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Introduction: Optimizing naloxone dosing in the context of increasing fentanyl and ultra-potent opioid (UPO) prevalence is an important consideration for emergency health care providers. The goal of this systematic review was to evaluate the association between initial and cumulative naloxone doses on effective reversal and adverse events in undifferentiated and fentanyl/UPO overdoses. Methods: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings from July to October 2018 and back to 1972. Our search included pertinent indexing terms for UPOs. We included interventional and observational studies reporting on naloxone administration for opioid toxicity reversal in people ≥12 years old. Additionally, we accessed non-traditional evidence sources (case reports and series) given this rapidly changing field. We conducted inclusion screens, data extraction and quality assessments in duplicate. We summarized study characteristics and where reported, analyzed number of patients with clinical response. Response was defined as not receiving further naloxone doses and remaining alive. Results: We included 174 studies (108 case reports and series, 55 observational, 9 interventional) with 26,660 subjects (median age 35.1; 74.2% male). We observed lower response among patients exposed to fentanyl/UPO versus heroin for initial naloxone doses ≤0.4mg (56.8% versus 80.2%) and > 0.4mg (27.0% versus 82.1%). Mean cumulative doses were higher for fentanyl/UPO (2.10 mg, SD 1.80 mg) versus heroin (1.48 mg, SD 1.68 mg) overdoses. In North American studies the median cumulative dose used was higher for fentanyl/UPO versus heroin overdoses. A dose-response curve for fentanyl/UPO studies showed marked variability in doses among responders, indicating heterogeneity. Adverse events reporting was inconsistent; 10% of subjects experienced withdrawal based on studies in which they were reported. Conclusion: This is the first systematic review to summarize proportion of patients with clinical response by naloxone dose provided. While variable reporting, study quality, heterogeneity, and our outcome definitions limit the conclusions we can draw, it appears that higher initial doses and in some cases, higher cumulative naloxone doses were used and may be necessary to reverse toxicity due to fentanyl/UPO compared to other opioids. High-quality prospective studies assessing effectiveness and safety are needed.
Introduction: Increasing opioid prescribing has been linked to an epidemic of opioid misuse. Our objective was to synthesize available evidence about patient-, prescriber-, medication-, and system-level risk factors for developing opioid misuse from prescribed opioids among patients presenting with pain unrelated to cancer. Our hypothesis was that we would identify risk factors predisposing patients to developing opioid misuse. Methods: We developed a systematic search strategy and applied it to nine electronic reference databases and six clinical trial registries. We hand searched related journals and conference proceedings, the reference lists of included studies, and the top 100 hits on Google. We included studies where a medical professional exposed adults or children to an opioid through a prescription. We excluded studies with over 50% cancer patients, palliative patients, and those with illicit opioid initiation. Two reviewers independently reviewed titles, abstracts, and full texts, and extracted data using standardized forms. We assessed study quality using risk of bias. We synthesized effect sizes of dichotomous risk factors on opioid misuse using inverse variance random-effects meta-analysis, and the inverse variance-weighted mean difference between opioid misusers and non-misusers for continuously measured factors. We conducted an a priori defined subgroup analysis among opioid-naïve patients. Results: Among 9,629 studies, 67 met our inclusion criteria. Among those who had been prescribed outpatient opioids, the following factors were associated with the development of misuse: a prior history of illicit drug use (OR: 4.21, 95% CI: 2.31-7.65), recent benzodiazepine use (OR: 2.57, 95% CI: 1.23-5.38), any mental health diagnosis (OR: 2.45, 95% CI: 1.91-3.15), any short acting (IR) opioid prescription (OR: 2.40, 95% CI: 1.15-5.02), younger age (OR: 2.19, 95%CI: 1.81-2.64), and male sex (OR: 1.23, 95% CI: 1.10-1.36). Among studies limiting their population to opioid-naïve patients, younger age was the most significant risk factor for opioid misuse (OR: 5.42, 95% CI:1.51-19.43). Conclusion: Of the risk factors examined, non-cancer pain patients with a prior history of substance use or mental health diagnoses were at highest risk for prescription opioid misuse. Younger opioid-naïve patients were at highest risk of misuse. Clinicians should consider these risk factors when managing acute pain in the emergency department.
