Genomic investigations of unexplained acute hepatitis in children.

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

North American tree migration paced by climate in the West, lagging in the East.

Tree fecundity and recruitment have not yet been quantified at scales needed to anticipate biogeographic shifts in response to climate change. By separating their responses, this study shows coherence across species and communities, offering the strongest support to date that migration is in progress with regional limitations on rates. The southeastern continent emerges as a fecundity hotspot, but it is situated south of population centers where high seed production could contribute to poleward population spread. By contrast, seedling success is highest in the West and North, serving to partially offset limited seed production near poleward frontiers. The evidence of fecundity and recruitment control on tree migration can inform conservation planning for the expected long-term disequilibrium between climate and forest distribution.

Population genomic structure of a widespread, urban-dwelling mammal: The eastern grey squirrel (Sciurus carolinensis).

Urbanization is a persistent and widespread driver of global environmental change, potentially shaping evolutionary processes due to genetic drift and reduced gene flow in cities induced by habitat fragmentation and small population sizes. We tested this prediction for the eastern grey squirrel (Sciurus carolinensis), a common and conspicuous forest-dwelling rodent, by obtaining 44K SNPs using reduced representation sequencing (ddRAD) for 403 individuals sampled across the species' native range in eastern North America. We observed moderate levels of genetic diversity, low levels of inbreeding, and only a modest signal of isolation-by-distance. Clustering and migration analyses show that estimated levels of migration and genetic connectivity were higher than expected across cities and forested areas, specifically within the eastern portion of the species' range dominated by urbanization, and genetic connectivity was less than expected within the western range where the landscape is fragmented by agriculture. Landscape genetic methods revealed greater gene flow among individual squirrels in forested regions, which likely provide abundant food and shelter for squirrels. Although gene flow appears to be higher in areas with more tree cover, only slight discontinuities in gene flow suggest eastern grey squirrels have maintained connected populations across urban areas in all but the most heavily fragmented agricultural landscapes. Our results suggest urbanization shapes biological evolution in wildlife species depending strongly on the composition and habitability of the landscape matrix surrounding urban areas.

Evaluation of bovine colostrum replacer supplementation to improve weaning transition in Holstein dairy calves.

The objective of this randomized controlled trial was to evaluate the efficacy of supplementing bovine colostrum replacer during weaning to reduce intestinal permeability and improve gain. For this experiment, 65 calves were enrolled and housed individually until 70 d of age. Calves were fed milk replacer (150 g/L) 3 times daily with 9 L/d, 10.5 L/d, 11.25 L/d, and 12 L/d offered from d 1-7, d 8-14, d 15-21, d 22-56, respectively. Calves were weaned over 8 d from d 57-64, receiving a total of 7.8 L in 2 meals/d from d 57-60 and 3.8 L/d in one feeding from d 61-64. At d 57, calves were blocked by birth weight and randomly assigned to one of 2 treatments, equal in metabolizable energy, which were fed once daily during weaning from d 57-64: control (CON; n = 31 calves): 3.8 L milk replacer (150 g/L) fed by nipple bottle, or colostrum supplementation (COL; n = 34): a mixture of 1 L bovine colostrum replacer (125 g/L) and 3 L milk replacer (150 g/L) with 3.8 L of the mixture fed by nipple bottle. Serum IgG was measured within 48 h of birth and body weight was taken at d 0, 57, 60, 64, 70, 77, and 84. Starter intake and bovine respiratory disease (BRD) score were measured daily from d 50-70 and fecal consistency was examined daily from d 56-70. Serum ß-hydroxybutyrate (BHB) and lung consolidation were evaluated at d 57, 64, and 70 and intestinal permeability was assessed by recovery of chromium-EDTA, lactulose, and d-mannitol from plasma after oral administration at d 56 and 65. There was no difference in body weight between treatment groups at the start of weaning, but COL were 2.79 kg (95% CI: 0.90-4.68) and 2.76 kg (95% CI: 0.86-4.65) heavier than CON at d 77 and 84, respectively. Additionally, COL tended to gain 100.00 g/d more than CON calves (95% CI: -10.41-207.13) from d 57-84. There were no differences in any of the other variables measured. Supplementation of bovine colostrum replacer during weaning may improve weight gain, but the mechanism of action is not clear.

Association between ATP luminometry of feeding equipment and environmental and health parameters of preweaned calves on dairy farms.

