The relationship between wearable-derived sleep features and relapse in Major Depressive Disorder.

BACKGROUND: Changes in sleep and circadian function are leading candidate markers for the detection of relapse in Major Depressive Disorder (MDD). Consumer-grade wearable devices may enable remote and real-time examination of dynamic changes in sleep. Fitbit data from individuals with recurrent MDD were used to describe the longitudinal effects of sleep duration, quality, and regularity on subsequent depression relapse and severity. METHODS: Data were collected as part of a longitudinal observational mobile Health (mHealth) cohort study in people with recurrent MDD. Participants wore a Fitbit device and completed regular outcome assessments via email for a median follow-up of 541 days. We used multivariable regression models to test the effects of sleep features on depression outcomes. We considered respondents with at least one assessment of relapse (n = 218) or at least one assessment of depression severity (n = 393). RESULTS: Increased intra-individual variability in total sleep time, greater sleep fragmentation, lower sleep efficiency, and more variable sleep midpoints were associated with worse depression outcomes. Adjusted Population Attributable Fractions suggested that an intervention to increase sleep consistency in adults with MDD could reduce the population risk for depression relapse by up to 22 %. LIMITATIONS: Limitations include a potentially underpowered primary outcome due to the smaller number of relapses identified than expected. CONCLUSION: Our study demonstrates a role for consumer-grade activity trackers in estimating relapse risk and depression severity in people with recurrent MDD. Variability in sleep duration and midpoint may be useful targets for stratified interventions.

MicroRNA regulation of islet and enteroendocrine peptides: Physiology and therapeutic implications for type 2 diabetes.

The pathogenesis of type 2 diabetes (T2D) is associated with dysregulation of glucoregulatory hormones, including both islet and enteroendocrine peptides. Microribonucleic acids (miRNAs) are short noncoding RNA sequences which post transcriptionally inhibit protein synthesis by binding to complementary messenger RNA (mRNA). Essential for normal cell activities, including proliferation and apoptosis, dysregulation of these noncoding RNA molecules have been linked to several diseases, including diabetes, where alterations in miRNA expression within pancreatic islets have been observed. This may occur as a compensatory mechanism to maintain beta-cell mass/function (e.g., downregulation of miR-7), or conversely, lead to further beta-cell demise and disease progression (e.g., upregulation of miR-187). Thus, targeting miRNAs has potential for novel diagnostic and therapeutic applications in T2D. This is reinforced by the success seen to date with miRNA-based therapeutics for other conditions currently in clinical trials. In this review, differential expression of miRNAs in human islets associated with T2D will be discussed along with further consideration of their effects on the production and secretion of islet and incretin hormones. This analysis further unravels the therapeutic potential of miRNAs and offers insights into novel strategies for T2D management.

Legitimizing evidence: The trans-institutional life of evidence-based practice.

Evidence-based practice (EBP) has become a dominant paradigm in North American behavioral health and social service provision. Once a model of expert decision-making that asked practitioners to search through the "best available evidence" to inform their clinical decisions and select interventions, EBP is now better understood as a complex system of legitimation that designates particular methods and-by extension-their practitioners as "evidence-based." While critics worry that EBP forecloses professional discretion by imposing particular epistemic virtues of intervention science, this ethnographic case demonstrates that 1) EBP legitimates professional actors, methods, and organizations at least as much as it hampers them and 2) a wide range of "extra-scientific" actors are involved in producing and legitimating the evidence of evidence-based practice, including policy makers, public and private insurers, state agencies, charitable foundations, registries and clearinghouses, health and human service organizations, and helping professionals themselves. Once we recognize the range of actors and institutions involved in basing and legitimating evidence, and the rhetorical work of tethering scientific terms to resonant political and economic discourses, we learn that there is nothing self-evident about evidence-based practice. Drawing on the social scientific study of expertise and focusing empirically on how one behavioral intervention earns and retains its status as an EBP, this study traces the trans-institutional life of evidence and the continual need to legitimate it as a base for behavioral health practice.

Predictors of engagement with remote sensing technologies for symptom measurement in Major Depressive Disorder.

