Pneumococcal carriage and disease in adults in England 2011-2019: the importance of adults as a reservoir for pneumococcus in communities.

BACKGROUND: Pneumococcal carriage in children has been extensively studied, but carriage in healthy adults and its relationship to invasive pneumococcal disease (IPD) is less understood. METHODS: Nasal wash samples from adults without close contact with young children (Liverpool, UK), 2011-2019, were cultured, and culture-negative samples tested by PCR. Pneumococcal carriage in adults 18-44 years was compared with carriage among PCV-vaccinated children 13-48 months (nasopharyngeal swabs, Thames Valley, UK) and IPD data for England for the same ages for 2014-2019. Age-group specific serotype invasiveness was calculated and used with national IPD data to estimate carriage serotype distributions for adults aged 65+ years. RESULTS: In total 98 isolates (97 carriers) were identified from 1,631 adults aged 18+ years (age and sex standardized carriage prevalence 6.4%), with only three identified solely by PCR. Despite different carriage and IPD serotype distributions between adults and children, serotype invasiveness was highly correlated (R=0.9). Serotypes 3, 37 and 8 represented a higher proportion of adult carriage than expected from direct low-level transmission from children to adults. The predicted carriage serotype distributions for 65+ years aligned more closely with the carriage serotype distribution for young adults than young children. CONCLUSIONS: The nasal wash technique is highly sensitive; additional benefit of PCR is limited. Comparison of carriage serotype distributions suggests some serotypes may be circulating preferentially within these specific young adults. Our data suggest that for some serotypes carried by adults 65+ years, other adults may be an important reservoir for transmission. Age groups such as older children should also be considered.

Machine Learning-Based Identification of Mating Type and Metalaxyl Response in Phytophthora infestans Using SSR Markers.

Phytophthora infestans is the causal agent of late blight in potato. The occurrence of P. infestans with both A1 and A2 mating types in the field may result in sexual reproduction and the generation of recombinant strains. Such strains with new combinations of traits can be highly aggressive, resistant to fungicides, and can make the disease difficult to control in the field. Metalaxyl-resistant isolates are now more prevalent in potato fields. Understanding the genetic structure and rapid identification of mating types and metalaxyl response of P. infestans in the field is a prerequisite for effective late blight disease monitoring and management. Molecular and phenotypic assays involving molecular and phenotypic markers such as mating types and metalaxyl response are typically conducted separately in the studies of the genotypic and phenotypic diversity of P. infestans. As a result, there is a pressing need to reduce the experimental workload and more efficiently assess the aggressiveness of different strains. We think that employing genetic markers to not only estimate genotypic diversity but also to identify the mating type and fungicide response using machine learning techniques can guide and speed up the decision-making process in late blight disease management, especially when the mating type and metalaxyl resistance data are not available. This technique can also be applied to determine these phenotypic traits for dead isolates. In this study, over 600 P. infestans isolates from different populations-Estonia, Pskov region, and Poland-were classified for mating types and metalaxyl response using machine learning techniques based on simple sequence repeat (SSR) markers. For both traits, random forest and the support vector machine demonstrated good accuracy of over 70%, compared to the decision tree and artificial neural network models whose accuracy was lower. There were also associations (p < 0.05) between the traits and some of the alleles detected, but machine learning prediction techniques based on multilocus SSR genotypes offered better prediction accuracy.

Primary care usage at the end of life: a retrospective cohort study of cancer patients using linked primary and hospital care data.