The objective of this study was to examine the influence of different environmental factors on ATP luminometry measurements of feeding equipment and to investigate associations with health of preweaned calves and the levels of ATP identified through luminometry. On 50 commercial dairy farms in Quebec, Canada, ATP luminometry measurements (in relative light units (RLU)) were obtained using the direct swabbing technique with Hygiena UltraSnap swabs and a liquid rinsing technique with the same swab for automatic milk feeders (AMF), bottles, buckets, esophageal tube feeders (ET), milk replacer, nipples and water. During this visit, environmental factors (including temperature, air draft, humidity, ammonia, and bacterial count) were collected and a clinical examination (including respiratory score and fecal score) was performed for all preweaned calves present at the farm. This process was repeated 4 times in a year, leading to collection of luminometer results, environmental parameters, and overall health of calves for each season per farm. Overall, a difference in luminometer results was seen between the different periods sampled for all feeding equipment (except the ET), milk replacer and water, showing higher RLU values in spring and summer and lower values in autumn and winter. When comparing RLU measurements with environmental factors, only a low to negligible correlation could be found. When feeding equipment was classified as not contaminated or contaminated based on previously described cut-off values, a good agreement within a farm for the different seasons was noticed only for nipples (Gwet's agreement AC1 = 0.64), with a poor to moderate agreement for other feeding equipment. Regarding the different models of nipples, 'Peach Teat' nipples showed higher RLU values compared with 'Merricks' nipples models. An association was seen between the proportion of preweaned calves suffering from diarrhea on the farm and the contamination of AMF based on ATP luminometry (logistic regression estimate = 0.52, P = 0.04). For other feeding equipment, milk replacer and water, no significant associations were found. This study showed that ATP luminometry measurements of feeding equipment from preweaned calves are susceptible to seasonality and type of nipple. Thus, these factors should be taken into consideration when interpreting results. Additionally, an association could be made between diarrhea in preweaned calves and the contamination of AMF based on ATP luminometry, showing the potential clinical importance of this on-farm hygiene assessment tool.

Reduction in mucosa thickness is associated with changes in immune function in the colon mucosa during the weaning transition in Holstein bull dairy calves.

This study aims to characterize changes in the structure and the molecules related to immune function in the colon mucosa in dairy calves during the weaning transition (weaned at week 6 of age). Colon mucosa thickness, measured at week 5 to 8 and 12 of age, decreased for 2 weeks after weaning, but then recovered. Colon mucosa's transcriptome profiling at week 5, 7, and 12 of age was obtained using RNA-sequencing. Functional analysis showed that pathways related to immune function were up-regulated postweaning. A weighted gene co-expression network analysis identified 17 immune function related genes, expressed higher postweaning, which were negatively correlated with colon mucosa thickness, suggesting that these genes may be involved in colon mucosa inflammation and recovery from mucosa thickness decrement during the weaning transition. As such, it is important to determine the function of immune cells in the colon mucosa during the weaning transition in dairy calves.

Transcriptome profiling revealed that key rumen epithelium functions change in relation to short-chain fatty acids and rumen epithelium-attached microbiota during the weaning transition.

This study aims to characterize the functional changes of the rumen epithelium associated with ruminal short-chain fatty acid (SCFA) concentration and epithelium-attached microbes during the weaning transition in dairy calves. Ruminal SCFA concentrations were determined, and transcriptome and microbiota profiling in biopsied rumen papillae were obtained from Holstein calves before and after weaning using RNA- and amplicon sequencing. Metabolic pathway analysis showed that pathways related to SCFA metabolism and cell apoptosis were up- and down-regulated postweaning, respectively. Functional analysis showed that genes related to SCFA absorption, metabolism, and protective roles against oxidative stress were positively correlated with ruminal SCFA concentrations. The relative abundance of epithelium-attached Rikenellaceae RC9 gut group and Campylobacter was positively correlated with genes involved in SCFA absorption and metabolism, suggesting that these microbes can cooperatively affect host functions. Future research should examine the contribution of attenuated apoptosis on rumen epithelial functional shifts during the weaning transition.

Acceptability of a virtual prostate cancer survivorship care model in rural Australia: A multi-methods, single-centre feasibility pilot.

