'Care and Prevent': rationale for investigating skin and soft tissue infections and AA amyloidosis among people who inject drugs in London.

BACKGROUND: Skin and soft tissue infections (SSTIs) are a leading cause of morbidity and mortality among people who inject drugs (PWID). International data indicate up to one third of PWID have experienced an SSTI within the past month. Complications include sepsis, endocarditis and amyloid A (AA) amyloidosis. AA amyloidosis is a serious sequela of chronic SSTI among PWID. Though there is a paucity of literature reporting on AA amyloidosis among PWID, what has been published suggests there is likely a causal relationship between AA amyloidosis and injecting-related SSTI. If left untreated, AA amyloidosis can lead to renal failure; premature mortality among diagnosed PWID is high. Early intervention may reverse disease. Despite the high societal and individual burden of SSTI among PWID, empirical evidence on the barriers and facilitators to injecting-related SSTI prevention and care or the feasibility and acceptability of AA amyloidosis screening and treatment referral are limited. This study aims to fill these gaps and assess the prevalence of AA amyloidosis among PWID. METHODS: Care and Prevent is a UK National Institute for Health Research-funded mixed-methods study. In five phases (P1-P5), we aim to assess the evidence for AA amyloidosis among PWID (P1); assess the feasibility of AA amyloidosis screening, diagnostic and treatment referral among PWID in London (P2); investigate the barriers and facilitators to AA amyloidosis care (P3); explore SSTI protection and risk (P4); and co-create harm reduction resources with the affected community (P5). This paper describes the conceptual framework, methodological design and proposed analysis for the mixed-methods multi-phase study. RESULTS: We are implementing the Care and Prevent protocol in London. The systematic review component of the study has been completed and published. Care and Prevent will generate an estimate of AA amyloidosis prevalence among community recruited PWID in London, with implications for the development of screening recommendations and intervention implementation. We aim to recruit 400 PWID from drug treatment services in London, UK. CONCLUSIONS: Care and Prevent is the first study to assess screening feasibility and the prevalence of positive proteinuria, as a marker for AA amyloidosis, among PWID accessing drug treatment services. AA amyloidosis is a serious, yet under-recognised condition for which early intervention is available but not employed.

The impact of sea ice conditions on breeding decisions is modulated by body condition in an arctic partial capital breeder.

Determining how environmental conditions interact with individual intrinsic properties is important for unravelling the underlying mechanisms that drive variation in reproductive decisions among migratory species. We investigated the influence of sea ice conditions and body condition at arrival on the breeding propensity, i.e. the decision to reproduce or not within a single breeding season, and timing of laying in migrating common eiders (Somateria mollissima) breeding in the Arctic. Using Radarsat satellite images acquired from 2002 to 2013, we estimated the proportion of open water in the intertidal zone in early summer to track the availability of potential foraging areas for pre-breeding females. Timing of ice-breakup varied by up to 20 days across years and showed strong relationship with both breeding propensity and the timing of laying of eiders: fewer pre-breeding individuals were resighted nesting in the colony and laying was also delayed in years with late ice-breakup. Interestingly, the effect of sea ice dynamics on reproduction was modulated by the state of individuals at arrival on the breeding grounds: females arriving in low condition were more affected by a late ice-breakup. Open water accessibility in early summer, a likely proxy of food availability, is thus crucial for reproductive decisions in a (partial) capital breeder. Our predictive capacity in determining how Arctic-breeding seabirds respond to changes in environmental conditions will require incorporating such cross-seasonal cumulative effects.

Cliff-nesting seabirds influence production and sediment chemistry of lakes situated above their colony.