BACKGROUND: Remote sensing for the measurement and management of long-term conditions such as Major Depressive Disorder (MDD) is becoming more prevalent. User-engagement is essential to yield any benefits. We tested three hypotheses examining associations between clinical characteristics, perceptions of remote sensing, and objective user engagement metrics. METHODS: The Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) study is a multicentre longitudinal observational cohort study in people with recurrent MDD. Participants wore a FitBit and completed app-based assessments every two weeks for a median of 18 months. Multivariable random effects regression models pooling data across timepoints were used to examine associations between variables. RESULTS: A total of 547 participants (87.8% of the total sample) were included in the current analysis. Higher levels of anxiety were associated with lower levels of perceived technology ease of use; increased functional disability was associated with small differences in perceptions of technology usefulness and usability. Participants who reported higher system ease of use, usefulness, and acceptability subsequently completed more app-based questionnaires and tended to wear their FitBit activity tracker for longer. All effect sizes were small and unlikely to be of practical significance. LIMITATIONS: Symptoms of depression, anxiety, functional disability, and perceptions of system usability are measured at the same time. These therefore represent cross-sectional associations rather than predictions of future perceptions. CONCLUSIONS: These findings suggest that perceived usability and actual use of remote measurement technologies in people with MDD are robust across differences in severity of depression, anxiety, and functional impairment.

The moment of tooth: rate, fate and pattern of Pacific lingcod dentition revealed by pulse-chase.

Tooth replacement rates of polyphyodont cartilaginous and bony fishes are hard to determine because of a lack of obvious patterning and maintaining specimens long enough to observe replacement. Pulse-chase is a fluorescent technique that differentially colours developing mineralized tissue. We present in situ tooth replacement rate and position data for the oral and pharyngeal detentions of Ophiodon elongatus (Pacific lingcod). We assessed over 10 000 teeth, in 20 fish, and found a daily replacement rate of about two teeth (3.6% of the dentition). The average tooth is in the dental battery for 27 days. The replacement was higher in the lower pharyngeal jaw (LPJ). We found no difference between replacement rates of feeding and non-feeding fish, suggesting feeding was not a driver of tooth replacement. Lingcod teeth have both a size and location fate; smaller teeth at one spot will not grow into larger teeth, even if a large tooth nearby is lost. We also found increased rates of replacement at the posterior of the LPJ relative to the anterior. We propose that lingcod teeth do not migrate in the jaw as they develop; their teeth are fated in size and location, erupting in their functional position.

The role of loneliness in the development of depressive symptoms among partnered dementia caregivers: Evidence from the English Longitudinal Study of Aging.

BACKGROUND: Depressive symptoms are highly prevalent among partnered dementia caregivers, but the mechanisms are unclear. This study examined the mediating role of loneliness in the association between dementia and other types of care on subsequent depressive symptoms. METHODS: Prospective data from partnered caregivers were drawn from the English Longitudinal Study of Aging. The sample consisted of 4,672 partnered adults aged 50-70 living in England and Wales, followed up between 2006-2007 and 2014-2015. Caregiving was assessed across waves 3 (2006-2007), 4 (2008-2009), and 5 (2010-2011), loneliness at wave 6 (2012-2013), and subsequent depressive symptoms at wave 7 (2014-15). Multivariable logistic regression models were used to assess the association between caregiving for dementia and depressive symptoms compared to caregiving for other illnesses (e.g., diabetes, coronary heart disease (CHD), cancer, and stroke). Binary mediation analysis was used to estimate the indirect effects of caregiving on depressive symptoms via loneliness. RESULTS: Care for a partner with dementia was associated with higher odds of depressive symptoms at follow-up compared to those not caring for a partner at all (odds ratio [OR] = 2.6, 95% confidence intervals [CI]: 1.4, 5.1). This association was partially mediated by loneliness (34%). Care for a partner with other conditions was also associated with higher odds of depressive symptoms compared to non-caregiving partners (OR = 1.7, 95% CI: 1.2, 2.5), but there was no evidence of an indirect pathway via loneliness. CONCLUSION: Loneliness represents an important contributor to the relationship between dementia caregiving and subsequent depressive symptoms; therefore, interventions to reduce loneliness among partnered dementia caregivers should be considered.

A systematic review of cellular therapies for the treatment of limbal stem cell deficiency affecting one or both eyes.

