Cervical Cancer Among Women With HIV in South Carolina During the Era of Effective Antiretroviral Therapy.

OBJECTIVES: We aimed to determine whether women with HIV (WWH) and cervical cancer were more likely to experience cancer-related death and to be diagnosed with cervical cancer at a younger age and in more advanced stages. MATERIALS AND METHODS: This is a retrospective cohort study of all women diagnosed with cervical cancer in South Carolina from 1998 to 2018. Deidentified data were obtained from 2 statewide databases. A survival analysis was performed to evaluate differences in cancer survival between women with and without HIV. Wilcoxon rank sum test was used to determine differences in the median age at cancer diagnosis. χ2 test was used to assess differences in cancer stage according to HIV status. RESULTS: Four thousand three hundred fourteen women were diagnosed with cervical cancer, and 53 (1.2%) had HIV infection. Survival time in months was similar between WWH and HIV-negative women (86 months [interquartile range {IQR} = 32-146] and 62 months [IQR = 18-153], p = .37; log-rank p = .26). Compared with HIV-negative women, WWH were less likely to experience cervical cancer-related death (36% vs. 19%, p = .005). Women with HIV were diagnosed with cervical cancer at a younger age (44 [IQR = 37-54] vs. 49 [IQR = 39-61], p = .02). Cervical cancer stage was similar at diagnosis between groups (tumor node metastasis stage, p = .97, and Surveillance, Epidemiology, and End Results summary stage, p = .41). CONCLUSIONS: Women with HIV were younger at diagnosis than HIV-negative women, but they were no more likely to die from or have more advanced cervical cancer. Women with HIV were not more likely to develop cervical cancer before the age of 21 years and earlier screening is likely unnecessary.

Manía unipolar: un ineludible diagnóstico: revisión de la literatura a propósito de un caso / Unipolar mania: an unavoidable diagnosis: case report and literature review

Resumen Introducción: La manía unipolar (MU) es un trastorno que se comporta de manera distinta al trastorno bipolar-I (TB-I), sin embargo, no es considerado como una entidad independiente por los manuales diagnósticos vigentes, sino que es incluido dentro del diagnóstico de TB-I. Caso clínico: Hombre de 21 años presenta cuadro clínico de 3 meses de evolución caracterizado por ánimo exaltado y síntomas psicóticos congruentes al estado de ánimo. El paciente niega episodios depresivos previos. Se instaura tratamiento con litio y aripiprazol que resulta satisfactorio, sin presentar recurrencias tras 5 años de seguimiento. Revisión de la literatura y discusión: Los manuales diagnósticos describen que para diagnosticar TB-I no se requiere la presencia de un episodio depresivo mayor, lo que implica que pacientes con MU quedan dentro de la misma categoría diagnóstica que pacientes con TB-I. Diferencias entre MU y TB-I han sido demostradas en estudios epidemiológicos, clínicos y genéticos, por lo tanto, incluir pacientes heterogéneos dentro de la misma categoría podría dificultar la interpretación de estudios y limitar los avances en el conocimiento de ambos trastornos. Conclusión: De la revisión de la literatura se sugiere que la MU debe ser reconocida como un diagnóstico independiente. A pesar de su baja prevalencia, al validarlo como tal, en un futuro podríamos contar con mayor cantidad y mejor calidad de datos sobre este. De esta forma se podrá definir de manera más concreta sus características distintivas, y por consiguiente mejorar el abordaje clínico de estos pacientes.

