The dispersion of spherical droplets in source-sink flows and their relevance to the COVID-19 pandemic.

In this paper, we investigate the dynamics of spherical droplets in the presence of a source-sink pair flow field. The dynamics of the droplets is governed by the Maxey-Riley equation with the Basset-Boussinesq history term neglected. We find that, in the absence of gravity, there are two distinct behaviors for the droplets: small droplets cannot go further than a specific distance, which we determine analytically, from the source before getting pulled into the sink. Larger droplets can travel further from the source before getting pulled into the sink by virtue of their larger inertia, and their maximum traveled distance is determined analytically. We investigate the effects of gravity, and we find that there are three distinct droplet behaviors categorized by their relative sizes: small, intermediate-sized, and large. Counterintuitively, we find that the droplets with a minimum horizontal range are neither small nor large, but of intermediate size. Furthermore, we show that in conditions of regular human respiration, these intermediate-sized droplets range in size from a few µm to a few hundred µm. The result that such droplets have a very short range could have important implications for the interpretation of existing data on droplet dispersion.

Female rugby union injuries in New Zealand: A review of five years (2013-2017) of Accident Compensation Corporation moderate to severe claims and costs.

OBJECTIVES: To provide epidemiological data and related costs for moderate-to-serious and serious injury claims for women's rugby union in New Zealand. DESIGN: A retrospective analytical review of injury entitlement claims for women's rugby from 2013 to 2017. METHODS: Data were analysed by year of competition, age, body site and injury type for total and moderate-to-severe (MSC) Accident Compensation Corporation (ACC) claims and costs. RESULTS: Over 2013 to 2017 there were 26,070 total claims for female rugby union costing $18,440,812 [AD$16,956,998]. The 15-19-year age group recorded 40% (n=1,009) of the total female rugby union Moderate-to-serious and serious (MSC) claims and 41% ($5,419,157 [AD$4,983,112]) of the total female rugby union MSC costs. The knee was the most commonly recorded injury site accounting for 40.3% (n=1,007) of MSC claims and 46.9% ($6,229,714 [AD$5,728732]) of MSC costs with an average cost of $1,245,943 ±$217,796 [AD$595,351 ±AD$104,070] per-year for female rugby union. CONCLUSIONS: This is the first study to report the nature and related costs for moderate-to-serious and serious injury claims for women's rugby union in New Zealand. A total of 26,070 injury claims were lodged over the duration of the study but only 9.6% (n=2,501) of these were classified as MSC injury entitlement claims. Participants 25 years and older accounted for 31% of the female rugby union player claims. Females in the over 35-year age groups compete against younger participants which may account for the higher mean cost per-claim seen as the age groups increase in years until they retire from the game.

A strain-mediated corrosion model for bioabsorbable metallic stents.

This paper presents a strain-mediated phenomenological corrosion model, based on the discrete finite element modelling method which was developed for use with the ANSYS Implicit finite element code. The corrosion model was calibrated from experimental data and used to simulate the corrosion performance of a WE43 magnesium alloy stent. The model was found to be capable of predicting the experimentally observed plastic strain-mediated mass loss profile. The non-linear plastic strain model, extrapolated from the experimental data, was also found to adequately capture the corrosion-induced reduction in the radial stiffness of the stent over time. The model developed will help direct future design efforts towards the minimisation of plastic strain during device manufacture, deployment and in-service, in order to reduce corrosion rates and prolong the mechanical integrity of magnesium devices. STATEMENT OF SIGNIFICANCE: The need for corrosion models that explore the interaction of strain with corrosion damage has been recognised as one of the current challenges in degradable material modelling (Gastaldi et al., 2011). A finite element based plastic strain-mediated phenomenological corrosion model was developed in this work and was calibrated based on the results of the corrosion experiments. It was found to be capable of predicting the experimentally observed plastic strain-mediated mass loss profile and the corrosion-induced reduction in the radial stiffness of the stent over time. To the author's knowledge, the results presented here represent the first experimental calibration of a plastic strain-mediated corrosion model of a corroding magnesium stent.

Navigating physical activity engagement following a diagnosis of cancer: A qualitative exploration.