DESIGN: A multi-methods, single-centre pilot comprising a quasi-experimental pre-/post-test design and an exploratory qualitative study. SETTING: A rural Australian hospital and health service. PARTICIPANTS: Men newly diagnosed with localised prostate cancer who were scheduled to undergo, or had undergone, radical or robotic prostatectomy surgery within the previous 3 months. INTERVENTION: The intervention comprised a 12-week virtual care program delivered via teleconference by a specialist nurse, using a pre-existing connected care platform. The program was tailored to the post-operative recovery journey targeting post-operative care, psychoeducation, problem-solving and goal setting. MAIN OUTCOME MEASURES: Primary outcome: program acceptability. SECONDARY OUTCOMES: quality of life; prostate cancer-related distress; insomnia severity; fatigue severity; measured at baseline (T1); immediately post-intervention (T2); and 12 weeks post-intervention (T3). RESULTS: Seventeen participants completed the program. The program intervention showed very high levels (≥4/5) of acceptability, appropriateness and feasibility. At T1, 47% (n = 8) of men reported clinically significant psychological distress, which had significantly decreased by T3 (p = 0.020). There was a significant improvement in urinary irritative/obstructive symptoms (p = 0.030) and a corresponding decrease in urinary function burden (p = 0.005) from T1 to T3. CONCLUSIONS: This pilot has shown that a tailored nurse-led virtual care program, incorporating post-surgical follow-up and integrated low-intensity psychosocial care, is both acceptable to rural participants and feasible in terms of implementation and impact on patient outcomes.

How to measure mast seeding?

The periodic production of large seed crops, or masting, is a widespread phenomenon in perennial plants. This behavior can enhance the reproductive efficiency of plants, leading to increased fitness, and produce ripple effects on food webs. While variability from year to year is a defining characteristic of masting, the methods used to quantify this variability are highly debated. The commonly used coefficient of variation lacks the ability to account for the serial dependence in mast data and can be influenced by zeros, making it a less suitable choice for various applications based on individual-level observations, such as phenotypic selection, heritability, and climate change studies, which rely on individual-plant-level datasets that often contain numerous zeros. To address these limitations, we present three case studies and introduce volatility and periodicity, which account for the variance in the frequency domain by emphasizing the significance of long intervals in masting. By utilizing examples of Sorbus aucuparia, Pinus pinea, Quercus robur, Quercus pubescens, and Fagus sylvatica, we demonstrate how volatility captures the effects of variance at both high and low frequencies, even in the presence of zeros, leading to improved ecological interpretations of the results. The growing availability of long-term, individual-plant datasets promises significant advancements in the field, but requires appropriate tools for analysis, which the new metrics provide.

High flow nasal cannula for respiratory support in term infants.