Introduction: Unipolar mania (UM) is a disorder that behaves differently from bipolar-I disorder (BP-I), however, it is not considered an independent entity by current diagnostic manuals, but rather included within the diagnosis of BP-I. Case report: A 21-year-old man presented a 3-month-long episode characterized by exalted mood and mood-congruent psychotic symptoms. The patient denies previous depressive episodes. Treatment with lithium and aripiprazole was established, which was satisfactory, not showing recurrence after 5 years of follow-up. Literature review and discussion: Diagnostic manuals describe that to diagnose BP-I the presence of a major depressive episode is not required, which implies that patients with UM fall into the same diagnostic category as patients with BP-I. Differences between UM and BP-I have been demonstrated in epidemiological, clinical, and genetic studies, therefore, including heterogeneous patients within the same category could hinder the interpretation of studies and limit advances in the knowledge of both disorders. Conclusion: Based on the literature review, it is suggested that UM should be recognized as an independent diagnosis. Despite its low prevalence, by validating it as such, in the future we could have more and better-quality data about this diagnosis. In this way, its distinctive characteristics can be defined more concretely, and therefore improve the clinical approach of these patients.

Financial Incentives for Preventing Postpartum return to Smoking (FIPPS): study protocol for a three-arm randomised controlled trial.

BACKGROUND: Financial incentives are an effective way of helping women to stop smoking during pregnancy. Unfortunately, most women who stop smoking at this time return to smoking within 12 months of the infant's birth. There is no evidence for interventions that are effective at preventing postpartum smoking relapse. Financial incentives provided after the birth may help women to sustain cessation. This randomised controlled trial will assess the effectiveness and cost-effectiveness of financial incentives to help women who are abstinent from smoking at end-of-pregnancy to avoid return to smoking up to 12 months postpartum. METHODS: This is a UK-based, multi-centre, three-arm, superiority, parallel group, individually randomised controlled trial, with 1:1:1 allocation. It will compare the effectiveness of two financial incentive interventions with each other (one intervention for up to 3 months postpartum offering up to £120 of incentives (£60 for the participant and £60 for a significant other support); the other for up to 12 months postpartum with up to £300 of incentives (£240 for the participant and £60 for a significant other support) and with a no incentives/usual care control group. Eligible women will be between 34 weeks gestation and 2 weeks postpartum, abstinent from smoking for at least 4 weeks, have an expired carbon monoxide (CO) reading < 4 parts per million (ppm), aged at least 16 years, intend remaining abstinent from smoking after the birth and able to speak and read English. The primary outcome is self-reported, lapse-free, smoking abstinence from the last quit attempt in pregnancy until 12 months postpartum, biochemically validated by expired CO and/or salivary cotinine or anabasine. Outcomes will be analysed by intention-to-treat and regression models used to compare the proportion of abstinent women between the two intervention groups and between each intervention group and the control group. An economic evaluation will assess the cost-effectiveness of offering incentives and a qualitative process evaluation will examine barriers and facilitators to trial retention, effectiveness and implementation. DISCUSSION: This pragmatic randomised controlled trial will test whether offering financial incentives is effective and cost-effective for helping women to avoid smoking relapse during the 12 months after the birth of their baby. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number 55218215 . Registered retrospectively on 5th June 2019.

Total Synthesis and Computational Investigations of Sesquiterpene-Tropolones Ameliorate Stereochemical Inconsistencies and Resolve an Ambiguous Biosynthetic Relationship.

The sesquiterpene-tropolones belong to a distinctive structural class of meroterpene natural products with impressive biological activities, including anticancer, antifungal, antimalarial, and antibacterial. In this article, we describe a concise, modular, and cycloaddition-based approach to a series of sesquiterpene mono- and bistropolones, including (-)-epolone B, (+)-isoepolone B, (±)-dehydroxypycnidione, and (-)-10-epi-pycnidione. Alongside the development of a general strategy to access this unique family of metabolites were computational modeling studies that justified the diastereoselectivity observed during key cycloadditions. Ultimately, these studies prompted stereochemical reassignments of the pycnidione subclass and shed additional light on the biosynthesis of these remarkable natural products.

Experiences and attitudes of hereditary cancer screening patients in a consumer directed testing model.