This qualitative descriptive study explored cancer survivors' experiences of barriers and facilitators to undertaking physical activity to inform how services and professionals might offer better support. Purposive and theoretical sampling was used to recruit 25 people who were up to 5 years post-cancer diagnosis. Participants took part in face to face, semi-structured interviews, and transcripts were analysed using thematic analysis. The analysis identified five interrelated themes which represented cancer survivors' views: 1) You're on your own-a sense of abandonment post-treatment, and lack of sufficient and tailored information; 2) Dis-ease-disruption to self and identity, and a heightened awareness of physical self and fragility; 3) Becoming acclimatised-physical activity in the face of treatment-related side effects and residual impairment; 4) Importance of others-encouragement and support from health professionals, family and friends, and cancer-specific exercise groups; 5) Meanings people ascribed to physical activity-these were central and could help or hinder engagement. Our findings suggest being able to live well and re-engage in meaningful activities following a diagnosis of cancer is both complex and challenging. There appear to be gaps in current service provision in supporting the broader health and well-being of cancer survivors.

The effect of colostrum storage conditions on dairy heifer calf serum immunoglobulin G concentration and preweaning health and growth rate.

The objective of the present study was to compare serum IgG concentration, weight gain, and health characteristics in Irish spring-born dairy calves fed colostrum stored using a range of conditions. Immediately after birth, 75 dairy heifer calves were assigned to 1 of 5 experimental colostrum treatments: (1) fresh pasteurized colostrum, fed immediately after pasteurization; (2) fresh colostrum, fed immediately after collection but not pasteurized; (3) colostrum stored unpasteurized at 4°C in a temperature-controlled unit for 2d before being fed to calves; (4) colostrum stored unpasteurized at 13°C in a temperature-controlled unit for 2d before being fed to calves; and (5) colostrum stored unpasteurized at 22°C in a temperature-controlled unit for 2d before being fed to calves. All colostrum had IgG concentrations >50g/L and was fed to calves promptly after birth. Blood samples were obtained from calves via the jugular vein at 0h (before colostrum feeding) and at 24h of age to determine the rate of passive transfer of IgG; individual calf live-weights were recorded to monitor weight gain (kg/d) from birth to weaning. Colostrum stored in warmer conditions (i.e., 22°C) had >42 times more bacteria present and a pH that was 0.85 units lower and resulted in a serum IgG concentration that was almost 2 times lower compared with colostrum that was pasteurized, untreated, or stored at 4°C for 2d. Colostrum stored at 4°C for 2d had more bacteria present than pasteurized and fresh colostrum but did not result in reduced calf serum IgG concentrations. Average daily weight gain from birth to weaning did not differ among treatments. Even if colostrum has sufficient IgG (>50g/L) but cannot be fed to calves when freshly collected, storage at ≤4°C for 2d is advisable to ensure adequate passive transfer when it is consumed by the calf.

Energetic and Metabolic Power Demands of National Rugby League Match-Play.

The purpose of this study was to apply a time-motion model to estimate and describe the energy expenditure and metabolic power demands of playing positions in elite rugby league match-play, utilizing Global Positioning System (GPS) devices. 18 elite rugby league players participated in this study. Players' positional groups included: outside backs (n=59 files, n=4 players), adjustables (n=74 files, n=4 players), wide-running (n=104 files, n=7 players) and hit-up forwards (n=36 files, n=3 players). Outside backs expended the greatest total energy (40.1±5.0 kJ·kg(-1)) per match, equivalent to 8.1%, 26.6% and 61.9% greater energy than adjustables, wide-running and hit-up forwards, respectively. Adjustables attained an anaerobic index 7.3% higher than wide-running forwards, 19.7% higher than hit-up forwards (p=0.001) and 43.2% higher than outside backs (p<0.001). Wide-running forwards achieved an anaerobic index (0.34±0.04) 11% and 32.8% higher than hit-up forwards (p=0.001) and outside backs (p<0.001), respectively. Mean power of adjustables (10.0±0.9 W·kg(-1)) was significantly higher than all other groups (outside backs: 28.8%, 7.8±1.0; hit-up: 12.4%, 8.9±0.6; and wide-running: 8.7%, 9.2±0.7 forwards) (p<0.001). Energetics indices indicated differing metabolic demands for all positional groups, suggesting position-specific conditioning drills are required to replicate the energetic demands of match-play.