Despite the magnitude and protracted nature of the Rohingya refugee situation, there is limited information on the culture, mental health and psychosocial wellbeing of this group. This paper, drawing on a report commissioned by the United Nations High Commissioner for Refugees (UNHCR), aims to provide a comprehensive synthesis of the literature on mental health and psychosocial wellbeing of Rohingya refugees, including an examination of associated cultural factors. The ultimate objective is to assist humanitarian actors and agencies in providing culturally relevant Mental Health and Psychosocial Support (MHPSS) for Rohingya refugees displaced to Bangladesh and other neighbouring countries.
We conducted a systematic search across multiple sources of information with reference to the contextual, social, economic, cultural, mental health and health-related factors amongst Rohingya refugees living in the Asia-Pacific and other regions. The search covered online databases of diverse disciplines (e.g. medicine, psychology, anthropology), grey literature, as well as unpublished reports from non-profit organisations and United Nations agencies published until 2018.
The legacy of prolonged exposure to conflict and persecution compounded by protracted conditions of deprivations and displacement is likely to increase the refugees' vulnerability to wide array of mental health problems including posttraumatic stress disorder, anxiety, depression and suicidal ideation. High rates of sexual and gender-based violence, lack of privacy and safe spaces and limited access to integrated psychosocial and mental health support remain issues of concern within the emergency operation in Bangladesh. Another challenge is the limited understanding amongst the MHPSS personnel in Bangladesh and elsewhere of the language, culture and help-seeking behaviour of Rohingya refugees. While the Rohingya language has a considerable vocabulary for emotional and behavioural problems, there is limited correspondence between these Rohingya terms and western concepts of mental disorders. This hampers the provision of culturally sensitive and contextually relevant MHPSS services to these refugees.
The knowledge about the culture, context, migration history, idioms of distress, help-seeking behaviour and traditional healing methods, obtained from diverse sources can be applied in the design and delivery of culturally appropriate interventions. Attention to past exposure to traumatic events and losses need to be paired with attention for ongoing stressors and issues related to worries about the future. It is important to design MHPSS interventions in ways that mobilise the individual and collective strengths of Rohingya refugees and build on their resilience.
Tissue engineering aims to grow artificial tissues in vitro to replace those in the body that have been damaged through age, trauma or disease. A recent approach to engineer artificial cartilage involves seeding cells within a scaffold consisting of an interconnected 3D-printed lattice of polymer fibres combined with a cast or printed hydrogel, and subjecting the construct (cell-seeded scaffold) to an applied load in a bioreactor. A key question is to understand how the applied load is distributed throughout the construct. To address this, we employ homogenisation theory to derive equations governing the effective macroscale material properties of a periodic, elastic–poroelastic composite. We treat the fibres as a linear elastic material and the hydrogel as a poroelastic material, and exploit the disparate length scales (small inter-fibre spacing compared with construct dimensions) to derive macroscale equations governing the response of the composite to an applied load. This homogenised description reflects the orthotropic nature of the composite. To validate the model, solutions from finite element simulations of the macroscale, homogenised equations are compared to experimental data describing the unconfined compression of the fibre-reinforced hydrogels. The model is used to derive the bulk mechanical properties of a cylindrical construct of the composite material for a range of fibre spacings and to determine the local mechanical environment experienced by cells embedded within the construct.
Vancomycin is a commonly prescribed empiric antibiotic used when methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected. In this study, we aimed to determine the rate of culture-positive infection requiring vancomycin therapy.
