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Objectives: This study explored the potential of non‐parametric and complexity analysis metrics to detect changes in activity post‐ketamine and their association with depressive symptomatology. Methods: Individuals with treatment‐resistant depression (TRD: n = 27, 16F, 35.9 ± 10.8 years) and healthy volunteers (HVs: n = 9, 4F, 36.4 ± 9.59 years) had their activity monitored during an inpatient, double‐blind, crossover study where they received an infusion of ketamine or saline placebo. All participants were 18–65 years old, medication‐free, and had a MADRS score ≥20. Non‐parametric metrics averaged over each study day, metrics derived from complexity analysis, and traditionally calculated non‐parametric metrics averaged over two weeks were calculated from the actigraphy time series. A separate analysis was conducted for a subsample (n = 17) to assess the utility of these metrics in a hospital setting. Results: In HVs, lower intradaily variability was observed within daily rest/activity patterns post‐ketamine versus post‐placebo (F = 5.16(1,15), p = 0.04). No other significant effects of drug or drug‐by‐time or correlations between depressive symptomatology and activity were detected. Conclusions: Weak associations between non‐parametric variables and ketamine were found but were not consistent across actigraphy measures. Clinical Trial registration: ClinicalTrials.gov, NCT00088699. [ABSTRACT FROM AUTHOR]

Background and Aims: Lysosomal acid lipase deficiency (LAL‐D) is a rare, autosomal recessive disease involving lysosomal accumulation of cholesteryl esters and triglycerides. The International Lysosomal Acid Lipase Deficiency Registry (NCT01633489), established in 2013 to understand LAL‐D natural history and long‐term outcomes, is accessible to centres caring for patients diagnosed by deficient LAL activity and/or biallelic pathogenic LIPA variants. We describe the registry population enrolled through 2 May 2022. Methods: In this prospective observational study, we analysed demographic and baseline clinical characteristics of children (ages ≥6 months to <18 years) and adults diagnosed with LAL‐D. Results: Of 228 patients with confirmed disease, 61% were children; 202/220 (92%) with data on race were white. Median age was 5.5 years at sign/symptom onset and 10.5 years at diagnosis; median time from sign/symptom onset to diagnostic testing was 3.3 years. The most common manifestations raising suspicion of disease were elevated alanine (70%) and aspartate aminotransferase levels (67%) and hepatomegaly (63%). Among 157 with reported LIPA mutations, 70 were homozygous and 45 were compound heterozygous for the common exon 8 splice junction pathogenic variant (E8SJM‐1). Seventy percent (159/228) of patients had dyslipidaemia. Among 118 with liver biopsies, 63% had microvesicular steatosis exclusively, 23% had mixed micro‐ and macrovesicular steatosis and 47% had lobular inflammation. Of 78 patients with fibrosis‐stage data, 37% had bridging fibrosis and 14% had cirrhosis. Conclusions: Although LAL‐D signs/symptoms occur early, diagnosis is often delayed. Abnormal transaminase levels associated with hepatomegaly and dyslipidaemia should raise suspicion and prompt earlier diagnosis of LAL‐D. Trial registration number: NCT01633489. [ABSTRACT FROM AUTHOR]

Objectives: Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID‐19, COVID‐19 vaccinations, and vaccine hesitancy and change in these variables over a 9‐month period in a UK cohort. Methods: The COPE study cohort (n = 11,113) was recruited via an online survey at enrolment in March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow‐up data were available for 6942 people at 3 months (June/July 2020) and 5037 at 12 months (March/April 2021) post‐enrolment. Measures included demographics, perceived threat of COVID‐19, perceived control, intention to accept or decline a COVID‐19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross‐sectionally at 3 and 12 months to assess the association between motivational factors and vaccine hesitancy. Longitudinal changes in motivational variables for vaccine‐hesitant and non‐hesitant groups were examined using mixed‐effect analysis of variance models. Results: Fear of COVID‐19, perceived susceptibility to COVID‐19, and perceived personal control over COVID‐19 infection transmission decreased between the 3‐ and 12‐month surveys. Vaccine hesitancy at 12 months was independently associated with low fear of the disease and more negative attitudes towards COVID‐19 vaccination. Specific barriers to COVID‐19 vaccine uptake included concerns about safety and efficacy in light of its rapid development, mistrust of government and pharmaceutical companies, dislike of coercive policies, and perceived lack of relaxation in COVID‐19‐related restrictions as the vaccination programme progressed. Conclusions: Decreasing fear of COVID‐19, perceived susceptibility to the disease, and perceptions of personal control over reducing infection‐transmission may impact future COVID‐19 vaccination uptake. [ABSTRACT FROM AUTHOR]

