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The aim of the study was to investigate the properties of sodium caseinate dispersions and oil-in-water emulsions obtained from cows' milk of either A1/A1, A1/A2, or A2/A2 β-casein phenotype. Protein structural characterisation was examined using Fourier Transform Infrared and Nuclear Magnetic Resonance spectroscopies, with physicochemical and interfacial properties assessed by analysing adsorbed protein content, hydrophobicity, solubility, and emulsion stability of the samples. Results showed variations in the secondary structure of all samples dependent of the presence of A1 or A2 β-caseins. The main differences included greater amounts of α-helix and β-sheet in A1/A1 and A1/A2 sodium caseinate dispersions that influenced their lower solubility, while random coils/polyproline II helixes were found only in A2/A2 sodium caseinate dispersion. In contrast, upon adsorption on the interface of A2/A2 sodium caseinate emulsion, the protein adopted ordered conformational motifs. This conformational shift supposedly arose from structural differences between the two β-casein proteoforms, which most likely enhanced the emulsion properties of A2/A2 sodium caseinate compared to either A1/A1 or A1/A2 sodium caseinates. The A2 β-casein in both, A1/A2 and A2/A2 sodium caseinates, appears to be able to more rapidly reach the oil droplet surface and was more efficient as emulsifying agent. The current results demonstrated that the conformational rearrangement of proteins upon adsorption to emulsion interfaces was dependent not only on hydrophobicity and on solubility, but also on the conformational flexibility of A1/A1, A1/A2, and A2/A2 β-casein phenotypes. These findings can assist in predicting the behaviour of sodium caseinates during relevant industrial processing.

Background Yersiniosis is one of the most common food-borne zoonoses in Europe, but there are large variations in the reported incidence between different countries. Aim We aimed to describe the trends and epidemiology of laboratory-confirmed Yersinia infections in England and estimate the average annual number of undiagnosed Yersinia enterocolitica cases, accounting for under-ascertainment. Methods We analysed national surveillance data on Yersinia cases reported by laboratories in England between 1975 and 2020 and enhanced surveillance questionnaires from patients diagnosed in a laboratory that has implemented routine Yersinia testing of diarrhoeic samples since 2016. Results The highest incidence of Yersinia infections in England (1.4 cases per 100,000 population) was recorded in 1988 and 1989, with Y. enterocolitica being the predominant species. The reported incidence of Yersinia infections declined during the 1990s and remained low until 2016. Following introduction of commercial PCR at a single laboratory in the South East, the annual incidence increased markedly (13.6 cases per 100,000 population in the catchment area between 2017 and 2020). There were notable changes in age and seasonal distribution of cases over time. The majority of infections were not linked to foreign travel and one in five patients was admitted to hospital. We estimate that around 7,500 Y. enterocolitica infections may be undiagnosed in England annually. Conclusions Findings suggest a considerable number of undiagnosed yersiniosis cases in England, with possibly important changes in the epidemiology. The apparently low incidence of yersiniosis in England is probably due to limited laboratory testing.

Background Complex polymorphisms in the polypeptide chain of bovine β-casein are responsible for the genetic variants that give rise to different bioactive peptides during in vitro and ex vivo digestion, or food fermentation. One specific group of bioactive peptides, known as β-casomorphins, are opioid-agonists for μ-receptors and have been suggested to assume an active role in the development of various non-communicable diseases, including diabetes mellitus, cardiovascular diseases, neurological disorders, pulmonary inflammation, to name a few. Their potential bioactivity and role in human health is dependent on their release from the latent form within the primary structure of β-casein, which can occur during the manufacture of dairy products or during gastric and intestinal digestion. Consequently, β-casomorphins can be either completely hydrolysed or absorbed in the gut or be transferred into the blood stream and internal organs in their intact form. Their biological function as opioid agonists is expressed in the gut, thus upon epithelial translocation they may affect various physiological states, such as causing gastrointestinal issues, bloating, and lactose intolerance. Scope and approach This review evaluated the possible disadvantages and potential beneficial effects of β-casomorphins on human health, within the scope of in vitro and ex vivo studies. Applying a systematic approach, a literature search was performed across four electronic databases (Scopus, Web of Science, PubMed, and Cochrane) to identify suitable studies. Key findings and conclusions The data mined from in vitro and ex vivo trials on the health impact of β-casomorphins is both inconclusive and limited to completely support the possible adverse or potential beneficial health effects of β-casomorphins. These peptides are usually further cleaved in the gut, which prevents their migration across the gut-blood-brain barrier. Nevertheless, in some individuals that are immunocompromised, their condition increases permeability of the gut barrier often referred to as a "leaky gut" condition. Thus, the absorption of β-casomorphins appears possible. This may indicate that the presence of β-casomorphins can affect gastrointestinal functions only. However, since the overall concern with β-casomorphins appears debatable and not well defined, more experimental trials are required to investigate the metabolic pathways of these identified peptides, their release during digestion, and subsequent fate after the digestion process. Consequently, repeatability of the findings under a number of other laboratory conditions is required before the data can be fully substantiated. Due to the rapidly evolving nature of the issue and emerging studies in this field, further exploration into the bioactivity of β-casomorphins is warranted.