Improvements in feed efficiency of beef cattle have the potential to increase producer profitability and simultaneously lower the environmental footprint of beef production. Although there are many different approaches to measuring feed efficiency, residual feed intake (RFI) has increasingly become the measure of choice. Defined as the difference between an animal’s actual and predicted feed intake (based on weight and growth), RFI is conceptually independent of growth and body size. In addition, other measurable traits related to energy expenditure such as estimates of body composition can be included in the calculation of RFI to also force independence from these traits. Feed efficiency is a multifactorial and complex trait in beef cattle and inter-animal variation stems from the interaction of many biological processes influenced, in turn, by physiological status and management regimen. Thus, the purpose of this review was to summarise and interpret current published knowledge and provide insight into research areas worthy of further investigation. Indeed, where sufficient suitable reports exist, meta-analyses were conducted in order to mitigate ambiguity between studies in particular. We have identified a paucity of information on the contribution of key biological processes, including appetite regulation, post-ruminal nutrient absorption, and cellular energetics and metabolism to the efficiency of feed utilisation in cattle. In addition, insufficient information exists on the relationship between RFI status and productivity-related traits at pasture, a concept critical to the overall lifecycle of beef production systems. Overall, published data on the effect of RFI status on both terminal and maternal traits, coupled with the moderate repeatability and heritability of the trait, suggest that breeding for improved RFI, as part of a multi-trait selection index, is both possible and cumulative, with benefits evident throughout the production cycle. Although the advent of genomic selection, with associated improved prediction accuracy, will expedite the introgression of elite genetics for feed efficiency within beef cattle populations, there are challenges associated with this approach which may, in the long-term, be overcome by increased international collaborative effort but, in the short term, will not obviate the on-going requirement for accurate measurement of the primary phenotype.
Crib–biting is a stereotypic behaviour performed by approximately 5% of captive domestic horses. Dietary factors have been strongly associated with the development of oral stereotypies and risk factors for crib–biting, identified in recent epidemiological studies, include feeding high concentrate and/or low forage diets (Waters et al., 2002). Experimental work has shown that such diets are likely to result in increased gastric acidity (Murray and Eichorn, 1996; Nadeau et al., 2000). We therefore propose that young horses initiate crib–biting in an attempt to produce alkaline saliva to buffer their stomachs when alternative opportunities for mastication are limited. The aim of this study was to determine whether there was an association between crib–biting behaviour and stomach condition in foals.
Foals that had recently started to perform crib–biting were recruited into the study and compared with non–stereotypic foals. The stomachs of 15 crib-biting foals and 9 normal foals were examined using a video endoscope.
An ambition of depression biomarker research is to augment psychometric and cognitive assessment of clinically relevant phenomena with neural measures. Although such applications have been slow to arrive, we observe a steady evolution of the idea and anticipate emerging technologies with some optimism. To highlight critical themes and innovations in depression biomarker research, we take as our point of reference a specific research narrative. We begin with an early model of frontal-limbic dysfunction, which represents a conceptual shift from localized pathology to understanding symptoms as an emergent property of distributed networks. Over the decades, this model accommodates perspectives from neurology, psychiatry, clinical, and cognitive neuroscience, and preserves past insight as more complex methods become available. We also track the expanding mission of brain biomarker research: from the development of diagnostic tools to treatment selection algorithms, measures of neurocognitive functioning and novel targets for neuromodulation. To conclude, we draw from this particular research narrative future directions for biomarker research. We emphasize integration of measurement modalities to describe dynamic change in domain-general networks, and we speculate that a brain-based framework for psychiatric problems may dissolve classical diagnostic and disciplinary boundaries. (JINS, 2017, 23, 870–880)
Auditory hallucinations (AH) are often considered a sign of a psychotic disorder. This is promoted by the DSM-5 category of Other Specified Schizophrenia Spectrum And Other Psychotic Disorder (OSSSOPD), the diagnostic criteria for which are fulfilled with the sole presence of persistent AH, in the absence of any other psychotic symptoms. And yet, persistent AH are not synonymous with having a psychotic disorder, and should therefore not be uncritically treated as such. Many people who seek treatment for persistent AH have no other psychotic symptoms, have preserved reality-testing capacities, and will never develop a schizophrenia spectrum disorder. Instead, hallucinations may be the result of many different causes, including borderline personality disorder, post-traumatic stress disorder (PTSD), hearing loss, sleep disorders or brain lesions, and they may even occur outside the context of any demonstrable pathology. In such cases, the usage of the DSM-5 diagnosis of OSSSOPD would be incorrect, and it may prompt unwarranted treatment with antipsychotic medication. We therefore argue that a DSM-5 diagnosis of Schizophrenia Spectrum Disorder (or any other type of psychotic disorder) characterized by AH should require at least one more symptom listed under the A-criterion (i.e. delusions, disorganized speech, disorganized or catatonic behavior or negative symptoms). Adhering to these more stringent criteria may help to distinguish between individuals with persistent AH which are part of a psychotic disorder, for whom antipsychotic medication may be helpful, and individuals with AH in the absence of such a disorder who may benefit from other approaches (e.g. different pharmacological interventions, improving coping style, trauma-related therapy).
