Genome wide association studies for carcass traits measured by video image analysis in crossbred lambs

This is the first UK genome wide association study investigating potential links between Video Image Analysis (VIA) carcass traits and molecular polymorphisms in crossbred sheep. Phenotypic and genotypic data were collected from two crossbred lamb populations: Texel x Scotch Mule (TxSM, n = 2330) and Texel x Lleyn (TxL, n = 3816). Traits measured included live weights at birth, eight weeks and weaning (∼15 weeks). VIA-predicted traits included total weights and weights of fat, muscle and bone in the whole carcass and primal (hind leg, saddle, shoulder) regions. Within-breed heritabilities estimated for the VIA traits ranged from 0.01 to 0.70, indicating potential for inclusion of some traits in breeding programmes. The two crossbred populations differed in SNPs associated with different traits. Two SNPs on chromosomes two (s74618.1) and eight (s68536.1), respectively, reached genome-wise significance for TxSM, explaining &lt;1% of trait variance, for whole carcass fat and muscle weights, hind leg and saddle fat weights and shoulder bone weights. For TxL, four SNPs reached genome-wise significance, on chromosome two for hind leg muscle weight (OAR2_117,959,202 and OAR2_11804335), on chromosome 10 for whole carcass bone weight (OAR19_8,995,957.1), and on chromosome 19 for weaning weight (s40847.1), each explaining &lt;1% of trait genetic variation. Differences in apparent genetic control of carcass traits may be influenced by the lambs' cross-breed, but also by management decisions affecting environmental variance and trait definitions, which should be understood in order to define protocols for incorporation of carcass traits into (cross)breeding programmes. Implications: Combining VIA-measured carcass traits with conventional production traits in a breeding programme could potentially improve the production and product quality of meat sheep. Phenotypes for VIA traits could be collected relatively easily if VIA machines were present at all abattoir sites. The current study and future Genome Wide Association Studies may help to identify potentially informative molecular markers, that explain large proportions of the genetic variance observed in VIA-measured carcass traits. Including this information in the estimation of breeding values could increase the accuracy of prediction, increasing the potential rate of genetic improvement for product quality. This study confirms the polygenic architecture of the investigated carcass traits, with a small number of molecular markers that each explain a small amount of genetic variation. Further studies across breed types are recommended to further test and validate molecular markers for traits related to lamb carcass quality, as measured by video image analysis.</p

Mesoscopic Capacitors: A Statistical Analysis

The capacitance of mesoscopic samples depends on their geometry and physical properties, described in terms of characteristic times scales. The resulting ac admittance shows sample to sample fluctuations. Their distribution is studied here -through a random-matrix model- for a chaotic cavity capacitively coupled to a backgate: it is observed from the distribution of scattering time delays for the cavity, which is found analytically for the orthogonal, unitary, and symplectic universality classes, one mode in the lead connecting the cavity to the reservoir and no direct scattering. The results agree with numerical simulations.Comment: 4 pages (Revtex), 4 PS figures. Minor corrections. New e-mail address: [email protected] [email protected] e-mail address: [email protected]

Periodic and Aperiodic Bunching in the Addition Spectra of Quantum Dot

We study electron addition spectra of quantum dots in a broad range of electron occupancies starting from the first electron. Spectra for dots containing <200 electrons reveal a surprising feature. Electron additions are not evenly spaced in gate voltage. Rather, they group into bunches. With increasing electron number the bunching evolves from occurring randomly to periodically at about every fifth electron. The periodicity of the bunching and features in electron tunneling rates suggest that the bunching is associated with electron additions into spatially distinct regions within the dots.Comment: 4 pages, 2 figures. Submitted to PR

