Prevention of respiratory virus transmission by resident memory CD8+ T cells.

An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd immunity. Although this strategy has proved successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies1. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to respond rapidly to respiratory virus infections2-6. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to the extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8+ T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8+ T cells requires the antiviral cytokine interferon-γ (IFNγ) and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8+ T cells in the respiratory tract can have important roles in protecting the host against viral disease and limiting viral spread throughout the population.

The complex polyploid genome architecture of sugarcane.

Sugarcane, the world's most harvested crop by tonnage, has shaped global history, trade and geopolitics, and is currently responsible for 80% of sugar production worldwide1. While traditional sugarcane breeding methods have effectively generated cultivars adapted to new environments and pathogens, sugar yield improvements have recently plateaued2. The cessation of yield gains may be due to limited genetic diversity within breeding populations, long breeding cycles and the complexity of its genome, the latter preventing breeders from taking advantage of the recent explosion of whole-genome sequencing that has benefited many other crops. Thus, modern sugarcane hybrids are the last remaining major crop without a reference-quality genome. Here we take a major step towards advancing sugarcane biotechnology by generating a polyploid reference genome for R570, a typical modern cultivar derived from interspecific hybridization between the domesticated species (Saccharum officinarum) and the wild species (Saccharum spontaneum). In contrast to the existing single haplotype ('monoploid') representation of R570, our 8.7 billion base assembly contains a complete representation of unique DNA sequences across the approximately 12 chromosome copies in this polyploid genome. Using this highly contiguous genome assembly, we filled a previously unsized gap within an R570 physical genetic map to describe the likely causal genes underlying the single-copy Bru1 brown rust resistance locus. This polyploid genome assembly with fine-grain descriptions of genome architecture and molecular targets for biotechnology will help accelerate molecular and transgenic breeding and adaptation of sugarcane to future environmental conditions.

Cholestenoic acid as endogenous epigenetic regulator decreases hepatocyte lipid accumulation in vitro and in vivo.

Cholestenoic acid (CA) has been reported as an important biomarker of many severe diseases, but its physiological and pathological roles remain unclear. This study aimed to investigate the potential role of CA in hepatic lipid homeostasis. Enzyme kinetic studies revealed that CA specifically activates DNA methyltransferases 1 (DNMT1) at low concentration with EC50 = 1.99 × 10-6 M and inhibits the activity at higher concentration with IC50 = 9.13 × 10-6 M, and specifically inhibits DNMT3a, and DNMT3b activities with IC50= 8.41 × 10-6 M and IC50= 4.89 × 10-6 M, respectively. In a human hepatocyte in vitro model of high glucose (HG)-induced lipid accumulation, CA significantly increased demethylation of 5mCpG in the promoter regions of over 7,000 genes, particularly those involved in master signaling pathways such as calcium-AMPK and 0.0027 at 6 h. RNA sequencing analysis showed that the downregulated genes are affected by CA encoding key enzymes, such as PCSK9, MVK, and HMGCR, which are involved in cholesterol metabolism and steroid biosynthesis pathways. In addition, untargeted lipidomic analysis showed that CA significantly reduced neutral lipid levels by 60% in the cells cultured in high-glucose media. Administration of CA in mouse metabolic dysfunction-associated steatotic liver disease (MASLD) models significantly decreases lipid accumulation, suppresses the gene expression involved in lipid biosynthesis in liver tissues, and alleviates liver function. This study shows that CA as an endogenous epigenetic regulator decreases lipid accumulation via epigenetic regulation. The results indicate that CA can be considered a potential therapeutic target for the treatment of metabolic disorders.NEW & NOTEWORTHY To our knowledge, this study is the first to identify the mitochondrial monohydroxy bile acid cholestenoic acid (CA) as an endogenous epigenetic regulator that regulates lipid metabolism through epigenome modification in human hepatocytes. The methods used in this study are all big data analysis, and the results of each part show the global regulation of CA on human hepatocytes rather than narrow point effects.

Photo-induced structural dynamics of o-nitrophenol by ultrafast electron diffraction.