We present coordinated spectroscopic and photometric observations obtained during the present bright phase of the luminous variable star S Dor in the LMC. High resolution spectrograms in the satellite UV and in the visual range were obtained with IUE and with CASPEC (attached to the ESO 3.6-m telescope), respectively. Moreover, photometric UBVRIJHKL observations were carried out.
Lower and middle income countries (LMICs) are home to >80% of the global population, but mental health researchers and LMIC investigator led publications are concentrated in 10% of LMICs. Increasing research and research outputs, such as in the form of peer reviewed publications, require increased capacity building (CB) opportunities in LMICs. The National Institute of Mental Health (NIMH) initiative, Collaborative Hubs for International Research on Mental Health reaches across five regional ‘hubs’ established in LMICs, to provide training and support for emerging researchers through hub-specific CB activities. This paper describes the range of CB activities, the process of monitoring, and the early outcomes of CB activities conducted by the five research hubs.
The indicators used to describe the nature, the monitoring, and the early outcomes of CB activities were developed collectively by the members of an inter-hub CB workgroup representing all five hubs. These indicators included but were not limited to courses, publications, and grants.
Results for all indicators demonstrate a wide range of feasible CB activities. The five hubs were successful in providing at least one and the majority several courses; 13 CB recipient-led articles were accepted for publication; and nine grant applications were successful.
The hubs were successful in providing CB recipients with a wide range of CB activities. The challenge remains to ensure ongoing CB of mental health researchers in LMICs, and in particular, to sustain the CB efforts of the five hubs after the termination of NIMH funding.
We show that there exists a simple geometric picture for the geometries of protoplanetary disks around Herbig Ae/Be stars that explains the two main kinds of spectral energy distributions found for these objects, and that makes predictions that are qualitatively in agreement with currently available spatially resolved images and/or interferometric measurements. Also it qualitatively explains the phenomenon of UX Orionis variability.
The provision of prescribed vitamin D to all aged-care residents has been implemented in New Zealand as part of a government-led falls prevention programme. To our knowledge, there has been no evaluation of this universal programme on vitamin D status and functional and health outcomes. Thus, we aimed to determine 25-hydroxyvitamin D (25(OH)D) concentrations and their predictors in aged-care residents across the country and to investigate whether the government-funded programme was associated with adequate vitamin D status.
Cross-sectional survey of sociodemographic, biochemical, anthropometric, dietary and health characteristics. Blood samples were analysed for serum 25(OH)D and other biochemical measures. Multiple regression was used to examine predictors of vitamin D status.
Sixteen residential aged-care facilities throughout New Zealand.
Residents aged ≥60 years with residency duration >12 weeks (n 309).
Mean serum 25(OH)D was 89·9 (95 % CI 85·2, 94·5) nmol/l and monthly supplements (1250 µg (50 000 IU)) were taken by 75 % of all residents. Of those not taking a funded supplement, 65·3 % had serum 25(OH)D <50 nmol/l compared with only 1·5 % of supplement users. Being female, residing at lower latitude, increasing duration of aged-care residency and raised serum α1-acid glycoprotein were positively associated with higher 25(OH)D concentrations. Supplemental vitamin D from all sources was the strongest predictor, increasing serum 25(OH)D levels by more than 70 nmol/l. Furthermore, 25 % of participants had serum 25(OH)D levels >125 nmol/l.