Seabirds that congregate in large numbers during the breeding season concentrate marine-derived nutrients to their terrestrial nesting sites, and these nutrients disperse and enhance production in nearby terrestrial, freshwater and marine ecosystems. In the Canadian Arctic, large seabird colonies (>100,000 breeding pairs) nest on cliff faces that drain directly in the ocean, ultimately returning the nutrients back to the marine environment from which they were derived. However, strong winds blowing up cliff faces could transport nutrients up in elevation and onto surrounding terrestrial and aquatic environments. Here, we assess the degree to which seabird nutrients and metals have been delivered to coastal lakes near Hudson Strait (Nunavut, Canada) over the past century. Three lakes located at a higher elevation and increasing distance from a thick-billed murre (Uria lomvia) colony (~400,000 breeding pairs) were sampled for surface water chemistry. In addition, algal assemblages, nitrogen isotopes, and metal/metalloids were analyzed in four dated sediment cores. Elevated nutrients and major ions, as well as an enriched δ15N signature in the sediment cores, were measured in the lake <100m from the cliff, whilst no comparable changes were recorded in lakes >1km from the seabird colony. In contrast, similar oligotrophic and benthic diatom assemblages were identified in all three lakes, suggesting that diatoms were not influenced by enhanced nutrient inputs in this Arctic environment. Chemical tracers (e.g., total mercury) and algal assemblages in the lake near the colony suggest climate warming since ~1950 was the most likely driver of limnological changes, but this effect was muted in the more distant lakes. These pronounced changes in the seabird-impacted lake suggest that, with warming air temperatures and diminished lake ice cover, longer growing seasons may allow for aquatic organisms to more fully exploit the seabird nutrient subsidies.

Short communication: Ovine leukocyte telomere length is associated with variation in the cortisol response to systemic bacterial endotoxin challenge.

Stress has been associated with biological aging and numerous age-related diseases. This may be due, in part, to accelerated shortening of telomeres, which are critical genomic structures that cap and protect chromosomal ends. Dysfunction of the hypothalamic-pituitary-adrenal axis may indirectly contribute to telomere shortening if an animal reacts too strongly or weakly to a stressor, leading to accelerated biological aging. In this study, outbred Rideau-Arcott sheep were stress challenged with Escherichia coli endotoxin and classified as high, middle, or low cortisol responders to investigate a potential relationship between cortisol response and age, and telomere length. In the present study, no association was found between age and telomere length. The study, however, revealed shorter telomeres in high and low cortisol responders compared with the middle cortisol responders, which suggests that health and longevity may be compromised in extreme high- and low-stress-responding sheep.

Telomere length and telomerase activity in bovine pre-implantation embryos in vitro.

Telomeres are specialized structures that cap the ends of chromosomes and help to maintain genomic integrity and stability. Telomeres undergo dynamic changes during embryo development, which also represents an important stage for telomere elongation through telomerase enzyme activity. The objectives of this study were to examine changes in telomere length and telomerase activity from the early oocyte, through to the blastocysts stage of development, and the expression of factors with the potential to directly regulate telomeres. In vitro-produced bovine embryos were lysed and analysed for either relative telomere length, or telomerase activity using quantitative real-time PCR protocols. Our results reveal that relative telomere length is the shortest in the presumptive zygote stage of development and gradually increases to the blastocyst stage. We also demonstrate that differences between the mean telomere lengths throughout these stages are statistically significant (p < 0.05). Telomerase activity in the stages examined appears relatively constant until the blastocyst, where the highest level of activity is detected, leading to a significant difference in telomerase activity across embryonic stages (p < 0.005). Bovine telomerase RNA component (bTERC) expression levels were highest in the blastocyst, TERF1 transcripts showed little change in expression, and TERF2 expression decreased in the blastocysts (p < 0.05). Our results suggest that a complex integration of telomere-related RNA and proteins influences the regulatory mechanisms involved in 'reprogramming' of telomeres during early embryonic stages.

The chromosomal polymorphism of Drosophila subobscura: a microevolutionary weapon to monitor global change.

The Palaearctic species Drosophila subobscura recently invaded the west coast of Chile and North America. This invasion helped to corroborate the adaptive value of the rich chromosomal polymorphism of the species, as the same clinal patterns than those observed in the original Palaearctic area were reproduced in the colonized areas in a relatively short period of time. The rapid response of this polymorphism to environmental conditions makes it a good candidate to measure the effect of the global rising of temperatures on the genetic composition of populations. Indeed, the long-term variation of this polymorphism shows a general increase in the frequency of those inversions typical of low latitudes, with a corresponding decrease of those typical of populations closer to the poles. Although the mechanisms underlying these changes are not well understood, the system remains a valid tool to monitor the genetic impact of global warming on natural populations.