Short communication: The effect of storage conditions over time on bovine colostral immunoglobulin G concentration, bacteria, and pH.

The objective of the present study was to measure the effect of storing colostrum in different conditions for varying amounts of time on IgG concentration, bacteria, and pH. In experiment 1, colostrum from 12 Holstein-Friesian cows (6 primiparous and 6 multiparous) was collected within 3h of calving, and colostrum from another 12 multiparous cows was collected within 3h of calving (6 cows) and >9h postpartum (6 cows). Aliquots were refrigerated or stored at room temperature for up to 72h, depending on treatment. In experiment 2, colostrum was collected from 6 multiparous cows within 9h of calving, and aliquots were stored for up to 72h in temperature-controlled units set at 4, 13, and 20°C. All colostrum samples were analyzed for IgG concentration, total bacteria count, and pH after 0, 6, 12, 24, 36, 48, 60, and 72h of storage. Storage conditions did not affect the IgG concentration of colostrum. Bacterial growth was most rapid in the first 6h of storage, reducing thereafter, but bacteria multiplied at a significantly greater rate when stored in warmer conditions (i.e., >4°C). The pH of colostrum was not significantly altered when stored at temperatures <13°C, but when stored at 20°C the pH significantly decreased after 24h of storage. Storing colostrum in warmer conditions significantly alters both total bacteria count and pH; consequently, colostrum should be stored at ≤4°C.

Questionnaire identifying management practices surrounding calving on spring-calving dairy farms and their associations with herd size and herd expansion.

Healthy calves are fundamental to any profitable dairy enterprise. Research to-date, has focused on year-round calving systems which experience many different challenges compared to spring-calving systems. The objective of the present study was to determine the on-farm dry cow, calving, and colostrum management practices of spring-calving dairy production systems, and quantify their associations with herd size and herd expansion status (i.e. expanding or not expanding). Information on these management practices was available from a survey of 262 Irish spring-calving dairy farmers, representative of the Irish national population. Herd expansion in the 2 years before, and the year that the survey was conducted was not associated with any of the management practices investigated. Fifty-three percent of respondents had an average calving season length of 10 to14 weeks with 35% of herds having a longer calving season. Previous research in cattle has documented that both colostrum source and feeding management are associated with the transmission of infectious disease from cow to calf. In the present study 60% of respondents fed calves colostrum from their own dam; however, 66% of those respondents allowed the calf to suckle the dam, 23% of survey respondents fed calves pooled colostrum. Larger herds were more likely (P<0.01) to use pooled colostrum supplies, while smaller herds were more likely (P<0.05) to allow the calf to suckle the dam. The majority (86%) of respondents had stored supplies of colostrum; average-sized herds had the greatest likelihood of storing colostrum (P<0.05), compared to other herd sizes; larger sized herds had a lesser likelihood (P<0.05) of storing colostrum in a freezer, compared to other herd sizes. Although freezing colostrum was the most common method used to store colostrum (54% of respondents), 17% of respondents stored colostrum at room temperature, 29% of which stored it at room temperature for greater than 4 days. The results from the present study indicate that a particular focus needs to be placed on calving and colostrum management because this study has highlighted a number of areas which are below international standards, and may have repercussions for calf health. Furthermore, management practices on larger farms could be improved and, as these represent the future of dairy farming, a focus needs to be placed on them. Expanding herds are not a particular concern as herd expansion, independent of herd size, does not seem to be associated with calving and colostrum management practices on Irish spring-calving dairy herds.

Improving the interface between informal carers and formal health and social services: a qualitative study.

