Comparing the responses of grain-fed feedlot cattle under moderate heat load and during subsequent recovery with those of feed-restricted thermoneutral counterparts: blood cells and inflammatory markers.

Given the climate projections for livestock rearing regions globally, understanding the inflammatory status of livestock under various heat loads will be informative to animal welfare and management. A survey of plasma inflammatory markers was conducted, and blood leucocyte counts followed to investigate the capacity of the ~ 500 kg grain fed Black Angus steer to respond to and recover from a moderate heat load challenge. Two sequential cohorts of 12 steers were housed in climate-controlled rooms (CCR) for 18 days. A thermally challenged (TC) group (n = 2 × 6) experienced five consecutive periods: PreChallenge, Challenge, and Recovery within the CCR, and 40 days in outdoor pens (PENS and Late PENS). PreChallenge (5 days) and Recovery (7 days) delivered thermoneutral conditions, whereas in Challenge the TC steers experienced a diurnal temperature range of 28-35 °C. A feed-restricted thermoneutral (FRTN) treatment (n = 2 × 6) was run concurrently to differentiate between responses to reduced feed intake alone and moderate heat stress. Blood neutrophil counts were particularly sensitive to moderate heat load with higher numbers during Challlenge and in PENs. The plasma concentrations of TNFα and IL-1ß were depressed in the TC group compared to the FRTN counterparts and remained so for 40 days after Challenge. Linear relationships of the concentrations of IL-1ß, IL-10, and haptoglobin with rumen temperature or dry matter intake detected in the FRTN group were altered or absent in the TC group. The findings suggest significant impacts of moderate heat load on the inflammatory status of feedlot cattle.

Comparing the responses of grain fed feedlot cattle under moderate heat load and during subsequent recovery with those of feed restricted thermoneutral counterparts: metabolic hormones.

We set out to determine the impact of moderate heat load on the plasma concentrations of a suite of hormones involved in regulating energy metabolism and feed intake. The responses of the thermally challenged (TC) feedlot steers were compared to those of feed restricted thermoneutral (FRTN) steers. Two sequential cohorts of twelve 518 ± 23 kg Black Angus steers on finisher grain ration were housed in climate-controlled rooms (CCR) for 18 days and returned to outdoor pens for 40 days. The TC group was subjected to a diurnal range of 28-35 °C for 7 days (Challenge) but held in thermoneutral conditions beforehand (PreChallenge), and in Recovery (after Challenge). The FRTN group was held in thermoneutral conditions and feed restricted throughout. Blood was collected over the three periods in CCR and two periods in outdoor pens for 40 days (PENS and Late PENS). Plasma concentrations of prolactin, thyroid stimulating hormone, insulin, leptin, adiponectin and thyroxine (T4) were determined during the five periods. Whilst the pituitary hormones were relatively stable, there were differences in plasma leptin, adiponectin and T4 between the two groups during Challenge and Recovery, and occasionally in PENS. The interaction of the plasma hormone concentrations and rumen temperature and DMI were also investigated. Whilst the positive relationship between DMI and leptin was confirmed, we found a strong negative relationship between adiponectin and rumen temperature, and a strong positive relationship between adiponectin and dry matter intake (DMI) in the TC steers only.

Comparing the responses of grain fed feedlot cattle under moderate heat load and during subsequent recovery with those of feed restricted thermoneutral counterparts: plasma biochemistry.

Responses to heat stress in ruminants reflect the integration of local climatic conditions, environment/production system and the animal's homeostatic and homeorhetic capacities. Thus, the goal of ameliorating heat stress requires experimental settings that, within limits, closely resemble the target production system and cohort. We investigated the blood biochemical changes of two sequential cohorts of twelve 518 ± 23 kg grain fed Black Angus steers. Each cohort consisted of two treatments of 6 head/group: a thermally challenged (TC) treatment and a feed restricted thermoneutral (FRTN) treatment. Both groups were housed in climate controlled rooms for 19 days, with the TC group experiencing three distinct periods: PreChallenge, Challenge and Recovery. PreChallenge and Recovery delivered thermoneutral conditions, while Challenge consisted of 7 days of moderate diurnal heat load. The FRTN group was maintained in thermoneutral conditions at all times. Both groups were then relocated to outdoor pens for a further 40 days to detect any enduring change to metabolism as a consequence of the treatments. We compared blood biochemical responses of the treatments and inferred likely metabolic changes. Relative to the FRTN group, the TC animals experienced limited supply of triglycerides, cholesterol and glutamine during moderate heat load, suggesting constraints to energy metabolism. Lower blood urea during Recovery and in outdoor pens implied a requirement to capture N rather than allow its excretion. Altered liver enzyme profiles indicated a higher level of hepatic stress in the TC group. By the completion of feedlot finishing, the groups were not separable on most measures.