PURPOSE: This systematic review (SR) assessed the efficacy, safety and cost-effectiveness of cell-based therapy to manage limbal stem cell deficiency (LSCD), a sight-threatening orphan condition most frequently associated with severe chemical or thermal burns. LSCD has historically been treated by transplanting limbal tissue. In 1997, a new treatment, cultured limbal epithelial autografts, was described for unilateral LSCD. In cases of bilateral disease cultured autologous oral mucosa stem cells have been used. The relative efficacy of different cultured tissue procedures is unknown. METHODS: A protocol was registered with PROSPERO (CRD42017081117). Searches were conducted in 14 databases and 6 conference websites. Two reviewers independently selected studies, conducted data extraction and assessed risk of bias. One reviewer extracted individual patient data (IPD); a second checked extracted data. Data were assessed to determine the feasibility of statistical analysis, with Bayesian synthesis used to estimate improvement achieved by different treatments. RESULTS: Fifty-two studies were eligible for inclusion (1113 eyes); 41 studies (716 eyes) reported IPD. No evidence was identified on cost-effectiveness. This SR was unable to confirm that any of the types of ex vivo cultured stem cell transplants identified for LSCD treatment were statistically superior when assessed against the outcomes of interest. CONCLUSIONS: We believe this SR is the first to include IPD analysis of LSCD data. There is no evidence for the superiority of any method of limbal stem cell transplant. Confirmation of the safety and efficacy of this treatment modality is challenging due to heterogeneity within and between the studies identified. Therefore, recommendations for future research are proposed.

Mobile telephone delivered contingency management for encouraging adherence to supervised methadone consumption: feasibility study for an RCT of clinical and cost-effectiveness (TIES).

BACKGROUND: Prescription methadone or buprenorphine enables people with opioid use disorder to stop heroin use safely while avoiding withdrawal. To ensure methadone is taken as prescribed and to prevent diversion onto the illicit market, people starting methadone take their daily dose under a pharmacist's supervision. Many patients miss their daily methadone dose risking withdrawal, craving for heroin and overdose due to loss of heroin tolerance. Contingency management (CM) can improve medication adherence, but remote delivery using technology may be resource-light and cost-effective. We developed an innovative way to deliver CM by mobile telephone. Software monitors patients' attendance and supervised methadone consumption through an internet self-login at the pharmacy and sends reinforcing text messages to patients' mobile telephones. A linked system sends medication adherence reports to prescribers and provides early warning alerts of missed doses. A pre-paid debit card system provides financial incentives. METHODS: A cluster randomised controlled trial design was used to test the feasibility of conducting a future trial of mobile telephone CM to encourage adherence to supervised methadone in community pharmacies. Each cluster (drug service/3 allied pharmacies) was randomly allocated to provide patient's presenting for a new episode of opiate agonist treatment (OAT) with either (a) mobile telephone text message CM, (b) mobile telephone text message reminders, or (c) no text messages. We assessed acceptability of the interventions, recruitment, and follow-up procedures. RESULTS: Four drug clinics were approached and three recruited. Thirty-three pharmacists were approached and 9 recruited. Over 3 months, 173 individuals were screened and 10 enrolled. Few patients presented for OAT and high numbers were excluded due to receiving buprenorphine or not attending participating pharmacies. There was 96% consistency in recording medication adherence by self-login vs. pharmacy records. In focus groups, CM participants were positive about using self-login, the text messages, and debit card. Prescribers found weekly reporting, time saving, and allowed closer monitoring of patients. Pharmacists reported that the tablet device was easy to host. CONCLUSION: Mobile telephone CM worked well, but a planned future trial will use modified eligibility criteria (existing OAT patients who regularly miss their methadone/buprenorphine doses) and increase the number of participating pharmacies. TRIAL REGISTRATION: The trial is retrospectively registered, ISRCTN 58958179 .

Modeling drug delivery from multiple emulsions.

We present a mechanistic model of drug release from a multiple emulsion into an external surrounding fluid. We consider a single multilayer droplet where the drug kinetics are described by a pure diffusive process through different liquid shells. The multilayer problem is described by a system of diffusion equations coupled via interlayer conditions imposing continuity of drug concentration and flux. Mass resistance is imposed at the outer boundary through the application of a surfactant at the external surface of the droplet. The two-dimensional problem is solved numerically by finite volume discretization. Concentration profiles and drug release curves are presented for three typical round-shaped (circle, ellipse, and bullet) droplets and the dependency of the solution on the mass transfer coefficient at the surface analyzed. The main result shows a reduced release time for an increased elongation of the droplets.

