Randomised controlled trial of a psychotherapeutic intervention to improve quality of life and other outcomes in people who repeatedly self-harm: FReSH START study protocol.

BACKGROUND: Self-harm is a major public health challenge, and repeated self-harm is common in those attending hospital following an episode. Evidence suggests psychological interventions could help people who self-harm, but few definitive studies have assessed their clinical and cost-effectiveness. Repeated self-harm is associated with poor quality of life, depression, suicide and increased health service costs which justify the development of psychotherapeutic interventions tailored for people with repeated self-harm. METHODS: FReSH START is a multicentre individually 1:1 randomised controlled trial evaluating the clinical and cost-effectiveness of standard care plus psychological therapy or standard care alone for adults (≥ 18 years) presenting at an emergency department (ED) with repeated self-harm. Recruiting 630 participants, it includes an internal pilot, economic evaluation and process evaluation. The intervention will be delivered by mental health staff working in acute settings, with experience of assessing and managing risk in people presenting to emergency services with self-harm. Staff will be trained and supervised to deliver one of three specially adapted therapies: psychodynamic interpersonal therapy, cognitive behavioural therapy or acceptance and commitment therapy. Participants allocated to the intervention will receive one of the adapted therapies according to therapist allocation for up to 6 months via 12 weekly, one to one, 45-50-min sessions. The primary outcome is quality of life measured by the Clinical Outcomes in Routine Evaluation Outcome Measure at 12 months post-randomisation. Secondary outcomes include suicidal intent, depression and cost-effectiveness. Data are collected using hospital attendance records and online/postal/telephone questionnaires at 6 and 12 months post-randomisation, with resource use additionally collected at 3 and 9 months. DISCUSSION: This protocol outlines a randomised controlled trial to investigate whether modified therapies are cost-effective and improve quality of life for people who repeatedly self-harm. Few interventions are proven to be deliverable in the NHS for this population. This study is strengthened by the involvement of qualified mental health workers experienced in managing risk as therapists. TRIAL REGISTRATION: Registered on August 03, 2021. IRAS number: 297939. ISRCTN: https://doi.org/10.1186/ISRCTN73357210 . REC reference: 21/EE/0145. SPONSOR: University of Leeds.

Multi-scale habitat assessment of pronghorn migration routes.

We studied the habitat selection of pronghorn (Antilocapra americana) during seasonal migration; an important period in an animal's annual cycle associated with broad-scale movements. We further decompose our understanding of migration habitat itself as the product of both broad- and fine-scale behavioral decisions and take a multi-scale approach to assess pronghorn spring and fall migration across the transboundary Northern Sagebrush Steppe region. We used a hierarchical habitat selection framework to assess a suite of natural and anthropogenic features that have been shown to influence selection patterns of pronghorn at both broad (migratory neighborhood) and fine (migratory pathway) scales. We then combined single-scale predictions into a scale-integrated step selection function (ISSF) map to assess its effectiveness in predicting migration route habitat. During spring, pronghorn selected for native grasslands, areas of high forage productivity (NDVI), and avoided human activity (i.e., roads and oil and natural gas wells). During fall, pronghorn selected for native grasslands, larger streams and rivers, and avoided roads. We detected avoidance of paved roads, unpaved roads, and wells at broad spatial scales, but no response to these features at fine scales. In other words, migratory pronghorn responded more strongly to anthropogenic features when selecting a broad neighborhood through which to migrate than when selecting individual steps along their migratory pathway. Our results demonstrate that scales of migratory route selection are hierarchically nested within each other from broader (second-order) to finer scales (third-order). In addition, we found other variables during particular migratory periods (i.e., native grasslands in spring) were selected for across scales indicating their importance for pronghorn. The mapping of ungulate migration habitat is a topic of high conservation relevance. In some applications, corridors are mapped according to telemetry location data from a sample of animals, with the assumption that the sample adequately represents habitat for the entire population. Our use of multi-scale modelling to predict resource selection during migration shows promise and may offer another relevant alternative for use in future conservation planning and land management decisions where telemetry-based sampling is unavailable or incomplete.

The Impact of Stressor Exposure and Glucocorticoids on Anxiety and Fear.