Using realist review to inform intervention development: methodological illustration and conceptual platform for collaborative care in offender mental health.

BACKGROUND: This paper reports how we used a realist review, as part of a wider project to improve collaborative mental health care for prisoners with common mental health problems, to develop a conceptual platform. The importance of offenders gaining support for their mental health, and the need for practitioners across the health service, the criminal justice system, and the third sector to work together to achieve this is recognised internationally. However, the literature does not provide coherent analyses of how these ambitions can be achieved. This paper demonstrates how a realist review can be applied to inform complex intervention development that spans different locations, organisations, professions, and care sectors. METHODS: We applied and developed a realist review for the purposes of intervention development, using a three-stage process. (1) An iterative database search strategy (extending beyond criminal justice and offender health) and groups of academics, practitioners, and people with lived experience were used to identify explanatory accounts (n = 347). (2) From these accounts, we developed consolidated explanatory accounts (n = 75). (3) The identified interactions between practitioners and offenders (within their organisational, social, and cultural contexts) were specified in a conceptual platform. We also specify, step by step, how these explanatory accounts were documented, consolidated, and built into a conceptual platform. This addresses an important methodological gap for social scientists and intervention developers about how to develop and articulate programme and implementation theory underpinning complex interventions. RESULTS: An integrated person-centred system is proposed to improve collaborative mental health care for offenders with common mental health problems (near to and after release) by achieving consistency between the goals of different sectors and practitioners, enabling practitioners to apply scientific and experiential knowledge in working judiciously and reflectively, and building systems and aligning resources that are centred on offenders' health and social care needs. CONCLUSIONS: As part of a broader programme of work, a realist review can make an important contribution to the specification of theoretically informed interventions that have the potential to improve health outcomes. Our conceptual platform has potential application in related systems of health and social care where integrated, and person-centred care is a goal.

Involving disabled children and young people as partners in research: a systematic review.

Children and young people can be valuable partners in research, giving their unique perspectives on what and how research should be done. However, disabled children are less commonly involved in research than their non-disabled peers. This review investigated how disabled children have been involved as research partners; specifically how they have been recruited, the practicalities and challenges of involvement and how these have been overcome, and impacts of involvement for research, and disabled children and young people. The INVOLVE definition of involvement and the Equality and Human Rights Commission definition of disability were used. Relevant bibliographic databases were searched. Websites were searched for grey literature. Included studies had involved disabled children and young people aged 5-25 years in any study design. Reviews, guidelines, reports and other documents from the grey literature were eligible for inclusion. Twenty-two papers were included: seven reviews, eight original research papers, three reports, three guidelines and one webpage. Nine examples of involvement were identified. Recommendations included developing effective communication techniques, using flexible methods that can be adapted to needs and preferences, and ensuring that sufficient support and funding is available for researchers undertaking involvement. Positive impacts of involvement for disabled children included increased confidence, self-esteem and independence. Positive impacts for research were identified. Involving disabled children in research can present challenges; many of these can be overcome with sufficient time, planning and resources. More needs to be done to find ways to involve those with non-verbal communication. Generally, few details were reported about disabled children and young people's involvement in studies, and the quality of evidence was low. Although a range of positive impacts were identified, the majority of these were authors' opinions rather than data. There remains scope for methodological research to inform appropriate approaches to public and patient involvement in childhood disability research.

Clinical effectiveness and cost-effectiveness of second- and third-generation left ventricular assist devices as either bridge to transplant or alternative to transplant for adults eligible for heart transplantation: systematic review and cost-effectiveness model.