The photo-induced dynamics of o-nitrophenol, particularly its photolysis, has garnered significant scientific interest as a potential source of nitrous acid in the atmosphere. Although the photolysis products and preceding photo-induced electronic structure dynamics have been investigated extensively, the nuclear dynamics accompanying the non-radiative relaxation of o-nitrophenol on the ultrafast timescale, which include an intramolecular proton transfer step, have not been experimentally resolved. Herein, we present a direct observation of the ultrafast nuclear motions mediating photo-relaxation using ultrafast electron diffraction. This work spatiotemporally resolves the loss of planarity which enables access to a conical intersection between the first excited state and the ground state after the proton transfer step, on the femtosecond timescale and with sub-Angstrom resolution. Our observations, supported by ab initio multiple spawning simulations, provide new insights into the proton transfer mediated relaxation mechanism in o-nitrophenol.

The impact of musculoskeletal ill health on quality of life and function after critical care: a multicentre prospective cohort study.

Physical disability is a common component of post-intensive care syndrome, but the importance of musculoskeletal health in this population is currently unknown. We aimed to determine the musculoskeletal health state of intensive care unit survivors and assess its relationship with health-related quality of life; employment; and psychological and physical function. We conducted a multicentre prospective cohort study of adults admitted to intensive care for > 48 h without musculoskeletal trauma or neurological insult. Patients were followed up 6 months after admission where musculoskeletal health state was measured using the validated Musculoskeletal Health Questionnaire score. Of the 254 participants, 150 (59%) had a musculoskeletal problem and only 60 (24%) had received physiotherapy after discharge. Functional Comorbidity Index, Clinical Frailty Scale, duration of intensive care unit stay and prone positioning were all independently associated with worse musculoskeletal health. Musculoskeletal health state moderately correlated with quality of life, rs = 0.499 (95%CI 0.392-0.589); anxiety, rs = -0.433 (95%CI -0.538 to -0.315); and depression, rs = -0.537 (95%CI -0.631 to -0.434) (all p < 0.001). Patients with a musculoskeletal problem were less physically active than those without a problem (median (IQR [range]) number of 30 min physical activity sessions per week 1 (0-3.25 [0-7]) vs. 4 (1-7 [0-7]), p < 0.001, respectively). This study found that musculoskeletal health problems were common after intensive care unit stay. However, we observed that < 25% of patients received physical rehabilitation after discharge home. Our work has identified potential high-risk groups to target in future interventional studies.

Pretreatment characteristics associated with symptom reduction during group cognitive processing therapy versus exposure therapy for PTSD: an exploratory study of Veterans.

Exposure and cognitive-based therapies are both effective for PTSD, but knowledge of which intervention is best for which patient is lacking. This lack of knowledge is particularly noticeable for group treatments, as no study has examined whether responses to different group therapies are associated with different pretreatment characteristics. Here, we explored whether pretreatment levels of three types of psychological characteristics-PTSD symptom clusters, posttraumatic cognitions, and emotion regulation difficulties-were associated with symptom reduction during group-delivered cognitive versus exposure-based PTSD treatment. Participants were Veterans with PTSD drawn from two previous clinical trials: one of group CPT (GCPT; n = 32) and the other of group-based exposure therapy (GBET; n = 21). Growth curve modeling was used to identify pretreatment variables that predicted weekly PTSD symptom changes during each therapy. Higher posttraumatic cognitions at pretreatment predicted steeper PTSD symptom reduction during GCPT but not GBET. Additionally, symptom reduction during each therapy was associated with different pretreatment emotion regulation difficulties: difficulties with goal-directed behavior for GBET and lack of emotional clarity and limited access to emotion regulation strategies for GCPT. These findings suggest that assigning Veterans to a group PTSD therapy that better matches their pretreatment psychological profile might facilitate a better therapeutic response.

Examining the effects of prenatal alcohol exposure on performance of the sustained attention to response task in children with an FASD.

Prenatal alcohol exposure (PAE), the leading known cause of childhood developmental disability, has long-lasting effects extending throughout the lifespan. It is well documented that children prenatally exposed to alcohol have difficulties inhibiting behavior and sustaining attention. Thus, the Sustained Attention to Response Task (SART), a Go/No-go paradigm, is especially well suited to assess the behavioral and neural functioning characteristics of children with PAE. In this study, we utilized neuropsychological assessment, parent/guardian questionnaires, and magnetoencephalography during SART random and fixed orders to assess characteristics of children 8-12 years old prenatally exposed to alcohol compared to typically developing children. Compared to neurotypical control children, children with a Fetal Alcohol Spectrum Disorder (FASD) diagnosis had significantly decreased performance on neuropsychological measures, had deficiencies in task-based performance, were rated as having increased Attention-Deficit/Hyperactivity Disorder (ADHD) behaviors and as having lower cognitive functioning by their caretakers, and had decreased peak amplitudes in Broadmann's Area 44 (BA44) during SART. Further, MEG peak amplitude in BA44 was found to be significantly associated with neuropsychological test results, parent/guardian questionnaires, and task-based performance such that decreased amplitude was associated with poorer performance. In exploratory analyses, we also found significant correlations between total cortical volume and MEG peak amplitude indicating that the reduced amplitude is likely related in part to reduced overall brain volume often reported in children with PAE. These findings show that children 8-12 years old with an FASD diagnosis have decreased amplitudes in BA44 during SART random order, and that these deficits are associated with multiple behavioral measures.

