Evidence for a High Affinity, Saturable, Prenylation-Dependent p21(Ha- Ras) Binding Site in Plasma Membranes

Oncogenic p21(ras) proteins can only exert their stimulation of cellular proliferation when plasma membrane-associated. This membrane association has an absolute requirement for post-translational modification with isoprenoids. The mechanism by which isoprenoids participate in the specific association of p21(ras) with plasma membranes is the subject of this report. We present in vitro evidence for a plasma membrane binding protein for p21(ras) that can recognize the isoprenoid substituent and, therefore, may facilitate the localization of p21(ras)

Two Experimental Tests of the Halperin-Lubensky-Ma Effect at the Nematic-Smectic-A Phase Transition

We have conducted two quantitative tests of predictions based on the Halperin-Lubensky-Ma (HLM) theory of fluctuation-induced first-order phase transitions. First, we explore the effect of an external magnetic field on the nematic-smectic-A (NA) transition in a liquid crystal. Second, we examine the dependence of the first-order discontinuity as a function of mixture concentration in pure 8CB and three 8CB-10CB mixtures. We find the first quantitative evidence for deviations from the HLM theory.Comment: 4 pages, 2 figure

Improving practice in community-based settings: a randomized trial of supervision – study protocol

Background: Evidence-based treatments for child mental health problems are not consistently available in public mental health settings. Expanding availability requires workforce training. However, research has demonstrated that training alone is not sufficient for changing provider behavior, suggesting that ongoing intervention-specific supervision or consultation is required. Supervision is notably under-investigated, particularly as provided in public mental health. The degree to which supervision in this setting includes ‘gold standard’ supervision elements from efficacy trials (e.g., session review, model fidelity, outcome monitoring, skill-building) is unknown. The current federally-funded investigation leverages the Washington State Trauma-focused Cognitive Behavioral Therapy Initiative to describe usual supervision practices and test the impact of systematic implementation of gold standard supervision strategies on treatment fidelity and clinical outcomes. Methods/Design The study has two phases. We will conduct an initial descriptive study (Phase I) of supervision practices within public mental health in Washington State followed by a randomized controlled trial of gold standard supervision strategies (Phase II), with randomization at the clinician level (i.e., supervisors provide both conditions). Study participants will be 35 supervisors and 130 clinicians in community mental health centers. We will enroll one child per clinician in Phase I (N = 130) and three children per clinician in Phase II (N = 390). We use a multi-level mixed within- and between-subjects longitudinal design. Audio recordings of supervision and therapy sessions will be collected and coded throughout both phases. Child outcome data will be collected at the beginning of treatment and at three and six months into treatment. Discussion This study will provide insight into how supervisors can optimally support clinicians delivering evidence-based treatments. Phase I will provide descriptive information, currently unavailable in the literature, about commonly used supervision strategies in community mental health. The Phase II randomized controlled trial of gold standard supervision strategies is, to our knowledge, the first experimental study of gold standard supervision strategies in community mental health and will yield needed information about how to leverage supervision to improve clinician fidelity and client outcomes. Trial registration ClinicalTrials.gov NCT0180026

Biomechanical evolution of solid bones in large animals: a microanatomical investigation

International audienc

External-field-induced tricritical point in a fluctuation-driven nematic-smectic-A transition

We study theoretically the effect of an external field on the nematic-smectic-A (NA) transition close to the tricritical point, where fluctuation effects govern the qualitative behavior of the transition. An external field suppresses nematic director fluctuations, by making them massive. For a fluctuation-driven first-order transition, we show that an external field can drive the transition second-order. In an appropriate liquid crystal system, we predict the required magnetic field to be of order 10 T. The equivalent electric field is of order $1 V/\mu m$.Comment: revtex, 4 pages, 1 figure; revised version, some equations have been modifie

Still policing the crisis?

Writing this has been a troubling experience. Returning to a text 30 years on in this way combines intellectual, political and personal reflections in an unsettling way. These range from a powerful attachment to processes of collective or collaborative intellectual work that Policing the Crisis (PTC; Hall et al., 1978) embodied and enhanced to a rather depressed sense of how many things the book got right about the trajectory of the British social formation in the mid 1970s (other futures might have been preferable). And above all, there is a sense of what the book stands for in the emergence of cultural studies as an institutionalized academic field. As a way of trying to digest these different responses, I have tried to address three sorts of questions: why PTC mattered, where it belongs and why it continues to have echoes in the present

Mindfulness-Oriented Recovery Enhancement vs Supportive Group Therapy for Co-occurring Opioid Misuse and Chronic Pain in Primary Care: A Randomized Clinical Trial