Anxiety disorders and trauma- and stressor-related disorders, such as posttraumatic stress disorder (PTSD), are common and are associated with significant economic and social burdens. Although trauma and stressor exposure are recognized as a risk factors for development of anxiety disorders and trauma or stressor exposure is recognized as essential for diagnosis of PTSD, the mechanisms through which trauma and stressor exposure lead to these disorders are not well characterized. An improved understanding of the mechanisms through which trauma or stressor exposure leads to development and persistence of anxiety disorders or PTSD may result in novel therapeutic approaches for the treatment of these disorders. Here, we review the current state-of-the-art theories, with respect to mechanisms through which stressor exposure leads to acute or chronic exaggeration of avoidance or anxiety-like defensive behavioral responses and fear, endophenotypes in both anxiety disorders and trauma- and stressor-related psychiatric disorders. In this chapter, we will explore physiological responses and neural circuits involved in the development of acute and chronic exaggeration of anxiety-like defensive behavioral responses and fear states, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoid hormones.

Successful management of primary nontuberculous mycobacterial infection of hepatic allograft following orthotopic liver transplantation for hepatitis C.

Nontuberculous mycobacteria are a rare cause of disease in solid organ and hematopoietic stem cell transplant recipients. The impact of mycobacterial infections in transplant recipients necessitates prompt diagnosis and early initiation of therapy. However, diagnosis remains difficult and there is a lack of specific recommendations for the choice of anti-mycobacterial drugs, duration of therapy, and monitoring of graft function as well as immunosuppression in these patients. Issues involved in the management are illustrated by an index case of hepatic allograft infection due to Mycobacterium avium complex.

Restoration of foothills rough fescue grassland following pipeline disturbance in southwestern Alberta.

The effects of pipeline construction and reclamation techniques on the restoration of rough fescue plant communities following pipeline construction in southwestern Alberta, Canada were evaluated after 7-40 years. The pipeline construction right-of-way (ROW) sites varied from no recovery of rough fescue grassland to moderate recovery. The ROW sites had a higher proportion of introduced grasses and forbs, less topsoil, and poorer rangeland health than the adjacent undisturbed grassland. Within the ROW sites, less topsoil was present on those with larger diameter pipe and which had topsoil fully stripped from the ROW during construction. Introduced grasses, Festuca ovina (sheep fescue) and Poa compressa (Canada bluegrass), succeeded in establishment following seeding and persisted for at least 40 years. Poa pratensis (Kentucky bluegrass) dominated many of the ROW sites. Contributing factors to moderate recovery of rough fescue grassland were related to post-growing season pipeline construction, ideally, between August and March, summer or fall seeding, and minimum disturbance trench-only stripping. Reclamation practices appeared more important than time since restoration in the restoration of rough fescue grassland.

The geography of conflict between elk and agricultural values in the Cypress Hills, Canada.

Complex ecological issues like depredation and its management are determined by multiple factors acting at more than one scale and are interlinked with complex human social and economic behaviour. Depredation by wild herbivores can be a major obstacle to agricultural community support for wildlife conservation. For three decades, crop and fence damage, competition with livestock for native rangeland and tame pasture, and depredation of stored feed by elk (Cervus elaphus canadensis) have been the cause of conflict with agricultural producers in the Cypress Hills, Alberta and Saskatchewan. Tolerance of elk presence on private lands is low because few benefits accrue to private landowners; rather they largely perceive elk as a public resource produced at their expense. Government management actions have focused on abatement inputs (e.g., population reduction; fencing) and compensation, but incentives to alter land use patterns (crop choice and location) in response to damages have not been considered. Nor has there been information on spatial structure of the elk population that would allow targeted management actions instead of attempting to manage the entire population. In this study we analysed the spatial structure of the Cypress Hills elk population, the distribution of the elk harvest in relation to agricultural conflicts, developed models of the spatial patterns of conflict fields, and evaluated compensation patterns for damage by wild herbivores. We propose modifications to current abatement and compensation programs and discuss alternative approaches involving changes to agricultural land use patterns that may reduce the intensity of conflicts with elk, and increase the acceptance capacity of landowners.

Wood bison population recovery and forage availability in northwestern Canada.