BACKGROUND: Since 2015, the Information is Power initiative has offered free and reduced cost hereditary cancer screening to the North Alabama population with a consumer-initiated model. Patients received pre-test and post-test education through a genetic counseling video. Positive results also received a call from a genetic counselor. OBJECTIVE: We surveyed past Information is Power patients to assess if video education and electronic result delivery addressed the needs of a hereditary cancer screening population. METHODS: An electronic survey was sent out to Information is Power patients who opted into research contact. The survey assessed participant knowledge, satisfaction with result delivery, and perceived uncertainty after receiving test results. RESULTS: 213 participants completed the survey. Eighteen percent of participants would have preferred individual communication with a genetics specialist about their results. Over 99 % of survey participants correctly interpreted a positive result, while 73 % correctly interpreted a negative result. Overall, participants were certain about the impact of their genetic test results. PRACTICE IMPLICATIONS: These findings support a model of population genetic testing and genetic counseling that is sustainable while meeting the educational needs of most participants. Observed misconceptions surrounding a negative result should be highlighted in future population screening patient resources to meet patient needs.

The effects of short-term low energy availability, achieved through diet or exercise, on cognitive function in oral contraceptive users and eumenorrheic women.

To date, no research has explored the effects of low energy availability on cognitive performance using dietary and exercise regimens relevant to athletes. Twenty female participants (10 eumenorrheic, 10 oral contraceptive [OC] users) completed three 3-day conditions: 1) controlled-balanced energy availability without exercise (BAL; 45 kcal·kg lean body mass [LBM]-1·day-1); 2) diet-induced low energy availability without exercise (DIET; 15 kcal·kg LBM-1·day-1); and 3) exercise-induced low energy availability (EX; 15 kcal·kg LBM-1·day-1, including 30 kcal·kg LBM-1·day-1 treadmill running at 70% maximal oxygen uptake). A cognitive test battery was completed before and after each 3-day condition. Mental rotation test accuracy improved in the BAL condition, but there was a decline in accuracy in the EX condition (BAL, +2.5%; EX, -1.4%; P = 0.042, d = 0.85). DIET (+1.3%) was not different to BAL or EX (P > 0.05). All other measures of cognitive performance were not affected by condition (P > 0.05) and OC use did not affect cognitive responses (P > 0.05). Accuracy in the mental rotation test was impaired when low energy availability was induced through increased exercise energy expenditure. All other aspects of cognition were unaffected by 3 days of low energy availability through diet or exercise. OC use did not mediate the effect of low energy availability on cognition. Novelty: Cognitive function was not affected by 3 days of diet-induced low energy availability. Only spatial awareness was impaired during 3 days of exercise-induced low energy availability. Reproductive hormones affected spatial awareness independent of energy availability.

Pregnant women's use of e-cigarettes in the UK: a cross-sectional survey.

OBJECTIVE: To estimate prevalence of vaping in pregnancy. Compare characteristics and attitudes between exclusive smokers and vapers, and between exclusive vapers and dual users (smoke and vape). DESIGN: Cross-sectional survey. SETTING: Hospitals across England and Scotland. POPULATION: Pregnant women attending antenatal clinics in 2017. METHODS: Women at 8-24 weeks' gestation completed screening questions about their smoking and vaping. Current or recent ex-smokers and/or vapers completed a full detailed survey about vaping and smoking. MAIN OUTCOME MEASURES: The prevalence of vaping, characteristics and attitudes of women who vape and/or smoke. RESULTS: Of 3360 pregnant women who completed screening questions, 515 (15.3%, 95% CI 14.1-16.6) were exclusive smokers, 44 (1.3%, 95% CI 1.0-1.8) exclusive vapers and 118 (3.5%, 95% CI 2.9-4.2) dual users. In total, 867 (25.8%) women completed the full survey; compared with smokers (n = 434), vapers (n = 140) were more likely to hold higher educational qualifications (odds ratio [OR) 1.51, 95% CI 1.01-2.25). Compared with exclusive vapers (n = 33), dual users (n = 107) were younger (OR 0.91 95% CI 0.85-0.98) and less likely to hold high qualifications (OR 0.43, 95% CI 0.20-0.96). Compared with smokers, dual users were more likely to be planning to quit smoking (OR 2.27, 95% CI 1.24-4.18). Compared with smokers, vapers were more likely to think vaping was safer than smoking (78.6% versus 36.4%). CONCLUSIONS: One in 20 pregnant women report vaping, and most also smoke. Dual users are more motivated towards stopping smoking than smokers. Where women have tried but cannot stop smoking, clinicians could encourage them to consider vaping for smoking cessation. TWEETABLE EXTRACT: One in 20 women report vaping during pregnancy but of those that do vape, most also smoke, despite having intentions to quit.