BACKGROUND: Reports about the impact of caring vary widely, but a consistent finding is that the role is influenced (for better or worse) by how formal services respond to, and work with informal carers and of course the cared for person. OBJECTIVE: We aimed to explore the connection between informal and formal cares and identify how a positive connection or interface might be developed and maintained. DESIGN: We undertook a qualitative descriptive study with focus groups and individual interviews with informal carers, formal care service providers and representatives from carer advocacy groups. Content analysis was used to identify key factors impacting on the interface between informal and formal carers and propose specific recommendations for service development. SETTING: Community setting including urban and rural areas of New Zealand. PARTICIPANTS AND METHODS: Seventy participants (the majority informal carers) took part in 13 focus groups and 22 individual interviews. RESULTS: Four key themes were derived: Quality of care for the care recipient; Knowledge exchange (valuing carer perspectives); One size does not fit all (creating flexible services); and A constant struggle (reducing the burden services add). An optimum interface to address these key areas was proposed. CONCLUSION: In addition to ensuring quality care for the care recipient, specific structures and processes to support a more positive interface appear warranted if informal carers and services are to work well together. An approach recognising the caring context and carer expertise may decrease the additional burden services contribute, and reduce conflicting information and resultant confusion and/or frustration many carers experience.

Thick drops on a slowly oscillating substrate.

We examine the evolution of a liquid drop on an inclined substrate oscillating vertically. The oscillations are weak and slow, which makes the liquid's inertia and viscosity negligible (so that the drop's shape is determined by a balance of surface tension, gravity, and vibration-induced inertial force). No assumptions are made about the drop's thickness, which extends our previous results on thin drops [Benilov, Phys. Rev. E 84, 066301 (2011)] to more realistic situations. It is shown that, if the amplitude of the substrate's oscillations exceeds a certain threshold value ε(*), the drop climbs uphill. ε(*), however, strongly depends on the thickness of the drop, which, in turn, depends on the liquid's equilibrium contact angle ß[over ¯]. In particular, there is a dramatic decrease in ε(*) when ß[over ¯] exceeds a certain threshold, which means that thick drops climb uphill for a much weaker vibration of the substrate. At the same time, the frequency range of the substrate's vibration within which drops climb uphill becomes much narrower.

Severe acute disseminated encephalomyelitis: a paediatric intensive care population-based study.

There is a paucity of literature on the epidemiology of severe acute disseminated encephalomyelitis (ADEM). We describe a Paediatric Intensive Care Unit (PICU) population-based study to determine the epidemiology and clinical characteristics of children with ADEM requiring PICU admission or resulting in death. Anonymized data from the Paediatric Intensive Care Audit Network (PICANet) were obtained for all children under 16 years with a diagnosis of ADEM admitted to 25 PICUs in England and Wales (2004-2008). The Office for National Statistics (ONS) mortality database was also searched. In total, 27 PICANet cases (13 females:14 males; median age 4.8 years) were ascertained and all were alive on discharge. In addition, three cases were identified from the ONS mortality database. Of the 27 PICANet cases, clinical features included; seizures (n = 5); upper airway respiratory obstruction/stridor (n = 2); unspecified encephalopathy (n = 27); and polyfocal neurological deficits (n = 6). The median duration of ventilation was 3 days. Inotropic support was required in 4/27 patients, and one patient had invasive intracranial pressure monitoring. None received plasmapheresis. We conclude that the incidence of childhood ADEM admitted to the PICU in England and Wales is approximated at 0.5 per million children/year, thus representing approximately one quarter of children admitted with ADEM (denominator: 2009 Canadian surveillance data).

Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation.