Forage availability was assessed to determine sustainable stocking rates for eight broadly defined vegetation types (Treed Uplands, Treed Lowlands, Mixed Tall Shrub/Sedge, Closed-canopied Willow, and Open-canopied Willow, Meadow, Wetland Grass, Wetland Sedge) for use by wood bison (Bison bison athabascae), a threatened subspecies, in the Canadian boreal forest of northern Alberta. Clip plots (n=108) were used to sample peak availability of herbs and current annual growth of Salix spp. in late summer. Graminoid wetlands dominated by Carex atherodes, Carex aquatilis, Carex utriculata, Scolochloa festucacea, or Calamagrostis stricta produced 1975-4575 kg ha(-1) of fair to good quality forage, whereas treed stands produced < 250 kg ha(-1) of forb-dominated forage (>85% content), which was below a published 25% foraging efficiency threshold of 263 kg ha(-1) for bison. Upland forests that dominate the region produced < or = 1 animal unit day (AUD) of forage per hectare in summer. Most forest understory plants were of poor forage value, suggesting the potential sustainable stocking rate of such areas was actually < or = 0.3 AUD ha(-1), with even lower rates during winter due to snow cover. Herbaceous wetlands contained approximately 78 AUD ha(-1) of forage, but were considered largely unavailable in summer because of flooding and soft organic soils that make access difficult. Conversion of prime foraging habitat to agricultural land, forest expansion due to fire control, and a warmer and wetter climatic regime after the mid-1900s likely contributed to a regional reduction in carrying capacity. It is hypothesized that substantial recovery of the wood bison population toward historical levels will be constrained in northern Alberta by the availability of summer forage, and the limited extent of graminoid wetlands that provide winter foraging habitat.

The ecological future of the North American bison: conceiving long-term, large-scale conservation of wildlife.

Many wide-ranging mammal species have experienced significant declines over the last 200 years; restoring these species will require long-term, large-scale recovery efforts. We highlight 5 attributes of a recent range-wide vision-setting exercise for ecological recovery of the North American bison (Bison bison) that are broadly applicable to other species and restoration targets. The result of the exercise, the "Vermejo Statement" on bison restoration, is explicitly (1) large scale, (2) long term, (3) inclusive, (4) fulfilling of different values, and (5) ambitious. It reads, in part, "Over the next century, the ecological recovery of the North American bison will occur when multiple large herds move freely across extensive landscapes within all major habitats of their historic range, interacting in ecologically significant ways with the fullest possible set of other native species, and inspiring, sustaining and connecting human cultures." We refined the vision into a scorecard that illustrates how individual bison herds can contribute to the vision. We also developed a set of maps and analyzed the current and potential future distributions of bison on the basis of expert assessment. Although more than 500,000 bison exist in North America today, we estimated they occupy <1% of their historical range and in no place express the full range of ecological and social values of previous times. By formulating an inclusive, affirmative, and specific vision through consultation with a wide range of stakeholders, we hope to provide a foundation for conservation of bison, and other wide-ranging species, over the next 100 years.

Whole-genome association study of bipolar disorder.

We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372,193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P=6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 x 10(-8), TSPAN8; P=7.57 x 10(-7) and EGFR; P=8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case-control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.

Differentiation of tundra/taiga and boreal coniferous forest wolves: genetics, coat colour and association with migratory caribou.

The grey wolf has one of the largest historic distributions of any terrestrial mammal and can disperse over great distances across imposing topographic barriers. As a result, geographical distance and physical obstacles to dispersal may not be consequential factors in the evolutionary divergence of wolf populations. However, recent studies suggest ecological features can constrain gene flow. We tested whether wolf-prey associations in uninterrupted tundra and forested regions of Canada explained differences in migratory behaviour, genetics, and coat colour of wolves. Satellite-telemetry data demonstrated that tundra wolves (n = 19) migrate annually with caribou (n = 19) from denning areas in the tundra to wintering areas south of the treeline. In contrast, nearby boreal coniferous forest wolves are territorial and associated year round with resident prey. Spatially explicit analysis of 14 autosomal microsatellite loci (n = 404 individuals) found two genetic clusters corresponding to tundra vs. boreal coniferous forest wolves. A sex bias in gene flow was inferred based on higher levels of mtDNA divergence (F(ST) = 0.282, 0.028 and 0.033; P < 0.0001 for mitochondrial, nuclear autosomal and Y-chromosome markers, respectively). Phenotypic differentiation was substantial as 93% of wolves from tundra populations exhibited light colouration whereas only 38% of boreal coniferous forest wolves did (chi(2) = 64.52, P < 0.0001). The sharp boundary representing this discontinuity was the southern limit of the caribou migration. These findings show that substantial genetic and phenotypic differentiation in highly mobile mammals can be caused by prey-habitat specialization rather than distance or topographic barriers. The presence of a distinct wolf ecotype in the tundra of North America highlights the need to preserve migratory populations.

Prescribed burning effects on summer elk forage availability in the subalpine zone, Banff National Park, Canada.