BACKGROUND: Respiratory failure or respiratory distress in infants is the most common reason for non-elective admission to hospitals and neonatal intensive care units. Non-invasive methods of respiratory support have become the preferred mode of treating respiratory problems as they avoid some of the complications associated with intubation and mechanical ventilation. High flow nasal cannula (HFNC) therapy is increasingly being used as a method of non-invasive respiratory support. However, the evidence pertaining to its use in term infants (defined as infants ≥ 37 weeks gestational age to the end of the neonatal period (up to one month postnatal age)) is limited and there is no consensus of opinion regarding the safety and efficacy HFNC in this population. OBJECTIVES: To assess the safety and efficacy of high flow nasal cannula oxygen therapy for respiratory support in term infants when compared with other forms of non-invasive respiratory support. SEARCH METHODS: We searched the following databases in December 2022: Cochrane CENTRAL; PubMed; Embase; CINAHL; LILACS; Web of Science; Scopus. We also searched the reference lists of retrieved studies and performed a supplementary search of Google Scholar. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated the use of high flow nasal cannula oxygen therapy in infants ≥ 37 weeks gestational age up to one month postnatal age (the end of the neonatal period). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, performed data extraction, and assessed risk of bias in the included studies. Where studies were sufficiently similar, we performed a meta-analysis using mean differences (MD) for continuous data and risk ratios (RR) for dichotomous data, with their respective 95% confidence intervals (CIs). For statistically significant RRs, we calculated the number needed to treat for an additional beneficial outcome (NNTB). We used the GRADE approach to evaluate the certainty of the evidence for clinically important outcomes. MAIN RESULTS: We included eight studies (654 participants) in this review. Six of these studies (625 participants) contributed data to our primary analyses. Four studies contributed to our comparison of high flow nasal cannula (HFNC) oxygen therapy versus continuous positive airway pressure (CPAP) for respiratory support in term infants. The outcome of death was reported in two studies (439 infants) but there were no events in either group. HFNC may have little to no effect on treatment failure, but the evidence is very uncertain (RR 0.98, 95% CI 0.47 to 2.04; 3 trials, 452 infants; very low-certainty evidence). The outcome of chronic lung disease (need for supplemental oxygen at 28 days of life) was reported in one study (375 participants) but there were no events in either group. HFNC may have little to no effect on the duration of respiratory support (any form of non-invasive respiratory support with or without supplemental oxygen), but the evidence is very uncertain (MD 0.17 days, 95% CI -0.28 to 0.61; 4 trials, 530 infants; very low-certainty evidence). HFNC likely results in little to no difference in the length of stay at the intensive care unit (ICU) (MD 0.90 days, 95% CI -0.31 to 2.12; 3 trials, 452 infants; moderate-certainty evidence). HFNC may reduce the incidence of nasal trauma (RR 0.16, 95% CI 0.04 to 0.66; 1 trial, 78 infants; very low-certainty evidence) and abdominal overdistension (RR 0.22, 95% CI 0.07 to 0.71; 1 trial, 78 infants; very low-certainty evidence), but the evidence is very uncertain. Two studies contributed to our analysis of HFNC versus low flow nasal cannula oxygen therapy (LFNC) (supplemental oxygen up to a maximum flow rate of 2 L/min). The outcome of death was reported in both studies (95 infants) but there were no events in either group. The evidence suggests that HFNC may reduce treatment failure slightly (RR 0.44, 95% CI 0.21 to 0.92; 2 trials, 95 infants; low-certainty evidence). Neither study reported results for the outcome of chronic lung disease (need for supplemental oxygen at 28 days of life). HFNC may have little to no effect on the duration of respiratory support (MD -0.07 days, 95% CI -0.83 to 0.69; 1 trial, 74 infants; very low-certainty evidence), length of stay at the ICU (MD 0.49 days, 95% CI -0.83 to 1.81; 1 trial, 74 infants; very low-certainty evidence), or hospital length of stay (MD -0.60 days, 95% CI -2.07 to 0.86; 2 trials, 95 infants; very low-certainty evidence), but the evidence is very uncertain. Adverse events was an outcome reported in both studies (95 infants) but there were no events in either group. The risk of bias across outcomes was generally low, although there were some concerns of bias. The certainty of evidence across outcomes ranged from moderate to very low, downgraded due to risk of bias, imprecision, indirectness, and inconsistency. AUTHORS' CONCLUSIONS: When compared with CPAP, HFNC may result in little to no difference in treatment failure. HFNC may have little to no effect on the duration of respiratory support, but the evidence is very uncertain. HFNC likely results in little to no difference in the length of stay at the intensive care unit. HFNC may reduce the incidence of nasal trauma and abdominal overdistension, but the evidence is very uncertain. When compared with LFNC, HFNC may reduce treatment failure slightly. HFNC may have little to no effect on the duration of respiratory support, length of stay at the ICU, or hospital length of stay, but the evidence is very uncertain. There is insufficient evidence to enable the formulation of evidence-based guidelines on the use of HFNC for respiratory support in term infants. Larger, methodologically robust trials are required to further evaluate the possible health benefits or harms of HFNC in this patient population.

Factors that influence development of speech pathology skills required for videofluoroscopic swallowing studies.

BACKGROUND: Perceptual, cognitive and previous clinical experience may influence a novice Videofluoroscopic Swallowing Study (VFSS) analyst's trajectory towards competency. Understanding these factors may allow trainees to be better prepared for VFSS training and may allow training to be developed to accommodate differences between trainees. AIMS: This study explored a range of factors previously suggested in the literature as influencing the development of novice analysts' VFSS skills. We hypothesised that knowledge of swallow anatomy and physiology, visual perceptual skills, self-efficacy and interest, and prior clinical exposure would all influence VFSS novice analysts' skill development. METHODS & PROCEDURES: Participants were undergraduate speech pathology students recruited from an Australian university, who had completed the required theoretical units in dysphagia. Data assessing the factors of interest were collected-the participants identified anatomical structures on a still radiographic image, completed a physiology questionnaire, completed subsections of the Developmental Test of Visual Processing-Adults, self-reported the number of dysphagia cases they managed on placement, and self-rated their confidence and interest. Data for 64 participants relating to the factors of interest were compared with their ability to accurately identify swallowing impairments following 15 h of VFSS analytical training, using correlation and regression analysis. OUTCOMES & RESULTS: Success in VFSS analytical training was best predicted by clinical exposure to dysphagia cases and the ability to identify anatomical landmarks on still radiographic images. CONCLUSIONS & IMPLICATIONS: Novice analysts vary in the acquisition of beginner-level VFSS analytical skill. Our findings suggest that speech pathologists who are new to VFSS may benefit from clinical exposure to dysphagia cases, sound foundational knowledge of anatomy relevant to swallowing and the ability to see the anatomical landmarks on still radiographic images. Further research is required to equip VFSS trainers and trainees for training, to understand differences between learners during skill development. WHAT THIS PAPER ADDS: What is already known on the subject The existing literature suggests that no vice Video fluoroscopic Swallowing Study (VFSS) analysts training may be influenced by their personal characteristics and experience. What this study adds This study found that student clinicians, clinical exposure to dysphagia cases and their ability to identify anatomical landmarks relevant to swallowing on still radiographic images prior to training best predicted their ability to identify swallowing impairments after training. What are the clinical implications of this work? Given the expense of training health professionals, further research is required into the factors that successfully prepare clinicians for VFSS training, including clinical exposure, foundational knowledge of anatomy relevant to swallowing and the ability to identify the anatomical landmarks on still radiographic images.