Residents taking supplemental vitamin D had adequate vitamin D status; however monitoring of long-term supplementation should be considered, due to the high proportion of participants with high serum 25(OH)D levels.
The late stages of stellar evolution of stars with low or intermediate mass (1 M⊙ to 8 M⊙) are characterized by extensive mass loss, which can be traced in their circumstellar environment. Here we consider the case of IRAS 16342-3814, a bipolar proto planetary nebula which shows very high velocity (~ 50 km s-1) OH maser emission (Sahai et al. 1999). We present the complete Infrared Space Observatory (ISO) spectrum and an infrared TIMMI2 Q-band image of this source. Based on these data we discuss the composition and geometry of the circumstellar dust in IRAS 16342-3814.
We report the discovery of carbonates in the Planetary Nebulae NGC 6302 and NGC 6537 (Kemper et al. 2002). In the ISO LWS spectra far-infrared features have been identified with calcite and dolomite by comparison with laboratory spectra of these minerals. This is the first time that carbonates have been identified outside the solar system. In a follow-up study (Kemper et al., in prep.) a detailed analysis of the mineral composition of the dust in NGC 6302 is presented.
We present Infrared Space Observatory (ISO) spectra of 14 isolated Herbig Ae/Be stars. The IR spectra were combined with photometric data from the UV to the sub-mm region. We defined two key groups, based upon the spectral shape of the IR region. The results can be summarized as follows (see also Meeus et al. 2001): (1) the continuum of the IR to sub-mm region can be reconstructed by the sum of a power-law and a cool component, which can be represented by a black body. Possible locations for these components are an optically thick, geometrically thin disc (power-law component) and an optically thin flared region (black body); (2) remarkably, some sources lack the silicate bands; (3) PAH bands are present in at least 50% of our sample; with one exception, PAHs are not present in sources which only show a power-law continuum in the IR; (4) the dust in HAEBE stars shows strong evidence for coagulation; this dust processing is unrelated to any of the central star properties.
ISO has opened new infrared windows for spectroscopy, enabling detailed studies of the composition of the dust particles present in circumstellar disks. For oxygen-rich dust, and in particular for silicates, a forest of new features has been discovered, and comparison with laboratory data has enabled the identification of most of them. Of special relevance is the detection of crystalline silicates, which present themselves as a new diagnostic for studying the formation of comets and planetesimals in the disks surrounding young and, surprisingly, also evolved stars.
We investigate the structure of extended dust shells around optical carbon stars in the far-infrared and in optical light. In the optical we have discovered that R Scl and U Ant are associated with circularly extended emission, the radii of which are about 20″ and 58″, respectively. The emission is probably scattered light of the central star by dust grains in their circumstellar shells. In the far-infrared we have discovered a double shell structure surrounding U Ant in high resolution IRAS images, which is direct evidence of a periodic change of mass-loss on a time-scale of the order of 104 years in the AGB evolution. Relating the two shells to two consecutive thermal pulses allows for a self-consistent determination of the interpulse period, core-mass, luminosity, and distance. Direct mapping of Y CVn at 90 and 160 μm with ISOPHOT on board ISO has revealed a very extended detached dust shell around this star. The mass-loss rate is found to have decreased drastically by two orders of magnitude 1.4×104 years ago, which should be an important clue to the understanding of J-type stars.
Low and intermediate mass stars leave the Asymptotic Giant Branch (AGB) when the mass in their H-rich envelope is less than about 0.01 M⊙, and the high mass loss drops several orders of magnitude. The central star rapidly evolves to the left part of the HR diagram along a track of constant luminosity (e.g. Schönberner 1983). In principle the evolution of the central star to higher Teff and the expansion and cooling of the AGB remnant are easy to calculate. In practice several complicating factors arise which make it much more difficult to predict the morphology and properties of post-AGB stars, such as binarity, post-AGB mass loss and aspherical AGB mass loss. Binarity of post-AGB stars affects the morphology of the circumstellar environment, and it affects evolutionary timescales and surface chemical abundances of the components in the system. This review discusses some properties of binary post-AGB stars.