Estimated health impacts from maritime transport in the Mediterranean region and benefits from the use of cleaner fuels.

Ship traffic emissions degrade air quality in coastal areas and contribute to climate impacts globally. The estimated health burden of exposure to shipping emissions in coastal areas may inform policy makers as they seek to reduce exposure and associated potential health impacts. This work estimates the PM2.5-attributable impacts in the form of premature mortality and cardiovascular and respiratory hospital admissions, from long-term exposure to shipping emissions. Health impact assessment (HIA) was performed in 8 Mediterranean coastal cities, using a baseline conditions from the literature and a policy case accounting for the MARPOL Annex VI rules requiring cleaner fuels in 2020. Input data were (a) shipping contributions to ambient PM2.5 concentrations based on receptor modelling studies found in the literature, (b) population and health incidence data from national statistical registries, and (c) geographically-relevant concentration-response functions from the literature. Long-term exposure to ship-sourced PM2.5 accounted for 430 (95% CI: 220-650) premature deaths per year, in the 8 cities, distributed between groups of cities: Barcelona and Athens, with >100 premature deaths/year, and Nicosia, Brindisi, Genoa, Venice, Msida and Melilla, with tens of premature deaths/year. The more stringent standards in 2020 would reduce the number of PM2.5-attributable premature deaths by 15% on average. HIA provided a comparative assessment of the health burden of shipping emissions across Mediterranean coastal cities, which may provide decision support for urban planning with a special focus on harbour areas, and in view of the reduction in sulphur content of marine fuels due to MARPOL Annex VI in 2020.

The complex experience of psoriasis related skin pain: a qualitative study.

Background and aims Psoriasis is a common chronic skin condition, causing skin lesions with thickened and scaling skin, as well as erythema and inflammation that may involve painful sores, cracks, and pustules. Previously psoriasis was regarded as a painless skin condition. However, over the past decade studies show that skin pain is a frequently reported and bothersome symptom in patients with psoriasis. There is however a lack of rich narratives describing the experience of skin pain in these patients. The aims of this qualitative study were therefore to explore in depth how patients experience psoriasis-related skin pain, and how they deal with it. Methods Thirteen patients with psoriasis were recruited from a dermatology ward and outpatient clinic. One of the investigators (TML) performed individual, semi-structured interviews at an undisturbed room in the hospital. Interviews were thematically analyzed using the method of Systematic Text Condensation as described by Malterud (2012). Results Three main themes were identified from the interviews. First, the skin pain experience was complex. Patients used a variety of adjectives and metaphors to describe their pain, and their skin was sensitive to stimuli of every-day activities. Itch was a common cosymptom, and could both mask pain but also cause severe pain due to excessive scratching and damage to the skin. Second, skin pain had a negative impact on patients' life. Skin pain reduced their physical activity level, impaired their sleep, and made them irritable, depressed, unconcentrated on tasks, as well as withdrawn from other people and social activities. Third, patients dealt with their skin pain in various ways. Although some took action to relieve the pain and distract themselves from pain, most of the patients applied maladaptive and passive coping strategies such as put up with it, avoid painful activities, become fearful or trivialize their pain. Conclusions The experience of psoriasis related skin pain is complex. The pain has a major negative impact on patients' life in terms of physical, emotional, cognitive, and social functions. Patients use a variety of adaptive but most frequently maladaptive coping strategies in order to deal with their skin pain. Implications This study provides new and in-depth knowledge on psoriasis related skin pain. This information is valuable for further work on pain assessment tools and pain management recommendations customized for skin pain experienced by patients with psoriasis.

The effectiveness of psychological interventions for fatigue in cancer survivors: systematic review of randomised controlled trials.