Transcriptome analysis revealed that delaying first colostrum feeding postponed ileum immune system development of neonatal calves.

Our objective was to evaluate the effect of colostrum feeding times on genome-wide gene expression of neonatal calves. In total, twenty-seven calves were assigned to three colostrum feeding treatments: within 45 min (TRT0h, n = 9), 6 h (TRT6h, n = 9) and 12 h (TRT12h, n = 9). Ileum tissues were collected at 51 h and transcriptomic analysis was conducted. Uniquely expressed genes were identified in TRT0h group with enriched "Antigen Presentation" function. Meanwhile, the weighted gene co-expression network analysis (WGCNA) identified four significant gene modules (|correlation| > 0.50 and P ≤ 0.05). In particular, Turquoise gene module with the enriched "Cadherin binding involved in cell-cell adhesion" and "Cell-cell adherences junction" GO terms were significantly correlated with Faecalibacterium prausnitzii (R = -0.70, P < 0.01) and Bifidobacterium (R = -0.55, P < 0.01). Our findings suggest feeding colostrum without delay could stimulate the expression of genes involved in immune function development related to host response and microbial colonization in neonatal claves.

The Neurological Hand Deformity Classification: Construct validity, test-retest, and inter-rater reliability.

BACKGROUND: The Neurological Hand Deformity Classification (NHDC) is an impairment-based tool that classifies hand deformity into one of two ordinal scales: flexion or extension deformities. Classification is made from live observation or from recorded video footage. Differentiation between the levels is determined by wrist position and wrist and finger movement. PURPOSE: To examine aspects of validity and reliability of the NHDC. STUDY DESIGN: A measurement study design. METHODS: Data from a convenience sample of 127 children with cerebral palsy, 66 males: 61 females, ranging in age from 8 months to 15 years, across all Manual Ability Classification System levels I to V, were analyzed. Construct validity was assessed by testing predetermined hypotheses of relationships between the NHDC and measures of body function and activity measures with observed performance using the Chi Squared Test of Independence and Spearman Correlation Coefficient. Test-retest and inter-rater reliability were assessed by calculating agreement between repeated measures and paired raters using weighted kappa and Cohen's kappa with 95% confidence intervals. RESULTS: Predicted hypotheses for the NHDC were met in nine of 10 Spearman's rho correlations with body structure measures and in 2 of 7 correlations with activity measures. Test-retest for flexion deformities: κw = 0.84; 95% CI 0.70-0.98; and extension deformities: κ = 1.0; 95% CI 1.0-1.0 was good to excellent; inter-rater reliability for flexion deformities: κw = 0.76; 95% CI 0.67-0.85; and extension deformities κ = 0.75; 95% CI 0.43-1.0 was moderate to excellent. CONCLUSION: Expected relationships between the NHDC and other measures, stability between repeated measures and acceptable between-rater agreement supports confidence classifying hand deformity in children with cerebral palsy with the NHDC.