SummaryBackgroundThe Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused byStreptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidisandStreptococcus agalactiae. Here we analyse the incidence and distribution of disease during the first two years of the pandemic.MethodsLaboratories in 30 countries/territories representing five continents submitted case data from 2018-2021 to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype/group were examined. Interrupted time series analyses quantified the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models estimated effect sizes and forecasted counterfactual trends by hemisphere.FindingsOverall, 116,841 cases were analysed: 76,481 (2018-2019, pre-pandemic) plus 40,360 (2020-2021, pandemic). During the pandemic there was a significant reduction in the risk of disease caused byS pneumoniae(risk ratio: 0.47; 95% confidence interval: 0.40-0.55),H influenzae(0.51; 0.40-0.66) andN meningitidis(0.26; 0.21-0.31), whereas no significant changes were observed for the non-respiratory-transmitted pathogenS agalactiae(1.02; 0.75-1.40). No major changes in the distribution of cases were observed when stratified by patient age or serotype/group. An estimated 36,289 (17,145-55,434) cases of invasive bacterial disease were averted during the first two years of the pandemic among IRIS participating countries/territories.InterpretationCOVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused byS pneumoniae, H influenzaeandN meningitidisduring the first two years of the pandemic, but cases began to increase in some countries as pandemic restrictions were lifted.Research in contextEvidence before this studyEarly in the COVID-19 pandemic the IRIS Consortium reported a significant reduction in invasive disease due to respiratory-transmitted bacterial pathogens, which was associated with the implementation of COVID-19 stringency measures and changes in human social behaviour. All 26 countries/territories participating in IRIS at the time experienced a significant reduction in infections between January and May 2020, compared with the previous two years. In particular,S pneumoniaeinfections decreased by 68% at four weeks after COVID-19 containment measures were imposed, and by 82% at eight weeks.Added value of this studyThese new data from the expanded IRIS Consortium across 30 countries/territories demonstrated a sustained reduction in invasive disease throughout the first two years of the COVID-19 pandemic. Using time series modelling, we estimated that over 36,000 cases of invasive bacterial disease were averted in 2020-2021 among the countries participating in IRIS; however, minor increases in disease in the latter half of 2021 require close monitoring to understand the nature of re-emerging cases.Implications of all the available evidenceFuture epidemics and pandemics will occur, and we need to understand not only the pathogen that is directly responsible for the pandemic, but also that population-level responses to an epidemic or pandemic more broadly affect overall human health and other microbes. IRIS provides evidence for the effects of such public health responses on severe invasive bacterial infections across many countries. Moreover, these IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to healthcare service planning and provision of policies.

The accuracy and flexibility of artificial intelligence (AI) systems often comes at the cost of a decreased ability to offer an intuitive explanation of their predictions. This hinders trust and discourage adoption of AI in healthcare, exacerbated by concerns over liabilities and risks to patients’ health in case of misdiagnosis. Providing an explanation for a model’s prediction is possible due to recent advances in the field of interpretable machine learning. We considered a data set of hospital admissions linked to records of antibiotic prescriptions and susceptibilities of bacterial isolates. An appropriately trained gradient boosted decision tree algorithm, supplemented by a Shapley explanation model, predicts the likely antimicrobial drug resistance, with the odds of resistance informed by characteristics of the patient, admission data, and historical drug treatments and culture test results. Applying this AI-based system, we found that it substantially reduces the risk of mismatched treatment compared with the observed prescriptions. The Shapley values provide an intuitive association between observations/data and outcomes; the associations identified are broadly consistent with expectations based on prior knowledge from health specialists. The results, and the ability to attribute confidence and explanations, support the wider adoption of AI in healthcare.

Worldwide milk production is predominantly founded on indoor, high-concentrate feeding systems, whereas pasture-based feeding systems are most common in New Zealand and Ireland but have received greater attention recently in countries utilizing conventional systems. Consumer interest in 'pasture-fed' dairy products has also increased, arising from environmental, ethical, and nutritional concerns. A substantial body of research exists describing the effect of different feeding strategies on the composition of milk, with several recent studies focusing on the comparison of pasture- and concentrate-based feeding regimes. Significant variation is typically observed in the gross composition of milk produced from different supplemental feeds, but various changes in the discrete composition of macromolecular components in milk have also been associated with dietary influence, particularly in relation to the fatty acid profile. Changes in milk composition have also been shown to have implications for milk and dairy product processability, functionality and sensory properties. Methods to determine the traceability of dairy products or verify marketing claims such as 'pasture-fed' have also been established, based on compositional variation due to diet. This review explores the effects of feed types on milk composition and quality, along with the ultimate effect of diet-induced changes on milk and dairy product functionality, with particular emphasis placed on pasture- and concentrate-based feeding systems.