New genera, species and combinations in the Pseudomicrocara Armstrong group (Coleoptera: Scirtidae) based on morphology supported by mitochondrial and nuclear gene sequence data.

The Australian Scirtidae genus Pseudomicrocara Armstrong, previously shown to be polyphyletic, is revised using both morphology and sequence data from the mitochondrial gene cytochrome oxidase subunit 1 and two nuclear genes, elongation factor 1-alpha and topoisomerase. Twenty-three genera, 16 of which are new, are recognised based on morphology, primarily of the mandibles and maxillary palpi, and male and female genitalia. Maximum likelihood and Bayesian phylogenetic analyses were used to examine relationships among species from 21 of the 23 recognised genera. Fifteen of the genera were recovered as distinct lineages. A further six, Accolabass Watts, Anocyphon gen. nov., Copiacyphon gen. nov., Nasutuscyphon gen. nov., Pseudomicrocara and Saprocyphon gen. nov. were considered to be genera based on both morphology and phylogenetic analysis but their species composition is uncertain and will require more work to confirm. The 17 new genera are fully described, keys are provided to all the genera in the Pseudomicrocara group, and to all the species in the genera Copiacyphon gen. nov., Spilotocyphon gen. nov., Accolabass Watts, Saltuscyphon gen. nov. and Vadumcyphon gen. nov. The male aedeagi of all new genera and species are illustrated, as are the female prehensors of some species.                The following genera are described as new: Alpestriscyphon gen. nov., Anthocara gen. nov., Anocyphon gen. nov., Copiacyphon gen. nov., Furcacyphon gen. nov., Latuscara gen. nov., Pictacara gen. nov., Nasutuscyphon gen. nov., Nektriscyphon gen. nov., Pumiliocara gen. nov., Ruborcara gen. nov., Saltuscyphon gen. nov., Saprocyphon gen. nov., Sisyracyphon gen. nov., Spilotocyphon gen. nov., Tenebriocyphon gen. nov. and Vadumcyphon gen. nov. A total of 45 new combinations are proposed. The following species are described as new: Accolabass monteithi sp. nov.; Alpestriscyphon bartlefrere sp. nov., Al. spurgeon sp. nov.; Anocyphon lepus sp. nov.; Copiacyphon brindaleensis sp. nov., C. cardinalis sp. nov., C. dytikos sp. nov.; Pumiliocara peneparva sp. nov.; Ruborcara saintae sp. nov.; Saltuscyphon montanus sp. nov., Sal. teraniaensis sp. nov.; Saprocyphon bithongensis sp. nov.; Sisyracyphon brisbanensis sp. nov., S. bulburinensis sp. nov.; Spilotocyphon occidentalis sp. nov., Sp. orientalis sp. nov., Sp. zwicki sp. nov.; Vadumcyphon centralis sp. nov., V. rugosus sp. nov. A checklist of all Australian taxa in the redefined Pseudomicrocara group is included.                Sequence data of the Argentinian species Pseudomicrocara antarctica (Fairmaire) is included. Phylogenetic analyses place this species as a distinct lineage within the Pseudomicrocara group.

Biosynthesis of the fungal glyceraldehyde-3-phosphate dehydrogenase inhibitor heptelidic acid and mechanism of self-resistance.