OBJECTIVES: To systematically review the effectiveness and cost-effectiveness of palivizumab for the prevention of respiratory syncytial virus (RSV) in children and examine prognostic factors to determine whether subgroups can be identified with important differences in cost-effectiveness. DATA SOURCES: Bibliographic databases were searched from inception to March 2007 for literature on the effectiveness and cost-effectiveness of prophylaxis with palivizumab. REVIEW METHODS: The literature was systematically reviewed and current economic evaluations were analysed to identify which parameters were driving the different cost-effectiveness estimates. A probabilistic decision-analytical model was built to assess the cost-effectiveness of prophylaxis with palivizumab for children at risk of RSV infection and the parameters populated with the best estimates thought most applicable to the UK. We also constructed a new model, the Birmingham Economic Evaluation (BrumEE). Cost-effectiveness analyses were undertaken from both NHS and societal perspectives. RESULTS: Two randomised controlled trials (RCTs) were identified. Prophylaxis with palivizumab for preterm infants without chronic lung disease (CLD) or children with CLD resulted in a 55% reduction in RSV hospital admission: 4.8% (48/1002) in the palivizumab group and 10.6% (53/500) in the no prophylaxis group (p = 0.0004). Prophylaxis with palivizumab was associated with a 45% reduction in hospitalisation rate RSV among children with coronary heart disease (CHD). Hospitalisation rates for RSV were 5.3% (34/639) in the palivizumab group and 9.7% (63/648) in the no prophylaxis group (p = 0.003). Of existing economic evaluations, 3 systematic reviews and 18 primary studies were identified. All the systematic reviews concluded that the potential costs of palivizumab were far in excess of any potential savings achieved by decreasing hospital admission rates, and that the use of palivizumab was unlikely to be cost-effective in all children for whom it is recommended, but that its continued use for particularly high-risk children may be justified. The incremental cost-effectiveness ratios (ICERs) of the primary studies varied 17-fold for life-years gained (LYG), from 25,800 pounds/LYG to 404,900 pounds/LYG, and several hundred-fold for quality-adjusted life-years (QALYs), from 3200 pounds/QALY to 1,489,700 pounds/QALY for preterm infants without CLD or children with CLD. For children with CHD, the ICER varied from 5300 pounds/LYG to 7900 pounds/LYG and from 7500 pounds/QALY to 68,700 pounds/QALY. An analysis of what led to the discrepant ICERs showed that the assumed mortality rate for RSV infection was the most important driver. The results of the BrumEE confirm that palivizumab does not reach conventional levels of cost-effectiveness in any of the licensed indications if used for all eligible children. CONCLUSIONS: Prophylaxis with palivizumab is clinically effective for the reducing the risk of serious lower respiratory tract infection caused by RSV infection and requiring hospitalisation in high-risk children, but if used unselectively in the licensed population, the ICER is double that considered to represent good value for money in the UK. The BrumEE shows that prophylaxis with palivizumab may be cost-effective (based on a threshold of 30,000 pounds/QALY) for children with CLD when the children have two or more additional risk factors. Future research should initially focus on reviewing systematically the major uncertainties for patient subgroups with CLD and CHD and then on primary research to address the important uncertainties that remain.

Ascending placentitis in the mare: A review.

Ascending placentitis is a condition that occurs late in pregnancy when bacteria enter the sterile uterus from the lower reproductive tract. It leads to abortion or the birth of premature and weakened foals. Early detection and treatment of this condition is vital for ensuring the production of a viable foal.Mares with ascending placentitis often present in late term pregnancy with signs of premature udder development and premature lactation. There may be a vulvar discharge. Early detection of placental problems is possible using trans-abdominal or trans-rectal ultrasonography. Hormones such as progesterone and relaxin may be measured as indicators of foetal stress and placental failure. Postpartum foetal membranes may be thickened and contain a fibronecrotic exudate. The region most affected is the cervical star. Definitive diagnosis of ascending placentitis is by histopathological examination of the chorioallantoic membrane.Ideal treatment strategies are aimed at curing the infection and prolonging the pregnancy to as close to term as possible and consist of anti-microbials, anti-inflammatories and hormonal support.Swabs are taken from affected mares to determine antibiotic sensitivity and to aid in treatment of foals born from these mares which are at risk of becoming septic. If detected early enough, the chances of producing a viable foal are greatly increased.

Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland.

The LXRs (liver X receptors) (LXRalpha and LXRbeta) are nuclear hormone receptors that are activated by oxysterols, endogenous oxidative metabolites of cholesterol. These receptors regulate an integrated network of genes that control whole body cholesterol and lipid homoeostasis. A brief overview of the mechanism of this regulation by LXRs in the liver, macrophage and intestine will be outlined, followed by data from our recent work demonstrating that LXRalpha is crucial in maintaining adrenal cholesterol homoeostasis. In the adrenal gland, oxysterols are formed as intermediates in the conversion of cholesterol into steroid hormones and can act as endogenous activators of LXR. We have found using both gain- and loss-of-function models that LXR acts to maintain free cholesterol below toxic levels in the adrenal gland, through the co-ordinated regulation of genes involved in cholesterol efflux [ABCA1 (ATP-binding-cassette transporter A1)], storage (sterol-regulatory-element-binding protein-1c and apolipoprotein E) and metabolism to steroid hormones (steroidogenic acute regulatory protein). Furthermore, we show that under chronic dietary stress, the adrenal glands of LXR-null mice (and not wild-type mice) accumulate free cholesterol. These results support the role of LXR as a global regulator of cholesterol homoeostasis, where LXR provides a safety valve to limit free cholesterol in tissues experiencing high cholesterol flux.