PURPOSE: Health service use is most intensive in the final year of a person's life, with 80% of this expenditure occurring in hospital. Close involvement of primary care services has been promoted to enhance quality end-of-life care that is appropriate to the needs of patients. However, the relationship between primary care involvement and patients' use of hospital care is not well described. This study aims to examine primary care use in the last year of life for cancer patients and its relationship to hospital usage. METHODS: Retrospective cohort study in Victoria, Australia, using linked routine care data from primary care, hospital and death certificates. Patients were included who died related to cancer between 2008 and 2017. RESULTS: A total of 758 patients were included, of whom 88% (n = 667) visited primary care during the last 6 months (median 9.1 consultations). In the last month of life, 45% of patients were prescribed opioids, and 3% had imaging requested. Patients who received home visits (13%) or anticipatory medications (15%) had less than half the median bed days in the last 3 months (4 vs 9 days, p < 0.001, 5 vs 10 days, p = 0.001) and 1 month of life (0 vs 2 days, p = 0.002, 0 vs 3 days, p < 0.001), and reduced emergency department presentations (32% vs 46%, p = 0.006, 31% vs 47% p < 0.001) in the final month. CONCLUSION: This study identifies two important primary care processes-home visits and anticipatory medication-associated with reduced hospital usage and intervention at the end of life.

Do NO, N2O, N2 and CO2 fluxes differ in soils sourced from cropland and varying riparian buffer vegetation? An incubation study.

Riparian buffers are expedient interventions for water quality functions in agricultural landscapes. However, the choice of vegetation and management affects soil microbial communities, which in turn affect nutrient cycling and the production and emission of gases such as nitric oxide (NO), nitrous oxide (N2O), nitrogen gas (N2) and carbon dioxide (CO2). To investigate the potential fluxes of the above-mentioned gases, soil samples were collected from a cropland and downslope grass, willow and woodland riparian buffers from a replicated plot scale experimental facility. The soils were re-packed into cores and to investigate their potential to produce the aforementioned gases via potential denitrification, a potassium nitrate (KNO3 -) and glucose (labile carbon)-containing amendment, was added prior to incubation in a specialized laboratory DENItrification System (DENIS). The resulting NO, N2O, N2 and CO2 emissions were measured simultaneously, with the most NO (2.9 ± 0.31 mg NO m-2) and N2O (1413.4 ± 448.3 mg N2O m-2) generated by the grass riparian buffer and the most N2 (698.1 ± 270.3 mg N2 m-2) and CO2 (27,558.3 ± 128.9 mg CO2 m-2) produced by the willow riparian buffer. Thus, the results show that grass riparian buffer soils have a greater NO3 - removal capacity, evidenced by their large potential denitrification rates, while the willow riparian buffers may be an effective riparian buffer as its soils potentially promote complete denitrification to N2, especially in areas with similar conditions to the current study.

Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

De novo membranous nephropathy in a pig-to-baboon kidney xenograft: A new xenograft glomerulopathy.

De novo membranous nephropathy (dnMN) is an uncommon immune complex-mediated late complication of human kidney allografts that causes proteinuria. We report here the first case of dnMN in a pig-to-baboon kidney xenograft. The donor was a double knockout (GGTA1 and ß4GalNT1) genetically engineered pig with a knockout of the growth hormone receptor and addition of 6 human transgenes (hCD46, hCD55, hTBM, hEPCR, hHO1, and hCD47). The recipient developed proteinuria at 42 days posttransplant, which progressively rose to the nephrotic-range at 106 days, associated with an increase in serum antidonor IgG. Kidney biopsies showed antibody-mediated rejection (AMR) with C4d and thrombotic microangiopathy that eventually led to graft failure at 120 days. In addition to AMR, the xenograft had diffuse, global granular deposition of C4d and IgG along the glomerular basement membrane on days 111 and 120. Electron microscopy showed extensive amorphous subepithelial electron-dense deposits with intervening spikes along the glomerular basement membrane. These findings, in analogy to human renal allografts, are interpreted as dnMN in the xenograft superimposed on AMR. The target was not identified but is hypothesized to be a pig xenoantigen expressed on podocytes. Whether dnMN will be a significant problem in other longer-term xenokidneys remains to be determined.

Impacts of reduced synthetic fertiliser use under current and future climates: Exploration using integrated agroecosystem modelling in the upper River Taw observatory, UK.