Overcoming resistance to bioactive small molecules is a significant challenge for health care and agriculture. As a result, efforts to uncover the mechanisms of resistance are essential to the development of new antibiotics, anticancer drugs and pesticides. To study how nature evolves resistance to highly potent natural products, we examined the biosynthesis and mechanism of self-resistance of the fungal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor heptelidic acid (HA). HA is a nanomolar inhibitor of GADPH through the covalent modification of the active site cysteine thiol. The biosynthetic pathway of HA was elucidated, which uncovered the enzymatic basis of formation of the epoxide warhead. Structure-activity relationship study using biosynthetic intermediates established the importance of the fused lactone ring system in HA. The molecular basis of HA inhibiting human GAPDH was illustrated through the crystal structure of Hs-GAPDH covalently bound with HA. A GAPDH isozyme HepG encoded in the HA cluster was characterized to be less sensitive to HA, and therefore contribute to self-resistance for the producing host. Comparison of the crystal structures of human GAPDH and HepG showed mutations both within and remote to the active site can contribute to resistance of inactivation, which was confirmed through mutagenesis. Due to the critical role GAPDH plays in aerobic glycolysis and other cellular functions, knowledge of HA mode of action and self-resistance mechanism could accelerate the development of improved inhibitors.

Dalton's and Amagat's laws fail in gas mixtures with shock propagation.

A shock propagating through a gas mixture leads to pressure, temperature, and density increases across the shock front. Rankine-Hugoniot relations correlating pre- and post-shock quantities describe a calorically perfect gas but deliver a good approximation for real gases, provided the pre-shock conditions are well characterized with a thermodynamic mixing model. Two classic thermodynamic models of gas mixtures are Dalton's law of partial pressures and Amagat's law of partial volumes. We measure post-shock temperature and pressure in experiments with nonreacting binary mixtures of sulfur hexafluoride and helium (two dramatically disparate gases) and show that neither model can accurately predict the observed values, on time scales much longer than that of the shock front passage, due to the models' implicit assumptions about mixture behavior on the molecular level. However, kinetic molecular theory can help account for the discrepancy. Our results provide starting points for future theoretical work, experiments, and code validation.

Structural basis for stereoselective dehydration and hydrogen-bonding catalysis by the SAM-dependent pericyclase LepI.

LepI is an S-adenosylmethionine (SAM)-dependent pericyclase that catalyses the formation of the 2-pyridone natural product leporin C. Biochemical characterization has shown that LepI can catalyse stereoselective dehydration to yield a reactive (E)-quinone methide that can undergo bifurcating intramolecular Diels-Alder (IMDA) and hetero-Diels-Alder (HDA) cyclizations from an ambimodal transition state, as well as a [3,3]-retro-Claisen rearrangement to recycle the IMDA product into leporin C. Here, we solve the X-ray crystal structures of SAM-bound LepI and in complex with a substrate analogue, the product leporin C, and a retro-Claisen reaction transition-state analogue to understand the structural basis for the multitude of reactions. Structural and mutational analysis reveals how nature evolves a classic methyltransferase active site into one that can serve as a dehydratase and a multifunctional pericyclase. Catalysis of both sets of reactions employs H133 and R295, two active-site residues that are not found in canonical methyltransferases. An alternative role of SAM, which is not found to be in direct contact with the substrate, is also proposed.

Highly coherent, watt-level deep-UV radiation via a frequency-quadrupled Yb-fiber laser system.

We demonstrate a 1.4 W continuous-wave (CW) laser at 243.1 nm. The radiation is generated through frequency quadrupling the output of a ytterbium-doped fiber amplifier system. which produces >10 W of CW power at 972.5 nm. We demonstrate absolute frequency control by locking the laser to an optical frequency comb and exciting the 1S-2S transition in atomic hydrogen. This frequency-stabilized, high-power deep-UV laser is of significant interest for precision spectroscopy of simple and exotic atoms, two-photon laser cooling of hydrogen, and Raman spectroscopy.

Kyphomelic dysplasia, Pierre Robin Sequence and pregnant.

We present the anaesthetic management of a parturient with kyphomelic dysplasia and Pierre Robin Sequence who underwent elective caesarean delivery. Potential anaesthetic issues and management strategies are discussed.

Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients.

