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1.
Lancet ; 402 Suppl 1: S2, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37997059

RESUMO

BACKGROUND: Evidence on workplace bullying and harassment (WBH) in the UK has not used probability-sample surveys with robust mental health assessments. This study aimed to profile the prevalence and nature of WBH in England, identify inequalities in WBH exposure, and quantify adjusted associations with mental health. METHODS: Data were from the 2014 Adult Psychiatric Morbidity Survey, a cross-sectional probability-sample survey of the household population in England, interviewed with verbal informed consent. Criteria for inclusion in the secondary analysis were being aged 16-70 years and in paid work in the past month (n=3838). Common mental disorders were assessed using the Clinical Interview Schedule-Revised and mental wellbeing using the Warwick-Edinburgh Mental Wellbeing Scale. Analyses were weighted. We examined associations between past-year WBH and current common mental disorders using multivariable regression modelling, adjusting for demographic and socioeconomic factors. Interaction terms tested for gender differences in associations. The study received ethics approval (ETH21220-299). FINDINGS: One in ten employees (10·6% (weighted), n=444/3838) reported past-year experience of WBH, with rates higher in women (12·2%, n=284/2189); those of mixed, multiple, and other ethnicity (21·0%, n=15/92); and people in debt (15·2%, n=50/281) or living in cold homes (14·6%, n=42/234). Most commonly identified perpetrators of WBH were line managers (53·6%, n=244/444) or colleagues (42·8%, n=194/444). Excessive criticism (49·3%, n=212/444), verbal abuse (42·6%, n=187/444), and humiliation (31·4%, n=142/444) were the most common types. WBH was associated with all adverse mental health indicators, including common mental disorders (adjusted odds ratio [aOR] 2·65, 95% CI 2·02-3·49), and 11 of 14 mental wellbeing indicators, including lower levels of confidence (aOR 0·57, 0·46-0·72) and of closeness to others (aOR 0·57, 0·46-0·72). Patterns of association between WBH and mental health were similar in men and women. INTERPRETATION: These findings reinforce a need for more cohesive UK legislation at the national level; guidance on recognition of bullying behaviours for employees, managers, and human resources at the organisational level, focusing on prevention and early intervention, and increased awareness of the impact of WBH on mental health among health-service practitioners. Study limitations include reliance on cross-sectional data collected before pandemic-related and other major changes in workplace practices. Longitudinal data are needed to improve evidence on causality and the longevity of mental health impacts. FUNDING: UK Prevention Research Partnership.


Assuntos
Bullying , Estresse Ocupacional , Adulto , Masculino , Humanos , Feminino , Saúde Mental , Prevalência , Estudos Transversais , Estudos de Amostragem , Inquéritos e Questionários
2.
BMC Public Health ; 24(1): 1147, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658961

RESUMO

BACKGROUND: Evidence on workplace bullying and harassment (WBH) in the UK has not used probability-sample surveys with robust mental health assessments. This study aimed to profile the prevalence and nature of WBH in England, identify inequalities in exposure, and quantify adjusted associations with mental health. METHODS: Data were from the 2014 Adult Psychiatric Morbidity Survey, a cross-sectional probability-sample survey of the household population in England. Criteria for inclusion in the secondary analysis were being aged 16-70 years and in paid work in the past month (n = 3838). Common mental disorders (CMDs) were assessed using the Clinical Interview Schedule-Revised and mental wellbeing using the Warwick-Edinburgh Mental Wellbeing Scale. Analyses were weighted. We examined associations between past-year WBH and current CMD using multivariable regression modelling, adjusting for sociodemographic factors. Interaction terms tested for gender differences in associations. The study received ethical approval (ETH21220-299). RESULTS: One in ten employees (10.6%, n = 444/3838) reported past-year experience of WBH, with rates higher in women (12.2%, n = 284/2189), those of mixed, multiple, and other ethnicity (21.0%, n = 15/92), and people in debt (15.2%, n = 50/281) or living in cold homes (14.6%, n = 42/234). Most commonly identified perpetrators of WBH were line managers (53.6%, n = 244/444) or colleagues (42.8%, n = 194/444). Excessive criticism (49.3%, n = 212/444), verbal abuse (42.6%, n = 187/444), and humiliation (31.4%, n = 142/444) were the most common types. WBH was associated with all indicators of poor mental health, including CMD (adjusted odds ratio [aOR] 2.65, 95% CI 2.02-3.49), and 11 of 14 mental wellbeing indicators, including lower levels of confidence (aOR 0.57, 0.46-0.72) and closeness to others (aOR 0.57, 0.46-0.72). Patterns of association between WBH and mental health were similar in men and women. CONCLUSIONS: These findings reinforce a need for more cohesive UK legislation against WBH; guidance on recognition of bullying behaviours for employees, managers, and human resources, focusing on prevention and early intervention, and increased awareness of the impact of WBH on mental health among health service practitioners. Limitations include reliance on cross-sectional data collected before pandemic-related and other changes in workplace practices. Longitudinal data are needed to improve evidence on causality and the longevity of mental health impacts.


