Calcitriol in the Management of Secondary Hyperparathyroidism of Renal Failure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90092/1/j.1875-9114.1996.tb03644.x.pd

Polarisation of equine pregnancy outcome associated with a maternal MHC class I allele: preliminary evidence

Identification of risk factors which are associated with severe clinical signs can assist in the management of disease outbreaks and indicate future research areas. Pregnancy loss during late gestation in the mare compromises welfare, reduces fecundity and has financial implications for horse owners. This retrospective study focussed on the identification of risk factors associated with pregnancy loss among 46 Thoroughbred mares on a single British stud farm, with some but not all losses involving equid herpesvirus-1 (EHV-1) infection. In a sub-group of 30 mares, association between pregnancy loss and the presence of five common Thoroughbred horse haplotypes of the equine Major Histocompatibility Complex (MHC) was assessed. This involved development of sequence specific, reverse transcriptase polymerase chain reactions and in several mares, measurement of cytotoxic T lymphocyte activity. Of the 46 mares, 10 suffered late gestation pregnancy loss or neonatal foal death, five of which were EHV-1 positive. Maternal factors including age, parity, number of EHV-1 specific vaccinations and the number of days between final vaccination and foaling or abortion were not significantly associated with pregnancy loss. In contrast, a statistically significant association between the presence of the MHC class I B2 allele and pregnancy loss was identified, regardless of the fetus / foal’s EHV-1 status (p=0.002). In conclusion, this study demonstrated a significantly positive association between pregnancy loss in Thoroughbred mares and a specific MHC class I allele in the mother. This association requires independent validation and further investigation of the mechanism by which the mare’s genetic background contributes to pregnancy outcome

Growth and life history variability of the grey reef shark (Carcharhinus amblyrhynchos) across its range

For broadly distributed, often overexploited species such as elasmobranchs (sharks and rays), conservation management would benefit from understanding how life history traits change in response to local environmental and ecological factors. However, fishing obfuscates this objective by causing complex and often mixed effects on the life histories of target species. Disentangling the many drivers of life history variability requires knowledge of elasmobranch populations in the absence of fishing, which is rarely available. Here, we describe the growth, maximum size, sex ratios, size at maturity, and offer a direct estimate of survival of an unfished population of grey reef sharks (Carcharhinus amblyrhynchos) using data from an eight year tag-recapture study. We then synthesized published information on the life history of C. amblyrhynchos from across its geographic range, and for the first time, we attempted to disentangle the contribution of fishing from geographic variation in an elasmobranch species. For Palmyra’s unfished C. amblyrhynchos population, the von Bertalanffy growth function (VBGF) growth coefficient k was 0.05 and asymptotic length L∞ was 163.3 cm total length (TL). Maximum size was 175.5 cm TL from a female shark, length at maturity was estimated at 116.7–123.2 cm TL for male sharks, maximum lifespan estimated from VBGF parameters was 18.1 years for both sexes combined, and annual survival was 0.74 year-1. Consistent with findings from studies on other elasmobranch species, we found significant intraspecific variability in reported life history traits of C. amblyrhynchos. However, contrary to what others have reported, we did not find consistent patterns in life history variability as a function of biogeography or fishing. Ultimately, the substantial, but not yet predictable variability in life history traits observed for C. amblyrhynchos across its geographic range suggests that regional management may be necessary to set sustainable harvest targets and to recover this and other shark species globally

Polarisation of equine pregnancy outcome is associated with a maternal MHC class I allele