Background A number of randomised in vivo trials have to date investigated the health impacts of the genetic variants A1 and A2 of bovine β-casein. The primary difference between these two genetic variants is the mutation leading to an amino acid exchange at a position 67 in the peptide chain. This systematic review evaluated the effects of bovine milk, β-casein and pure β-casomorphin7, in the form of orally administered nutritional ingredients, on possible incidence and risk for chronic digestive discomfort and development of incurable conditions and diseases in human and animal randomised controlled trials. Scope and approach Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, searches were performed for publications across 7 electronic databases (Scopus, Embase, Web of Science, Medline, EBSCO, PubMed, and Cochrane) up to and until July 2020, to identify randomised controlled trials. The subsequent search results were screened for relevance firstly by title, then abstract, and the chosen ones by full text, with additional screening of included articles reference lists. Key findings and conclusions In total 2006 peer-reviewed journal articles were identified and after applying exclusion criteria, 19 studies were deemed suitable for inclusion. Human-based and animal-based results from the clinical in vivo studies demonstrated that consumption of A2 β-casein milk can lead to improved tolerance of milk via decline in the ubiquity of gut related discomfort. However, the exact mechanism for these effects or specific individuals that may benefit from A2 β-casein milk as opposed to A1 β-casein milk is still poorly understood. Notably, consumption of A2 β-casein milk had very low to completely no effect on the other health statuses investigated, particularly non-communicable diseases, such as cardiovascular diseases, neurological disorders, and diabetes. Based on current data, there is not sufficient evidence to merit public health authority recommendations related to the consumption and health associations of A1 β-casein milk or A2 β-casein milk. Interestingly, regardless of the scientific evidence between A2 β-casein milk and health, this milk continues to gain prominence on the market, thus further functional research is required to understand the mechanisms of action of these identified peptides and gene variants and any implications A1 or A2 β-casein milk may have on human health and techno-functional properties of milks.

Changes in the pH of skim milk and skim milk ultrafiltration permeate on heating from 25 to 140 °C were examined. Results showed that the decrease in pH with increase in temperature up to 140 °C was not linear. Hydrogen ion release due to changes in the milk mineral balance were responsible for the reduction in pH with increase in temperature. The presence of milk proteins offered little buffering against the drop in pH. The precipitation of calcium phosphate resulted in sediment in milk permeate heated above ∼70 °C, but this did not occur in skim milk, with the pH remaining lower in milk permeate after heat treatment when measured at 25 °C. This study has shown that in-line pH measurements of milk at ultra-high temperatures is feasible, and could prove useful at laboratory and pilot-scale for studying interactions within, and stability of, more complex formulations with added minerals.

Calcium chelating agents, such as sodium hexametaphosphate (SHMP), can be added to milk protein solutions to aid in rehydration; however, this leads to a concomitant increase in solution viscosity due to micelle swelling/dissociation. Crosslinking casein proteins using transglutaminase (TGase) can help retain casein micelle structure and maintain low viscosity. This study aimed to determine the water sorption and hydration properties of milk protein concentrate (MPC) powders, as influenced by the crosslinking of milk proteins and the addition of SHMP. Crosslinked casein protein (TG-MPC) powders without SHMP addition had improved wettability, water sorption and water diffusion compared to the non-crosslinked control (C-MPC) powder. All powders containing SHMP were found to have increased water sorption compared to control powders without SHMP addition. Powder dissolution data showed that increasing SHMP content increased powder rehydration particle size, compared to powders without SHMP addition, indicating increased particle swelling due to increased water absorption.

Objective: \ud The aim of this study was to estimate the cost-effectiveness of screening strategies for predicting LTBI that progresses to active tuberculosis (TB) in people with HIV.\ud \ud Design: \ud We developed a decision-analytical model that constituted a decision tree covering diagnosis of LTBI and a Markov model covering progression to active TB. The model represents the lifetime experience following testing for LTBI, and discounting costs, and benefits at 3.5% per annum in line with UK standards. We undertook probabilistic and one-way sensitivity analyses.\ud \ud Setting: \ud UK National Health Service and Personal Social Service perspective in a primary care setting.\ud \ud Participants: \ud Hypothetical cohort of adults recently diagnosed with HIV.\ud \ud Interventions: \ud Interferon-gamma release assays and tuberculin skin test.\ud \ud Main outcome measure: \ud Cost per quality-adjusted life year (QALY).\ud \ud Results: \ud All strategies except T-SPOT.TB were cost-effective at identifying LTBI, with the QFT-GIT-negative followed by TST5mm strategy being the most costly and effective. Results indicated that there was little preference between strategies at a willingness-to-pay threshold of £20 000. At thresholds above £40 000 per QALY, there was a clear preference for the QFT-GIT-negative followed by TST5mm, with a probability of 0.41 of being cost-effective. Results showed that specificity for QFT-GIT and TST5mm were the main drivers of the economic model.\ud \ud Conclusion: \ud Screening for LTBI has important public health and clinical benefits. Most of the strategies are cost-effective. These results should be interpreted with caution because of the paucity of studies included in the meta-analysis of test accuracy studies. Additional high-quality primary studies are needed to have a definitive answer about, which strategy is the most effective.

The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odd of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.