Histological examination of choroid plexus epithelia changes in schizophrenia.

BACKGROUND: The choroid plexus (CP) produces and secretes most of the cerebrospinal fluid (CSF) of the central nervous system. The CP is suggested to be regulated by descending neurons and by circulating factors and is involved in the interaction between central and peripheral inflammation. Quantitative imaging has demonstrated volumetric CP changes in psychosis, schizophrenia and depression. This study histologically examines CP epithelial cell morphology in these illnesses to identify the biological source of such volumetric changes. METHODS: Formalin-fixed paraffin-embedded (FFPE) blocks were obtained bilaterally from the lateral ventricles of 13 cases of sex- and age-matched brains from each of schizophrenia (SZ) with psychosis, major depressive disorder (MDD) and matched controls (NPD). FFPE blocks were sectioned at 7 µm and routinely stained for H&E. Morphological analysis of 180 CP epithelia/case was conducted blindly on digital images collected at x600 magnification. Calcification was assessed in all CP regions manually. RESULTS: Analysis with a General Linear Model demonstrated a significant effect of diagnosis on somal width (p = 0.006, R2 = 0.33 R2(adj) = 0.25) demonstrating increased somal width in SZ without psychotic medication versus controls (p = 0.032), but not in medicated SZ cases. No effects were observed in calcification. DISCUSSION: The epithelial cells that were examined were attached to the CP fibrous surface, so width expansion describes the primary methods for these cells to expand with adherence to this surface in SZ. The interaction of antipsychotic medication and diagnosis demonstrates that this is an illness-specific change mediated through the DA-system with likely neuronal origin. CP alterations were not found in MDD where they are instead generally associated with heightened allostatic load that was unknown in this cohort.

Effect of a standardized fluid management algorithm on acute kidney injury and mortality in pediatric patients on extracorporeal support.

Acute kidney injury (AKI), fluid overload (FO), and mortality are common in pediatric patients supported by extracorporeal membrane oxygenation (ECMO). The aim of this study is to evaluate if using a fluid management algorithm reduced AKI and mortality in children supported by ECMO. We performed a retrospective study of pediatric patients aged birth to 25 years requiring ECMO at a quaternary level children's hospital from 2007 to 2019 In October 2017, a fluid management algorithm was implemented for protocolized fluid removal after deriving a daily fluid goal using a combination of diuretics and ultrafiltration. Daily algorithm compliance was defined as ≥ 12 h on the algorithm each day. The primary and secondary outcomes were AKI and mortality, respectively, and were assessed in the entire cohort and the sub-analysis of children from the era in which the algorithm was implemented. Two hundred and ninety-nine (median age 5.3 months; IQR: 0.2, 62.3; 45% male) children required ECMO (venoarterial in 85%). The fluid algorithm was applied in 74 patients. The overall AKI rate during ECMO was 38% (26% severe-stage 2/3). Both AKI incidence and mortality were significantly lower in patients managed on the algorithm (p = 0.02 and p = 0.05). After adjusting for confounders, utilization of the algorithm was associated with lower odds of AKI (aOR: 0.40, 95%CI: 0.21, 0.76; p = 0.005) but was not associated with a reduction in mortality. In the sub-analysis, algorithm compliance of 80-100% was associated with a 54% reduction in mortality (ref: < 60% compliant; aOR:0.46, 95%CI:0.22-1.00; p = 0.05).  Conclusion: Among the entire cohort, the use of a fluid management algorithm reduced the odds of AKI. Better compliance on the algorithm was associated with lower mortality. Multicenter studies that implement systematic fluid removal may represent an opportunity for improving ECMO-related outcomes. What is Known: • Acute kidney injury and fluid overload are associated with morbidity and mortality in children supported by extracorporeal membrane oxygenation. What is New: • A systematic and protocolized approach to fluid removal in children supported by extracorporeal membrane oxygenation reduces acute kidney injury incidence. • Greater adherence to a protocolized fluid removal algorithm is associated with a reduction in mortality.