The effects of prescribed burning on forage abundance and suitability for elk (Cervus elaphus) during the snow-free season was evaluated in east-central Banff National Park, Canada. Six coniferous forest and mixed shrub-herb plant communities (n=144 plots), and 5223ha of burned (n=131) vegetation <12 years old were sampled using a stratified semi-random design. Sampling units represented various combinations of vegetation, terrain conditions, and stand ages that were derived from digital biophysical data, with plant communities the basic unit of analysis. Burning coniferous forest stands reduced woody biomass, and increased herbaceous forage from 146 to 790 kg/ha. Increases commonly occurred in the percent cover of hairy wild rye (Leymus innovatus (Beal) Pigler) and fireweed (Chamerion angustifolium (L.) Holub.). The herbaceous components of mixed shrub-herb communities increased from 336-747 kg/ha to 517-1104 kg/ha in response to burning (P<0.025, Mann-Whitney U-test). Browse biomass (mostly Salix spp. and Betula nana L.) increased >or=220% (P

A patient with an electrical burn treated by modified bilateral hemipelvectomy and disarticulation of the right arm.

A 23-year-old Hispanic worker sustained an electrical injury to 45% of his body when a crane hit a power line. Amputations of both legs, with bilateral partial hemipelvectomies, were required. A disarticulation of the right arm at the shoulder was also preformed. Resection of necrotic bowel, debridement of 95% of the abdominal wall, and resection of the genitalia was eventually required, with later reconstruction of the abdominal wall. After wound healing was complete, the patient was fitted with Jobst garments. A customized bucket prosthesis with a temperature control, to allow sitting upright, was provided. An electric wheel chair and a myoelectronic prosthetic arm were supplied. Rehabilitation was begun early.

'Flexispira rappini' strains represent at least 10 Helicobacter taxa.

'Flexispira rappini' is a provisional name given to gram-negative, microaerophilic, motile, spindle-shaped micro-organisms with spiral periplasmic fibres and bipolar tufts of sheathed flagella. Several investigators, including Kirkbride, Romero, and Archer isolated strains possessing this morphology. Previously, the phylogenetic position of three 'Flexispira rappini' strains was determined by 165 rRNA sequencing, which indicated that flexispira were members of the genus Helicobacter. As more organisms with 'F. rappini' morphology were isolated, it became apparent that there were multiple Helicobacter taxa with this distinctive morphology. The purpose of this study was to examine a collection of 36 'F. rappini' strains from diverse habitats by using 165 rRNA sequence analysis. The strains fell into 10 taxa, each possibly representing a novel Helicobacter species. Two of these flexispira taxa were previously named, by us, Helicobacter bilis and Helicobacter trogontum. Currently, none of the flexispira taxa contains enough phenotypically and genotypically characterized strains to be formally named 'Helicobacter rappinii'.

Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing.

Several recent studies suggest the isolation of stem cells in skeletal muscle, but the functional properties of these muscle-derived stem cells is still unclear. In the present study, we report the purification of muscle-derived stem cells from the mdx mouse, an animal model for Duchenne muscular dystrophy. We show that enrichment of desmin(+) cells using the preplate technique from mouse primary muscle cell culture also enriches a cell population expressing CD34 and Bcl-2. The CD34(+) cells and Bcl-2(+) cells were found to reside within the basal lamina, where satellite cells are normally found. Clonal isolation and characterization from this CD34(+)Bcl-2(+) enriched population yielded a putative muscle-derived stem cell, mc13, that is capable of differentiating into both myogenic and osteogenic lineage in vitro and in vivo. The mc13 cells are c-kit and CD45 negative and express: desmin, c-met and MNF, three markers expressed in early myogenic progenitors; Flk-1, a mouse homologue of KDR recently identified in humans as a key marker in hematopoietic cells with stem cell-like characteristics; and Sca-1, a marker for both skeletal muscle and hematopoietic stem cells. Intramuscular, and more importantly, intravenous injection of mc13 cells result in muscle regeneration and partial restoration of dystrophin in mdx mice. Transplantation of mc13 cells engineered to secrete osteogenic protein differentiate in osteogenic lineage and accelerate healing of a skull defect in SCID mice. Taken together, these results suggest the isolation of a population of muscle-derived stem cells capable of improving both muscle regeneration and bone healing.

Bacterial rhodopsin: evidence for a new type of phototrophy in the sea.