This human campylobacteriosis sentinel surveillance project was based at two sites in Oxfordshire and North East England chosen (i) to be representative of the English population on the Office for National Statistics urban-rural classification and (ii) to provide continuity with genetic surveillance started in Oxfordshire in October 2003. Between October 2015 and September 2018 epidemiological questionnaires and genome sequencing of isolates from human cases was accompanied by sampling and genome sequencing of isolates from possible food animal sources. The principal aim was to estimate the contributions of the main sources of human infection and to identify any changes over time. An extension to the project focussed on antimicrobial resistance in study isolates and older archived isolates. These older isolates were from earlier years at the Oxfordshire site and the earliest available coherent set of isolates from the national archive at Public Health England (1997/8). The aim of this additional work was to analyse the emergence of the antimicrobial resistance that is now present among human isolates and to describe and compare antimicrobial resistance in recent food animal isolates. Having identified the presence of bias in population genetic attribution, and that this was not addressed in the published literature, this study developed an approach to adjust for bias in population genetic attribution, and an alternative approach to attribution using sentinel types. Using these approaches the study estimated that approximately 70% of Campylobacter jejuni and just under 50% of C. coli infection in our sample was linked to the chicken source and that this was relatively stable over time. Ruminants were identified as the second most common source for C. jejuni and the most common for C. coli where there was also some evidence for pig as a source although less common than ruminant or chicken. These genomic attributions of themselves make no inference on routes of transmission. However, those infected with isolates genetically typical of chicken origin were substantially more likely to have eaten chicken than those infected with ruminant types. Consumption of lamb’s liver was very strongly associated with infection by a strain genetically typical of a ruminant source. These findings support consumption of these foods as being important in the transmission of these infections and highlight a potentially important role for lamb’s liver consumption as a source of Campylobacter infection. Antimicrobial resistance was predicted from genomic data using a pipeline validated by Public Health England and using BIGSdb software. In C. jejuni this showed a nine-fold increase in resistance to fluoroquinolones from 1997 to 2018. Tetracycline resistance was also common, with higher initial resistance (1997) and less substantial change over time. Resistance to aminoglycosides or macrolides remained low in human cases across all time periods. Among C. jejuni food animal isolates, fluoroquinolone resistance was common among isolates from chicken and substantially less common among ruminants, ducks or pigs. Tetracycline resistance was common across chicken, duck and pig but lower among ruminant origin isolates. In C. coli resistance to all four antimicrobial classes rose from low levels in 1997. The fluoroquinolone rise appears to have levelled off earlier and among animals, levels are high in duck as well as chicken isolates, although based on small sample sizes, macrolide and aminoglycoside resistance, was substantially higher than for C. jejuni among humans and highest among pig origin isolates. Tetracycline resistance is high in isolates from pigs and the very small sample from ducks. Antibiotic use following diagnosis was relatively high (43.4%) among respondents in the human surveillance study. Moreover, it varied substantially across sites and was highest among non-elderly adults compared to older adults or children suggesting opportunities for improved antimicrobial stewardship. The study also found evidence for stable lineages over time across human and source animal species as well as some tighter genomic clusters that may represent outbreaks. The genomic dataset will allow extensive further work beyond the specific goals of the study. This has been made accessible on the web, with access supported by data visualisation tools.

BACKGROUND: The relative accuracy of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) in identifying latent tuberculosis infection (LTBI) is uncertain.OBJECTIVE: To perform a systematic review and meta-analysis to compare the sensitivity and specificity of IGRAs and TST for the prediction of progression to clinical tuberculosis (TB).METHODS: We searched electronic databases (e.g., MEDLINE and EMBASE) from December 2009 to September 2018 for prospective studies that followed up individuals who had undergone testing with commercial IGRAs and/or TST but had not received treatment based on the test result. The sensitivity and specificity estimates were pooled using a Bayesian bivariate random-effects model.RESULTS: Twenty-five studies, mostly with moderate to high risk of bias and a mean follow-up time ranging from 1 to 5 years were included. TST (10–15 mm) tended to have lower sensitivity and higher specificity than QuantiFERON® Gold In-Tube, T-SPOT®.TB and TST (5 mm). The evidence did not indicate that any test outperformed the others due to wide and overlapping 95% credible intervals.CONCLUSION: The evidence following individuals who had undergone testing for LTBI and had progressed to clinical TB is sparse. We did not find that IGRAs were superior to TST or vice versa; however, as our findings are based on a small number of studies with methodological limitations and great uncertainty around the pooled estimates, the results should be interpreted with caution.

peer-reviewed This work aimed to model the effect of heat treatment on viscosity of milk protein concentrate (MPC) using kinetic data. MPC obtained after ultrafiltration was subjected to different time-temperature heat treatment combinations. Heat treatment at high temperature and short time (i.e., 100 or 120 °C×30 s) led to a significant increase in viscosity in MPC systems. Second-order reaction kinetic models proved a better fit than zero- or first-order models when fitted for viscosity response to heat treatment. A distinct deviation in the slope of the Arrhenius plot at 77.9 °C correlated to a significant increase in the rate of viscosity development at temperatures above this, confirming the transition of protein denaturation from the unfolding to the aggregation stage. This study demonstrated that heat-induced viscosity of MPC as a result of protein denaturation/aggregation can be successfully modelled in response to thermal treatment, providing useful new information in predicting the effect of thermal treatment on viscosity of MPC.