A T Cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years

Current influenza vaccines have reduced immunogenicity and are of uncertain efficacy in older adults. We assessed the safety and immunogenicity of MVA-NP+M1, a viral-vectored influenza vaccine designed to boost memory T cell responses, in a group of older adults.Thirty volunteers (aged 50-85) received a single intramuscular injection of MVA-NP+M1 at a dose of 1·5×10(8) plaque forming units (pfu). Safety and immunogenicity were assessed over a period of one year. The frequency of T cells specific for nucleoprotein (NP) and matrix protein 1 (M1) was determined by interferon-gamma (IFN-γ) ELISpot, and their phenotypic and functional properties were characterized by polychromatic flow cytometry. In a subset of M1-specific CD8(+) T cells, T cell receptor (TCR) gene expression was evaluated using an unbiased molecular approach.Vaccination with MVA-NP+M1 was well tolerated. ELISpot responses were boosted significantly above baseline following vaccination. Increases were detected in both CD4(+) and CD8(+) T cell subsets. Clonality studies indicated that MVA-NP+M1 expanded pre-existing memory CD8(+) T cells, which displayed a predominant CD27(+)CD45RO(+)CD57(-)CCR7(-) phenotype both before and after vaccination.MVA-NP+M1 is safe and immunogenic in older adults. Unlike seasonal influenza vaccination, the immune responses generated by MVA-NP+M1 are similar between younger and older individuals. A T cell-inducing vaccine such as MVA-NP+M1 may therefore provide a way to circumvent the immunosenescence that impairs routine influenza vaccination.ClinicalTrials.gov NCT00942071

Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination

Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, the capacity of peripheral vaccination to generate sustained immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Here we show using bronchoalveolar lavage samples that donors with history of both infection and vaccination have more airway mucosal SARS-CoV-2 antibodies and memory B cells than those only vaccinated. Infection also induces populations of airway spike-specific memory CD4+ and CD8+ T cells that are not expanded by vaccination alone. Airway mucosal T cells induced by infection have a distinct hierarchy of antigen specificity compared to the periphery. Spike-specific T cells persist in the lung mucosa for 7 months after the last immunising event. Thus, peripheral vaccination alone does not appear to induce durable lung mucosal immunity against SARS-CoV-2, supporting an argument for the need for vaccines targeting the airways

Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza virus that expresses an altered nucleoprotein sequence

Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes

Modeling “psychosis” in vitro by inducing disordered neuronal network activity in cortical brain slices

# The Author(s) 2009. This article is published with open access at Springerlink.com Introduction Dysregulation of neuronal networks has been suggested to underlie the cognitive and perceptual abnor-malities observed schizophrenia. Discussions An in vitro model of psychosis is proposed based on the two different approaches to cause aberrant networ

Effect of inpatient rehabilitation treatment ingredients on functioning, quality of life, length of stay, discharge destination, and mortality among older adults with unplanned admission: An overview review

BACKGROUND: To synthesise the evidence for the effectiveness of inpatient rehabilitation treatment ingredients (versus any comparison) on functioning, quality of life, length of stay, discharge destination, and mortality among older adults with an unplanned hospital admission. METHODS: A systematic search of Cochrane Library, MEDLINE, Embase, PsychInfo, PEDro, BASE, and OpenGrey for published and unpublished systematic reviews of inpatient rehabilitation interventions for older adults following an unplanned admission to hospital from database inception to December 2020. Duplicate screening for eligibility, quality assessment, and data extraction including extraction of treatment components and their respective ingredients employing the Treatment Theory framework. Random effects meta-analyses were completed overall and by treatment ingredient. Statistical heterogeneity was assessed with the inconsistency-value (I(2)). RESULTS: Systematic reviews (n = 12) of moderate to low quality, including 44 non-overlapping relevant RCTs were included. When incorporated in a rehabilitation intervention, there was a large effect of endurance exercise, early intervention and shaping knowledge on walking endurance after the inpatient stay versus comparison. Early intervention, repeated practice activities, goals and planning, increased medical care and/or discharge planning increased the likelihood of discharge home versus comparison. The evidence for activities of daily living (ADL) was conflicting. Rehabilitation interventions were not effective for functional mobility, strength, or quality of life, or reduce length of stay or mortality. Therefore, we did not explore the potential role of treatment ingredients for these outcomes. CONCLUSION: Benefits observed were often for subgroups of the older adult population e.g., endurance exercise was effective for endurance in older adults with chronic obstructive pulmonary disease, and early intervention was effective for endurance for those with hip fracture. Future research should determine whether the effectiveness of these treatment ingredients observed in subgroups, are generalisable to older adults more broadly. There is a need for more transparent reporting of intervention components and ingredients according to established frameworks to enable future synthesis and/or replication. TRIAL REGISTRATION: PROSPERO Registration CRD42018114323. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-022-03169-2