Effectiveness of interventions to prevent pressure injury in adults admitted to intensive care settings: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: The aim of the study was to investigate the effectiveness of interventions to prevent pressure injury in adults admitted to intensive care settings. REVIEW METHOD USED: This is a systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Five databases (CINAHL, MEDLINE, Scopus, Web of Science, and Embase) were searched in mid-2019. Searches were updated (in April 2020) to year end 2019. REVIEW METHODS: From an overarching systematic review and meta-analysis examining the effectiveness of pressure injury preventative interventions in adults admitted to acute hospital settings, trials conducted in intensive care were separated for an intensive care-specific synthesis. Two reviewers, with a third as an arbitrator, undertook study selection, data extraction, and risk-of-bias assessment. Included trials were grouped by intervention type for narrative synthesis and for random-effects meta-analysis using intention-to-treat data where appropriate. RESULTS: Overall, 26 trials were included. Ten intervention types were found (support surfaces, prophylactic dressings, positioning, topical preparations, continence management, endotracheal tube securement, heel protection devices, medication, noninvasive ventilation masks, and bundled interventions). All trials, except one, were at high or unclear risk of bias. Four intervention types (endotracheal tube securement, heel protection devices, medication, and noninvasive ventilation masks) comprised single trials. Support surface trials were limited to type (active, reactive, seating, other). Meta-analysis was undertaken for reactive surfaces, but the intervention effect was not significant (risk ratio = 0.24, p = 0.12, I2 = 51%). Meta-analyses demonstrated the effectiveness of sacral (risk ratio = 0.22, p < 0.001, I2 = 0%) and heel (risk ratio = 0.31, p = 0.02; I2 = 0%) prophylactic dressings for pressure injury prevention. CONCLUSIONS: Only prophylactic sacral and heel dressings demonstrated effectiveness in preventing pressure injury in adults admitted to intensive care settings. Further intensive care-specific trials are required across all intervention types. To minimise bias, we recommend that all future trials are conducted and reported as per relevant guidelines and recommendations.

Seed predation selects for reproductive variability and synchrony in perennial plants.

Annually variable and synchronous seed production by plant populations, or masting, is a widespread reproductive strategy in long-lived plants. Masting is thought to be selectively beneficial because interannual variability and synchrony increase the fitness of plants through economies of scale that decrease the cost of reproduction per surviving offspring. Predator satiation is believed to be a key economy of scale, but whether it can drive phenotypic evolution for masting in plants has been rarely explored. We used data from seven plant species (Quercus humilis, Quercus ilex, Quercus rubra, Quercus alba, Quercus montana, Sorbus aucuparia and Pinus pinea) to determine whether predispersal seed predation selects for plant phenotypes that mast. Predation selected for interannual variability in Mediterranean oaks (Q. humilis and Q. ilex), for synchrony in Q. rubra, and for both interannual variability and reproductive synchrony in S. aucuparia and P. pinea. Predation never selected for negative temporal autocorrelation of seed production. Predation by invertebrates appears to select for only some aspects of masting, most importantly high coefficient of variation, supporting individual-level benefits of the population-level phenomenon of mast seeding. Determining the selective benefits of masting is complex because of interactions with other seed predators, which may impose contradictory selective pressures.

Characterization of fecal branched-chain fatty acid profiles and their associations with fecal microbiota in diarrheic and healthy dairy calves.

Branched-chain fatty acids (BCFA) have recently been reported to play a role in human gut health during early life. However, little information is available on the fecal BCFA profiles in young ruminants and whether they are associated with the development of neonatal calf diarrhea. The objectives of this study were to (1) characterize BCFA profiles in feces collected from young calves, (2) compare the fecal BCFA composition between diarrheic and nondiarrheic dairy calves, and (3) explore the potential relationships between BCFA and microbiota in the feces. A total of 32 male Holstein dairy calves (13 ± 3 d old) with the same diet management were grouped as diarrheic (n = 16) or healthy (n = 16) based on fecal score (determined by liquid fecal consistency with some solid particles); diarrhea cases were defined as fecal score ≥2 for at least 2 d. Fecal samples were collected on the seventh day after calf arrival, and the fecal BCFA and microbial profiles were assessed using gas chromatograph and amplicon sequencing, respectively. In total, 7 BCFA were detected in the feces of all dairy calves; however, the concentrations of fecal BCFA differed between diarrheic and nondiarrheic calves. Specifically, the concentrations of iso-C16:0, iso-C17:0, anteiso-C17:0, and total even-chain BCFA were significantly higher in the feces of diarrheic calves. When the associations between BCFA and bacteria were studied, the relative abundance of Eggerthella was positively correlated with the concentrations of iso-C16:0 (ρ = 0.67), iso-17:0 (ρ = 0.77), anteiso-C17:0 (ρ = 0.73), and iso-C18:0 (ρ = 0.65), whereas the relative abundance of Subdoligranulum was positively correlated with the concentrations of iso-C14:0 (ρ = 0.62), iso-C15:0 (ρ = 0.78), and anteiso-C15:0 (ρ = 0.63). Use of random forest algorithm showed that BCFA such as anteiso-C15:0, iso-C16:0, iso-C17:0, iso-C18:0, and total even-chain BCFA could be used as biomarkers to differentiate diarrheic calves from healthy ones. Our findings generated fundamental knowledge on the potential roles of BCFA in neonatal calf gut health. Follow-up studies with larger animal populations are warranted to validate the feasibility of using BCFA as indicators of health status in neonatal calves.