Nurse-delivered brief interventions for hazardous drinkers with alcohol-related facial trauma: a prospective randomised controlled trial.

AIMS: To assess the impact of two methods of brief nurse-delivered brief interventions in reducing drinking variables in hazardous drinkers with alcohol-related facial injuries. METHODS: A randomised controlled trial of two brief interventions involving hazardous drinkers with facial trauma in three Oral and Maxillofacial Surgery outpatient clinics in the West of Scotland; 194 patients were recruited and randomised to have either a nurse-led brief motivational intervention (intervention group) or a leaflet about alcohol misuse (control group). Patients were followed up at 3 and 12 months after the intervention and drinking variables reassessed. RESULTS: A brief motivational intervention for alcohol provided by a nurse was more effective than a leaflet in helping some patients with facial trauma to reduce their alcohol consumption 12 months after the intervention (p<0.05). CONCLUSIONS: Facial trauma in the West of Scotland is strongly associated with alcohol misuse and is a recurrent disease, particularly among those who drink heavily. A nurse-delivered brief motivational intervention is effective in helping patients with high scores in the Alcohol Use Disorders Identification Test to reduce their drinking, and this effect was apparent 12 months after the intervention.

Introduction history of Drosophila subobscura in the New World: a microsatellite-based survey using ABC methods.

Drosophila subobscura is a Palearctic species that was first observed in South and North America in the early 1980s, and that rapidly invaded broad latitudinal ranges on both continents. To trace the source and history of this invasion, we obtained genotypic data on nine microsatellite loci from two South American, two North American and five European populations of D. subobscura. We analysed these data with traditional statistics as well as with an approximate Bayesian computation (ABC) framework. ABC methods yielded the strongest support for the scenario involving a serial introduction with founder events from Europe into South America, and then from South America into North America. Stable effective population size of the source population was very large (around one million individuals), and the propagule size was notably smaller for the introduction into South America (i.e. high bottleneck severity index with only a few effective founders) but considerably larger for the subsequent introduction into North America (i.e. low bottleneck severity index with around 100-150 effective founders). Finally, the Mediterranean region of Europe (and most likely Barcelona from the localities so far analysed) is proposed as the source of the New World flies, based on mean individual assignment statistics.

Severe illness and death among injecting drug users in Scotland: a case-control study.

Between April and September 2000, 60 injecting drug users in Scotland died or were hospitalized with severe illness. Laboratory investigations suggested that Clostridium novyi and other bacteria were important aetiological agents. To determine associated environmental/behavioural factors a case-control study was undertaken with 19 'definite' and 32 'probable' cases in Glasgow, Scotland. For every deceased case (n=19), up to three proxy individuals were interviewed. Three controls were identified for each case. Multivariate logistic regression analyses compared (i) all cases and controls; (ii) definite cases and matched controls; (iii) probable cases and matched controls. In all three analyses injecting into muscle or skin and injecting most of the time with a filter used by someone else were the variables most strongly associated with illness. Comparing only muscle-injecting cases and controls, cases were significantly more likely to have injected larger amounts of heroin per average injection than were controls. The findings make an important epidemiological contribution to the understanding of the public health and clinical implications of the contamination of illicit drugs by histotoxic clostridia.

Continuous factor VIII infusion therapy in patients with haemophilia A undergoing surgical procedures with plasma-derived or recombinant factor VIII concentrates.

We describe the experience of a single medical centre with continuous factor VIII (FVIII) infusion therapy in a cohort of patients undergoing elective surgery. Twenty-eight patients had a total of 45 procedures. Intraoperative haemostasis was considered excellent in all 45 cases. FVIII levels were maintained between 46% and 191% of normal (median, 103%) for 2-7 days. Bleeding occurred after five procedures (11%) at times when factor VIII levels were within haemostatic range. No patient required reoperation to control bleeding. There were no cases of sepsis related to continuous infusion of factor VIII. We conclude that continuous infusion: (1) is a safe and effective means of replacement therapy in patients with haemophilia undergoing surgery; (2) provides easier monitoring and more constant coagulation factor levels; and (3) has the potential to decrease the cost of replacement therapy by reducing overall usage of product.