The intensification of farming and increased nitrogen fertiliser use, to satisfy the growing population demand, contributed to the extant climate change crisis. Use of synthetic fertilisers in agriculture is a significant source of anthropogenic Greenhouse Gas (GHG) emissions, especially potent nitrous oxide (N2O). To achieve the ambitious policy target for net zero by 2050 in the UK, it is crucial to understand the impacts of potential reductions in fertiliser use on multiple ecosystem services, including crop production, GHG emissions and soil organic carbon (SOC) storge. A novel integrated modelling approach using three established agroecosystem models (SPACSYS, CSM and RothC) was implemented to evaluate the associated impacts of fertiliser reduction (10%, 30% and 50%) under current and projected climate scenarios (RCP2.6, RCP4.5 and RCP8.5) in a study catchment in Southwest England. 48 unique combinations of soil types, climate conditions and fertiliser inputs were evaluated for five major arable crops plus improved grassland. With a 30% reduction in fertiliser inputs, the estimated yield loss under current climate ranged between 11% and 30% for arable crops compared with a 20-24% and 6-22% reduction in N2O and methane emissions, respectively. Biomass was reduced by 10-25% aboveground and by <12% for the root system. Relative to the baseline scenario, soil type dependent reductions in SOC sequestration rates are predicted under future climate with reductions in fertiliser inputs. Losses in SOC were more than doubled under the RCP4.5 scenario. The emissions from energy use, including embedded emissions from fertiliser manufacture, was a significant source (14-48%) for all arable crops and the associated GWP20.

The Variability of Phytophthora infestans Isolates Collected from Estonian Islands in the Baltic Sea.

Knowledge of a pathogen's genetic variability and population structure is of great importance to effective disease management. In this study, 193 isolates of Phytophthora infestans collected from three Estonian islands were characterized over 3 years using simple sequence repeat (SSR) marker data complemented by information on their mating type and resistance to metalaxyl. In combination with SSR marker data from samples in the neighboring Pskov region of Northwest Russia, the impact of regional and landscape structure on the level of genetic exchange was also examined. Among the 111 P. infestans isolates from Estonian islands, 49 alleles were detected among 12 SSR loci, and 59 SSR multilocus genotypes were found, of which 64% were unique. The genetic variation was higher among years than that among islands, as revealed by the analysis of molecular variance. The frequency of metalaxyl-resistant isolates increased from 9% in 2012 to 30% in 2014, and metalaxyl resistance was most frequent among A1 isolates. The test for isolation by distance among the studied regions was not significant, and coupled with the absence of genetic differentiation, the result revealed gene flow and the absence of local adaptation. The data are consistent with a sexual population in which diversity is driven by an annual germination of soilborne oospores. The absence of shared genotypes over the years has important implications when it comes to the management of diseases. Such population diversity can make it difficult to predict the nature of the outbreak in the coming year as the genetic makeup is different for each year.

Soil erosion, sediment sources, connectivity and suspended sediment yields in UK temperate agricultural catchments: Discrepancies and reconciliation of field-based measurements.

Robust understanding of the fine-grained sediment cascades of temperate agricultural catchments is essential for supporting targeted management for addressing the widely reported sediment problem. Within the UK, many independent field-based measurements of soil erosion, sediment sources and catchment suspended sediment yields have been published. However, attempts to review and assess the compatibility of these measurements are limited. The data available suggest that landscape scale net soil erosion rates (∼38 t km-2 yr-1 for arable and ∼26 t km-2 yr-1 grassland) are comparable to the typical suspended sediment yield of a UK catchment (∼44 t km2 yr-1). This finding cannot, however, be reconciled easily with current prevailing knowledge that agricultural topsoils dominate sediment contributions to watercourses, and that catchment sediment delivery ratios are typically low. Channel bank erosion rates can be high at landscape scale (27 km-2 yr-1) and account for these discrepancies but would need to be the dominant sediment source in most catchments, which does not agree with a review of sediment sources for the UK made in the recent past. A simple and robust colour-based sediment source tracing method using hydrogen peroxide sample treatment is therefore used in fifteen catchments to investigate their key sediment sources. Only in two of the catchments are eroding arable fields likely to be important sediment sources, supporting the alternative hypothesis that bank erosion is likely to be the dominant source of sediment in many UK catchments. It is concluded that the existing lines of evidence on the individual components of the fine sediment cascade in temperate agricultural catchments in the UK are difficult to reconcile and run the risk of best management interventions being targeted inappropriately. Recommendations for future research to address paucities in measured erosion rates, sediment delivery ratios and suspended sediment yields, validate sediment source fingerprinting results, consider the sources of sediment-associated organic matter, and re-visit soil erosion and sediment cascade model parameterisation are therefore made.