Unleashing the full power of LHCb to probe stealth new physics.

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.

Age-dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury.

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Military Brain Injury working group. Regressions were used to examine TBI- and mTBI-related associations in NMF-derived components while adjusting for age, sex, post-traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age-dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age-dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans.

Diet and irritable bowel syndrome: an update from a UK consensus meeting.

There has been a renewed interest in the role of dietary therapies to manage irritable bowel syndrome (IBS), with diet high on the agenda for patients. Currently, interest has focussed on the use of traditional dietary advice (TDA), a gluten-free diet (GFD) and the low FODMAP diet (LFD). A consensus meeting was held to assess the role of these dietary therapies in IBS, in Sheffield, United Kingdom.Evidence for TDA is from case control studies and clinical experience. Randomised controlled trials (RCT) have demonstrated the benefit of soluble fibre in IBS. No studies have assessed TDA in comparison to a habitual or sham diet. There have been a number of RCTs demonstrating the efficacy of a GFD at short-term follow-up, with a lack of long-term outcomes. Whilst gluten may lead to symptom generation in IBS, other components of wheat may also play an important role, with recent interest in the role of fructans, wheat germ agglutinins, as well as alpha amylase trypsin inhibitors. There is good evidence for the use of a LFD at short-term follow-up, with emerging evidence demonstrating its efficacy at long-term follow-up. There is overlap between the LFD and GFD with IBS patients self-initiating gluten or wheat reduction as part of their LFD. Currently, there is a lack of evidence to suggest superiority of one diet over another, although TDA is more acceptable to patients.In view of this evidence, our consensus group recommends that dietary therapies for IBS should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Given the lack of dietetic services, novel approaches such as employing group clinics and online webinars may maximise capacity and accessibility for patients. Further research is also required to assess the comparative efficacy of dietary therapies to other management strategies available to manage IBS.

Direct Measurement of Resonances in

We have performed the first direct measurement of two resonances of the ^{7}Be(α,γ)^{11}C reaction with unknown strengths using an intense radioactive ^{7}Be beam and the DRAGON recoil separator. We report on the first measurement of the 1155 and 1110 keV resonance strengths of 1.73±0.25(stat)±0.40(syst) eV and 125_{-25}^{+27}(stat)±15(syst) meV, respectively. The present results have reduced the uncertainty in the ^{7}Be(α,γ)^{11}C reaction rate to ∼9.4%-10.7% over T=1.5-3 GK, which is relevant for nucleosynthesis in the neutrino-driven outflows of core-collapse supernovae (νp process). We find no effect of the new, constrained reaction rate on νp-process nucleosynthesis.

Robust Bottom-Up Gold Filling of Deep Trenches and Gratings.

This work extends an extreme variant of superconformal Au electrodeposition to deeper device architectures while exploring factors that constrain its function and the robustness of void-free processing. The unconventional bottom-up process is used to fill diffraction gratings with trenches 94 µm deep and 305 µm deep, with aspect ratios (height/width) of just below 20 and 15, respectively, in near-neutral 0.16 mol·L-1 Na3Au(SO3)2 + 0.64 mol·L-1 Na2SO3 electrolyte containing 50 µmol·L-1 Bi3+. Although the aspect ratios are modest compared to previously demonstrated void-free filling beyond AR = 60, the deepest trenches filled exceed those in previous work by 100 µm - a nearly 50 % increase in depth. Processes that substantially accelerate the start of bottom-up deposition demonstrate a linkage between transport and void-free filling. Final profiles are highly uniform across 65 mm square gratings because of self-passivation inherent in the process. Electron microscopy and electron backscatter diffraction confirm the fully dense Au and void-free filling suggested by the electrochemical measurements. X-ray transmission "fringe visibility" average more than 80 % at 50 kV X-ray tube voltage across the deeper gratings and 70 % at 40 kV across the shallower gratings, also consistent with uniformly dense, void-free fill across the gratings.

A survey of hospice day services in the United Kingdom & Republic of Ireland : how did hospices offer social support to palliative care patients, pre-pandemic?