peer-reviewed Direct supersonic steam injection, direct steam infusion, and indirect tubular heating were each applied to protein-enriched skim milk-based beverages with 4, 6 and 8% (w/w) total protein, and the effect of final heat temperature on the physical properties of these beverages was investigated. Supersonic steam injection resulted in significantly lower levels of denaturation of β-lactoglobulin (34.5%), compared to both infusion (76.3%) and tubular (97.1%) heating technologies. Viscosity, particle size and accelerated physical stability of formulations did not differ significantly between the heating technologies, while noticeable colour differences due to heat treatment (mainly attributed to increasing b* value) were observed, particularly for tubular heating. Overall, the extent of protein denaturation in high-protein dairy products was significantly influenced by the particular heating technology applied. The application of supersonic steam injection technology, with rapid heating and high shear characteristics, may enable differenciated product characteristics for ready-to-drink ambient-delivery high-protein dairy beverages. Industrial relevance: The design and application of novel direct supersonic steam injection technology was comprehensively studied and found to provide significant benefits over direct steam infusion and indirect tubular heating technologies for skim milk-based protein beverages. This type of injection heating system resulted in heat-treated formulations with lower levels of denatured whey proteins, compared to tubular and infusion heating, offering an alternative opportunity to the industry in terms of producing shelf-stable dairy protein beverages.

Identification of those at greatest risk of death due to the substantial threat of COVID-19 can benefit from novel approaches to epidemiology that leverage large datasets and complex machine-learning models, provide data-driven intelligence, and guide decisions such as intensive-care unit admission (ICUA). The objective of this study is two-fold, one substantive and one methodological: substantively to evaluate the association of demographic and health records with two related, yet different, outcomes of severe COVID-19 (viz., death and ICUA); methodologically to compare interpretations based on logistic regression and on gradient-boosted decision tree (GBDT) predictions interpreted by means of the Shapley impacts of covariates. Very different association of some factors, e.g., obesity and chronic respiratory diseases, with death and ICUA may guide review of practice. Shapley explanation of GBDTs identified varying effects of some factors among patients, thus emphasising the importance of individual patient assessment. The results of this study are also relevant for the evaluation of complex automated clinical decision systems, which should optimise prediction scores whilst remaining interpretable to clinicians and mitigating potential biases., Author summary The design is a retrospective cohort study of 13954 in-patients of ages ranging from 1 to 105 year (IQR: 56, 70, 81) with a confirmed diagnosis of COVID-19 by 28th June 2020. This study used multivariable logistic regression to generate odd ratios (ORs) multiply adjusted for 37 covariates (comorbidities, demographic, and others) selected on the basis of clinical interest and prior findings. Results were supplemented by gradient-boosted decision tree (GBDT) classification to generate Shapley values in order to evaluate the impact of the covariates on model output for all patients. Factors are differentially associated with death and ICUA and among patients. Deaths due to COVID-19 were associated with immunosuppression due to disease (OR 1.39, 95% CI 1.10–1.76), type-2 diabetes (OR 1.31, 95% CI 1.17–1.46), chronic respiratory disease (OR 1.19, 95% CI 1.05–1.35), age (OR 1.56/10-year increment, 95% CI 1.51–1.61), and male sex (OR 1.54, 95% CI 1.42–1.68). Associations of ICUA with some factors differed in direction (e.g., age, chronic respiratory disease). Self-reported ethnicities were strongly but variably associated with both outcomes. GBDTs had similar performance (ROC-AUC, ICUA 0.83, death 0.68 for GBDT; 0.80 and 0.68 for logistic regression). We derived importance scores based on Shapley values which were consistent with the ORs, despite the underlying machine-learning model being intrinsically different to the logistic regression. Chronic heart disease, hypertension, other comorbidities, and some ethnicities had Shapley impacts on death ranging from positive to negative among different patients, although consistently associated with ICUA for all. Immunosuppressive disease, type-2 diabetes, and chronic liver and respiratory diseases had positive impacts on death with either positive or negative on ICUA. We highlight the complexity of informing clinical practice and public-health interventions. We recommend that clinical support systems should not only predict patients at risk, but also yield interpretable outputs for validation by domain experts.

What you need to know Lateral flow devices (LFDs) are being used to test asymptomatic people for covid-19 as part of the approach in the UK and elsewhere to control the spread of the disease and to enable society to reopen.1234 The risks and benefits of using LFDs for widespread testing of asymptomatic people are the subject of ongoing uncertainty and debate.1567 Despite concerns about accuracy, LFD tests continue to be widely used. In the week ending 19 May, 4.9 million registered tests were undertaken in England.8 People taking a test receive advice on what their result means and what they should do; however, the widespread use of these tests means doctors may increasingly be asked about them (for example, when patients with a recent result present to services). This practice pointer considers how to interpret and communicate results from LFD tests based on our current understanding of the tests’ performance. Lateral flow devices can detect the presence of a target substance in a liquid, typically in a single use disposable …