BACKGROUND: Fatigue is a common symptom in cancer patients that can persist beyond the curative treatment phase. This systematic review evaluated the effectiveness of psychological interventions for cancer-related fatigue in post-treatment cancer survivors. METHODS: We searched relevant online databases and sources of grey literature. Randomised controlled trials (RCTs) evaluating psychological interventions in adult cancer patients after the completion of treatment, with fatigue as an outcome measure, were included. Two review authors extracted data independently from the selected studies and assessed the methodological quality using the Cochrane Collaboration Risk of Bias Tool. RESULTS: Thirty-three psychological interventions were identified. The sample size of the included studies varied between 28 and 409, with 4525 participants overall. Twenty-three of the included studies reported a significant effect of the interventions on reducing fatigue in cancer survivors. Most interventions focused on psychoeducation, mindfulness, cognitive or behaviour therapy-oriented strategies. However, studies differed widely in terms of measurement tools used to assess fatigue, mode, duration and frequency of the intervention delivery. CONCLUSIONS: This review showed some tentative support for psychological interventions for fatigue after cancer treatment. However, as the RCTs were heterogeneous in nature and the number of high-quality studies was limited, definitive conclusions are not yet possible. With the growing need for stage-specific research in cancer, this review sought to inform current practice and to summarise the existing evidence base of randomised controlled trials in the area. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42014015219.

Increased operational costs of electricity generation in the Delaware River and Estuary from salinity increases due to sea-level rise and a deepened channel.

Like many estuaries in the world, salinity levels in the Delaware River and Estuary are expected to increase due to a deepened navigational channel and sea-level rise. This study estimated operational cost increases resulting from increased ambient salinity likely to be incurred at PSEG-Hope Creek, an evaporatively cooled electricity generating station. To estimate cost increases, a linked physical-economic model was developed to generate daily forecasts of salinity and the resulting changes in facility's cooling water treatment and pumping requirements. Salinity increases under potential future bathymetric configurations were simulated using a hydrodynamic model. On an equivalent annual basis (discounted at 5%), average cost increases were $0.4M per year, or approximately 0.1% of estimated total annual operating costs for the facility. Methods developed here could be employed at other facilities anticipating future salinity increases. Results inform cost-benefit analyses for dredging projects and contribute to estimates of the indirect costs to society from carbon emissions through sea-level rise. Future research refinements can focus on modeling changes in suspended sediment concentrations and estimating their impacts on operational costs.

Impact of childhood and adulthood psychological health on labour force participation and exit in later life.

BACKGROUND: Adulthood psychological health predicts labour force activity but few studies have examined childhood psychological health. We hypothesized that childhood psychological ill-health would be associated with labour force exit at 55 years. METHOD: Data were from the 55-year follow-up of the National Child Development Study (n = 9137). Labour force participation and exit (unemployment, retirement, permanent sickness, homemaking/other) were self-reported at 55 years. Internalizing and externalizing problems in childhood (7, 11 and 16 years) and malaise in adulthood (23, 33, 42, 50 years) were assessed. Education, social class, periods of unemployment, partnership separations, number of children, and homemaking activity were measured throughout adulthood. RESULTS: Childhood internalizing and externalizing problems were associated with unemployment, permanent sickness and homemaking/other at 55 years, after adjustment for adulthood psychological health and education: one or two reports of internalizing was associated with increased risk for unemployment [relative risk (RR) 1.59, 95% confidence interval (CI) 1.12-2.25; RR 2.37, 95% CI 1.48-3.79] and permanent sickness (RR 1.32, 95% CI 1.00-1.74; RR, 1.48, 95% CI 1.00-2.17); three reports of externalizing was associated with increased risk for unemployment (RR 2.26, 95% CI 1.01-5.04), permanent sickness (RR 2.63, 95% CI 1.46-4.73) and homemaking/other (RR 1.95, 95% CI 1.00-3.78). CONCLUSIONS: Psychological ill-health across the lifecourse, including during childhood, reduces the likelihood of working in older age. Support for those with mental health problems at different life stages and for those with limited connections to the labour market, including homemakers, is an essential dimension of attempts to extend working lives.

Jagged1 expression by osteoblast-lineage cells regulates trabecular bone mass and periosteal expansion in mice.