INTRODUCTION: Social support is described by patients and other stakeholders to be a valuable component of palliative day care. Less is known about the range of hospice services that have been used in practice that facilitate social support. An online survey aimed to gain an overview of all hospice day services that facilitated social support for adults outside of their own homes. METHODS: An online survey was distributed via email to people involved in managing hospice day services. Questions were asked on hospice characteristics, including staff and volunteer roles. Respondents were asked to identify services they felt offered social support to patients. Data collection took place between August 2017 and May 2018. RESULTS: Responses were received from 103 hospices in the UK and ROI (response rate 49.5%). Results provide an overview of hospice day and outpatient services that offer social support to patients. These are: multi-component interventions, activity groups, formal support groups, befriending, and informal social activities. Multi-component interventions, such as palliative day care, were the most commonly reported. Their stated aims tend to focus on clinical aspects, but many survey respondents considered these multicomponent interventions to be the 'most social' service at their hospice. The survey also identified a huge variety of activity groups, as well as formal therapeutic support groups. Informal 'social-only' activities were present, but less common. Over a third of all the services were described as 'drop in'. Most responding hospices did not routinely use patient reported outcome measures in their 'most social' services. CONCLUSIONS: The survey documents hospice activity in facilitating social support to be diverse and evolving. At the time of data collection, many hospices offered multiple different services by which a patient might obtain social support outside of their own home and in the presence of other patients.

Re-assessing the importance of linear type traits in predicting genetic merit for survival in an aging Holstein-Friesian dairy cow population.

The cumulative improvement achieved in the genetic merit for reproductive performance in dairy populations will likely improve dairy cow longevity; therefore, it is time to reassess whether linear type traits are still suitable predictors of survival in an aging dairy cow population. The objective of the present study was therefore to estimate the genetic correlations between linear type traits and survival from one parity to the next and, in doing so, evaluate if those genetic correlations change with advancing parity. After edits, 152,894 lactation survival records (first to ninth parity) were available from 52,447 Holstein-Friesian cows, along with linear type trait records from 52,121 Holstein-Friesian cows. A series of bivariate random regression models were used to estimate the genetic covariances between survival in different parities and each linear type trait. Heritability estimates for survival per parity ranged from 0.02 (SE = 0.004; first parity) to 0.05 (SE = 0.01; ninth parity). Pairwise genetic correlations between survival among different parities varied from 0.42 (first and ninth parity) to 1.00 (eighth to ninth parity), with the strength of these genetic correlations being inversely related to the interval between the compared parities. The genetic correlations between survival and the individual linear type traits varied across parities for 9 of the 20 linear type traits examined, but the correlations with only 3 of these linear type traits strengthened as the cows aged; these 3 traits were rear udder height, teat length, and udder depth. Given that linear type traits are frequently scored in first parity and are genetically correlated with survival in older parities, they may be suitable early predictors of survival, especially for later parity cows. Additionally, the direction of the genetic correlations between survival and rear udder height, teat length, and udder depth did not change between parities; hence, selection for survival in older parities using these linear type traits should not hinder genetic improvement for survival in younger parities.

Exploiting genetic variability in the trajectory of lactation yield and somatic cell score with each progressing parity.

The inclusion of reproductive performance in dairy cow breeding schemes has resulted in a cumulative improvement in genetic merit for reproductive performance; this improvement should manifest in longer productive lives through a reduced requirement for involuntary culling. Nonetheless, the average length of dairy cow productive life has not changed in most populations, suggesting that risk factors for culling, especially in older cows, are possibly more associated with lower yield or high somatic cell score (SCS) than compromised reproductive performance. The objective of the present study was to understand the dynamics of lactation yields and SCS in dairy cows across parities and, in doing so, quantify the potential to alter this trajectory through breeding. After edits, 3,470,520 305-d milk, fat, and protein yields, as well as milk fat and protein percentage and somatic cell count records from 1,162,473 dairy cows were available for analysis. Random regression animal models were used to identify the parity in which individual cows reached their maximum lactation yields, and highest average milk composition and SCS; also estimated from these models were the (co)variance components for yield, composition, and SCS per parity across parities. Estimated breeding values for all traits per parity were calculated for cows reaching ≥fifth parity. Of the cows included in the analyses, 91.0%, 92.2%, and 83.4% reached maximum milk, fat, and protein yield in fifth parity, respectively. Conversely, 95.9% of cows reached their highest average fat percentage in first parity and 62.9% of cows reached their highest average protein percentage in third parity. In contrast to both milk yield and composition traits, 98.4% of cows reached their highest average SCS in eighth parity. Individual parity estimates of heritability for milk yield traits, milk composition, and SCS ranged from 0.28 to 0.44, 0.47 to 0.69, and 0.13 to 0.23, respectively. The strength of the genetic correlations per trait among parities was inversely related to the interval between the parities compared; the weakest genetic correlation was 0.67 (standard error = 0.02) between milk yield in parities 1 and 8. Eigenvalues and eigenfunctions of the additive genetic covariance matrices for all investigated traits revealed potential to alter the trajectory of parity profiles for milk yield, milk composition, and SCS. This was further demonstrated when evaluating the trajectories of animal estimated breeding values per parity.

