Influence of Porcine Plasma Supplementation on Gestating Sow Serum IGF-1 Concentration and Litter Weights

The objective of this pilot study was to determine the effect of dietary porcine plasma on circulating insulin-like growth factor 1 (IGF-1) concentrations in gestating sows and characteristics of their litters. Primiparous and multiparous sows were randomly allocated to two treatment groups of sows fed a basal diet or sows fed the basal diet plus 6 g of porcine plasma throughout gestation. On 4 periods during gestation and farrowing, blood was collected for IGF-1 analysis. After farrowing, gestation length, number born, birth weight, and total litter weight were recorded. There were no three-way or two-way interactions between treatments, day of gestation, or parity for sow IGF-1 concentration (P\u3e0.142). Treatment also did not affect (P=0.117) sow IGF-1 concentration. There were no treatment × parity or treatment effects on litter measures (P=0.170). Feeding porcine plasma at the low level employed in the study did not improve sow IGF-1 or litter measures. Keywords: Piglets, Fetal Growth, Porcine Plasm

Nursing Reduction Strategies to Enhance Estrus in Lactating Sows and Effects on Performance of Pigs to Market Weight

A total of 135 sows (PIC 1050), ranging from parity 1 to 5 (2.6 ± 1.4), were used in 5 consecutive farrowing groups (February to August). The objectives were to evaluate different suckling reduction strategies for inducing lactational estrus and the effects on sow fertility and piglet growth. Litter size was equalized within parity (11.5 ± 1.1 piglets) at d 2 after farrowing. At d 18, sows were assigned to 1 of 5 treatments (n = 26 to 28) based on parity, farrowing date, and suckled litter size. Treatments were: 1) control; 2) sows that were paired within parity and placed in adjacent stalls, on d 18 all but 5 of the lightest piglets were weaned, and the remaining piglets were combined and alternated between sows at 12 h intervals until d 25 (ALT); 3) piglets separated from sows for 12 h/d from d 18 to 25 (SEP); 4) all but the 5 lightest piglets weaned on d 18, split-weaning (SW); and 5) piglets separated from sows for 24 h on d 18 (24HR). Controls were weaned at d 21 with other treatments weaned at d 25. All sows were provided nose-to-nose contact with a mature boar for 5 min/d from d 18 until weaning without removing them from farrowing crates. Creep feed and water were provided from d 14 to weaning. Offspring ADG was recorded to market for 2 farrowing groups. Sow backfat and BW losses during lactation were similar across treatments. Of the 106 sows subjected to reduced suckling, 80 (76%) expressed estrus during lactation. The SEP and 24HR sows were in estrus earlier (P \u3c 0.05) than SW sows. A tendency for reduced conception rate was observed in SEP and 24HR sows (P \u3c 0.10) versus control and SW sows. Creep feed disappearance was greatest (P \u3c 0.01) for SEP and 24HR litters, and pig ADG from d 18 to 32 was reduced (P \u3c 0.05). No negative effects (P \u3e 0.05) on final BW or carcass composition were observed for the reduced suckling treatments. Altered suckling treatments differed in their ability to induce lactational estrus and their impact on gain immediately post-weaning. However, no benefits were observed for pig growth to market weight

Patterns of brain structural connectivity differentiate normal weight from overweight subjects

AbstractBackgroundAlterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks.AimTo apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements.MethodsStructural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals.Results1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42 morphological features, achieved 69% accuracy in discriminating overweight from normal weight. In both brain signatures regions of the reward, salience, executive control and emotional arousal networks were associated with lower morphological values in overweight individuals compared to normal weight individuals, while the opposite pattern was seen for regions of the somatosensory network.Conclusions1. An increased BMI (i.e., overweight subjects) is associated with distinct changes in gray-matter and fiber density of the brain. 2. Classification algorithms based on white-matter connectivity involving regions of the reward and associated networks can identify specific targets for mechanistic studies and future drug development aimed at abnormal ingestive behavior and in overweight/obesity

Modeling accuracy as a function of response time with the generalised linear mixed effects model

In psycholinguistic studies using error rates as a response measure, response times (RT) are most often analyzed independently of the error rate, although it is widely recognized that they are related. In this paper we present a mixed effects logistic regression model for the error rate that uses RT as a trial-level fixed- and random-effect regression input. Production data from a translation–recall experiment are analyzed as an example. Several model comparisons reveal that RT improves the fit of the regression model for the error rate. Two simulation studies then show how the mixed effects regression model can identify individual participants for whom (a) faster responses are more accurate, (b) faster responses are less accurate, or (c) there is no relation between speed and accuracy. These results show that this type of model can serve as a useful adjunct to traditional techniques, allowing psycholinguistic researchers to examine more closely the relationship between RT and accuracy in individual subjects and better account for the variability which may be present, as well as a preliminary step to more advanced RT–accuracy modeling

Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.This work was supported by the Portuguese Foundation for Science and Technology individual fellowship (CNA) www.fct.pt, a National Institutes of Health Grant R01 AI106725 (SMB) www.nih.gov, and a Center for AIDS Research Grant P30 AI 060354 (SMB) www.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Diffusion MRI quality control and functional diffusion map results in ACRIN 6677/RTOG 0625: A multicenter, randomized, phase II trial of bevacizumab and chemotherapy in recurrent glioblastoma

Functional diffusion mapping (fDM) is a cancer imaging technique that quantifies voxelwise changes in apparent diffusion coefficient (ADC). Previous studies have shown value of fDMs in bevacizumab therapy for recurrent glioblastoma multiforme (GBM). The aim of the present study was to implement explicit criteria for diffusion MRI quality control and independently evaluate fDM performance in a multicenter clinical trial (RTOG 0625/ACRIN 6677). A total of 123 patients were enrolled in the current multicenter trial and signed institutional review board-approved informed consent at their respective institutions. MRI was acquired prior to and 8 weeks following therapy. A 5-point QC scoring system was used to evaluate DWI quality. fDM performance was evaluated according to the correlation of these metrics with PFS and OS at the first follow-up time-point. Results showed ADC variability of 7.3% in NAWM and 10.5% in CSF. A total of 68% of patients had usable DWI data and 47% of patients had high quality DWI data when also excluding patients that progressed before the first follow-up. fDM performance was improved by using only the highest quality DWI. High pre-treatment contrast enhancing tumor volume was associated with shorter PFS and OS. A high volume fraction of increasing ADC after therapy was associated with shorter PFS, while a high volume fraction of decreasing ADC was associated with shorter OS. In summary, DWI in multicenter trials are currently of limited value due to image quality. Improvements in consistency of image quality in multicenter trials are necessary for further advancement of DWI biomarkers

The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis.

BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI -4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Examining gradients in ecosystem novelty: fish assemblage structure in an invaded Everglades canal system

Novel ecosystems result from a combination of altered historical abiotic regimes and new species assemblages. In freshwater systems, novel environmental conditions often result from large-scale changes to hydrological connectivity as well as species invasions. Novel environmental conditions may affect the survival of aquatic fauna by altering dispersal patterns and resource fluctuations, and/or may impose physiological constraints on native species evolutionarily adapted to particular environments. Further, novel systems can provide insight into processes driving community structure because re-sorting or filtering of regional biota is a likely consequence of decoupling from historical conditions. Although several studies document the presence of novel conditions, few examine variation or gradients in novelty. The Florida Everglades is a highly invaded and hydrologically altered system characterized by a large network of canals that compartmentalize the ecosystem and act to both increase and decrease connectivity. Little is known about how canals in this region function as habitat for native and nonnative fishes, the extent to which these canals may function as novel habitats, and how these habitat characteristics may influence distribution, abundance, and assembly patterns. In this study, we examined native and nonnative fish assemblages along a gradient of novelty, defined as the loss of wetland connectivity, influence of the natural hydrological regime, and habitat complexity (well connected to leveed canals). As novelty increased, native species richness and abundance strongly declined and the contribution of nonnatives increased to nearly 50%. Vast differences in community structure across the novelty gradient were strongly influenced by spatial factors and secondarily by hydrological factors, while habitat and abiotic factors were of very low relevance. Natives and nonnatives had opposing responses to key hydrological and habitat characteristics. Abundance of native fishes declined with decreased connectivity to adjacent marshes and canal littoral zone width, while nonnative fishes increased significantly in the most novel canals. Our results suggest that the inherent loss of natural environmental conditions and subsequent replacement by novel ones can lead to extensive changes in fish community structure. Success or failure at maintaining native assemblages will rely heavily on natural resource manager\u27s ability to incorporate natural environmental characteristics with ecosystem restoration

Stability Properties of Underdominance in Finite Subdivided Populations

In isolated populations underdominance leads to bistable evolutionary dynamics: below a certain mutant allele frequency the wildtype succeeds. Above this point, the potentially underdominant mutant allele fixes. In subdivided populations with gene flow there can be stable states with coexistence of wildtypes and mutants: polymorphism can be maintained because of a migration-selection equilibrium, i.e., selection against rare recent immigrant alleles that tend to be heterozygous. We focus on the stochastic evolutionary dynamics of systems where demographic fluctuations in the coupled populations are the main source of internal noise. We discuss the influence of fitness, migration rate, and the relative sizes of two interacting populations on the mean extinction times of a group of potentially underdominant mutant alleles. We classify realistic initial conditions according to their impact on the stochastic extinction process. Even in small populations, where demographic fluctuations are large, stability properties predicted from deterministic dynamics show remarkable robustness. Fixation of the mutant allele becomes unlikely but the time to its extinction can be long