BACKGROUND: The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA detected by screening patients with a stable creatinine remains unclear. METHODS: One hundred three patients younger than 18years receiving a first, kidney alone transplant between December 1, 2007, and December 31, 2013, underwent DSA screening every 3months for 2years posttransplant, with additional testing as clinically indicated. No treatment was given for DSAs in the absence of biopsy-proven rejection. RESULTS: Twenty (19%) patients had dnDSA first detected on a screening test, and 13 (13%) patients had dnDSA first detected on a for-cause test. Mean follow-up time posttransplant was 4.4years. Screening-detected dnDSA was associated with an increased risk of rejection within 3years, microvascular inflammation, and C4d staining on a 2-year protocol biopsy. In a Cox proportional hazards regression, screening-detected dnDSA was not associated with time to 30% decline in estimated glomerular filtration rate (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.30-2.00; P=0.598) or graft loss. dnDSA first detected on for-cause testing was associated with a 2.8 times increased risk of decline in graft function (95% CI, 1.08-7.27; P=0.034) and a 7.34 times increased risk of graft loss (95% CI, 1.37-39.23 P=0.020) compared with those who did not develop dnDSA. CONCLUSIONS: The clinical setting in which dnDSA is first detected impacts the association between dnDSA and graft function. Further research is needed to clarify the role of dnDSA screening in pediatric kidney transplantation.

Human papillomavirus vaccination acceptance and hesitancy in South Africa: Research and policy agenda.

Cervical cancer is responsible for one-quarter of a million deaths per year worldwide. In South Africa (SA), cervical cancer is the leading cause of cancer deaths among women aged 15 - 44 years. Human papillomavirus (HPV) vaccines provide a safe and highly effective means to reduce the burden of cervical cancer. The World Health Organization initiated a plan for the elimination of cervical cancer; the programme's success relies on the introduction and high uptake of HPV vaccines globally. SA introduced a school-based HPV vaccination programme in 2014, but uptake is not as high as expected. Suboptimal HPV vaccination coverage may result from various factors, including vaccine hesitancy. Vaccine-hesitant parents may delay or refuse HPV vaccination for their daughters. Tailored interventions are needed to address this. However, knowledge regarding vaccine hesitancy and policies to address this hesitancy in SA are currently limited. While SA has taken commendable steps in cervical cancer prevention by implementing and financing the HPV vaccination programme, it is imperative that there are clear policies in place to help strengthen the programme. These policies need to clarify areas of uncertainty that may lead to mistrust, and pre-empt factors that will cause hesitancy. Equally important is that local research should be conducted to better understand HPV vaccination hesitancy and other determinants of uptake to further inform and shape national policies.

Radiotherapy-induced reactivation of neurotrophic human herpes viruses: Overview and management.

PURPOSE: Infection by Human Herpes Viruses (HHV) types 1-3, are prevalent throughout the world. It is known that radiotherapy can reactivate HHVs, but it is unclear how and to what extent reactivations can interact with or affect radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo-radiotherapy, diagnosis and management so as to optimize cancer treatment in the setting of active HHV infection. Our secondary aim is to emphasize the need for further research to elucidate the potential adverse effects of active HHV infection in irradiated tumor tissue and to design optimal management strategies to incorporate into cancer management guidelines. MATERIALS AND METHODS: The literature regarding herpetic infection, herpetic reactivation, and recurrence occurring during radiotherapy and that regarding treatment guidelines for herpetic infections are reviewed. We aim to provide the oncologist with a reference for the infectious dangers of herpetic reactivation in patients under their care and well established methods for prevention, diagnosis, and treatment of such infections. Pain management is also considered. CONCLUSIONS: In the radiotherapeutic setting, serologic assays for HSV-1 and HSV-2 are feasible and can alert the clinician to patients at risk for viral reactivation. RT-PCR is specific in identifying the exact viral culprit and is the preferred diagnostic method to measure interventional efficacy. It can also differentiate between herpetic infection and radionecrosis. The MicroTrak® HSV1/HSV2/VZV staining kit has high sensitivity and specificity in acute lesions, is also the most rapid means to confirm diagnosis. Herpetic reactivation and recurrences during radiotherapy can cause interruptions, cessations, or prolongations of the radiotherapeutic course, thus decreasing the biologically effective dose, to sub-therapeutic levels. Active HHV infection within the treatment volume results in increased tumor radio-resistance and potentially sub-therapeutic care if left untreated. Visceral reactivations may result in fatality and therefore, a high index of suspicion is important to identify these active infections. The fact that such infections may be mistaken for acute and/or late radiation effects, leading to less than optimal treatment decisions, makes knowledge of this problem even more relevant. To minimize the risk of these sequelae, prompt anti-viral therapy is recommended, lasting the course of radiotherapy.