Haemorrhage into a popliteal cyst: an unusual complication of haemophilia A.

A 7(1/2)-year-old boy with severe haemophilia A had increasing discomfort and pain in his left knee after sledding on ice and landing on his knees. Left knee pain persisted for days despite recombinant factor VIII replacement. Imaging studies showed that by day 10 a popliteal cyst had ruptured, with diffusion of blood into the calf muscles. This case illustrates another possible bleeding complication in patients with a bleeding disorder and a popliteal cyst.

Potential of specialist drug services to deliver hepatitis B vaccination.

The city of Glasgow has a large population of injecting drug users (IDUs) who are likely to be susceptible to acute hepatitis B infection. We evaluated the effectiveness of a hepatitis B vaccination programme delivered at three existing types of services for IDUs. It was found that while uptake rates were generally low, they were higher at services where throughput of patients was lower, where clients had continuing relationships with services and where staff training and confidence were better.

Intrauterine correction of factor VIII (FVIII) deficiency.

This is the first published report documenting the successful use of intrauterine infusion of factor VIII (FVIII) in order to reduce the risk of intracranial haemorrhage in a foetus with documented haemophilia A. This approach provides another option for management of newborns with documented coagulation factor deficiency. The subsequent development of an inhibitor directed against FVIII is believed to be related to exposure to exogenous FVIII in the presence of an inversion mutation and not to the intrauterine procedure.

Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912.

PURPOSE: To determine the toxicity and response rate in children treated with dexamethasone, etoposide, cisplatin, high-dose cytarabine, and L-asparaginase (DECAL) for recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). PATIENTS AND METHODS: Ninety-seven children with recurrent NHL (n = 68) or HD (n = 29) were enrolled. Treatment consisted of two cycles of DECAL, then bone marrow transplantation or up to four cycles of ifosfamide, mesna, and etoposide alternating with DECAL maintenance therapy. RESULTS: After two cycles of DECAL induction therapy, complete response (CR) or partial response (PR) was reported in 19 (65.5%; 10 CRs and nine PRs) of 29 patients with HD and 29 (41.6%; 23 CRs and six PRs) of 68 patients with NHL. When only 24 patients with HD and 58 patients with NHL who were assessable for response were considered, the response rates were 79.2% (19 of 24 patients) and 50.0% (29 of 58 patients), respectively. Five-year event-free survival was 26% +/- 9% and 23% +/- 5% in patients with HD and NHL, respectively. Five-year survival was 31% +/- 14% and 30% +/- 6%, respectively. Although median time to treatment failure was significantly longer in patients with HD (EFS, P =.002; survival, P =.011), this difference did not translate into a higher long-term survival. Grade 3 or 4 toxic effects were observed during induction in 70 (72%) of 97 patients and during maintenance in 45 (70%) of 64 courses of DECAL therapy. Pancytopenia and systemic infections in particular were frequently observed. Other toxic effects were uncommon. Although not a formal part of the therapy or the study design, 42 patients who responded to therapy who underwent bone marrow transplant did not show any benefit from this approach. CONCLUSION: DECAL is an effective and tolerable salvage regimen for treating patients with recurrent NHL and HD.

Locomotor performance of Drosophila melanogaster: interactions among developmental and adult temperatures, age, and geography.

We explored the extent to which a phenotypic trait (walking speed) of Drosophila melanogaster is influenced by population, developmental temperature, adult temperature, and age. Our goals were to estimate the importance of these factors and to test the beneficial acclimation hypothesis. We measured speed of flies from two populations (the Congo and France) that developed at different temperatures (18, 25, and 29 degrees C) and were tested at different temperatures (18, 25, and 29 degrees C) and ages (2, 7, 13 days). Not surprisingly, speed increased strongly with test temperature. Speed was generally greatest for flies reared at an intermediate developmental temperature, contrary to the beneficial acclimation hypothesis, which predicts that speed would be greatest when influenced by interactions involving population. For example, speed was greatest for flies from France that developed at a low temperature, but for flies from the Congo that developed at a high temperature. The impact of developmental temperature declined with age. Surprisingly, speed actually increased with age for flies raised and maintained at a low temperature, but decreased with age for flies raised and maintained at an intermediate or at a high temperature. Thus, walking performance is highly dynamic phenotypically, complicating potential attempts to predict responses to selection on performance.