Identification of risk factors which are associated with severe clinical signs can assist in the management of disease outbreaks and indicate future research areas. Pregnancy loss during late gestation in the mare compromises welfare, reduces fecundity and has financial implications for horse owners. This retrospective study focussed on the identification of risk factors associated with pregnancy loss among 46 Thoroughbred mares on a single British stud farm, with some but not all losses involving equid herpesvirus-1 (EHV-1) infection. In a sub-group of 30 mares, association between pregnancy loss and the presence of five common Thoroughbred horse haplotypes of the equine Major Histocompatibility Complex (MHC) was assessed. This involved development of sequence specific, reverse transcriptase polymerase chain reactions and in several mares, EHV-1 specific, cytotoxic T lymphocyte activity. Of the 46 mares, 10 suffered late gestation pregnancy loss or neonatal foal death, five of which were EHV-1 positive. Maternal factors including age, parity, number of EHV-1 specific vaccinations and the number of days between final vaccination and foaling or abortion were not significantly associated with pregnancy loss. In contrast, a statistically significant association between the presence of the MHC class I B2 allele and pregnancy loss was identified, regardless of the fetus / foal’s EHV-1 status (p=0.002). In conclusion, this study demonstrated a significantly positive association between pregnancy loss in Thoroughbred mares and a specific MHC class I allele in the mother. This association requires independent validation and further investigation of the mechanism by which the mare’s genetic background contributes to pregnancy outcome

Resetting predator baselines in coral reef ecosystems

What did coral reef ecosystems look like before human impacts became pervasive? Early efforts to reconstruct baselines resulted in the controversial suggestion that pristine coral reefs have inverted trophic pyramids, with disproportionally large top predator biomass. The validity of the coral reef inverted trophic pyramid has been questioned, but until now, was not resolved empirically. We use data from an eight-year tag-recapture program with spatially explicit, capture-recapture models to re-examine the population size and density of a key top predator at Palmyra atoll, the same location that inspired the idea of inverted trophic biomass pyramids in coral reef ecosystems. Given that animal movement is suspected to have significantly biased early biomass estimates of highly mobile top predators, we focused our reassessment on the most mobile and most abundant predator at Palmyra, the grey reef shark (Carcharhinus amblyrhynchos). We estimated a density of 21.3 (95% CI 17.8, 24.7) grey reef sharks/km2, which is an order of magnitude lower than the estimates that suggested an inverted trophic pyramid. Our results indicate that the trophic structure of an unexploited reef fish community is not inverted, and that even healthy top predator populations may be considerably smaller, and more precarious, than previously thought

Listening to patients with cancer: using a literary based research method to understand patient-focussed care

Objective In spite of considerable attention, patients diagnosed with cancer continue to report poor experiences of care. The root causes of this remain unclear. This exploratory study aimed to investigate new ways of understanding the experience of patients with cancer, using a literary-based research approach. Design Interviews were undertaken with four patients diagnosed with high grade brain cancers at least six months from diagnosis and with people (n = 5) identified by the patients as important in their care pathway. Interview transcripts were analysed by humanities academics as pieces of literature, where each patient’s story was told from more than one person’s perspective. The academics then came together in a facilitated workshop to agree major themes within the patient experiences. The themes were presented at a patient and carer event involving 70 participants to test the validity of the insights. Results Insights into the key issues for patients with cancer could be grouped into six themes: accountability; identity; life context; time; language; rigour and emotion. Patients often held a different perspective to the traditionally held medical views of what constitutes good care. For example, patients did not see any conflict between a doctor having scientific rigour and portraying emotion. Conclusions One key feature of the approach was its comparative nature: Patients often held different views from those traditionally held by physicians of what constitutes health and good outcomes. This revealed aspects that may be considered by health care professionals when designing improvements. Proposals for further testing are discussed, with a particular emphasis on the need for sensitivity to individual differences in experiences

Disrupted white matter integrity in treatment-resistant schizophrenia

Treatment response in schizophrenia is heterogeneous and has been posited to divide into three distinct subcategories: treatment-responsive (first-line responders; FLR), treatment-resistant (TRS, responding to clozapine), and ultra-treatment-resistant schizophrenia (UTRS, requiring augmented antipsychotic therapy). Previous work suggests that white matter abnormalities drive antipsychotic resistance but little work has been carried out to identify differences between those with TRS and those with UTRS. The current study aimed to establish whether differences in white matter structure are present across both treatment-resistant subtypes of schizophrenia or if UTRS is distinct from TRS. Diffusion-weighted images were acquired for 18 individuals with TRS, 14 with UTRS, 18 FLR and 20 healthy controls. Measures of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and parallel diffusivity (PD) were obtained using tract-based spatial statistics. Analysis of variance (ANOVA) and post-hoc between-groups t-tests interrogating differences were conducted for each white matter measure. Those with TRS had lower FA than healthy controls across widespread regions of the brain, including the superior longitudinal fasciculus, corpus callosum, thalamic radiation, corticospinal tract, internal capsule, corona radiata and fronto-occipital fasciculus (p<.05 FWE-corrected). Lower FA was also observed in those with TRS compared with UTRS in the superior longitudinal fasciculus (p<.05 FWE-corrected). However, post-hoc tests failed to survive corrections for multiple comparisons across the 12 post-hoc contrasts. No differences in MD, PD or RD were observed between groups. These data suggest that TRS is distinct from UTRS and that lower FA could act as a biomarker of treatment resistance in people with schizophrenia