Effect of partial exchange of lactose with fat in milk replacer on ad libitum feed intake and performance in dairy calves.

Compared with Holstein whole milk, commercial milk replacers (MR) for calves deliver relatively high levels of lactose and low levels of fat, and protein levels are rather comparable, resulting in a lower energy density and energy-to-protein ratio of the diet. Thus, the objective of this study was to determine the effects of partially exchanging lactose with fat in MR on voluntary feed intake, growth performance, and feeding behavior. Thirty-two male Holstein calves (2.1 ± 0.16 d of age, 46.4 ± 0.77 kg of body weight; BW) were assigned to 16 blocks of 2 calves per block based on arrival date and serum IgG. Within each block, calves were randomly assigned to 2 treatments: a high-lactose MR (HL; 17% fat; 44% lactose), or a high-fat MR (HF; 23% fat; 37% lactose). Lactose was exchanged by fat on a weight per weight basis, resulting in a 6% difference in metabolizable energy density per kilogram of MR. The experiment was divided into 3 phases: preweaning (P1; 0-35 d), weaning (P2; 36-56 d), and postweaning (P3; 57-84 d). For the first 2 wk of P1, calves were individually housed, fed their respective MR ad libitum through teat buckets, and provided access to water. At 14.2 ± 0.5 d of age, calves were group-housed (4 blocks/pen, 8 calves) and housed in group pens for the remainder of the study. In the group pens, calves were fed ad libitum MR, starter feed, chopped wheat straw, and water via automated feeders. During P2, calves were gradually weaned until complete milk withdrawal by 57 d and then monitored until 84 d (P3). Measurements included daily intakes and feeding behavior (rewarded and unrewarded visits), weekly BW and body measurements, and biweekly blood samples. Increasing fat content at the expense of lactose decreased MR intake during P1 by 15% (HL = 1.32 ± 0.04; HF = 1.17 ± 0.04 kg of dry matter per day), whereas total starter intake was not affected by MR composition. Once MR was restricted during P2, HL calves were reported to have more unrewarded visits to the automatic milk feeder than HF calves (11.9 ± 0.95 vs. 8.4 ± 1.03 visits/d, respectively). Crude protein intake was higher for HL calves during P1 (352.1 ± 11.2 vs. 319.6 ± 11.6 g/d), which was attributed to the higher intake of MR during that period, and metabolizable energy intake and protein-to-energy ratio remained comparable between treatments. Plasma cholesterol and nonesterified fatty acids levels were higher in HF calves as a consequence of the diet. Nevertheless, final BW (84 d) did not differ between treatments. Overall, calves fed ad libitum seemed to regulate their intake of MR based on its energy density, without significant effects on solid feed intake and overall growth.

Predicting morbidity and mortality using automated milk feeders: A scoping review.

Automated milk feeders (AMF) are computerized systems that provide producers with a tool that can be used to more efficiently raise dairy calves and allow for easier implementation of a high plane of nutrition during the milk feeding phase. Automated milk feeders also have the ability to track individualized behavioral data, such as milk consumption, drinking speed, and the number of rewarded and unrewarded visits to the feeder, that could potentially be used to predict disease development. The objective of this scoping review was to characterize the body of literature investigating the use of AMF data to predict morbidity and mortality in dairy calves during the preweaning stage. This review lists the parameters that have been examined for associations with disease in calves and identify discrepancies found in the literature. Five databases and relevant conference proceedings were searched. Eligible studies focused on the use of behavioral parameters measured by AMF to predict morbidity or mortality in preweaned dairy calves. Two reviewers independently screened titles and abstracts from 6,675 records identified during the literature search. After title and abstract screening, 382 studies were included and then assessed at the full-text level. Of these, 56 studies fed calves using an AMF and provided some measure of morbidity or mortality. Thirteen examined AMF parameters for associations with morbidity or mortality. The studies were completed in North America (n = 6), Europe (n = 6), and New Zealand (n = 1). The studies varied in sample size, ranging from 30 to 1,052 calves with a median of 100 calves. All 13 studies included enteric disease as an outcome and 11 studies evaluated respiratory disease. Of the studies measuring enteric disease, 8 provided disease definitions (n = 8/13, 61.2%); however, for respiratory disease, only 5 provided a disease definition (n = 5/11, 45.5%). Disease definitions and thresholds varied greatly between studies, with 10 using some form of health scoring. When evaluating feeding metrics as indicators of disease, all 13 studies investigated milk consumption and 6 and 7 studies investigated drinking speed and number of rewarded and unrewarded visits, respectively. Overall, this scoping review identified that daily milk consumption, drinking speed, and rewarded and unrewarded visits may provide insight into early disease detection in preweaned dairy calves. However, the disparity in reporting of study designs and results between included studies made comparisons challenging. In addition, to aid with the interpretation of studies, standardized disease outcomes should be used to improve the utility of this primary research.

