The downside of tobacco control? Smoking and self-stigma: a systematic review

Objective Little is known about the consequences of tobacco smoking stigma on smokers and how smokers may internalize smoking-related stigma. This review summarizes existing literature on tobacco smoking self-stigma, investigating to what extent smokers are aware of negative stereotypes, agree with them and apply them to themselves. Methods We carried out a systematic search of Pubmed/Web of Science/PsycInfo databases for articles related to smoking self-stigma through June 2013. Reference lists and citations of included studies were also checked and experts were contacted. After screening articles for inclusion/exclusion criteria we performed a quality assessment and summarized findings according to the stages of self-stigma as conceptualized in Corrigan's progressive model of self-stigma (aware, agree, apply and harm). Initial searches yielded 570 articles. Results Thirty of these articles (18 qualitative and 12 quantitative studies) met criteria for our review. Awareness of smoking stigma was virtually universal across studies. Coping strategies for smoking stigma and the degree to which individuals who smoke internalized this stigma varied both within and across studies. There was considerable variation in positive, negative, and non-significant consequences associated with smoking self-stigma. Limited evidence was found for subgroup differences in smoking-related stigma. Conclusion While there is some evidence that smoking self-stigma leads to reductions in smoking, this review also identified significant negative consequences of smoking self-stigma. Future research should assess the factors related to differences in how individuals respond to smoking stigma. Public health strategies which limit the stigmatization of smokers may be warranted

The FUV to Near-IR Morphologies of Luminous Infrared Galaxies in the GOALS Sample

We compare the morphologies of a sample of 20 LIRGs from the Great Observatories All-sky LIRG Survey (GOALS) in the FUV, B, I and H bands, using the Gini (G) and M20 parameters to quantitatively estimate the distribution and concentration of flux as a function of wavelength. HST images provide an average spatial resolution of ~80 pc. While our LIRGs can be reliably classified as mergers across the entire range of wavelengths studied here, there is a clear shift toward more negative M20 (more bulge-dominated) and a less significant decrease in G values at longer wavelengths. We find no correlation between the derived FUV G-M20 parameters and the global measures of the IR to FUV flux ratio, IRX. Given the fine resolution in our HST data, this suggests either that the UV morphology and IRX are correlated on very small scales, or that the regions emitting the bulk of the IR emission emit almost no FUV light. We use our multi-wavelength data to simulate how merging LIRGs would appear from z~0.5-3 in deep optical and near-infrared images such as the HUDF, and use these simulations to measure the G-M20 at these redshifts. Our simulations indicate a noticeable decrease in G, which flattens at z >= 2 by as much as 40%, resulting in mis-classifying our LIRGs as disk-like, even in the rest-frame FUV. The higher redshift values of M20 for the GOALS sources do not appear to change more than about 10% from the values at z~0. The change in G-M20 is caused by the surface brightness dimming of extended tidal features and asymmetries, and also the decreased spatial resolution which reduced the number of individual clumps identified. This effect, seen as early as z~0.5, could easily lead to an underestimate of the number of merging galaxies at high-redshift in the rest-frame FUV.Comment: Accepted for publication in the Astronomical Journal. The total page count is 15 pages with 13 figures and 1 Tabl

Service user and caregiver involvement in mental health system strengthening in low- and middle-income countries: a cross-country qualitative study

The aims of this paper are to: (i) explore the experiences of involvement of mental health service users, their caregivers, mental health centre heads and policy makers in mental health system strengthening in three low- and middle-income countries (LMICs) (Ethiopia, Nepal and Nigeria); (ii) analyse the potential benefits and barriers of such involvement; and (iii) identify strategies required to achieve greater service user and caregiver participation. A cross-country qualitative study was conducted, interviewing 83 stakeholders of mental health services. Our analysis showed that service user and caregiver involvement in the health system strengthening process was an alien concept for most participants. They reported very limited access to direct participation. Stigma and poverty were described as the main barriers for involvement. Several strategies were identified by participants to overcome existing hurdles to facilitate service user and caregiver involvement in the mental health system strengthening process, such as support to access treatment, mental health promotion and empowerment of service users. This study suggests that capacity building for service users, and strengthening of user groups would equip them to contribute meaningfully to policy development from informed perspectives. Involvement of service users and their caregivers in mental health decision-making is still in its infancy in LMICs. Effective strategies are required to overcome existing barriers, for example making funding more widely available for Ph.D. studies in participatory research with service users and caregivers to develop, implement and evaluate approaches to involvement that are locally and culturally acceptable in LMICs