Are subjectively scored linear type traits suitable predictors of the genetic merit for feed intake in grazing Holstein-Friesian dairy cows?

Measuring dry matter intake (DMI) in grazing dairy cows using currently available techniques is invasive, time consuming, and expensive. An alternative to directly measuring DMI for use in genetic evaluations is to identify a set of readily available animal features that can be used in a multitrait genetic evaluation for DMI. The objectives of the present study were thus to estimate the genetic correlations between readily available body-related linear type traits and DMI in grazing lactating Holstein-Friesian cows, but importantly also estimate the partial genetic correlations between these linear traits and DMI, after adjusting for differences in genetic merit for body weight. Also of interest was whether the predictive ability derived from the estimated genetic correlations materialized upon validation. After edits, a total of 8,055 test-day records of DMI, body weight, and milk yield from 1,331 Holstein-Friesian cows were available, as were chest width, body depth, and stature from 47,141 first lactation Holstein-Friesian cows. In addition to considering the routinely recorded linear type traits individually, novel composite traits were defined as the product of the linear type traits as an approximation of rumen volume. All linear type traits were moderately heritable, with heritability estimates ranging from 0.27 (standard error = 0.14) to 0.49 (standard error = 0.15); furthermore, all linear type traits were genetically correlated (0.29 to 0.63, standard error 0.14 to 0.12) with DMI. The genetic correlations between the individual linear type traits and DMI, when adjusted for genetic differences in body weight, varied from -0.51 (stature) to 0.48 (chest width). These genetic correlations between DMI and linear type traits suggest linear type traits may be useful predictors of DMI, even when body weight information is available. Nonetheless, estimated genetic merit of DMI derived from a multitrait genetic evaluation of linear type traits did not correlate strongly with actual DMI in a set of validation animals; the benefit was even less if body weight data were also available.

Do early responders and treatment non-responders offer guidance to make CPT group a more effective treatment?

BACKGROUND: Treatment dropout has been problematic with evidence-based treatments for posttraumatic stress disorder (PTSD), including cognitive processing therapy (CPT). This study sought to evaluate whether CPT group contributed to symptom improvement among treatment completers and non-completers. METHODS: Sixty-one Iraq and Afghanistan combat Veterans self-selected CPT group or treatment as usual (TAU) forming a convenience sample. Defining treatment completion as attending at least nine sessions: 18 completed treatment, 20 dropped-out (DOs); 20 completed TAU, 3 lost to TAU follow-up. RESULTS: Multiple Regression revealed significant pre-post-treatment improvement, the Clinician-Administered PTSD Scale (CAPS-IV, F(5, 40.1) = 2.53, p = 0.0436). Reviewing DOs' last available PTSD Checklist-Military Version scores before leaving treatment, six achieved clinically significant improvement of >10 points; seven a clinically reliable change of 5-10 points. CONCLUSION: These findings highlight that CPT group may be effective at reducing trauma-related symptoms among treatment completers and dropouts and point to the utility of a clinical definition of good treatment end-state.

Isolated paracetamol-induced acute kidney injury: a systematic review.

AIM: We sought to characterise the syndrome of isolated paracetamol-induced acute kidney injury (AKI), whose incidence and mechanisms are poorly understood. METHODS: Using systematic review methodology, fifty-six papers relating to paracetamol-induced AKI were identified. RESULTS: 24 cases of isolated paracetamol-induced AKI were identified and compared to 87 identified cases of concurrent renal and hepatic injury. Paracetamol-induced AKI became detectable 3-4 days after exposure; liver injury, where it occurred, preceded AKI detection by 1 day. Risk factors affecting hepatotoxicity risk do not appear to influence isolated AKI, with no clear associated factors except younger age (mean 18.8 versus 33.1 years). CONCLUSIONS: Isolated paracetamol-induced AKI appears commoner in younger patients. Paracetamol-induced AKI occurs late and may go undetected by current treatment guidelines.