Purpose: The World Health Organization is developing a Package of Eye Care Interventions (PECI) to support the integration of eye health care into national health programmes. Interventions included in the PECI should be based on robust evidence where available. Refractive error is a leading cause of blindness and vision impairment and is a PECI priority condition. The aim of this study was to provide high‐quality evidence to support the development of the PECI by identifying and critically appraising clinical practice guidelines (CPGs), and extracting recommendations for refractive error interventions. Methods: We searched for CPGs on refractive error published in the last 10 years. We conducted the searches initially in February and March 2019 and repeated them in March 2020. We evaluated the quality of potentially relevant guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. Results: We identified 12 high‐quality CPGs relevant to refractive error, written by six organisations from three high‐income countries. Organisations used a variety of frameworks to assess the strength of recommendations based on available evidence, with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) being most common. Vision screening for children aged 3 to 5 years was recommended consistently. Evidence for screening and eye evaluations at other ages was weaker, although ophthalmic professional organisations consistently recommended regular evaluations. Recommendations on optical and laser correction of refractive error were limited and did not consider implications for low resource settings. Interventions for slowing myopia progression in children were recommended, but these will need regular updating as new evidence emerges. Conclusions: Current high‐quality guidelines on refractive error have been formulated in high‐income countries. Recommendations focused on prevention and treatment of refractive error in low‐and middle‐income countries are lacking. Regular updating of systematic reviews and CPGs is essential to ensure that robust evidence is promptly appraised and incorporated into recommendations for eye health care practitioners. [ABSTRACT FROM AUTHOR]

By clinical whole exome sequencing, we identified 12 individuals with ages 3 to 37 years, including three individuals from the same family, with a consistent phenotype of intellectual disability (ID), macrocephaly, and overgrowth of adenoid tissue. All 12 individuals harbored a rare heterozygous variant in ZBTB7A which encodes the transcription factor Zinc finger and BTB‐domain containing protein 7A, known to play a role in lympho‐ and hematopoiesis. ID was generally mild. Fetal hemoglobin (HbF) fraction was elevated 2.2%–11.2% (reference value <2% in individuals > 6 months) in four of the five individuals for whom results were available. Ten of twelve individuals had undergone surgery at least once for lymphoid hypertrophy limited to the pharynx. In the most severely affected individual (individual 1), airway obstruction resulted in 17 surgical procedures before the age of 13 years. Sleep apnea was present in 8 of 10 individuals. In the nine unrelated individuals, ZBTB7A variants were novel and de novo. The six frameshift/nonsense and four missense variants were spread throughout the gene. This is the first report of a cohort of individuals with this novel syndromic neurodevelopmental disorder. [ABSTRACT FROM AUTHOR]