Aberrant white matter microstructure in treatment-resistant schizophrenia

Treatment response in schizophrenia divides into three subcategories: treatment-responsive (first-line responders; FLR), treatment-resistant (TRS), and ultra-treatment-resistant schizophrenia (UTRS). White matter abnormalities could drive antipsychotic resistance but little work has investigated differences between TRS and UTRS. The current study aimed to establish whether differences in white matter structure are present across both treatment-resistant subtypes or if UTRS is distinct from TRS. Diffusion-weighted images were acquired for 18 individuals with TRS, 14 with UTRS, 18 FLR and 20 healthy controls. Measures of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were obtained using tract-based spatial statistics. Analysis of variance and post-hoc t-tests were conducted for each measure. Those with TRS had lower FA than healthy controls in superior longitudinal fasciculus, corpus callosum, thalamic radiation, corticospinal tract, internal capsule, corona radiata and fronto-occipital fasciculus (p<.05 FWE-corrected). Lower FA was also observed in TRS compared with UTRS in the superior longitudinal fasciculus (p<.05 FWE-corrected). No post-hoc tests survived corrections for multiple comparisons and no differences in MD, AD or RD were observed. These data suggest that microstructural deficits in white matter could contribute to TRS but suggest that other mechanisms may be more relevant for UTRS

Coordination risk and cost impacts on economic development in poor rural areas

This paper addresses issues relevant to a critical problem in economic development: how to get rapid pro-poor economic growth in poor rural areas in Africa and South Asia where most of the world’s dollar a day poor live. It examines constraints to the development of coordinated exchange systems in poor rural areas, focusing on the core problem of thin markets and low density of economic activity in these areas. Transaction cost and risk analysis is integrated into a conventional neoclassical production economics framework to describe the existence of low level equilibrium traps in transactions and supply chains and to generate important insights for development policy

Functional network dysconnectivity as a biomarker of treatment resistance in schizophrenia.

Schizophrenia may develop from disruptions in functional connectivity regulated by neurotransmitters such as dopamine and acetylcholine. The modulatory effects of these neurotransmitters might explain how antipsychotics attenuate symptoms of schizophrenia and account for the variable response to antipsychotics observed in clinical practice. Based on the putative mechanisms of antipsychotics and evidence of disrupted connectivity in schizophrenia, we hypothesised that functional network connectivity, as assessed using network-based statistics, would exhibit differences between treatment response subtypes of schizophrenia and healthy controls. Resting-state functional MRI data were obtained from 17 healthy controls as well as individuals with schizophrenia who responded well to first-line atypical antipsychotics (first-line responders; FLR, n=18), had failed at least two trials of antipsychotics but responded to clozapine (treatment-resistant schizophrenia; TRS, n=18), or failed at least two trials of antipsychotics and a trial of clozapine (ultra-treatment-resistant schizophrenia; UTRS, n=16). Data were pre-processed using the Advanced Normalization Toolkit and BrainWavelet Toolbox. Network connectivity was assessed using the Network-Based Statistics toolbox in Matlab. ANOVA revealed a significant difference in functional connectivity between groups that extended between cerebellar and parietal regions to the frontal cortex (p<0.05). Post-hoc t-tests revealed weaker network connectivity in individuals with UTRS compared with healthy controls but no other differences between groups. Results demonstrated distinct differences in functional connectivity between individuals with UTRS and healthy controls. Future work must determine whether these changes occur prior to the onset of treatment and if they can be used to predict resistance to antipsychotics during first-episode psychosis