Extremely halophilic archaea contain retinal-binding integral membrane proteins called bacteriorhodopsins that function as light-driven proton pumps. So far, bacteriorhodopsins capable of generating a chemiosmotic membrane potential in response to light have been demonstrated only in halophilic archaea. We describe here a type of rhodopsin derived from bacteria that was discovered through genomic analyses of naturally occuring marine bacterioplankton. The bacterial rhodopsin was encoded in the genome of an uncultivated gamma-proteobacterium and shared highest amino acid sequence similarity with archaeal rhodopsins. The protein was functionally expressed in Escherichia coli and bound retinal to form an active, light-driven proton pump. The new rhodopsin exhibited a photochemical reaction cycle with intermediates and kinetics characteristic of archaeal proton-pumping rhodopsins. Our results demonstrate that archaeal-like rhodopsins are broadly distributed among different taxa, including members of the domain Bacteria. Our data also indicate that a previously unsuspected mode of bacterially mediated light-driven energy generation may commonly occur in oceanic surface waters worldwide.

Toward a healthy democracy.

Because it represents a revival of citizen responsibility, the Healthy Communities movement is not only a health and quality-of-life movement but a civic and democratic movement as well. Healthy Communities efforts need to seek meaningful partnerships with local governments and work their collaborative and citizen-based efforts into formal local political structures. As the foundation of the Healthy Communities movement, civic renewal should be elevated as a major theme and goal for its future.

Experience with the insertion of vena caval filters in acutely burned patients.

The use of inferior vena caval filters in patients at high risk of pulmonary emboli is a standard practice in many types of patients. The usefulness of such filters in acutely burned patients has yet to be established. Twenty inferior vena caval filters were inserted in burn patients. Five were inserted because of preexisting thromboembolic disease. Fifteen were placed prophylactically because of high-risk states, including prolonged immobilization, old age, bleeding problems, and obesity. There were no complications due to filter insertion. No postinsertion emboli were recognized. There were no cases of postinsertion thrombophlebitis. In this small series, the procedure appears to be effective and safe.

How a computer-based training module for the marine medic was developed.

This article is a discussion of how a prototype Computer-based Training (CBT) program module was developed by a team of people representing different nationalities and from various professions including nursing, engineering, and medical graphics. Multimedia solutions that would facilitate the training of Marine corpsmen to perform their mission as first responder in combat incidents were examined. Three separate software models were evaluated. The prototype chosen was selected because of its simplicity, user-friendliness, and cost effectiveness.

Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine.

Two families of small peptides that bind to the human thrombopoietin receptor and compete with the binding of the natural ligand thrombopoietin (TPO) were identified from recombinant peptide libraries. The sequences of these peptides were not found in the primary sequence of TPO. Screening libraries of variants of one of these families under affinity-selective conditions yielded a 14-amino acid peptide (Ile-Glu-Gly-Pro-Thr-Leu-Arg-Gln-Trp-Leu-Ala-Ala-Arg-Ala) with high affinity (dissociation constant approximately 2 nanomolar) that stimulates the proliferation of a TPO-responsive Ba/F3 cell line with a median effective concentration (EC50) of 400 nanomolar. Dimerization of this peptide by a carboxyl-terminal linkage to a lysine branch produced a compound with an EC50 of 100 picomolar, which was equipotent to the 332-amino acid natural cytokine in cell-based assays. The peptide dimer also stimulated the in vitro proliferation and maturation of megakaryocytes from human bone marrow cells and promoted an increase in platelet count when administered to normal mice.

p53 overexpression in squamous cell carcinoma of the esophagus.

BACKGROUND: Coastal South Carolina has a high incidence of squamous cell carcinoma of the esophagus (SCCE) among black residents. Overexpression and mutations of the p53 tumor suppressor gene have been noted in SCCE from other high-incidence regions. The purpose of this study was to determine the frequency of p53 overexpression in this region both in patients with SCCE and in normal subjects. METHODS: Normal and malignant tissue obtained at esophagoscopy and normal esophageal mucosa (NEM) from random autopsies were studied with monoclonal antibodies to the p53 gene product. Total cellular RNA was extracted from SCCE, reverse transcribed to complementary DNA, and a portion of the p53 gene was amplified via polymerase chain reaction and sequenced. RESULTS: Immunohistochemical studies on SCCE from nine patients showed that six (67%) were positive, two (22%) were negative, and one was indeterminate for p53 overexpression. The corresponding normal samples showed that three (33%) had p53-positive cells in the basal epithelial layer, whereas six did not. NEM from 18 random forensic cases displayed p53 overexpression in seven (39%). Eight of the nine tumors had p53 mutations. CONCLUSIONS: p53 overexpression and mutations are frequently found in SCCE from patients in coastal South Carolina. Overexpression in normal epithelium from random autopsy cases may indicate an inherited or acquired predisposition in this geographic region.