Physiotherapy service provision in a specialist adult cystic fibrosis service: A pre-post design study with the inclusion of an allied health assistant.

What is the impact of including an allied health assistant (AHA) role on physiotherapy service delivery in an acute respiratory service? A pragmatic pre-post design study examined physiotherapy services across two 3-month periods: current service delivery [P1] and current service delivery plus AHA [P2]. Clinical and non-clinical activity quantified as number, type and duration (per day) of all staff activity categorised for skill level (AHA, junior, senior). Physiotherapy service delivery increased in P2 compared to P1 (n = 4730 vs n = 3048). Physiotherapists undertook fewer respiratory (p < 0.001) and exercise treatments (p < 0.001) but increased reviews for inpatients (p < 0.001) and at multidisciplinary clinics in P2 (56% vs 76%, p < 0.01). The AHA accounted for 20% of all service provision. AHA activity comprised mainly non-direct clinical care including oversight of respiratory equipment use (e.g. supply, set-up, cleaning, loan audits) and other patient-related administrative tasks associated with delegation handovers, supervision and clinical documentation (72%), delegated supervision of established respiratory (5%) and exercise treatments (10%) and delegated exercise tests (3%). The AHA completed most of the exercise tests (n = 25). AHA non-direct clinical tasks included departmental management activities (11%). No adverse events were reported. AHA inclusion in an acute respiratory care service changed physiotherapy service provision. The AHA completed delegated routine clinical and non-clinical tasks. Physiotherapists increased clinic activity and annual reviews. Including an AHA role offers sustainable options for enhancing physiotherapy service provision in acute respiratory care.

Complement Targets Newborn Retinal Ganglion Cells for Phagocytic Elimination by Microglia.

Microglia play important roles in shaping the developing CNS, and at early stages they have been proposed to regulate progenitor proliferation, differentiation, and neuronal survival. However, these studies reveal contradictory outcomes, highlighting the complexity of these cell-cell interactions. Here, we investigate microglia function during embryonic mouse retina development, where only microglia, progenitors, and neurons are present. In both sexes, we determine that microglia primarily interact with retinal neurons and find that depletion of microglia via conditional KO of the Csf1 receptor results in increased density of retinal ganglion cells (RGCs). Pharmacological inhibition of microglia also results in an increase in RGCs, with no effect on retinal progenitor proliferation, RGC genesis, or apoptosis. We show that microglia in the embryonic retina are enriched for phagocytic markers and observe engulfment of nonapoptotic Brn3-labeled RGCs. We investigate the molecular pathways that can mediate cell engulfment by microglia and find selective downregulation of complement pathway components with microglia inhibition, and further show that C1q protein marks a subset of RGCs in the embryonic retina. KO of complement receptor 3 (CR3; Itgam), which is only expressed by microglia, results in increased RGC density, similar to what we observed after depletion or inhibition of microglia. Thus, our data suggest that microglia regulate neuron elimination in the embryonic mouse retina by complement-mediated phagocytosis of non-apoptotic newborn RGCs.SIGNIFICANCE STATEMENT Microglia are emerging as active and important participants in regulating neuron number in development, during adult neurogenesis, and following stem cell therapies. However, their role in these contexts and the mechanisms involved are not fully defined. Using a well-characterized in vivo system, we provide evidence that microglia regulate neuronal elimination by complement-mediated engulfment of nonapoptotic neurons. This work provides a significant advancement of the field by defining in vivo molecular mechanisms for microglia-mediated cell elimination. Our data add to a growing body of evidence that microglia are essential for proper nervous system development. In addition, we elucidate microglia function in the developing retina, which may shed light on microglia involvement in the context of retinal injury and disease.