Factors associated with the effectiveness and reach of NHS stop smoking services for pregnant women in England.

BACKGROUND: The UK National Health Service provides Stop Smoking Services for pregnant women (SSSP) but there is a lack of evidence concerning how these are best organised. This study investigates influences on services' effectiveness and also on their propensity to engage pregnant smokers with support in stopping smoking. METHODS: Survey data collected from 121/141 (86%) of SSSP were augmented with data from Hospital Episode Statistics and the 2011 UK National Census. 'Reach' or propensity to engage smokers with support was defined as the percentage of pregnant smokers setting a quit date with SSSP support, and 'Effectiveness' as the percentage of women who set a quit date who also reported abstinence at four weeks later. A bivariate (i.e. two outcome variable) response Markov Chain Monte Carlo model was used to identify service-level factors associated with the Reach and Effectiveness of SSSP. RESULTS: Beta coefficients represent a percentage change in Reach and Effectiveness by the covariate. Providing the majority of one-to-one contacts in a clinic rather than at home increased both Reach (%) (ß: 6.97, 95% CI: 3.34, 10.60) and Effectiveness (%) (ß: 7.37, 95% CI: 3.03, 11.70). Reach of SSSP was also increased when the population served was more deprived (ß for increase in Reach with a one unit increase in IMD score: 0.55, 95% CI: 0.25, 0.85), had a lower proportion of people with dependent children (ß: -2.52, 95% CI: -3.82, -1.22), and a lower proportion of people in managerial or professional occupations (ß: -0.31, 95% CI: -0.59, -0.03). The Effectiveness of SSSP was decreased in those areas that had a greater percentage of people >16 years with no educational qualifications (ß: -0.51, 95% CI: -0.95, -0.07). CONCLUSIONS: To engage pregnant smokers and to encourage them to quit, it may be more efficient for SSSP support to be focussed around clinics, rather than women's homes. Reach of SSSP is inversely associated with disadvantage and efforts should be made to contact these women as they are less likely to achieve abstinence in the short and longer term.

Comparison of chronic physical and emotional social defeat stress effects on mesocorticolimbic circuit activation and voluntary consumption of morphine.

Chronic social defeat stress (CSDS) is a well-established rodent model of depression that induces persistent social avoidance. CSDS triggers molecular adaptations throughout the mesocorticolimbic reward circuit, including changes in the activity of dopamine neurons in the ventral tegmental area (VTA), that may also influence drug reward. One limitation of traditional, physical CSDS (PS) is that injury complicates the study of opiate drugs like morphine. Thus, we sought to characterize a variation of CSDS, termed emotional CSDS (ES), that eliminates this confound. We assessed the effect of PS and ES on mesocorticolimbic circuit activation, VTA gene expression, and morphine intake. We found that PS and ES similarly induced ΔFosB in the hippocampus, but only PS significantly increased ΔFosB expression in the prefrontal cortex and striatum. In contrast, cFos expression was similarly reduced by both PS and ES. Interestingly, we found that PS and ES similarly increased voluntary morphine consumption immediately following stress, despite differences in the magnitude of the depressive phenotype and striatal ΔFosB expression at this time point. Combined, these data suggest that both stress paradigms may be useful for investigation of stress-induced changes in drug behavior.