Interactions among selection, gene flow, and drift affect the trajectory of adaptive evolution. In natural populations, the direction and magnitude of these processes can be variable across different spatial, temporal, or ontogenetic scales. Consequently, variability in evolutionary processes affects the predictability or stochasticity of microevolutionary outcomes. We studied an intertidal fish, Bathygobius cocosensis (Bleeker, 1854), to understand how space, time, and life stage structure genetic and phenotypic variation in a species with potentially extensive dispersal and a complex life cycle (larval dispersal preceding benthic recruitment). We sampled juvenile and adult life stages, at three sites, over three years. Genome‐wide SNPs uncovered a pattern of chaotic genetic patchiness, that is, weak‐but‐significant patchy spatial genetic structure that was variable through time and between life stages. Outlier locus analyses suggested that targets of spatially divergent selection were mostly temporally variable, though a significant number of spatial outlier loci were shared between life stages. Head shape, a putatively ecologically responsive (adaptive) phenotype in B. cocosensis also exhibited high temporal variability within sites. However, consistent spatial relationships between sites indicated that environmental similarities among sites may generate predictable phenotype distributions across space. Our study highlights the complex microevolutionary dynamics of marine systems, where consideration of multiple ecological dimensions can reveal both predictable and stochastic patterns in the distributions of genetic and phenotypic variation. Such considerations probably apply to species that possess short, complex life cycles, have large dispersal potential and fecundities, and that inhabit heterogeneous environments. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance is an under‐recognised metabolic defect and cardiovascular risk factor in Type 1 diabetes. Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes. We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double‐blind randomised, placebo‐controlled trial to measure the effect of metformin on tissue‐specific insulin resistance in adults with Type 1 diabetes. Methods: We will study 40 adults aged 20–55 years with Type 1 diabetes (HbA1c ≤80 mmol/mol [9.5%], fasting C‐peptide <0.3 nmol/L) and 20 age‐, gender‐ and body mass index (BMI)‐matched controls. Insulin sensitivity will be determined by the two‐step hyperinsulinaemic‐euglycaemic clamp method with deuterated glucose to document liver, muscle and adipose insulin sensitivity. Subjects with Type 1 diabetes will be randomised to metformin extended‐release 1500 mg daily or matched placebo for 26 weeks. The primary outcome is change in hepatic insulin sensitivity, assessed by change in basal rate of appearance (Ra) of glucose and suppression of endogenous glucose production (EGP) during the low‐dose stage of the clamp. Conclusion: The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes. This study may identify factors that predict an individual's response to metformin in Type 1 diabetes. Trial Registration: ACTRN12619001440112. [ABSTRACT FROM AUTHOR]

Daily rhythms are generated by the circadian timekeeping system, which is orchestrated by the master circadian clock in the suprachiasmatic nucleus (SCN) of mammals. Circadian timekeeping is endogenous and does not require exposure to external cues during development. Nevertheless, the circadian system is not fully formed at birth in many mammalian species and it is important to understand how SCN development can affect the function of the circadian system in adulthood. The purpose of the current review is to discuss the ontogeny of cellular and circuit function in the SCN, with a focus on work performed in model rodent species (i.e., mouse, rat, and hamster). Particular emphasis is placed on the spatial and temporal patterns of SCN development that may contribute to the function of the master clock during adulthood. Additional work aimed at decoding the mechanisms that guide circadian development is expected to provide a solid foundation upon which to better understand the sources and factors contributing to aberrant maturation of clock function. [ABSTRACT FROM AUTHOR]

Aims: To examine the cost‐effectiveness of hepatitis C virus (HCV) treatment of people who inject drugs (PWID), combined with medication‐assisted treatment (MAT) and syringe‐service programs (SSP), to tackle the increasing HCV epidemic in the United States. Design HCV transmission and disease progression models with cost‐effectiveness analysis using a health‐care perspective. Setting: Rural Perry County, KY (PC) and urban San Francisco, CA (SF), USA. Compared with PC, SF has a greater proportion of PWID with access to MAT or SSP. HCV treatment of PWID is negligible in both settings. Participants: PWID data were collected between 1998 and 2015 from Social Networks Among Appalachian People, U Find Out, Urban Health Study and National HIV Behavioral Surveillance System studies. Interventions and comparator: Three intervention scenarios modeled: baseline—existing SSP and MAT coverage with HCV screening and treatment with direct‐acting antiviral for ex‐injectors only as per standard of care; intervention 1—scale‐up of SSP and MAT without changes to treatment; and intervention 2—scale‐up as intervention 1 combined with HCV screening and treatment for current PWID. Measurements Incremental cost‐effectiveness ratios (ICERs) and uncertainty using cost‐effectiveness acceptability curves. Benefits were measured in quality‐adjusted life‐years (QALYs). Findings For both settings, intervention 2 is preferred to intervention 1 and the appropriate comparator for intervention 2 is the baseline scenario. Relative to baseline, for PC intervention 2 averts 1852 more HCV infections, increases QALYS by 3095, costs $21.6 million more and has an ICER of $6975/QALY. For SF, intervention 2 averts 36 473 more HCV infections, increases QALYs by 7893, costs $872 million more and has an ICER of $11 044/QALY. The cost‐effectiveness of intervention 2 was robust to several sensitivity analysis. Conclusions: Hepatitis C screening and treatment for people who inject drugs, combined with medication‐assisted treatment and syringe‐service programs, is a cost‐effective strategy for reducing hepatitis C burden in the United States. [ABSTRACT FROM AUTHOR]