Importance: Successful treatment of opioid misuse among people with chronic pain has proven elusive. Guidelines recommend nonopioid therapies, but the efficacy of mindfulness-based interventions for opioid misuse is uncertain. Objective: To evaluate the efficacy of Mindfulness-Oriented Recovery Enhancement (MORE) for the reduction of opioid misuse and chronic pain. Design, Setting, and Participants: This interviewer-blinded randomized clinical trial enrolled patients from primary care clinics in Utah between January 4, 2016, and January 16, 2020. The study included 250 adults with chronic pain receiving long-term opioid therapy who were misusing opioid medications. Interventions: Treatment with MORE (comprising training in mindfulness, reappraisal, and savoring positive experiences) or supportive group psychotherapy (control condition) across 8 weekly 2-hour group sessions. Main Outcomes and Measures: Primary outcomes were (1) opioid misuse assessed by the Drug Misuse Index (self-report, interview, and urine screen) and (2) pain severity and pain-related functional interference, assessed by subscale scores on the Brief Pain Inventory through 9 months of follow-up. Secondary outcomes were opioid dose, emotional distress, and ecological momentary assessments of opioid craving. The minimum intervention dose was defined as 4 or more completed sessions of MORE or supportive group psychotherapy. Results: Among 250 participants (159 women [63.6%]; mean [SD] age, 51.8 [11.9] years), 129 were randomized to the MORE group and 121 to the supportive psychotherapy group. Overall, 17 participants (6.8%) were Hispanic or Latino, 218 (87.2%) were White, and 15 (6.0%) were of other races and/or ethnicities (2 American Indian, 3 Asian, 1 Black, 2 Pacific Islander, and 7 did not specify). At baseline, the mean duration of pain was 14.7 years (range, 1-60 years), and the mean (SD) morphine-equivalent opioid dose was 101.0 (266.3) mg (IQR, 16.0-90.0 mg). A total of 203 participants (81.2%) received the minimum intervention dose (mean [SD], 5.7 [2.2] sessions); at 9 months, 92 of 250 participants (36.8%) discontinued the study. The overall odds ratio for reduction in opioid misuse through the 9-month follow-up period in the MORE group compared with the supportive psychotherapy group was 2.06 (95% CI, 1.17-3.61; P = .01). At 9 months, 36 of 80 participants (45.0%) in the MORE group were no longer misusing opioids compared with 19 of 78 participants (24.4%) in the supportive psychotherapy group. Mixed models demonstrated that MORE was superior to supportive psychotherapy through 9 months of follow-up for pain severity (between-group effect: 0.49; 95% CI, 0.17-0.81; P = .003) and pain-related functional interference (between-group effect: 1.07; 95% CI, 0.64-1.50; P < .001). Participants in the MORE group reduced their opioid dose to a greater extent than those in the supportive psychotherapy group. The MORE group also had lower emotional distress and opioid craving. Conclusions and Relevance: In this randomized clinical trial, among adult participants in a primary care setting, the MORE intervention led to sustained improvements in opioid misuse and chronic pain symptoms and reductions in opioid dosing, emotional distress, and opioid craving compared with supportive group psychotherapy. Despite attrition caused by the COVID-19 pandemic and the vulnerability of the sample, MORE appeared to be efficacious for reducing opioid misuse among adults with chronic pain. Trial Registration: ClinicalTrials.gov Identifier: NCT0260253

Air Quality and Human Health among a Low Income Community in the Highveld Priority Area

Human exposure to poor air quality is linked to adverse health effects. The largest burden of air pollution-related diseases is in developing countries where air pollution levels are also among the highest in the world. In South Africa, two geographic areas, the Vaal Triangle and the Highveld, have been identified for air quality managementinterventions to ensure compliance with National Air Quality Management Standards and to control potential harmful air pollution impacts on human health. The Highveld Priority Area (HPA) is characterised by intense mining, coal-fired power plants, industries, including iron and steel manufacturing, chemical plants, agricultural activity, motor vehicles and domestic fuel burning. Apart from two previous studies, no respiratory health studies have been carried out in the HPA. This paper describes the results of a recent, comprehensive study of ambient air quality, potential exposure to air pollution and air-related human health among a low income community living in the HPA in order to better understand the impact of air pollution on human health in South Africa

The use of routine outcome measures in two child and adolescent mental health services: a completed audit cycle

Background: Routine outcome measurement (ROM) is important for assessing the clinical effectiveness of health services and for monitoring patient outcomes. Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption of ROM in CAMHS has been supported by both national and local initiatives (such as government strategies, local commissioning policy, and research). Methods: With the aim of assessing how these policies and initiatives may have influenced the uptake of ROM within two different CAMHS we report the findings of two case-note audits: a baseline audit conducted in January 2011 and a re-audit conducted two years later in December 2012-February 2013. Results: The findings show an increase in both the single and repeated use of outcome measures from the time of the original audit, with repeated use (baseline and follow-up) of the Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing from 10% to 50% of cases. Re-audited case-notes contained more combined use of different outcome measures, with greater consensus on which measures to use. Outcome measures that were applicable across a wide range of clinical conditions were more likely to be used than symptom-specific measures, and measures that were completed by the clinician were found more often than measures completed by the service user. Conclusions: The findings show a substantial improvement in the use of outcome measures within CAMHS. These increases in use were found across different service organisations which were subject to different types of local service priorities and drivers