Mitochondrial DNA: Hotspot for potential gene modifiers regulating hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a prevalent and untreatable cardiovascular disease with a highly complex clinical and genetic causation. HCM patients bearing similar sarcomeric mutations display variable clinical outcomes, implying the involvement of gene modifiers that regulate disease progression. As individuals exhibiting mutations in mitochondrial DNA (mtDNA) present cardiac phenotypes, the mitochondrial genome is a promising candidate to harbor gene modifiers of HCM. Herein, we sequenced the mtDNA of isogenic pluripotent stem cell-cardiomyocyte models of HCM focusing on two sarcomeric mutations. This approach was extended to unrelated patient families totaling 52 cell lines. By correlating cellular and clinical phenotypes with mtDNA sequencing, potentially HCM-protective or -aggravator mtDNA variants were identified. These novel mutations were mostly located in the non-coding control region of the mtDNA and did not overlap with those of other mitochondrial diseases. Analysis of unrelated patients highlighted family-specific mtDNA variants, while others were common in particular population haplogroups. Further validation of mtDNA variants as gene modifiers is warranted but limited by the technically challenging methods of editing the mitochondrial genome. Future molecular characterization of these mtDNA variants in the context of HCM may identify novel treatments and facilitate genetic screening in cardiomyopathy patients towards more efficient treatment options

Assessing Trade-Offs in Large Marine Protected Areas

Large marine protected areas (LMPAs) are increasingly being established and have a high profile in marine conservation. LMPAs are expected to achieve multiple objectives, and because of their size are postulated to avoid trade-offs that are common in smaller MPAs. However, evaluations across multiple outcomes are lacking. We used a systematic approach to code several social and ecological outcomes of 12 LMPAs. We found evidence of three types of trade-offs: trade-offs between different ecological resources (supply trade-offs); trade-offs between ecological resource conditions and the well-being of resource users (supply-demand trade-offs); and trade-offs between the well-being outcomes of different resource users (demand trade-offs). We also found several divergent outcomes that were attributed to influences beyond the scope of the LMPA. We suggest that despite their size, trade-offs can develop in LMPAs and should be considered in planning and design. LMPAs may improve their performance across multiple social and ecological objectives if integrated with larger-scale conservation efforts. © 2018 Davies et al

Importance of the Active Site "Canopy" Residues in an O_2-Tolerant [NiFe]-Hydrogenase

The active site of Hyd-1, an oxygen-tolerant membrane-bound [NiFe]-hydrogenase from Escherichia coli, contains four highly conserved residues that form a “canopy” above the bimetallic center, closest to the site at which exogenous agents CO and O_2 interact, substrate H_2 binds, and a hydrido intermediate is stabilized. Genetic modification of the Hyd-1 canopy has allowed the first systematic and detailed kinetic and structural investigation of the influence of the immediate outer coordination shell on H_2 activation. The central canopy residue, arginine 509, suspends a guanidine/guanidinium side chain at close range above the open coordination site lying between the Ni and Fe atoms (N–metal distance of 4.4 Å): its replacement with lysine lowers the H_2 oxidation rate by nearly 2 orders of magnitude and markedly decreases the H_2/D_2 kinetic isotope effect. Importantly, this collapse in rate constant can now be ascribed to a very unfavorable activation entropy (easily overriding the more favorable activation enthalpy of the R509K variant). The second most important canopy residue for H_2 oxidation is aspartate 118, which forms a salt bridge to the arginine 509 headgroup: its mutation to alanine greatly decreases the H_2 oxidation efficiency, observed as a 10-fold increase in the potential-dependent Michaelis constant. Mutations of aspartate 574 (also salt-bridged to R509) to asparagine and proline 508 to alanine have much smaller effects on kinetic properties. None of the mutations significantly increase sensitivity to CO, but neutralizing the expected negative charges from D118 and D574 decreases O_2 tolerance by stabilizing the oxidized resting Ni^(III)–OH state (“Ni-B”). An extensive model of the catalytic importance of residues close to the active site now emerges, whereby a conserved gas channel culminates in the arginine headgroup suspended above the Ni and Fe

Closed-loop insulin delivery in inpatients with type 2 diabetes: a randomised, parallel-group trial.

