals with Type 1 diabetes.

Reproducibility of the plasma glucose response to moderate-intensity exercise in adolescents with Type 1 diabetes.

AIMS: The aim of the study was to evaluate the reproducibility of the plasma glucose response to moderate-intensity exercise performed on different days under controlled conditions in adolescents with Type 1 diabetes. METHODS: Eight adolescents with Type 1 diabetes on continuous subcutaneous insulin infusion completed two exercise sessions, each on two separate days, under basal insulin and fasting conditions. On each day, participants cycled twice for 30 min at 55% of their peak rate of oxygen consumption, with each exercise session separated by a 30-min rest. RESULTS: Plasma insulin levels were similar between testing days and exercise sessions. The mean absolute drop in plasma glucose from the commencement to the end of exercise was 1.6 ± 0.5 mmol/l on day 1 and 1.9 ± 0.7 mmol/l on day 2 (P = 0.3). In response to the first exercise session, plasma glucose levels relative to baseline did not change significantly (0.2 ± 0.6 and -0.2 ± 0.5 mmol/l on days 1 and 2). By contrast, the change in plasma glucose during the second exercise session was -1.1 ± 0.7 and -1.3 ± 0.7mmol/l on days 1 and 2, respectively. The mean absolute intra-individual difference in the change in plasma glucose between testing days were 0.7 ± 0.5 [95% confidence interval (CI) 0.4-1.0] and 0.7 ± 0.4 (95% CI 0.4-1.0) mmol/l, at the end of the first and second exercise sessions respectively. CONCLUSIONS: The plasma glucose response to moderate-intensity exercise under similar glycaemic and basal insulin conditions can be reproducible in adolescents with Type 1 diabetes.

Mechanisms of Filovirus Entry.

Filovirus entry into cells is complex, perhaps as complex as any viral entry mechanism identified to date. However, over the past 10 years, the important events required for filoviruses to enter into the endosomal compartment and fuse with vesicular membranes have been elucidated (Fig. 1). Here, we highlight the important steps that are required for productive entry of filoviruses into mammalian cells.

Vitamin D-binding protein as it is understood in 2016: is it a critical key with which to help to solve the calcitriol conundrum?

Background The misnamed 'vitamin' D is actually the hormone calcitriol (1,25 dihydroxyhydroxyvitamin D). It has a central regulatory role in calcium metabolism, and more widely in the immune system. The prohormone calcifediol (25 hydroxyvitamin D) is more easily measured in the laboratory and is the analyte used in reference interval formulation. Being highly lipid soluble, both calcifediol and calcitriol travel in the bloodstream on carriage proteins, principally on vitamin D-binding protein. Summary This review reports our current understanding of vitamin D-binding protein. Its genetic determinants and their effect on it and secondarily on calcifediol concentrations and assays are described. Its complex interplay with parathyroid hormone is considered. The analytical state of the art is translated into the challenge it imposes clinically, in the formulation of reference intervals and in their use in advising and managing patients. Several recent challenges thrown up to laboratories by percipient clinicians highlight the dilemma vitamin D-binding protein poses. A way forward is suggested.

Detection of tubule boundaries based on circular shortest path and polar-transformation of arbitrary shapes.

In studies of germ cell transplantation, counting cells and measuring tubule diameters from different populations using labelled antibodies are important measurement processes. However, it is slow and sanity grinding to do these tasks manually. This paper proposes a way to accelerate these processes using a new image analysis framework based on several novel algorithms: centre points detection of tubules, tubule shape classification, skeleton-based polar-transformation, boundary weighting of polar-transformed image, and circular shortest path smoothing. The framework has been tested on a dataset consisting of 27 images which contain a total of 989 tubules. Experiments show that the detection results of our algorithm are very close to the results obtained manually and the novel approach can achieve a better performance than two existing methods.

Which nanny--the state or industry? Wowsers, teetotallers and the fun police in public health advocacy.