Assessing the use of minimally invasive self-sampling at home for long-term monitoring of the microbiota within UK families.

Monitoring the presence of commensal and pathogenic respiratory microorganisms is of critical global importance. However, community-based surveillance is difficult because nasopharyngeal swabs are uncomfortable and painful for a wide age range of participants. We designed a methodology for minimally invasive self-sampling at home and assessed its use for longitudinal monitoring of the oral, nasal and hand microbiota of adults and children within families. Healthy families with two adults and up to three children, living in and near Liverpool, United Kingdom, self-collected saliva, nasal lining fluid using synthetic absorptive matrices and hand swabs at home every two weeks for six months. Questionnaires were used to collect demographic and epidemiological data and assess feasibility and acceptability. Participants were invited to take part in an exit interview. Thirty-three families completed the study. Sampling using our approach was acceptable to 25/33 (76%) families, as sampling was fast (76%), easy (76%) and painless (60%). Saliva and hand sampling was acceptable to all participants of any age, whereas nasal sampling was accepted mostly by adults and children older than 5 years. Multi-niche self-sampling at home can be used by adults and children for longitudinal surveillance of respiratory microorganisms, providing key data for design of future studies.

The effect of shear-dependent flocculation on the multimodality of effective particle size distributions in a gravel-bed river during high flows.

Purpose: Multimodal effective particle size distributions (EPSDs) develop as flocculation and particle breakage occur dynamically in a fluid shear and such distributions have been previously reported in coastal and estuarine waters to understand flocculation processes. Here, we use time varying multimodal EPSDs and hydraulic parameters (discharge and bed shear stress) to assess freshwater flocculation in a gravel-bed river in southern Alberta, Canada. Methods: Instantaneous discharge, volume concentration (VC), and EPSD of suspended solids were measured during three high discharge events at four study sites in a 10 km reach of the Crowsnest River. The EPSD and VC of suspended solids (< 500 µm) were measured in the centroid of flow with a LISST-200x. Bed shear stress for measured discharge was obtained using a flow model, MOBED. Results: Multimodal EPSDs consisted of primary particles, flocculi, microflocs, and macroflocs. Shear dependent flocculation was consistently observed for all sites and events, due to low and high shear stress flocculation, particle breakage, and mobilization of tributary sub-catchment derived particles. Higher shear stress limited flocculation to smaller floc sizes, while lower bed shear stress conditions created higher volumes of macroflocs. Conclusion: Flocculation and particle breakage processes based on relationships between particle size and hydraulic properties presented herein have implications for advancing fine sediment transport models by a variable cohesion factor as a function of floc size class.

The virulence of Dichelobacter nodosus, measured by the elastase test, is an important predictor for virulent footrot diagnosis in New South Wales sheep flocks.