Objective: A critical need exists to identify objective markers of suicide ideation. One potential suicide risk marker is the Suicide Implicit Association Task (S-IAT), a behavioral task that uses differential reaction times to compare the implicit association between the self and death to the implicit association between the self and life. Individuals with a stronger association between the self and death on the S-IAT are more likely to attempt suicide in the future. To better understand the neural underpinnings of the implicit association between self and either life or death, a functional magnetic resonance imaging (fMRI) version of the S-IAT was adapted and piloted in healthy volunteers.Method: An fMRI version of the S-IAT was administered to 28 healthy volunteers (ages 18-65, 14F/14M).Results: Behavioral results were comparable to those seen in non-scanner versions of the task. The task was associated with patterns of neural activation in areas relevant to emotional processing, specifically the insula and right ventrolateral prefrontal cortex.Conclusions: Performance on the S-IAT fMRI task may reflect scores obtained outside of the scanner. In future evaluations, this task could help assess whether individuals at increased risk of suicide display a different pattern of neural activation in response to self/death and self/life stimuli. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is highly prevalent and associated with considerable morbidity, yet its pathophysiology remains only partially understood. While numerous studies have investigated the neurobiological correlates of MDD, most have used only a single neuroimaging modality. In particular, diffusion tensor imaging (DTI) studies have failed to yield uniform results. In this context, examining key tracts and using information from multiple neuroimaging modalities may better characterize potential abnormalities in the MDD brain. This study analyzed data from 30 participants with MDD and 26 healthy participants who underwent DTI, magnetic resonance spectroscopy (MRS), resting‐state functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). Tracts connecting the subgenual anterior cingulate cortex (sgACC) and the left and right amygdala, as well as connections to the left and right hippocampus and thalamus, were examined as target areas. Reduced fractional anisotropy (FA) was observed in the studied tracts. Significant differences in the correlation between medial prefrontal glutamate concentrations and FA were also observed between MDD and healthy participants along tracts connecting the sgACC and right amygdala; healthy participants exhibited a strong correlation but MDD participants showed no such relationship. In the same tract, a correlation was observed between FA and subsequent antidepressant response to ketamine infusion in MDD participants. Exploratory models also suggested group differences in the relationship between DTI, fMRI, and MEG measures. This study is the first to combine MRS, DTI, fMRI, and MEG data to obtain multimodal indices of MDD and antidepressant response and may lay the foundation for similar future analyses. [ABSTRACT FROM AUTHOR]

Early modern medical literature is littered with complaints about the behaviour of male sexual health patients. Practitioners were particularly aggrieved that reckless consumption of food and alcohol and engaging in sexual activity undermined their efforts to cure the body. These complaints reveal that the relationship between medical practitioners and their male patients was sometimes difficult and characterized by the tense negotiation of authority. In addition to the neglect of prescribed regimens, space was used by patients in their attempts to exert authority and control over the patient/practitioner interaction. This article examines the ways in which patients and healers called upon and manipulated space in order to control the medical encounter. The article contributes to the historiography that explores the contexts in which manhood and masculinity were negotiated. While historians have focused on the relationship between male medical practitioners and female patients considering male experiences of medical treatment is equally as important. The article argues that space is just one element of the medical interaction that deserves further investigation and scrutiny. [ABSTRACT FROM AUTHOR]