There is no option for avoiding the 'Nanny'. The only option for communities is to make sensible choices about which 'Nanny' will dominate their lives and at what time, which 'Nanny' will make us healthy and which 'Nanny' will undermine our health and our freedoms. Those political ideologues who use 'nanny statism' largely do so to further their own agenda and are invariably inconsistent in how they apply their concept of non-interference. Who's afraid of the 'Nanny State' is not the question should be asking. Rather the question ought to be--which Nanny should cause the greatest concern? The prime reason that the 'Nanny State' conjures fear is that it is a threat to the freedoms that are a key element of democratic societies. The tenet understood by the concept of the 'Nanny State' is that the more regulation that is made by the State, the more freedoms are whittled away and it is the intention of the wowsers, the teetotallers and the fun police to do so. It is time to rethink the 'nanny' concept, from the narrow sense of loss of individual freedoms (and one which favours 'free enterprise' and money making interests of big industry) to that which enables individuals and populations freedom from domination. Such a change particularly pertains to our understandings of the role of government. Pettit's work in framing the notion of freedom in terms of 'dominance' rather than 'interference' is pertinent. It provides a more realistic way in which to understand why industry uses the 'Nanny State' argument. It is to maintain its own dominance (i.e. in matters of public health) rather than allowing governments to interfere with that dominance. Public health advocacy work is regularly undermined by the 'Nanny State' phrase. This paper explores a series of examples which illustrate how public health is being undermined by the 'Nanny Industry' and how industry uses fear of government regulation to maintain its own dominance, to maintain its profits and to do so at a significant financial and social cost to the community and to public health.

Can the study of self-assembly in solution lead to a good model for the nucleation pathway? The case of tolfenamic acid.

To further our understanding of the role of solution chemistry in directing nucleation processes new experimental and computational data are presented on the solution and crystallisation chemistry of tolfenamic acid (TA), a benchmark polymorphic compound. With these, and previously published data, we were able to establish that TA is rapidly fluctuating between conformers in solution with either solvated monomers or dimers present depending on the solvent. Hence, despite the fact that conformational polymorphs can be obtained from crystallisations in ethanol, we found no links between solution chemistry and crystallisation outcomes. We discuss the implications of these conclusions for the nature of the nucleation pathway via dimers and clusters and raise experimental questions about how best to undertake relevant crystallisation studies.

A mitochondrial malady: stubborn seizures and atypical migraine.

A 22-year-old female migraineur presented with recurrent convulsive status epilepticus and ataxia. Her epilepsy proved refractory to treatment, necessitating the use of five anti-epileptic drugs and a course of steroids. Genetic testing revealed compound heterozygosity for two mutations of the polymerase-? gene. The case highlights the clinical features and therapeutic challenges associated with this relatively common, but probably underrecognised, mitochondrial disease.

International study of objectively measured physical activity and sedentary time with body mass index and obesity: IPEN adult study.

BACKGROUND: Physical activity (PA) has been consistently implicated in the etiology of obesity, whereas recent evidence on the importance of sedentary time remains inconsistent. Understanding of dose-response associations of PA and sedentary time with overweight and obesity in adults can be improved with large-scale studies using objective measures of PA and sedentary time. The purpose of this study was to examine the strength, direction and shape of dose-response associations of accelerometer-based PA and sedentary time with body mass index (BMI) and weight status in 10 countries, and the moderating effects of study site and gender. METHODS: Data from the International Physical activity and the Environment Network (IPEN) Adult study were used. IPEN Adult is an observational multi-country cross-sectional study, and 12 sites in 10 countries are included. Participants wore an accelerometer for seven consecutive days, completed a socio-demographic questionnaire and reported height and weight. In total, 5712 adults (18-65 years) were included in the analyses. Generalized additive mixed models, conducted in R, were used to estimate the strength and shape of the associations. RESULTS: A curvilinear relationship of accelerometer-based moderate-to-vigorous PA and total counts per minute with BMI and the probability of being overweight/obese was identified. The associations were negative, but weakened at higher levels of moderate-to-vigorous PA (>50 min per day) and higher counts per minute. No associations between sedentary time and weight outcomes were found. Complex site- and gender-specific findings were revealed for BMI, but not for weight status. CONCLUSIONS: On the basis of these results, the current Institute of Medicine recommendation of 60 min per day of moderate-to-vigorous PA to prevent weight gain in normal-weight adults was supported. No relationship between sedentary time and the weight outcomes was present, calling for further examination. If moderator findings are confirmed, the relationship between PA and BMI may be country- and gender-dependent, which could have important implications for country-specific health guidelines.