Ovine footrot is a contagious bacterial disease that causes foot lesions, and depending on the virulence of the causative strains, may lead to severe underrunning of the hoof and lameness. Virulent footrot can be identified, treated and controlled more effectively than less virulent benign forms. The in vitro elastase test for virulence of the causative bacteria, Dichelobacter nodosus, has been used to support clinical diagnosis. However, not all laboratory-designated virulent D. nodosus strains cause clinical signs of virulent footrot. This study evaluated retrospectively how well the elastase test supported clinical footrot diagnosis in 150 sheep flocks examined for suspect footrot in New South Wales between August 2020 and December 2021. Flocks were included if measures of clinical disease, environmental conditions and the virulence of D. nodosus isolates were available. Variation in the elastase activity result between D. nodosus isolated from the same flock made bacterial virulence hard to interpret, but calculating the mean elastase rate for all isolates from the same flock made correlations between bacterial virulence and flock footrot diagnosis possible. Simplifying bacterial virulence into whether there were any elastase-positive D. nodosus isolates before 12 days increased the predictive value of elastase results for virulent diagnosis, compared with using the first day that any isolate was elastase positive or the percentage of elastase-positive isolates by 12 days, but not all clinically virulent flocks had isolates with elastase activity before 12 days. Logistic regression models were fitted to identify the minimum number of predictors for virulent footrot diagnosis, with models suggesting that virulent footrot diagnosis was best predicted by adding the elastase test result and environmental conditions to the prevalence of severe foot lesions (score 4 and 5). However, performing the same analysis with different breeds, ages of sheep and seasons might highlight other factors important in the diagnosis of virulent footrot.

Hydro-chemical responses at different scales in a rural catchment, UK, and implications for managing the unintended consequences of agriculture.

Diffuse pollutant transfers from agricultural land often constitute the bulk of annual loads in catchments and storm events dominate these fluxes. There remains a lack of understanding of how pollutants move through catchments at different scales. This is critical if the mismatch between the scales used to implement on-farm management strategies, compared to those used for assessment of environmental quality, is to be addressed. The aim of this study was to understand how the mechanisms of pollutant export may change when assessed at different scales and the corresponding implications for on-farm management strategies. A study was conducted within a 41 km2 catchment containing 3 nested sub-catchments, instrumented to monitor discharge and various water quality parameters. Storm data over a 24-month period were analysed and hysteresis (HI) and flushing (FI) indices calculated for two water quality variables that are typically of environmental significance; NO3-N and suspended sediment (SSC). For SSC, increasing spatial scale had little effect on the mechanistic interpretation of mobilisation and the associated on-farm management strategies. At the three smallest scales NO3-N was chemodynamic with the interpretation of dominant mechanisms changing seasonally. At these scales, the same on-farm management strategies would be recommended. However, at the largest scale, NO3-N appeared unaffected by season and chemostatic. This would lead to a potentially very different interpretation and subsequent on-farm measures. The results presented here underscore the benefits of nested monitoring for extracting mechanistic understanding of agricultural impacts on water quality. The application of HI and FI indicates that monitoring at smaller scales is crucial. At large scales, the complexity of the catchment hydrochemical response means that mechanisms become obscured. Smaller catchments more likely represent critical areas within larger catchments where mechanistic understanding can be extracted from water quality monitoring and used to underpin the selection of on-farm mitigation measures.

A diagnostic for quantifying secondary species emission from electrospray devices.

Measuring the polydisperse beam of charged species emitted by an electrospray device requires accurate measurements of current. Secondary species emission (SSE) caused by high-velocity nanodroplet or molecular ion impacts on surfaces contributes to substantial uncertainty in current measurements. SSE consists of both positive and negative species; hence, mitigating measurement uncertainty requires different considerations other than plasma diagnostic techniques. The probe and analysis methods described herein distinguish between current contributions from positive SSE, negative SSE, and primary species. Separating each contribution provides positive and negative SSE yield measurements and corrected current measurements that reflect the true primary current. Sources of measurement uncertainty in probe design are discussed, along with appropriate mitigation methods. The probe and analysis techniques are demonstrated on an ionic liquid electrospray operating in a droplet emission mode to obtain an angular distribution of positive and negative SSE yields for an ionic liquid electrospray.

Using the colour of recent overbank sediment deposits in two large catchments to determine sediment sources for targeting mitigation of catchment-specific management issues.