Importance To investigate the safety, effectiveness and follow‐up rates after transscleral diode laser cyclophotocoagulation as primary treatment for seeing eyes with primary open angle glaucoma in Bauchi, Nigeria. Background: There is a high prevalence of primary open angle glaucoma in Africa where adherence to medical treatment and acceptance of surgery are poor. Design Prospective case series. Participants: New glaucoma patients where surgical intervention was recommended. Methods: A diode 810 nm laser G‐probe was used under retrobulbar anaesthesia to deliver approximately 20 shots for 2000 ms, titrating the power. If both eyes were treated the first was the study eye. Repeat treatment offered if the intraocular pressure (IOP) was >21 mmHg on two consecutive visits. Main Outcome Measures: IOP < 22 mmHg, change in ≥2 lines of Snellen visual acuity (VA), and complications. Results: 201 out of 204 eyes with complete data analysed. Mean age 52 years, 17 (8.3%) eyes were re‐treated. Mean pre‐treatment IOP was 39 (SD 11) mmHg. 106 (53%) attended at 12 months when the mean IOP was 19 (7–45) mmHg; 77 (73%) had IOP < 22 mmHg. VAs were better in 13 (12.3%) and worse in 23 (21.7%) eyes. Postoperative complications included mild uveitis (5.5%), corneal oedema (2.5%), severe uveitis (0.5%) and transient hypotony (2.0%). No hypotony at 12 months. Conclusions and Relevance: Transscleral diode laser cyclophotocoagulation controlled IOP in almost three quarters of eyes at 12 months with short‐term preservation of vision and minimal complications. Poor follow‐up in this setting highlights the need for an effective, safe and acceptable treatment where regular follow‐up is less critical. [ABSTRACT FROM AUTHOR]

Abstract: The suprachiasmatic nucleus (SCN) is the neural network that drives daily rhythms in behavior and physiology. The SCN encodes environmental changes through the phasing of cellular rhythms across its anteroposterior axis, but it remains unknown what signaling mechanisms regulate clock function along this axis. Here we demonstrate that arginine vasopressin (AVP) signaling organizes the SCN into distinct anteroposterior domains. Spatial mapping of SCN gene expression using in situ hybridization delineated anterior and posterior domains for AVP signaling components, including complementary patterns of V1a and V1b expression that suggest different roles for these two AVP receptors. Similarly, anteroposterior patterning of transcripts involved in Vasoactive Intestinal Polypeptide‐ and Prokineticin2 signaling was evident across the SCN. Using bioluminescence imaging, we then revealed that inhibiting V1A and V1B signaling alters period and phase differentially along the anteroposterior SCN. V1 antagonism lengthened period the most in the anterior SCN, whereas changes in phase were largest in the posterior SCN. Further, separately antagonizing V1A and V1B signaling modulated SCN function in a manner that mapped onto anteroposterior expression patterns. Lastly, V1 antagonism influenced SCN period and phase along the dorsoventral axis, complementing effects on the anteroposterior axis. Together, these results indicate that AVP signaling modulates SCN period and phase in a spatially specific manner, which is expected to influence how the master clock interacts with downstream tissues and responds to environmental changes. More generally, we reveal anteroposterior asymmetry in neuropeptide signaling as a recurrent organizational motif that likely influences neural computations in the SCN clock network. [ABSTRACT FROM AUTHOR]

Purpose To summarise the results of recent Cochrane systematic reviews that have investigated whether nutritional supplements prevent or slow the progression of age-related macular degeneration ( AMD). Recent findings There is no good evidence from randomised controlled trials that the general population should be taking antioxidant vitamin supplements to reduce their risk of developing AMD later on in life. By contrast, there is moderate quality evidence that people with AMD may experience a delay in progression by taking specific antioxidant vitamin and mineral supplements. This finding is drawn from one large randomised controlled trial conducted in the USA in a relatively well-nourished population. Although observational studies have shown that the consumption of dietary omega 3 long chain polyunsaturated fatty acids may reduce the risk of progression to advanced AMD, two recently published randomised controlled trials failed to show any benefit of omega 3 supplements on AMD progression. Summary There is no high quality experimental evidence that nutritional supplementation is beneficial for the primary prevention of AMD. However, people with AMD may benefit from supplementation with antioxidant vitamins. There is currently no evidence to support increasing levels of omega 3 long chain polyunsaturated fatty acids in the diet for the explicit purpose of preventing or slowing the progression of AMD. [ABSTRACT FROM AUTHOR]