A vesicular stomatitis pseudovirus expressing the surface glycoproteins of influenza A virus.

Pseudotyped viruses bearing the glycoprotein(s) of a donor virus over the nucleocapsid core of a surrogate virus are widely used as safe substitutes for infectious virus in virology studies. Retroviral particles pseudotyped with influenza A virus glycoproteins have been used recently for the study of influenza hemagglutinin and neuraminidase-dependent processes. Here, we report the development of vesicular-stomatitis-virus-based pseudotypes bearing the glycoproteins of influenza A virus. We show that pseudotypes bearing the hemagglutinin and neuraminidase of H5N1 influenza A virus mimic the wild-type virus in neutralization assays and sensitivity to entry inhibitors. We demonstrate the requirement of NA for the infectivity of pseudotypes and show that viruses obtained with different NA proteins are significantly different in their transduction activities. Inhibition studies with oseltamivir carboxylate show that neuraminidase activity is required for pseudovirus production, but not for the infection of target cells with H5N1-VSV pseudovirus. The HA-NA-VSV pseudoviruses have high transduction titers and better stability than the previously reported retroviral pseudotypes and can replace live influenza virus in the development of neutralization assays, screening of potential antivirals, and the study of different HA/NA reassortants.

Transplanted germ cells persist long-term in irradiated ram testes.

Testicular germ cell transplantation provides a tool to study transgenesis, spermatogenesis and to increase production efficiency in livestock industries. Isolated testicular germ cells can be transplanted into testes of livestock breeds to generate sperm of donor origin. In sheep, methods have been developed previously to isolate cell populations from ram testes and transplant these into irradiated testes of recipient rams. This has resulted in rams producing sperm derived from the donor cells and a number of the recipient animals have produced donor-derived offspring from the introduced spermatogonial cells. Microsatellite genotyping data presented here demonstrates that these rams continue to produce sperm of donor origin for at least 5 years post-transplantation. This research provides new evidence of the stability of transplanted germ cells in a commercially important species, and with further refinements to cell isolation, transplantation and recipient preparation, this technology should find use in breeding systems to increase livestock production efficiency.

Baseline CD4+ T-cell counts predict HBV viral kinetics to adefovir treatment in lamivudine-resistant HBV-infected patients with or without HIV infection.

BACKGROUND: Coinfection with HIV and hepatitis B virus (HBV) substantially alters the course of HBV. Directly acting anti-HBV agents suppress HBV viral levels; however, the kinetics of HBV decline in mono- and coinfected persons have not been evaluated. We investigated the role of baseline CD4+ T-cell counts as a predictor of HBV response to adefovir (ADV) therapy in chronic HBV with and without HIV coinfection. METHODS: We conducted a double-blind, randomized, placebo-controlled study of HIV-infected (n = 12) and uninfected (n = 5) chronic HBV patients treated with ADV. Five HIV uninfected patients received ADV; the HIV+ patients received ADV or placebo for a total of 48 weeks. At the end of 48 weeks, all patients received open-label ADV for an additional 48 weeks. HBV, HIV viral loads, CD4+ T-cell counts, and safety labs were performed on days 0, 1, 3, 5, 7, 10, 14, and 28 and then every 4 weeks. RESULTS: Lower HBV slopes were observed among coinfected compared to monoinfected patients (P = .027 at 4 weeks, P = .019 at 24 weeks, and P = .045 at 48 weeks). Using a mixed model analysis, we found a significant difference between the slopes of the 2 groups at 48 weeks (P = .045). Baseline CD4+ T-cell count was the only independent predictor of HBV decline in all patients. CONCLUSION: HIV coinfection is associated with slower HBV response to ADV. Baseline CD4+ T-cell count and not IL28B genotype is an independent predictor of HBV decline in all patients, emphasizing the role of immune status on clearance of HBV.