The effective management of sediment losses in large river systems is essential for maintaining the water resources and ecosystem services they provide. However, budgetary, and logistical constraints often mean that the understanding of catchment sediment dynamics necessary to deliver targeted management is unavailable. This study trials the collection of accessible recently deposited overbank sediment and the measurement of its colour using an office document scanner to identify the evolution of sediment sources rapidly and inexpensively in two large river catchments in the UK. The River Wye catchment has experienced significant clean-up costs associated with post-flood fine sediment deposits in both rural and urban areas. In the River South Tyne, fine sand is fouling potable water extraction and fine silts degrade salmonid spawning habitats. In both catchments, samples of recently deposited overbank sediment were collected, fractionated to either <25 µm or 63-250 µm, and treated with hydrogen peroxide to remove organic matter before colour measurement. In the River Wye catchment, an increased contribution from sources over the geological units present in a downstream direction was identified and was attributed to an increasing proportion of arable land. Numerous tributaries draining different geologies allowed for overbank sediment to characterise material on this basis. In the River South Tyne catchment, a downstream change in sediment source was initially found. The River East Allen was identified as a representative and practical tributary sub-catchment for further investigation. The collection of samples of channel bank material and topsoils therein allowed channel banks to be identified as the dominant sediment source with an increasing but small contribution from topsoils in a downstream direction. In both study catchments, the colour of overbank sediments could quickly and inexpensively inform the improved targeting of catchment management measures.

Draining the specialized nursing brains, the emigration paradigm of Ghana: A cross-sectional study.

AIM: The study aimed to determine the emigration intentions of specialist nurses (SNs) and ascertain the influencing factors, implications and mitigating factors in Ghana. DESIGN: A cross-sectional study. METHODS: The sample was composed of 225 participants conveniently selected from a tertiary facility in Ghana. A turnover intention scale and the researchers' developed questionnaire were used to collect the data between June 1 and September 30, 2021. Data were analysed through descriptive statistics and linear regression. RESULTS: The composite mean score for specialist nurses' intention to migrate was high (mean = 3.43); and the push factors accounted for the intentions explaining 48.6% of the variation (R2  = 0.486, F(5, 219)  = 38.46, p < 0.001). The associated challenges of specialist nurses' emigration are increased cost of training new specialist nurses, poor quality of specialist nursing care, burnout syndrome among staff and poor patient health outcomes.

Protein quality as a complementary functional unit in life cycle assessment (LCA).

Goal and theoretical commentary: A number of recent life cycle assessment (LCA) studies have concluded that animal-sourced foods should be restricted-or even avoided-within the human diet due to their relatively high environmental impacts (particularly those from ruminants) compared with other protein-rich foods (mainly protein-rich plant foods). From a nutritional point of view, however, issues such as broad nutrient bioavailability, amino acid balances, digestibility and even non-protein nutrient density (e.g., micronutrients) need to be accounted for before making such recommendations to the global population. This is especially important given the contribution of animal sourced foods to nutrient adequacy in the global South and vulnerable populations of high-income countries (e.g., children, women of reproductive age and elderly). Often, however, LCAs simplify this reality by using 'protein' as a functional unit in their models and basing their analyses on generic nutritional requirements. Even if a 'nutritional functional unit' (nFU) is utilised, it is unlikely to consider the complexities of amino acid composition and subsequent protein accretion. The discussion herein focuses on nutritional LCA (nLCA), particularly on the usefulness of nFUs such as 'protein,' and whether protein quality should be considered when adopting the nutrient as an (n)FU. Further, a novel and informative case study is provided to demonstrate the strengths and weaknesses of protein-quality adjustment. Case study methods: To complement current discussions, we present an exploratory virtual experiment to determine how Digestible Indispensable Amino Acid Scores (DIAAS) might play a role in nLCA development by correcting for amino acid quality and digestibility. DIAAS is a scoring mechanism which considers the limiting indispensable amino acids (IAAs) within an IAA balance of a given food (or meal) and provides a percentage contribution relative to recommended daily intakes for IAA and subsequent protein anabolism; for clarity, we focus only on single food items (4 × animal-based products and 4 × plant-based products) in the current case exemplar. Further, we take beef as a sensitivity analysis example (which we particularly recommend when considering IAA complementarity at the meal-level) to elucidate how various cuts of the same intermediary product could affect the interpretation of nLCA results of the end-product(s). Recommendations: First, we provide a list of suggestions which are intended to (a) assist with deciding whether protein-quality correction is necessary for a specific research question and (b) acknowledge additional uncertainties by providing mitigating opportunities to avoid misinterpretation (or worse, dis-interpretation) of protein-focused nLCA studies. We conclude that as relevant (primary) data availability from supply chain 'gatekeepers' (e.g., international agri-food distributors and processors) becomes more prevalent, detailed consideration of IAA provision of contrasting protein sources needs to be acknowledged-ideally quantitatively with DIAAS being one example-in nLCA studies utilising protein as a nFU. We also contend that future nLCA studies should discuss the complementarity of amino acid balances at the meal-level, as a minimum, rather than the product level when assessing protein metabolic responses of consumers. Additionally, a broader set of nutrients should ideally be included when evaluating "protein-rich foods" which provide nutrients that extend beyond amino acids, which is of particular importance when exploring dietary-level nLCA.