Parental and developmental temperature effects on the thermal dependence of fitness in Drosophila melanogaster.

Cross-generational effects refer to nongenetic influences of the parental phenotype or environment on offspring phenotypes. Such effects are commonly observed, but their adaptive significance is largely unresolved. We examined cross-generational effects of parental temperature on offspring fitness (estimated via a serial-transfer assay) at different temperatures in a laboratory population of Drosophila melanogaster. Parents were reared at 18 degrees C, 25 degrees C, or 29 degrees C (Tpar) and then their offspring were reared at 18 degrees C, 25 degrees C, or 29 degrees C (Toff) to evaluate several competing hypotheses (including an adaptive one) involving interaction effects of parental and offspring temperature on offspring fitness. The results clearly show that hotter parents are better; in other words, the higher the temperature of the parents, the higher the fitness of their offspring, independent of offspring thermal environment. These data contradict the adaptive cross-generational hypothesis, which proposes that offspring fitness is maximal when the offspring thermal regime matches the parental one. Flies with hot parents have high fitness seemingly because their own offspring develop relatively quickly, not because they have higher fecundity early in life.

Prison admission health screening as a measure of health needs.

OBJECTIVE: To assess the validity of routine prison screening admission data for measuring health needs and planning health services. DESIGN: Retrospective descriptive study of routinely collected admission data. SETTING: The largest Scottish men's prison with an annual throughput of around 20,000 men. SUBJECTS: All adult male (> or = 21 years) prisoners admitted during January 1998. RESULTS: Nine hundred and six men were screened in January 1998. Thirty-eight per cent of men entering prison said they currently or had previously used illegal drugs and 22% of all admissions gave a history of intravenous drug use. Six men (0.7%) reported hepatitis C infection and two (0.2%) reported hepatitis B infection. A history of major mental illness was reported by 10% of all prisoners, 7% of drug users and 15% of problem drinkers. Deliberate self-harm was reported by 10% of all prisoners, 9% of drug users and 17% of problem drinkers. CONCLUSION: There is a high prevalence of reported substance misuse and its sequelae and mental illness in prisoners. However, mental illness, substance use and some infectious diseases (such as HIV, hepatitis B and hepatitis C) may be under-reported, possibly because of social stigma or low expectations of treatment in prison. Health screening on admission to prison presents a unique opportunity to identify health needs at an early stage. However, there is a need to improve detection of some stigmatized conditions if individual care and health service planning are to be improved.

Rapid evolution of wing size clines in Drosophila subobscura.

Parallel latitudinal clines across species and continents provide dramatic evidence of the efficacy of natural selection, however little is known about the dynamics involved in cline formation. For example, several drosophilids and other ectotherms increase in body and wing size at higher latitudes. Here we compare evolution in an ancestral European and a recently introduced (North America) cline in wing size and shape in Drosophila subobscura. We show that clinal variation in wing size, spanning more than 15 degrees of latitude, has evolved in less than two decades. In females from Europe and North America, the clines are statistically indistinguishable however the cline for North American males is significantly shallower than that for European males. We document that while overall patterns of wing size are similar on two continents, the European cline is obtained largely through changing the proximal portion of the wing, whereas the North American cline is largely in the distal portion. We use data from sites collected in 1986/1988 (Pegueroles et al. 1995) and our 1997 collections to compare synchronic (divergence between contemporary populations that share a common ancestor) and allochronic (changes over time within a population) estimates of the rates of evolution. We find that, for these populations, allochronically estimated evolutionary rates within a single population are over 0.02 haldanes (2800 darwins), a value similar in magnitude to the synchronic estimates from the extremes of the cline. This paper represents an expanded analysis of data partially presented in Huey et al. (2000).