The effect of a short sprint on postexercise whole-body glucose production and utilization rates in individuals with type 1 diabetes mellitus.

CONTEXT: Recently we showed that a 10-sec maximal sprint effort performed before or after moderate intensity exercise can prevent early hypoglycemia during recovery in individuals with type 1 diabetes mellitus (T1DM). However, the mechanisms underlying this protective effect of sprinting are still unknown. OBJECTIVE: The objective of the study was to test the hypothesis that short duration sprinting increases blood glucose levels via a disproportionate increase in glucose rate of appearance (Ra) relative to glucose rate of disappearance (Rd). SUBJECTS AND EXPERIMENTAL DESIGN: Eight T1DM participants were subjected to a euglycemic-euinsulinemic clamp and, together with nondiabetic participants, were infused with [6,6-(2)H]glucose before sprinting for 10 sec and allowed to recover for 2 h. RESULTS: In response to sprinting, blood glucose levels increased by 1.2 ± 0.2 mmol/liter (P < 0.05) within 30 min of recovery in T1DM participants and remained stable afterward, whereas glycemia rose by only 0.40 ± 0.05 mmol/liter in the nondiabetic group. During recovery, glucose Ra did not change in both groups (P > 0.05), but glucose Rd in the nondiabetic and diabetic participants fell rapidly after exercise before returning within 30 min to preexercise levels. After sprinting, the levels of plasma epinephrine, norepinephrine, and GH rose transiently in both experimental groups (P < 0.05). CONCLUSION: A sprint as short as 10 sec can increase plasma glucose levels in nondiabetic and T1DM individuals, with this rise resulting from a transient decline in glucose Rd rather than from a disproportionate rise in glucose Ra relative to glucose Rd as reported with intense aerobic exercise.

Facilitative ecological interactions between invasive species: Arundo donax stands as favorable habitat for cattle ticks (Acari: Ixodidae) along the U.S.-Mexico border.

The cattle tick, Rhipicephalus (Boophilus) spp. is a key vector of protozoa that cause bovine babesiosis. Largely eradicated from most of the United States, the cattle tick continues to infest south Texas, and recent outbreaks in this area may signal a resurgence of cattle tick populations despite current management efforts. An improved understanding of the dynamic ecology of cattle fever ticks along the U.S.-Mexico border is required to devise strategies for sustainable eradication efforts. Management areas of the cattle tick overlap considerably with dense, wide infestations of the non-native, invasive grass known as giant reed (Arundo donax L.). Here we show that stands of giant reed are associated with abiotic and biotic conditions that are favorable to tick survival, especially when compared with other nearby habitats (open pastures of buffelgrass (Pennisetum ciliare) and closed canopy native forests). Overhead canopies in giant reed stands and native riparian forests reduce daily high temperature, which was the best abiotic predictor of oviposition by engorged females. In sites where temperatures were extreme, specifically open grasslands, fewer females laid eggs and the resulting egg masses were smaller. Pitfall trap collections of ground dwelling arthropods suggest a low potential for natural suppression of tick populations in giant reed stands. The finding that A. donax infestations present environmental conditions that facilitate the survival and persistence of cattle ticks, as well or better than native riparian habitats and open grasslands, represents an alarming complication for cattle fever tick management in the United States.