The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of newer antiepileptic drugs (AEDs) for epilepsy in children: gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate and vigabatrin. DATA SOURCES: Electronic databases. Drug company submissions. REVIEW METHODS: For the systematic review of clinical and cost-effectiveness, studies were assessed for inclusion according to predefined criteria. Data extraction and quality assessment were also undertaken. A decision-analytic model was constructed to estimate the cost-effectiveness of the newer agents in children with partial seizures, the only condition where there were sufficient trial data to inform a model. RESULTS: The quality of the randomised controlled trial (RCT) data was generally poor. For each of the epilepsy subtypes considered in RCTs identified for this review (partial epilepsy with or without secondary generalisation, Lennox-Gastaut syndrome, infantile spasms, absence epilepsy and benign epilepsy with centrotemporal spikes), there is some evidence from placebo-controlled trials that the newer agents tested are of some value in the treatment of these conditions. Where active controls have been used, the limited evidence available does not indicate a difference in effectiveness between newer and older drugs. The data are not sufficient to inform a prescribing strategy for any of the newer agents in any of these conditions. In particular, there is no clinical evidence to suggest that the newer agents should be considered as a first-choice treatment in any form of epilepsy in children. Annual drug costs of the newer agents ranges from around 400 pound to 1200 pound, depending on age and concomitant medications. An AED that is ineffective or has intolerable side-effects will only be used for a short period of time, and many patients achieving seizure freedom will successfully withdraw from drug treatment without relapsing. The results of the decision-analytic model do not suggest that the use of the newer agents in any of the scenarios considered is clearly cost-effective but, similarly, do not indicate that they are clearly not cost-effective. CONCLUSIONS: The prognosis for children diagnosed with epilepsy is generally good, with a large proportion responding well to the first treatment given. A substantial proportion, however, will not respond well to treatment, and for these patients the clinical goal is to find an optimal balance between the benefits and side-effects of any treatment given. For the newly, or recently, diagnosed population, the key question for the newer drugs is how soon they should be tried. The cost-effectiveness of using these agents early, in place of one of the older agents, will depend on the effectiveness and tolerability of these agents compared with the older agents; the evidence from the available trial data so far suggests that the newer agents are no more effective but may be somewhat better tolerated than the older agents, and so the cost-effectiveness for early use will depend on the trade-off between effectiveness and tolerability, both in terms of overall (long-term) treatment retention and overall utility associated with effects on seizure rate and side-effects. There are insufficient data available to estimate accurately the nature of this trade off either in terms of long-term treatment retention or utility. Better information is required from RCTs before any rational evidence-based prescribing strategy could be developed. Ideally, RCTs should be conducted from a 'public health' perspective, making relevant comparisons and incorporating outcomes of interest to clinicians and patients, with sufficiently long-term follow-up to determine reliably the clinical utility of different treatments, particularly with respect to treatment retention and the balance between effectiveness and tolerability. RCTs should mirror clinical practice with respect to diagnosis, focusing on defined syndromes or, where no syndrome is identified, on groups defined by specific seizure type(s) and aetiology. Epilepsy in children is a complex disease, with a variety of distinct syndromes and many alternative treatment options and outcomes. Diagnosis-specific decision-analytic models are required; further research may be required to inform parameter values adequately with respect to epidemiology and clinical practice.

Application of europium(III) chelate-dyed nanoparticle labels in a competitive atrazine fluoroimmunoassay on an ITO waveguide.