ObjectiveTo systemically review and critically appraise published studies of the association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19, including clinical course, morbidity and mortality outcomes.DesignSystematic review.Data sourcesMEDLINE (OVID), Embase (OVID), Cochrane Central Register of Controlled Trials, MedRxiv and BioRxiv preprint databases. COVID-19 databases of the WHO, Cochrane, CEBM Oxford and Bern University up to 10 June 2020.Study selectionStudies that assessed vitamin D supplementation and/or low serum vitamin D in patients acutely ill with, or at risk of, severe betacoronavirus infection (SARS-CoV, MERS-CoV, SARS-CoV-2).Data extractionTwo authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Downs and Black Quality Assessment Checklist.ResultsSearches elicited 449 papers, 59 studies were eligible full-text assessment and 4 met the eligibility criteria of this review. The four studies were narratively synthesised and included (1) a cross-sectional study (n=107) suggesting an inverse association between serum vitamin D and SARS-CoV-2; (2) a retrospective cohort study (348 598 participants, 449 cases) in which univariable analysis showed that vitamin D protects against COVID-19; (3) an ecological country level study demonstrating a negative correlation between vitamin D and COVID-19 case numbers and mortality; and (4) a case–control survey (n=1486) showing cases with confirmed/probable COVID-19 reported lower vitamin D supplementation. All studies were at high/unclear risk of bias.ConclusionThere is no robust evidence of a negative association between vitamin D and COVID-19. No relevant randomised controlled trials were identified and there is no robust peer-reviewed published evidence of association between vitamin D levels and severity of symptoms or mortality due to COVID-19. Guideline producers should acknowledge that benefits of vitamin D supplementation in COVID-19 are as yet unproven despite increasing interest.

Soy protein isolate (SPI) powders often have poor water solubility, particularly at pH values close to neutral, which is an attribute that is an issue for its incorporation into complex nutritional systems. Therefore, the objective of this study was to improve SPI solubility while maintaining low viscosity. Thus, the intention was to examine the solubility and rheological properties of a commercial SPI powder at pH values of 2.0, 6.9, and 9.0, and determine if heat treatment at acidic or alkaline conditions might positively influence protein solubility, once re-adjusted back to pH 6.9. Adjusting the pH of SPI dispersions from pH 6.9 to 2.0 or 9.0 led to an increase in protein solubility with a concomitant increase in viscosity at 20 °C. Meanwhile, heat treatment at 90 °C significantly improved the solubility at all pH values and resulted in a decrease in viscosity in samples heated at pH 9.0. All SPI dispersions measured under low-amplitude rheological conditions showed elastic-like behaviour (i.e., G′ &gt, G″), indicating a weak “gel-like” structure at frequencies less than 10 Hz. In summary, the physical properties of SPI can be manipulated through heat treatment under acidic or alkaline conditions when the protein subunits are dissociated, before re-adjusting to pH 6.9.

The in vitro antioxidant effects of the most potent antioxidants of rosemary, namely carnosol, carnosic acid and rosmarinic acid (c: ca: ra) were assessed in fat-filled milk powders (FFMPs) under accelerated conditions (40 °C and relative humidity (RH) 23%) over 90 days. Lipid oxidation was assessed in FFMPs by measuring peroxide values (PVs), thiobarbituric acid reactive substances (TBARS) and aroma volatiles using headspace (HS) solid-phase microextraction (SPME) coupled to gas-chromatography-mass spectrometry (GC-MS). The antioxidant potency of c: ca: ra exhibited a concentration-related effect (308 ppm &gt, 200 ppm &gt, 77 ppm), with the highest concentration being the most effective at controlling the formation of TBARS and PVs. At a concentration of 308 ppm c: ca: ra were particularly effective (p &lt, 0.05) in inhibiting all the evaluated oxidation indices (primary and secondary) compared to the control samples, but in some cases less effectively (p &lt, 0.05) than butylated hydroxyanisole: butylated hydroxytoluene (BHA: BHT) (200 ppm).

This study evaluated the effect of high-pressure nitrogen (N2) gas injection prior to spray drying on the subsequent rehydration properties of regular and agglomerated milk protein concentrate (MPC) powders. Conductivity measurements demonstrated a slower release of ions for powders produced using N2 injection (NI) as they took longer to wet and sink due to their lower density. However, analysis of particle size distribution on reconstitution at both 23 and 50 °C showed an improvement in powder dispersion with NI. Powder solubility, when measured at 23 °C, was higher for the NI powders, while agglomeration negatively impacted solubility. Confocal laser scanning microscopy analysis showed a faster diffusion of dye into MPC powder particles produced using NI. The improvement in powder dissolution with NI was attributed to higher porosity and the presence of air voids which facilitated increased water transfer and accelerated the breakdown of primary powder particles.

Comparing the pathogen genomes from several cases of an infectious disease has the potential to help us understand and control outbreaks. Many methods exist to reconstruct a phylogeny from such genomes, which represents how the genomes are related to one another. However, such a phylogeny is not directly informative about transmission events between individuals. TransPhylo is a software tool implemented as an R package designed to bridge the gap between pathogen phylogenies and transmission trees. TransPhylo is based on a combined model of transmission between hosts and pathogen evolution within each host. It can simulate both phylogenies and transmission trees jointly under this combined model. TransPhylo can also reconstruct a transmission tree based on a dated phylogeny, by exploring the space of transmission trees compatible with the phylogeny. A transmission tree can be represented as a coloring of a phylogeny where each color represents a different host of the pathogen, and TransPhylo provides convenient ways to plot these colorings and explore the results. This article presents the basic protocols that can be used to make the most of TransPhylo. © 2021 The Authors. Basic Protocol 1: First steps with TransPhylo Basic Protocol 2: Simulation of outbreak data Basic Protocol 3: Inference of transmission Basic Protocol 4: Exploring the results of inference