Automated virtual reality therapy to treat agoraphobic avoidance and distress in patients with psychosis (gameChange): a multicentre, parallel-group, single-blind, randomised, controlled trial in England with mediation and moderation analyses

Background: Automated delivery of psychological therapy using immersive technologies such as virtual reality (VR) might greatly increase the availability of effective help for patients. We aimed to evaluate the efficacy of an automated VR cognitive therapy (gameChange) to treat avoidance and distress in patients with psychosis, and to analyse how and in whom it might work. // Methods: We did a parallel-group, single-blind, randomised, controlled trial across nine National Health Service trusts in England. Eligible patients were aged 16 years or older, with a clinical diagnosis of a schizophrenia spectrum disorder or an affective diagnosis with psychotic symptoms, and had self-reported difficulties going outside due to anxiety. Patients were randomly assigned (1:1) to either gameChange VR therapy plus usual care or usual care alone, using a permuted blocks algorithm with randomly varying block size, stratified by study site and service type. gameChange VR therapy was provided in approximately six sessions over 6 weeks. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 6 (primary endpoint), and 26 weeks after randomisation. The primary outcome was avoidance of, and distress in, everyday situations, assessed using the self-reported Oxford Agoraphobic Avoidance Scale (O-AS). Outcome analyses were done in the intention-to-treat population (ie, all participants who were assigned to a study group for whom data were available). We performed planned mediation and moderation analyses to test the effects of gameChange VR therapy when added to usual care. This trial is registered with the ISRCTN registry, 17308399. // Findings: Between July 25, 2019, and May 7, 2021 (with a pause in recruitment from March 16, 2020, to Sept 14, 2020, due to COVID-19 pandemic restrictions), 551 patients were assessed for eligibility and 346 were enrolled. 231 (67%) patients were men and 111 (32%) were women, 294 (85%) were White, and the mean age was 37·2 years (SD 12·5). 174 patients were randomly assigned to the gameChange VR therapy group and 172 to the usual care alone group. Compared with the usual care alone group, the gameChange VR therapy group had significant reductions in agoraphobic avoidance (O-AS adjusted mean difference –0·47, 95% CI –0·88 to –0·06; n=320; Cohen's d –0·18; p=0·026) and distress (–4·33, –7·78 to –0·87; n=322; –0·26; p=0·014) at 6 weeks. Reductions in threat cognitions and within-situation defence behaviours mediated treatment outcomes. The greater the severity of anxious fears and avoidance, the greater the treatment benefits. There was no significant difference in the occurrence of serious adverse events between the gameChange VR therapy group (12 events in nine patients) and the usual care alone group (eight events in seven patients; p=0·37). // Interpretation: Automated VR therapy led to significant reductions in anxious avoidance of, and distress in, everyday situations compared with usual care alone. The mediation analysis indicated that the VR therapy worked in accordance with the cognitive model by reducing anxious thoughts and associated protective behaviours. The moderation analysis indicated that the VR therapy particularly benefited patients with severe agoraphobic avoidance, such as not being able to leave the home unaccompanied. gameChange VR therapy has the potential to increase the provision of effective psychological therapy for psychosis, particularly for patients who find it difficult to leave their home, visit local amenities, or use public transport. // Funding: National Institute of Health Research Invention for Innovation programme, National Institute of Health Research Oxford Health Biomedical Research Centre