We have demonstrated the use of an optical indium tin oxide (ITO) (quartz) waveguide as a new platform for immunosensors with fluorescent europium(III) chelate nanoparticle labels (Seradyn) in a competitive atrazine immunoassay. ITO as a solid surface facilitated the successful use of particulate labels in a competitive assay format. The limit of detection in the new nanoparticle assay was similar to a conventional ELISA. The effect of particle size on bioconjugate binding kinetics was studied using three sizes of bioconjugated particle labels (107, 304, and 396nm) and a rabbit IgG/anti-IgG system in a 96-well plate. A decrease in particle size resulted in faster binding but did not increase the assay sensitivity. Flux calculations based on the particle diffusivity prove that faster binding of the small particles in this study was primarily due to diffusion kinetics and not necessarily to a higher density of antibodies on the particle surface. The results suggest that ITO could make a good platform for an optical immunosensor using fluorescent nanoparticle labels in a competitive assay format for small molecule detection. However, when used in combination with fluorescent particulate labels, a highly sensitive excitation/detection system needs to be developed to fully utilize the kinetic advantage from small particle size. Different regeneration methods tested in this study showed that repeated washings with 0.1 M glycine-HCl facilitated the reuse of the ITO waveguide.

Autoantibody testing in children with newly diagnosed type 1 diabetes mellitus.

OBJECTIVES: To determine the role of autoantibody tests for autoimmune diseases in children with newly diagnosed type 1 diabetes mellitus. DATA SOURCES: MEDLINE, EMBASE and the Cochrane Library. Citation lists of included studies were scanned and relevant professional and patient websites reviewed. Laboratories and manufacturers were contacted to identify ongoing or unpublished research. REVIEW METHODS: Following scoping searches on thyroid and coeliac autoantibodies, a systematic review of autoantibody tests for diagnosis of coeliac disease was carried out. Studies were included where cohorts of untreated patients with unknown disease status were included, all patients had undergone the reference test (biopsy) and antibody tests, and sensitivity and specificity were reported or calculable. Selected studies were then evaluated against a quality checklist. Summary statistics of diagnostic accuracy, i.e. sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios, were calculated for all studies. A decision analytic model was developed to evaluate the cost utility of screening for coeliac disease at diagnosis of diabetes. RESULTS: All antibody tests for diagnosis of coeliac disease showed reasonably good diagnostic test accuracy. Studies reported variable measures of test accuracy, which may be due to aspects of study quality, differences in the tests and their execution in the laboratories, different populations and reference standards. The decision analytic model indicated screening for coeliac disease at diagnosis of diabetes was cost-effective. Sensitivity analyses exploring variations in the cost and disutility of gluten-free diet, the utilities attached to treated and untreated coeliac disease and the decrease in life expectancy associated with treated and untreated coeliac disease did substantially affect the cost-effectiveness of the screening strategies considered. CONCLUSIONS: In terms of test accuracy in testing for coeliac disease, immunoglobulin A (IgA) anti-endomysium is the most accurate test. If an enzyme-linked immunoassay test was required, which may be more suitable for screening purposes as it can be semi-automated, testing for IgA tissue transglutaminase is likely to be most accurate. The decision analytic model shows that the most accurate tests combined with confirmatory biopsy are the most cost-effective, whilst combinations of tests add little or no further value. There is limited information regarding test accuracy in screening populations with diabetes, and there is some uncertainty over whether the test characteristics would remain the same. Further research is required regarding the role of screening in silent coeliac disease and regarding long-term outcomes and complications of untreated coeliac disease.

Unmasking the dynamic interplay between efflux transporters and metabolic enzymes.

Drug efflux by intestinal P-glycoprotein (P-gp) is known to decrease the bioavailability of many CYP3A4 substrates. We have demonstrated that the interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase the opportunity for drug metabolism by determining bidirectional extraction ratios across CYP3A4-transfected Caco-2 cells for two dual P-gp/CYP3A4 substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as well as two negative control, CYP3A4 only substrates, midazolam and felodipine. Studies were carried out under control conditions, with a P-gp inhibitor (GG918) and with a dual inhibitor (cyclosporine). Measurement of intracellular concentration changes is an important component in calculating the extraction ratios. We hypothesize that the inverse orientation of P-gp and CYP3A4 in the liver will result in an opposite interactive effect in that organ. In vivo rat intestinal perfusion studies with K77 and rat liver perfusion studies with tacrolimus under control conditions and with inhibitors of CYP3A4 (troleandomycin), P-gp (GG918) and both CYP3A4/P-gp (cyclosporine) lend support to our hypotheses. These results serve as a template for predicting enzyme-transporter (both absorptive and efflux) interactions in the intestine and the liver.