Background:Reactive arthritis, irritable bowel syndrome (IBS), Guillain-Barré syndrome, ulcerative colitis, and Crohn's disease may be sequelae ofCampylobacteror non-typhoidalSalmonella(NTS) infections. Proton pump inhibitors (PPI) and antibiotics may increase the risk of gastrointestinal infections (GII); however, their impact on sequelae onset is unclear. We investigated the incidence of sequelae, their association with antibiotics and PPI prescription, and assessed the economic impact on the NHS. Methods:Data from the Clinical Practice Research Datalink for patients consulting their GP forCampylobacteror NTS infection, during 2000-2015, were linked to hospital, mortality, and Index of Multiple Deprivation data. We estimated the incidence of sequelae and deaths in the 12 months following GII. We conducted logistic regression modelling for the adjusted association with prescriptions. We compared differences in resource use and costs pre- and post-infection amongst patients with and without sequelae. Findings:Of 20,471 patients with GII (Campylobacter17,838), less than 2% (347) developed sequelae, with IBS (268) most common. AmongCampylobacterpatients, those with prescriptions for PPI within 12 months before and cephalosporins within 7-days before/after infection had elevated risk of IBS (adjusted odds ratio [aOR] 2.1, 1.5-2.9) and (aOR 3.6, 1.1-11.7) respectively.Campylobactersequelae lead to ∼ £1.3 million, (£750,000, £1.7 million) in additional annual NHS expenditure. Interpretation:Sequelae ofCampylobacterand NTS infections are rare but associated with increased NHS costs. Prior prescription of PPI may be a modifiable risk factor. Incidence of sequelae, healthcare resource use and costs are essential parameters for future burden of disease studies.

Identification of those at greatest risk of death due to the substantial threat of COVID-19 can benefit from novel approaches to epidemiology that leverage large datasets and complex machine-learning models, provide data-driven intelligence, and guide decisions such as intensive-care unit admission (ICUA). The objective of this study is two-fold, one substantive and one methodological: substantively to evaluate the association of demographic and health records with two related, yet different, outcomes of severe COVID-19 (viz., death and ICUA); methodologically to compare interpretations based on logistic regression and on gradient-boosted decision tree (GBDT) predictions interpreted by means of the Shapley impacts of covariates. Very different association of some factors, e.g., obesity and chronic respiratory diseases, with death and ICUA may guide review of practice. Shapley explanation of GBDTs identified varying effects of some factors among patients, thus emphasising the importance of individual patient assessment. The results of this study are also relevant for the evaluation of complex automated clinical decision systems, which should optimise prediction scores whilst remaining interpretable to clinicians and mitigating potential biases.Author summaryThe design is a retrospective cohort study of 13954 in-patients of ages ranging from 1 to 105 year (IQR: 56, 70, 81) with a confirmed diagnosis of COVID-19 by 28th June 2020. This study used multivariable logistic regression to generate odd ratios (ORs) multiply adjusted for 37 covariates (comorbidities, demographic, and others) selected on the basis of clinical interest and prior findings. Results were supplemented by gradient-boosted decision tree (GBDT) classification to generate Shapley values in order to evaluate the impact of the covariates on model output for all patients. Factors are differentially associated with death and ICUA and among patients.Deaths due to COVID-19 were associated with immunosuppression due to disease (OR 1.39, 95% CI 1.10-1.76), type-2 diabetes (OR 1.31, 95% CI 1.17-1.46), chronic respiratory disease (OR 1.19, 95% CI 1.05-1.35), age (OR 1.56/10-year increment, 95% CI 1.52-1.61), and male sex (OR 1.54, 95% CI1.42-1.68). Associations of ICUA with some factors differed in direction (e.g., age, chronic respiratory disease). Self-reported ethnicities were strongly but variably associated with both outcomes.GBDTs had similar performance (ROC-AUC, ICUA 0.83, death 0.68 for GBDT; 0.80 and 0.68 for logistic regression). We derived importance scores based on Shapley values which were consistent with the ORs, despite the underlying machine-learning model being intrinsically different to the logistic regression. Chronic heart disease, hypertension, other comorbidities, and some ethnicities had Shapley impacts on death ranging from positive to negative among different patients, although consistently associated with ICUA for all. Immunosuppressive disease, type-2 diabetes, and chronic liver and respiratory diseases had positive impacts on death with either positive or negative on ICUA.We highlight the complexity of informing clinical practice and public-health interventions. We recommend that clinical support systems should not only predict patients at risk, but also yield interpretable outputs for validation by domain experts.

peer-reviewed Low and high protein dairy powders are prone to caking and sticking and can also be highly insoluble; with powder storage conditions an important factor responsible for such issues. The aim of this study focused on the bulk and surface properties of anhydrous and humidified spray-dried milk protein concentrate (MPC) powders (protein content ~40, 50, 60, 70 or 80%, w/w). Water sorption isotherms, polarized light and scanning electron micrographs showed crystallized lactose in low protein powders at high water activities. High protein systems demonstrated increased bulk diffusion coefficients compared to low protein systems. Glass transition temperatures, α-relaxation temperatures and structural strength significantly decreased with water uptake. CLSM measurements showed that humidified systems have slower real time water diffusion compared to anhydrous systems. Overall, the rate of water diffusion was higher for low protein powders but high protein powders absorbed higher levels of water under high humidity conditions.