Loss-of-function mutations in the Notch ligand, Jagged1 (Jag1), result in multi-system developmental pathologies associated with Alagille syndrome (ALGS). ALGS patients present with skeletal manifestations including hemi-vertebrae, reduced bone mass, increased fracture incidence and poor bone healing. However, it is not known whether the increased fracture risk is due to altered bone homeostasis (primary) or nutritional malabsorption due to chronic liver disease (secondary). To determine the significance of Jag1 loss in bone, we characterized the skeletal phenotype of two Jag1-floxed conditional knockout mouse models: Prx1-Cre;Jag1(f/f) to target osteoprogenitor cells and their progeny, and Col2.3-Cre;Jag1(f/f) to target mid-stage osteoblasts and their progeny. Knockout phenotypes were compared to wild-type (WT) controls using quantitative micro-computed tomography, gene expression profiling and mechanical testing. Expression of Jag1 and the Notch target genes Hes1 and Hey1 was downregulated in all Jag1 knockout mice. Osteoblast differentiation genes were downregulated in whole bone of both groups, but unchanged in Prx1-Cre;Jag1(f/f) cortical bone. Both knockout lines exhibited changes in femoral trabecular morphology including decreased bone volume fraction and increased trabecular spacing, with males presenting a more severe trabecular osteopenic phenotype. Prx1-Cre;Jag1(f/f) mice showed an increase in marrow mesenchymal progenitor cell number and, counterintuitively, developed increased cortical thickness resulting from periosteal expansion, translating to greater mechanical stiffness and strength. Similar alterations in femoral morphology were observed in mice with canonical Notch signaling disrupted using Prx1-Cre-regulatable dominant-negative mastermind like-protein (dnMAML). Taken together, we report that 1) Jag1 negatively regulates the marrow osteochondral progenitor pool, 2) Jag1 is required for normal trabecular bone formation and 3) Notch signaling through homotypic Jag1 signaling in osteochondral progenitors, but not mature osteoblasts, inhibits periosteal expansion. Therefore, Jag1 signaling within the osteoblast lineage regulates bone metabolism in a compartment-dependent manner. Moreover, loss of Jag1 function in osteoblast lineage cells may contribute to the skeletal phenotype associated with ALGS.

Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges.

Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative.

Patient experiences living with split thickness skin grafts.

The standard of care for deep burns is autologous split thickness skin grafting. Although adequate to resurface a deep wound, the resulting skin is chronically abnormal. The purpose of this study was to describe the experience of patients with split thickness skin grafts to help guide future investigations related to skin regeneration. In this study, an interpretive description qualitative methodology was employed. Subjects participated in a two-part single patient interview that was recorded and transcribed. A nurse with experience in clinical burn care coded and interpreted the data. Participants were recruited through presentation to a university based outpatient burn clinic for follow up from autologous split thickness skin grafting. Eight male patients and four female patients 20-62 years old ranging 2-29 months post-skin grafting were enrolled in the study. The most significant concerns voiced by patients were identified and organized into five themes: (1) a new normal, (2) split thickness skin graft symptoms, (3) appearance of new skin, (4) coping, and (5) participation in future clinical trials. Participants reported that the abnormalities related to their split thickness skin grafts were significant enough that they would be willing to participate in a future clinical trial investigating new cell-based therapies.

The poetics of therapeutic practice: motivational interviewing and the powers of pause.

Motivational interviewing (MI) is an increasingly prominent behavioral therapy that draws from and claims to synthesize two American therapeutic traditions long thought to be antithetical-"client-centered" and "directive" approaches. This paper proposes that MI achieves its hallmark "client-centered directiveness" through the aesthetic management of the therapeutic encounter, and more particularly, through MI practitioners' marked use of silence. Drawing on data collected during the ethnographic study of MI trainings and the formal analysis of video-recorded MI sessions that are commonly used as models in such trainings, we identify three patterns of pause that regularly fall at specific grammatical junctures within seasoned MI practitioners' turns-at-talk. We demonstrate how these pauses allow MI practitioners to subtly direct the conversation while simultaneously displaying unequivocal signs of client-centeredness. In other words, we show how and explain why the poetics of pause matter to MI. In presenting this case, we more generally highlight practice poetics-that is, the aesthetic management of the style and delivery of a professional message with a particular practical aim in mind-suggesting that this is a central if under-appreciated aspect of therapeutic practices.

Fatal cutaneous anthrax in a heroin user.

BACKGROUND AND OBJECTIVE: Cutaneous anthrax usually has a mortality rate of less than 1 per cent. However, since December 2009 there have been more than 13 deaths in the UK due to anthrax-contaminated heroin. We therefore wish to raise clinical awareness of this treatable disease. CASE REPORT: We describe the case of a heroin user with an equivocal presentation of cellulitis in the neck. Within 36 hours, this led to death due to cutaneous anthrax. CONCLUSION: Whilst cutaneous anthrax remains rare, this case report aims to raise awareness of the fact that the symptoms and signs of this condition in intravenous drug users may not always fit the typical picture.