Evaluation of new instruments for screening and diagnosis of tics and tic disorders in a well-characterized sample of youth with tics and recruited controls.

Tics and tic disorders can significantly impact children, but limited screening tools and diagnostic challenges may delay access to care. The current study attempted to address these gaps by evaluating sensitivity and specificity of the Motor or Vocal Inventory of Tics (MOVeIT), a tic symptom screener, and the Description of Tic Symptoms (DoTS), a brief diagnostic assessment for tic disorders. Children (n=100, age 6-17 years old) with tic disorders attending a Tourette specialty clinic and a community-recruited sample without tics completed a gold-standard assessment by a tic expert; these evaluations were compared to child self-report and parent and teacher report versions of the MOVeIT, and child and parent versions of the DoTS. The parent and child MOVeIT met or exceeded pre-specified 85% sensitivity and specificity criteria for detecting the presence of tics when compared to a gold-standard tic expert diagnosis. The Teacher MOVeIT had lower sensitivity (71.4%) but good specificity (95.7%) for identifying any tic symptoms compared to gold standard. For determination of the presence or absence of any tic disorder, sensitivity of both parent and child DoTS was 100%; specificity of the parent DoTS was 92.7% and child DoTS specificity was 75.9%. More work may be needed to refine the teacher MOVeIT, but it is also recognized that tic expression may vary by setting. While the MOVeIT and DoTS parent and child questionnaires demonstrated adequate sensitivity and specificity for determining the presence of tics and tic disorders in this well-defined sample, additional testing in a general population is warranted.

A commentary on key methodological developments related to nutritional life cycle assessment (nLCA) generated throughout a 6-year strategic scientific programme.

Rothamsted Research (RRes) is the world's oldest agricultural research centre, notable for the development of the first synthetic fertilizer (superphosphate) and long-term farming experiments (LTEs) spanning over 170 years. In 2015, RRes recruited several life cycle assessment (LCA) experts and began adopting the method to utilize high resolution agronomical data covering livestock (primarily ruminants), grassland/forage productivity and quality, and arable systems established on its North Wyke Farm Platform (NWFP) and the LTEs. The NWFP is a UK 'National Bioscience Research Infrastructure' (NBRI) developed for informing and testing systems science utilising high-resolution data to determine whether it is possible to produce nutritious food sustainably. Thanks largely to the multidisciplinary knowledge at RRes, and its collaborators, its LCA Team has been at the forefront of methodological advances during a 6-year Institute Strategic Programme (ISP) 'Soil-to-Nutrition' (S2N). While S2N investigated the co-benefits and trade-offs of new mechanistic understanding of efficient nutrient use across scales from pot to landscape, this commentary specifically synthesizes progress in incorporating human nutrition in the context of environmental footprinting, known as 'nutritional LCA' (nLCA). We conclude our commentary with a brief discussion on future pathways of exploration and methodological developments covering various activities along entire agri-food supply-chains.