This study highlights differences in conformational and physicochemical characteristics of bovine skim milk and micellar casein from cows of different β-casein phenotypes. These genetic variants have been one of the predominant topics among dairy researchers due to their differences in β-casein structure, and thus their potential effects on dairy processing and human health. For characterising differences in milk protein structure, Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (1H NMR) spectroscopies combined with chemometric analysis were used. Additionally, physiochemical properties such as mineral content, particle size, and electrostatic charge in skim milk and micellar casein samples were analysed at 4 and 20 ᵒC. Results showed variation in the secondary structure of all three genetic variants independent of temperature. Moreover, the main differences involved a higher level of β-turn and α-helical structures in A1/A1 β-casein milk, while intermolecular β-sheets were more numerous in A1/A2 β-casein milk, whereas random or polyproline II (PPII) structures were more common in A2/A2 β-casein milk. Temperature slightly affected these differences, which was due to the dissociation of β-casein from the micelle at low temperature. In addition, A2/A2 β-casein milk and its micellar casein had a larger average particle size, which resulted in a lower negative ζ-potential. The A2/A2 β-casein samples contained greater amounts of phosphorus and less calcium compared to the other genetic variants of milk and their micellar caseins. The results also indicated that a combination of FTIR and 1H NMR spectroscopies could be used to establish conformational differences in milk and micellar caseins of different genetic variants.

The natural history of neonatal group B Streptococcus (GBS) is poorly understood. Little is known about the bacterial factors influencing the transmission of GBS from mother to neonate, or the development of invasive early-onset GBS disease (EOGBS) in colonized neonates. We reviewed whether bacterial load and molecular markers are associated with GBS vertical transmission and progression to EOGBS.We searched Medline, Embase, Cochrane and Web of Science from inception to October 10, 2016, for observational studies in English. We also hand-searched reference lists of relevant publications and experts cross-checked included studies. Two reviewers independently screened studies, extracted data and appraised the quality of included studies using the Quality in Prognosis Studies tool. We conducted random-effects meta-analyses where possible and narratively synthesized the evidence in text and tables.Seventeen studies were included from 1107 records retrieved from electronic databases and publication references. Meta-analyses of 3 studies showed that neonates colonized by serotype III had a higher risk of developing EOGBS than serotype Ia (pooled risk ratio: 1.51, 95% confidence interval: 1.12-2.03) and serotype II (risk ratio: 1.95, 95% confidence interval: 1.10-3.45). Eleven studies showed that in heavily colonized mothers, 2-3 times more neonates were colonized, and in heavily colonized neonates, up to 15 times more neonates had EOGBS, compared with light colonization. Most evidence was published before 2000 and was at risk of bias.Acknowledging the difficulty of natural history studies, well-controlled studies are needed to assess the predictive value of pathogen subtype and heavy load; they may be useful for better-targeted prevention.

peer-reviewed The effect of pH, adjusted using either hydrochloric acid (HCl), citric acid or sodium hydroxide, on calcium ion (Ca2+) activity, and consequent changes in viscosity and heat coagulation time (HCT) of milk protein concentrate (MPC) was investigated. Reducing the pH of MPC dispersions resulted in a reduction in their viscosity, which subsequently increased during heat treatment. The maximum heat stability of MPC was observed at pH 6.7. Reducing the pH of MPC from 6.7 to 6.2 resulted in a significant (P < 0.05) increase in Ca2+ activity, and reduction in HCT. Such changes were more extensive using HCl compared with citric acid. Increasing the pH greater than 6.7 also led to a reduction in HCT but a decrease in Ca2+ activity. These results demonstrate the importance of pH adjustment, and choice of acidulant, on Ca2+ activity, viscosity, and heat coagulation properties of MPC concentrates during processing.

Detecting gastrointestinal (GI) infection transmission among men who have sex with men (MSM) in England is complicated by a lack of routine sexual behavioural data. We investigated whether gender distributions might generate signals for increased transmission of GI pathogens among MSM. We examined the percentage male of laboratory-confirmed patient-episodes for patients with no known travel history for 10 GI infections of public health interest in England between 2003 and 2013, stratified by age and region. An adult male excess was observed forShigellaspp. (annual maximum 71% male); most pronounced for those aged 25–49 years and living in London, Brighton and Manchester. An adult male excess was observed every year forEntamoeba histolytica(range 59.8–76.1% male),Giardia(53.1–57.6%) andCampylobacter(52.1–53.5%) and for a minority of years for hepatitis A (max. 69.8%) and typhoidal salmonella (max. 65.7%). This approach generated a signal for excess male episodes for six GI pathogens, including a characterised outbreak ofShigellaamong MSM. Stratified analyses by geography and age group were consistent with MSM transmission forShigella. Optimisation and routine application of this technique by public health authorities elsewhere might help identify potential GI infection outbreaks due to sexual transmission among MSM, for further investigation.