Abstract: Drawing on identity development theory, the connection between engagement in sport and identity status was examined. First-year undergraduates (n = 116 sport-involved youth; 67% women; mean age = 18.58 yrs) completed measures of interpersonal and ideological identity status (achievement, moratorium, diffusion, foreclosure), along with behavioral (breadth, intensity) and psychological (e.g., enjoyment, competence) indicators of sport engagement. Using structural equation modeling, we examined the relation between latent sport engagement and identity status in interpersonal and ideological domains. As hypothesized, latent sport engagement predicted greater interpersonal (but not ideological) identity achievement. Consistent with identity development theory, an additional specific relation was observed between lower breadth of sport involvement and higher interpersonal identity achievement. Results demonstrate the value of examining behavioral and psychological indicators of sport engagement jointly, and support a growing body of research linking sport and positive youth development. [Copyright &y& Elsevier]

Aims Young injection drug users (IDU) are at high risk for hepatitis C virus (HCV). We sought to determine whether perceiving one's injecting partner to be HCV positive was associated with decreased odds of engaging in receptive needle/syringe sharing (RNS) or ancillary equipment sharing (AES) with that partner. Design Cross sectional study. Setting 2003 to 2007 in San Francisco. Participants 212 young (under age 30) IDU who were HCV antibody negative reported on 492 injecting partnerships. Measurements Self-reported RNS and AES within injecting partnerships. Findings RNS and AES (in the absence of RNS) occurred in 23% and 64% of injecting partnerships in the prior month. The odds of engaging in RNS were significantly lower for relationships in which the participant reported that his/her partner was HCV positive (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.25–0.95). This association was attenuated when adjusted for reusing one's own needle/syringe (adjusted OR 0.57; 95% CI 0.28–1.15). The odds of engaging in AES were lower for participants who did not know the HCV status of their partner, only among non-sexual partnerships (OR 0.47; 95% CI 0.29–0.76). Conclusions Because perceiving one's partner to be HCV positive was associated with decreased RNS, increased HCV testing and partner disclosure may be warranted. AES was common and was decreased only among non-sexual partnerships in which the HCV status of the partner was not known. This suggests that interventions to reduce AES in young IDU must be widespread. [ABSTRACT FROM AUTHOR]

Investigations of the neural correlates of face recognition have typically used old/new paradigms where subjects learn to recognize new faces or identify famous faces. Familiar faces, however, include one's own face, partner's and parents' faces. Using event-related fMRI, we examined the neural correlates of these personally familiar faces. Ten participants were presented with photographs of own, partner, parents, famous and unfamiliar faces and responded to a distinct target. Whole brain, two regions of interest (fusiform gyrus and cingulate gyrus), and multiple linear regression analyses were conducted. Compared with baseline, all familiar faces activated the fusiform gyrus; own faces also activated occipital regions and the precuneus; partner faces activated similar areas, but in addition, the parahippocampal gyrus, middle superior temporal gyri and middle frontal gyrus. Compared with unfamiliar faces, only personally familiar faces activated the cingulate gyrus and the extent of activation varied with face category. Partner faces also activated the insula, amygdala and thalamus. Regions of interest analyses and laterality indices showed anatomical distinctions of processing the personally familiar faces within the fusiform and cingulate gyri. Famous faces were right lateralized whereas personally familiar faces, particularly partner and own faces, elicited bilateral activations. Regression analyses show experiential predictors modulated with neural activity related to own and partner faces. Thus, personally familiar faces activated the core visual areas and extended frontal regions, related to semantic and person knowledge and the extent and areas of activation varied with face type. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Aims. To describe temporal trends in methamphetamine use among young injection drug users (IDU) in San Francisco. Design and Methods. Secondary analysis of cross-sectional baseline data collected for a longitudinal study of young IDU from 1998 to 2004. Participants were 1445 young IDU (<30 years old) who reported injection in the previous month, English-speaking, and recruited by street outreach methods. We examined trends for: lifetime (ever) and recent (30-day) methamphetamine use, including injected and non-injected, and by age group and sexual risk behaviour [men who have sex with men injecting drug users (MSM-IDU), male IDU (non-MSM) and female IDU]. Results. In 1998, 1999, 2000, 2001, 2003 and 2004 we interviewed 237, 276, 431, 310, 147 and 44 participants, respectively. Overall, median age was 22 years [interquartile range (IQR) 20 - 25], 30.3% were women and median duration of injecting was 4.4 years (IQR 2 - 7). Prevalence of methamphetamine use was high, with 50.1% reporting recent injection, but overall there were no temporal increases in reported 'ever' injected use. Recent methamphetamine injection (past 30 days) increased significantly, and peaked at 60% in 2003. MSM-IDU had higher methamphetamine injection ever (92.3%) and recently (59.5%) compared to heterosexual male (non-MSM) IDU (81.6% and 47.3%, respectively) and to female IDU (78.4% and 46.1%, respectively). Conclusions. Despite reports of ubiquitous increases in methamphetamine use, there were no significant increases in 6 years in ever injecting methamphetamine overall among young IDU. MSM-IDU who reported the highest methamphetamine use overall reported some increases in recent injected use. The methamphetamine 'epidemic' was probably under way among young IDU earlier than other populations. [Inglez-Dias A, Hahn JA, Lum PJ, Evans J, Davidson P, Page-Shafer K. Trends in methamphetamine use in young injection drug users in San Francisco from 1998 to 2004: the UFO Study. Drug Alcohol Rev 2008;27:286-291] [ABSTRACT FROM AUTHOR]