Efficacy of amitraz-impregnated collars on white-tailed deer (Artiodactyla: Cervidae) in reducing free-living populations of lone star ticks (Acari: Ixodidae).

Over a 7 yr period, we monitored the effect of a commercially available, amitraz impregnated anti-tick collar in controlling free-living populations of lone star ticks, Amblyomma americanum (L.) when manually fitted around necks of white-tailed deer, Odocoileus virginianus (Zimmermann). Study animals in treatment and control groups were confined in 38.8 ha game-fenced and densely vegetated treatment plots in South Texas. Tick densities during years 1 and 7 served as untreated pre- and posttreatment comparisons and treatments occurred during years 2 through 5. Reductions in tick densities in the treatment plot were compared against tick densities in a control plot having similar vegetation and numbers of untreated deer. During years of treatment, indices of control pressure ranged from 18.2 to 82.6 for nymphs and 16.9-78.7 for adults, and efficacy, expressed as percentage control during the final year of treatment, was 77.2 and 85.0%, respectively, for nymphal and adult ticks. These data show that acaricidal collar treatments provide efficacies very similar to those achieved with the existing ivermectin-medicated bait and '4-Poster' topical treatment technologies to control ticks feeding on wild white-tailed deer.

Distribution of Rhipicephalus (Boophilus) microplus and Rhipicephalus (Boophilus) annulatus (Acari: Ixodidae) infestations detected in the United States along the Texas/Mexico border.

Species identification and global positioning system coordinates of infestations of cattle fever ticks, Rhipicephalus (Boophilus) annulatus (Say) and Rhipicephalus (Boophilus) microplus (Canestrini), were determined for 790 specimens submitted to the National Veterinary Services Laboratory between 1 October 1999 and 30 September 2010. Cattle fever tick specimens obtained by personnel of the United States Department of Agriculture-Animal and Plant Health Inspection Service-Cattle Fever Tick Eradication Program from infested cattle and wildlife along the Texas/ Mexico border were submitted for identification, as required by the program. A geographic information system database was developed that incorporates location, collection, and infestation records. Submitted ticks came from 11 Texas counties and were comprised of 19.5% R. (B.) annulatus and 80.5% R. (B.) microplus. Maps produced from this study locate and define the parapatric boundary between R. (B.) annulatus and R. (B.) microplus.

A shorter interval between irradiation of recipient testis and germ cell transplantation is detrimental to recovery of fertility in rams.

The objective of the current study was to identify an optimal time period for donor cell transplantation after irradiation in sheep. The testes of recipient rams were treated with a single dose of 15 Gray (Gy) irradiation followed by germ cell transplantation either 3 or 6 weeks later. Transplantation of donor cells at 6 weeks after irradiation resulted in production of donor sperm by all five recipient rams compared with 4 of 11 rams transplanted at 3 weeks. Rams transplanted 3 weeks post-irradiation appeared to show reduced libido and fertility. Two rams produced sperm with low motility (< 20%) and two other rams were azoospermic. More than 1 year after cell transfer, there were heavy infiltrates of CD45-positive cells and more fibrous tissue in 9 of 14 recipient testes (seven rams) that received cells 3 weeks after irradiation. Taken together, these results suggest that the interval between irradiation of recipients and germ cell transplantation affects the success rate of the procedure, with a 6-week interval preferable. The elevated inflammatory/immune reaction may be responsible, at least in part, for the reduced fertility and low libido observed in the rams that received cells 3 weeks post-irradiation.

The relationship between solution structure and crystal nucleation: a neutron scattering study of supersaturated methanolic solutions of benzoic acid.

In this contribution, neutron scattering experiments (with isotopic substitution) of concentrated and supersaturated methanolic benzoic acid solutions combined with empirical potential structure refinement (EPSR) were used to investigate the time-averaged atomistic details of this system. Through the determination of radial distribution functions, quantitative details emerge of the solution coordination, its relationship to the nature of the crystalline phase, and the response of the solution to imposed supersaturation.