BACKGROUND: We assessed whether fully closed-loop insulin delivery (the so-called artificial pancreas) is safe and effective compared with standard subcutaneous insulin therapy in patients with type 2 diabetes in the general ward. METHODS: For this single-centre, open-label, parallel-group, randomised controlled trial, we enrolled patients aged 18 years or older with type 2 diabetes who were receiving insulin therapy. Patients were recruited from general wards at Addenbrooke's Hospital, Cambridge, UK. Participants were randomly assigned (1:1) by a computer-generated minimisation method to receive closed-loop insulin delivery (using a model-predictive control algorithm to direct subcutaneous delivery of rapid-acting insulin analogue without meal-time insulin boluses) or conventional subcutaneous insulin delivery according to local clinical guidelines. The primary outcome was time spent in the target glucose concentration range of 5·6-10·0 mmol/L during the 72 h study period. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01774565. FINDINGS: Between Feb 20, 2015, and March 24, 2016, we enrolled 40 participants, of whom 20 were randomly assigned to the closed-loop intervention group and 20 to the control group. The proportion of time spent in the target glucose range was 59·8% (SD 18·7) in the closed-loop group and 38·1% (16·7) in the control group (difference 21·8% [95% CI 10·4-33·1]; p=0·0004). No episodes of severe hypoglycaemia or hyperglycaemia with ketonaemia occurred in either group. One adverse event unrelated to study devices occurred during the study (gastrointestinal bleed). INTERPRETATION: Closed-loop insulin delivery without meal-time boluses is effective and safe in insulin-treated adults with type 2 diabetes in the general ward. FUNDING: Diabetes UK; European Foundation for the Study of Diabetes; JDRF; National Institute for Health Research Cambridge Biomedical Research Centre; Wellcome Trust.This study was supported by Diabetes UK (#14/0004878) and the European Foundation for the Study of Diabetes. Additional support for research on the artificial pancreas was received from the Juvenile Diabetes Research Foundation, National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z).This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/S2213-8587(16)30280-

CamAPS FX hybrid closed-loop with ultra-rapid lispro compared with standard lispro in adults with type 1 diabetes: a double-blind, randomized, crossover study.

INTRODUCTION To evaluate hybrid closed-loop with ultra-rapid insulin lispro (Lyumjev) compared with hybrid closed-loop with standard insulin lispro in adults with type 1 diabetes. MATERIALS AND METHODS In a single-center, double-blind, randomized, crossover study, 28 adults with type 1 diabetes (mean±SD: age 44.5±10.7, HbA1c 7.1±0.9% [54±10mmol/mol]) underwent two 8-week periods comparing hybrid closed-loop with ultra-rapid insulin lispro and hybrid closed-loop with standard insulin lispro in random order. CamAPS FX closed-loop system was used in both periods. RESULTS In an intention-to-treat analysis, the proportion of time sensor glucose was in target range (3.9 to 10mmol/L; primary endpoint) was greater with ultra-rapid lispro compared with standard insulin lispro (mean±SD: 78.7±9.8% vs. 76.2±9.6%; mean difference 2.5 percentage points [95%CI 0.8 to 4.2]; p=0.005). Mean sensor glucose was lower with ultra-rapid lispro compared with standard insulin lispro (7.9±0.8mmol/L vs. 8.1±0.9mmol/L; p=0.048). The proportion of time with sensor glucose <3.9mmol/L was similar between interventions (median [IQR] ultra-rapid lispro 2.3% [1.3-2.7%] vs. standard insulin lispro 2.1% [1.4-3.3%]; p=0.33). No severe hypoglycemia or ketoacidosis occurred. CONCLUSIONS The use of ultra-rapid lispro with CamAPS FX hybrid closed-loop increases time in range and reduces mean glucose with no difference in hypoglycemia compared with standard insulin lispro in adults with type 1 diabetes

Description, Utilisation and Results from a Telehealth Primary Care Weight Management Intervention for Adults with Obesity in South Carolina

Introduction: In the US, obesity rates are higher in rural areas than in urban areas. Rural access to treatment of obesity is limited by a lack of qualified clinicians and by transportation and financial barriers. We describe a telemedicine weight management programme, Wellness Connect, developed through a partnership of academic clinicians and rural primary care providers in South Carolina, and present utilisation and weight outcomes from seven patient cohorts. Methods: Eight bi-weekly sessions were provided via telemedicine videoconferencing for groups of patients at these rural primary care clinics. Protocol-based sessions were led by registered dietitians, exercise physiologists and clinical psychologists at a central urban location. Results: Of 138 patients who started the programme, 62% (N ¼ 86) of patients met the criteria for completion. Completers lost an average of 3.5% (standard deviation (SD) ¼ 3.9%) body weight, which was statistically significant (p \u3c.001) and corresponded with an average loss of 3.8 kg (SD ¼ 4.5 kg). There were no differences in weight change among clinics (p ¼.972). Overall, patients and providers reported satisfaction with the programme and identified several challenges to sustainability. Discussion: The use of innovative telemedicine interventions continues to be necessary to alleviate barriers to accessing evidence-based services to reduce chronic diseases and decrease obesity rates among rural populations