This article describes the processes and findings of a systematic review of research into the effectiveness of strategies to support pupils with emotional and behavioural difficulties (EBD) in mainstream primary schools. A search for studies carried out from 1975–1999 resulted in 265 citations, of which 96 were found to be within the scope of the review topic. Of these, 27 reported on 28 research studies, which could address the review question. Findings from these 28 studies indicated that a number of strategies, based on a range of theoretical frameworks, showed some positive impacts on pupil behaviour. However, the review highlighted a dearth of good quality research on strategy effectiveness. There is a need for higher quality research into strategies currently being used in schools. Practitioners, parents and children should all be involved in setting the parameters for interventions and research concerned with EBD. [ABSTRACT FROM AUTHOR]

Aims Assessment of young injectors' exposure and response to others' heroinrelated overdose. Design Cross-sectional survey. Setting San Francisco, CA, United States. Participants Nine hundred and seventy-three street-recruited current injectors under 30 years old, Measurements Self-reported experiences of witnessing heroin-related over- doses from structured interviews. Findings Seven hundred and nine of 973 (73%) had ever witnessed at least one heroin-related overdose, and 491 of 973 (50%) had witnessed an overdose in the last 12 months. Fourteen per cent of those who had witnessed an overdose in the past year reported that the outcome of the overdose was death. Emergency services were called to 52% of most recent witnessed overdoses. Cardiopulmonary resuscitation (CPR) or expired air resuscitation (EAR or 'rescue breathing') was performed in 61% of cases. Inappropriate strategies such as injection with stimulants or application of ice were rare. In 67% of cases in which emergency services were not called the witness said this was because the victim regained consciousness. In the remaining 33%, 56% stated emergency services were not called due to fear of the police. Conclusions Respondents were willing to act at overdoses at which they were present, but frequently did not do so in the most efficacious manner. Fear of police was identified as the most significant barrier to the ideal first response of calling emergency services. [ABSTRACT FROM AUTHOR]

There has been a recent increase in interest in the research review as a method of presenting cumulative data about the effects of educational policies and practices. This is part of a wider movement in 'evidence-informed policy-making' espoused by the current Government. In part, the interest as been sparked by the perceived success of the Cochrane Collaboration in medicine, which has set up a framework for conducting and verifying systematic reviews and meta-analyses of random controlled trials of medical interventions. A pilot project to apply the methods of systematic review has been carried out at the National Foundation for Educational Research. The subject of the review was 'Strategies to Support Pupils with Emotional and Behavioural Difficulties in Mainstream Primary Classrooms'. The article describes the process of the review, the adaptations of the 'medical model' to educational settings and discusses some of the implications of these for researchers and policy-makers. [ABSTRACT FROM AUTHOR]