BACKGROUND: Advanced heart failure (HF) is a debilitating condition for which heart transplant (HT) offers the best treatment option. However, the supply of donor hearts is diminishing and demand greatly exceeds supply. Ventricular assist devices (VADs) are surgically implanted pumps used as an alternative to transplant (ATT) or as a bridge to transplant (BTT) while a patient awaits a donor heart. Surgery and VADs are costly. For the NHS to allocate and deliver such services in a cost-effective way the relative costs and benefits of these alternative treatments need to be estimated. OBJECTIVES: To investigate for patients aged ≥ 16 years with advanced HF eligible for HT: (1) the clinical effectiveness and cost-effectiveness of second- and third-generation VADs used as BTT compared with medical management (MM); and (2) the clinical effectiveness and cost-effectiveness of second- and third-generation VADs used as an ATT in comparison with their use as BTT therapy. DATA SOURCES: Searches for clinical effectiveness studies covered years from 2003 to March 2012 and included the following data bases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), HTA databases [NHS Centre for Reviews and Dissemination (CRD)], Science Citation Index and Conference Proceedings (Web of Science), UK Clinical Research Network (UKCRN) Portfolio Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and National Library of Medicine (NLM) Gateway, Cochrane Central Register of Controlled Trials (CENTRAL), Current Controlled Trials and ClinicalTrials.gov. Reference lists of relevant articles were checked, and VAD manufacturers' websites interrogated. For economic analyses we made use of individual patient data (IPD) held in the UK Blood and Transplant Database (BTDB). REVIEW METHODS: Systematic reviews of evidence on clinical effectiveness and cost-effectiveness of second- and third-generation US Food and Drug Administration (FDA) and/or Conformité Européenne (CE) approved VADs. Publications from the last 5 years with control groups, or case series with 50 or more patients were included. Outcomes included survival, functional capacity (e.g. change in New York Heart Association functional classification), quality of life (QoL) and adverse events. Data from the BTDB were obtained. A discrete-time, semi-Markov, multistate model was built. Deterministic and probabilistic methods with multiple sensitivity analyses varying survival, utilities and cost inputs to the model were used. Model outputs were incremental cost-effectiveness ratios (ICERs), cost/quality-adjusted life-years (QALYs) gained and cost/life-year gained (LYG). The discount rate was 3.5% and the time horizon varied over 3 years, 10 years and lifetime. RESULTS: Forty publications reported clinical effectiveness of VADs and one study reported cost-effectiveness. We found no high-quality comparative empirical studies of VADs as BTT compared with MM or as ATT compared with BTT. Approximately 15-25% of the patients receiving a device had died by 12 months. Studies reported the following wide ranges for adverse events: 4-27% bleeding requiring transfusion; 1.5-40% stroke; 3.3-48% infection; 1-14% device failure; 3-30% HF; 11-32% reoperation; and 3-53% renal failure. QoL and functional status were reported as improved in studies of two devices [HeartMate II (HMII; Thoratec Inc., Pleasanton, CA, USA) and HeartWare (HW; HeartWare Inc., Framingham, MA, USA)]. At 3 years, 10 years and lifetime, the ICERs for VADs as BTT compared with MM were £122,730, £68,088 and £55,173 respectively. These values were stable to changes in survival of the MM group. Both QoL and costs were reduced by VADs as ATT compared with VADs as BTT giving ICERs in south-west quadrant of the cost effectiveness plain (cost saving/QALY sacrificed) of £353,467, £31,685 and £20,637 over the 3 years, 10 years and lifetime horizons respectively. Probabilistic analyses yielded similar results for both research questions. LIMITATIONS: Conclusions about the clinical effectiveness were limited by the lack of randomised controlled trials (RCTs) comparing the effectiveness of different VADs for BTT or comparing BTT with any alternative treatment and by the overlapping populations in published studies. Although IPD from the BTDB was used to estimate the cost-effectiveness of VADs compared with MM for BTT, the lack of randomisation of populations limited the interpretation of this analysis. CONCLUSIONS: At 3 years, 10 years and lifetime the ICERs for VADs as BTT compared with MM are higher than generally applied willingness-to-pay thresholds in the UK, but at a lifetime time horizon they approximate threshold values used in end of life assessments. VADs as ATT have a reduced cost but cause reduced QALYs relative to BTT. Future research should direct attention towards two areas. First, how any future evaluations of second- or third-generation VADs might be conducted. For ethical reasons a RCT offering equal probability of HT for each group would not be feasible; future studies should fully assess costs, long-term patient survival, QoL, functional ability and adverse events, so that these may be incorporated into economic evaluation agreement on outcomes measures across future studies. Second, continuation of accurate data collection in the UK database to encompass QoL data and comparative assessment of performance with other international centres. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Identification of an immuno-protective mucin-like protein, peritrophin-55, from the peritrophic matrix of Lucilia cuprina larvae.

A mucin-like glycoprotein, peritrophin-55 was isolated and purified from the peritrophic matrix of Lucilia cuprina larvae. When injected into sheep, peritrophin-55 induced an immune response that inhibited larval growth by 51-66% when larvae subsequently fed on sera from the vaccinated sheep. The protein may have potential use as an immunogen probably accompanying other antigens to protect sheep from the cutaneous myiasis caused by these larvae. Peritrophin-55 was uniformly distributed throughout the peritrophic matrix where it probably lubricates the surface of the peritrophic matrix and protects the midgut from invasion by bacteria. The protein consists of an 8-cysteine amino-terminal domain (peritrophin-B domain) and a carboxy-terminal proline and threonine-rich domain with high probability for extensive O-linked glycosylation. The gene consists of two exons separated by a small intron. Peritrophin-55 mRNA was only detected in the larval cardia and midgut and to a minor extent in the hindgut. Sequence upstream of the transcriptional start site contained a putative promoter region, sequence similar to an ecdysone response element, sequence related to the Drosophila transposon S element and a tetranucleotide repeat region. A putative Drosophila melanogaster ortholog or paralog of peritrophin-55 (CG7714) was located within a 3458 bp intron of the Cha gene (choline-O-acetyltransferase), but on the opposite strand. Comparison of the putative promoter regions of the peritrophin-55 and CG7714 genes revealed little similarity except for a small semi-conserved sequence that is suggestive of a common transcription factor-binding site possibly contributing to the highly restricted developmental and tissue-specific expression patterns of these genes.

Reduced oviposition of Boophilus microplus feeding on sheep vaccinated with vitellin.

The most abundant protein present in Boophilus microplus eggs, vitellin, was isolated and purified as a non-covalent complex of six glyco-polypeptides of Mr 44-107kDa. The protein complex bound haem. Immuno-blots demonstrated that antibodies raised to vitellin recognised a 200kDa polypeptide in the haemolymph of adult female ticks. This is consistent with the general proposal that in arthropods vitellin is derived by proteolytic processing from a large precursor protein, vitellogenin. In parallel with this study, an 80kDa glycoprotein (GP80) was independently purified from larvae of B. microplus using efficacy in vaccination trials as an assay. Antibodies to GP80 also recognised a 200kDa protein in the haemolymph of ticks and a major 87kDa polypeptide present in the vitellin complex. Conversely, antibodies to purified vitellin recognised GP80. The amino-terminal amino acid sequences of the 87kDa vitellin polypeptide and GP80 were identical for at least the first 11 residues and internal peptide sequences from both polypeptides were co-located in a single but incomplete deduced amino sequence of B. microplus vitellogenin. Thus, GP80 is a processed product from vitellogenin and highly related to but not completely identical with the 87kDa vitellin polypeptide. Vaccination trials in the model host sheep were performed with purified vitellin and GP80. Sheep vaccinated with either purified vitellin or GP80 returned significantly reduced numbers of engorged female ticks with decreased weights and reduced oviposition. In contrast, sheep vaccinated with recombinant hexahis-GP80, which was incorrectly folded and not glycosylated showed no significant effects on ticks. It was concluded that vitellin and GP80 could induce immune responses that partially protect sheep from the tick, B. microplus. However, critical protective epitopes are associated with the folding of the protein and/or the oligosaccharides attached to it.

Posthypnotic amnesia for material learned before or during hypnosis: explicit and implicit memory effects.

This article focuses on dissociations between explicit and implicit expressions of memory during posthypnotic amnesia (PHA). Despite evidence of such dissociations, experimental design in this area has not always been consistent with contemporary memory research. Within a paradigm that aimed for conceptual and methodological clarity, we presented 40 high and 38 low hypnotizable individuals with a word list either before or during hypnosis, gave them a PHA suggestion for the word list, and tested them on explicit and implicit memory tasks. In the absence of conscious recollection, highs showed equivalent levels of priming (perceptual and semantic) to lows. However, when analysis focused only on those highs who remained amnesic after the implicit memory tasks, we confirmed perceptual, but not semantic, priming. These findings highlight the impact of methodological choices on theoretical interpretations of memory performance following a suggestion for PHA.

Intact binocular function and absent ocular torsion in children with alternating skew on lateral gaze.

BACKGROUND: A form of skew deviation, called alternating skew on lateral gaze, resembles bilateral superior oblique overaction. Oblique muscle overaction has been recently speculated to result from loss of fusion with subsequent "free-wheeling" of the torsional control mechanisms of the eyes, causing sensory intorsion or extorsion with attendant superior or inferior oblique muscle overaction, respectively. We wanted to investigate whether loss of fusion plays a role in the pathogenesis of alternating skew on lateral gaze. SUBJECTS AND METHODS: We examined seven consecutive patients with posterior fossa tumors, enrolled in a multi-disciplinary pediatric neuro-oncology program, who displayed alternating skew on lateral gaze. All patients underwent a thorough ophthalmologic evaluation. RESULTS: Visual acuities in the study patients ranged from 20/20 to 20/40. Five of the seven patients were orthotropic, and showed 40 sec of arc stereopsis. Three patients showed associated downbeat nystagmus. No ocular torsion was found in any of the five patients who showed normal stereopsis upon inspection of fundus landmarks on indirect ophthalmoscopy. CONCLUSION: Patients with alternating skew on lateral gaze often have normal binocular vision and stereopsis, and lack ocular intorsion so typical of superior oblique overaction. Alternating skew on lateral gaze is neurologically mediated, with no role for defective fusion in its pathogenesis.