The Special Educational Needs Tribunal is now a permanent feature in the processing of appeals of parents against local authority decisions about their child. The National Foundation for Educational Research (NFER) was commissioned to look into the operation of such tribunals. Here Jennifer Evans describes the outcomes of that investigation, examining both the positive and negative aspects of decisions. The full report, Getting It Right: LEAs and the Special Educational Needs Tribunals, can be obtained from the Dissemination Unit, NFER, The Mere, Upton Park, Slough SL1 2DQ, price £6.00. [ABSTRACT FROM AUTHOR]

Explores the role of professionals employed in the special education section of local education authorities in Great Britain. Nature and effects of professional control in special education; Main outcomes of professional control; Discourses that underpin professional notions of special education.

Examines the approaches taken by local education authorities (LEA) in Great Britain to the funding and organization of provision for special educational needs (SEN) under local management of schools (LMS). Trends toward decentralization; LMS and the market; Market values; Special educational needs; Local educational authorities.

Attorneys, philosophers, bioethicists and health care professionals have vigorously debated how much state control there should be over an individual's or family's decision to discontinue life-sustaining treatment. Where treatment of a minor is involved, the debate becomes even more complex. The purposes of this study were to identify cases involving the withdrawal of life-sustaining treatment in children, to described the legal-sustaining treatment in children, to describe the legal response to, and the management of, these cases, to examine variables that influence decision making, and to determine what legal—ethical standards are used and how they are applied. In addition, the author reviewed the literature on children's understanding of death and competence to participate in treatment decision making and applied those findings to argue for greater involvement of children in decision making related to the use of life-sustaining treatment. [ABSTRACT FROM AUTHOR]

The passage of legislation is just one point in the process of negotiation and bargaining which formed the will to legislate and continues throughout the period of policy implementation. Using the 1981 Education Act as a case study, this paper develops a conceptual framework which sees education legislation as a significant reference point, a statement of government intent, but implementation as a political process involving negotiation, bargaining and compromise between different sectors of government, between central and local government, between education, health and social services, between administrators and professionals, and with parents. [ABSTRACT FROM AUTHOR]

Introduction: In the era of HIV treatment as prevention (TasP), evidence‐based interventions that optimize viral suppression among people who use stimulants such as methamphetamine are needed to improve health outcomes and reduce onward transmission risk. We tested the efficacy of positive affect intervention delivered during community‐based contingency management (CM) for reducing viral load in sexual minority men living with HIV who use methamphetamine. Methods: Conducted in San Francisco, this Phase II randomized controlled trial tested the efficacy of a positive affect intervention for boosting and extending the effectiveness of community‐based CM for stimulant abstinence to achieve more durable reductions in HIV viral load. From 2013 to 2017, 110 sexual minority men living with HIV who had biologically confirmed, recent methamphetamine use were randomized to receive a positive affect intervention (n = 55) or attention‐control condition (n = 55). All individual positive affect intervention and attention‐control sessions were delivered during three months of community‐based CM where participants received financial incentives for stimulant abstinence. The 5‐session positive affect intervention was designed to provide skills for managing stimulant withdrawal symptoms as well as sensitize individuals to natural sources of reward. The attention‐control condition consisted of neutral writing exercises and self‐report measures. Results: Men randomized to the positive affect intervention displayed significantly lower log10 HIV viral load at six, twelve and fifteen months compared to those in the attention‐control condition. Men in the positive affect intervention also had significantly lower risk of at least one unsuppressed HIV RNA (≥200 copies/mL) over the 15‐month follow‐up. There were concurrent, statistically significant intervention‐related increases in positive affect as well as decreases in the self‐reported frequency of stimulant use at six and twelve months. Conclusions: Delivering a positive affect intervention during community‐based CM with sexual minority men who use methamphetamine achieved durable and clinically meaningful reductions in HIV viral load that were paralleled by increases in positive affect and decreases in stimulant use. Further clinical research is needed to determine the effectiveness of integrative, behavioural interventions for optimizing the clinical and public health benefits of TasP in sexual minority men who use stimulants such as methamphetamine. [ABSTRACT FROM AUTHOR]