Assuntos
Bullying , Transtornos Mentais , Local de Trabalho , Humanos , Estudos Transversais , Masculino , Feminino , Adulto , Bullying/estatística & dados numéricos , Bullying/psicologia , Pessoa de Meia-Idade , Inglaterra/epidemiologia , Adolescente , Adulto Jovem , Prevalência , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Idoso , Local de Trabalho/psicologia , Local de Trabalho/estatística & dados numéricos , Inquéritos e Questionários , Saúde Mental/estatística & dados numéricos
3.
Environ Res ; 233: 116452, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37339694

RESUMO

Background The exposome approach can be a powerful tool for understanding the intertwining of social, physical, and internal influences that shape mental health and cognitive development throughout childhood. To distil conceptual models for subsequent analyses, the EU-funded project Early Environmental quality and Life-course mental health effects (Equal-Life) has conducted literature reviews on potential mediators linking the exposome to these outcomes. We report on a scoping review and a conceptual model of the role of restorative possibilities and physical activity. Methods Peer-reviewed studies published since the year 2000 in English, on the association between the exposome and mental health/cognition in children/adolescents, and quantitatively investigating restoration/restorative quality as a mediating variable were considered. Database searches were last updated in December 2022. We used an unstructured expert-driven approach to fill in gaps in the reviewed literature. Results Five records of three distinct studies were identified, indicating a scarcity of empirical evidence in this newly developing research area. Not only were these studies few in numbers, but also cross-sectional, lending only tentative support to the idea that perceived restorative quality of adolescent's living environment might mediate the association between greenspace and mental health. Physical activity emerged as a mediator leading to better psychological outcomes in restorative environments. We provide a critical discussion of potential caveats when investigating the restoration mechanism in children and propose a hierarchical model including restoration, physical activity, and relational dynamics between children and their environment, including social context, as well as restorative environments other than nature. Conclusions It is justified to further explore the role of restoration and physical activity as mediators in the association between early-life exposome and mental health/cognitive development. It is important to consider the child perspective and specific methodological caveats. Given the evolving conceptual definitions/operationalizations, Equal-Life will attempt to fill in a critical gap in the literature.


Assuntos
Exercício Físico , Saúde Mental , Humanos , Adolescente , Criança , Estudos Transversais , Meio Social , Cognição
4.
Environ Res ; 239(Pt 1): 117279, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37778607

RESUMO

Mental disorders among children and adolescents pose a significant global challenge. The exposome framework covering the totality of internal, social and physical exposures over a lifetime provides opportunities to better understand the causes of and processes related to mental health, and cognitive functioning. The paper presents a conceptual framework on exposome, mental health, and cognitive development in children and adolescents, with potential mediating pathways, providing a possibility for interventions along the life course. The paper underscores the significance of adopting a child perspective to the exposome, acknowledging children's specific vulnerability, including differential exposures, susceptibility of effects and capacity to respond; their susceptibility during development and growth, highlighting neurodevelopmental processes from conception to young adulthood that are highly sensitive to external exposures. Further, critical periods when exposures may have significant effects on a child's development and future health are addressed. The paper stresses that children's behaviour, physiology, activity pattern and place for activities make them differently vulnerable to environmental pollutants, and calls for child-specific assessment methods, currently lacking within today's health frameworks. The importance of understanding the interplay between structure and agency is emphasized, where agency is guided by social structures and practices and vice-versa. An intersectional approach that acknowledges the interplay of social and physical exposures as well as a global and rural perspective on exposome is further pointed out. To advance the exposome field, interdisciplinary efforts that involve multiple scientific disciplines are crucial. By adopting a child perspective and incorporating an exposome approach, we can gain a comprehensive understanding of how exposures impact children's mental health and cognitive development leading to better outcomes.


Assuntos
Expossoma , Adolescente , Humanos , Adulto Jovem , Adulto , Exposição Ambiental , Saúde Mental , Formação de Conceito , Cognição
5.
Health Expect ; 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37705302

RESUMO

BACKGROUND: UNderstanding Factors that explain Avoidable hospital admission Inequalities-Research study (UNFAIR) addresses how to reduce health inequalities, particularly for avoidable hospital admissions. Our Patient and Public Involvement and Engagement (PPIE) members broached that health inequalities are complex, challenging to understand and communicate. They identified a need to explore diverse views, including people who have a higher risk of health inequalities. With limited public-facing resources relating to the public's understanding or emotions around health inequalities, this project aimed to fill this gap using co-leadership and co-production. METHODS: Members of the public worked with researchers to co-produce and run PPIE workshops. This project was co-led by a member of the public and a researcher. One online workshop open to anyone in England accompanied by three face-to-face workshops were held. Public contributors, including people living in diverse communities, were invited. Inclusive involvement opportunities were offered including flexible ways of involvement and remuneration. To strengthen the key messages' rigour, transcriptions of the audio-recordings from each workshop, with facilitator notes, were analysed using thematic analysis. From the key messages, an animation was co-produced with public contributors with the public's voice being integral throughout. KEY MESSAGES: A total of 58 people took part capturing intersecting and multiple dimensions of marginalisation including people with a range of ages, genders, ethnicities, socioeconomic backgrounds, and members of communities who face exclusion (including people with learning difficulties and experiencing ill-health). The animation highlighted powerful lived experience, for example, some people are dying earlier than expected. Health inequalities conjured up powerful emotions, such as anger and hopelessness. Public views of how to address health inequalities included respecting, accepting and valuing everyone, regardless of, for example, where people live. The animation is publicly available for use by anyone, including decision makers across the health and care system. CONCLUSIONS: Through co-leadership and co-production, this project is an example of inclusive PPIE. This project provided a way for the public's voice to influence policy and practice to inform understanding and action to address health inequalities. The animation provides powerful insights into what health inequalities mean to people with examples of lived experience and corroborates the moral argument for action by decision makers. PATIENT AND PUBLIC CONTRIBUTION: Members of the public, including people who were affected or at higher risk of health inequalities, co-led this project and were involved as co-creators and developers from the inception of the project to completion. Their involvement was integral and documented in full throughout the project.

6.
Eur Heart J ; 42(21): 2072-2084, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33733673

RESUMO

AIMS: The aim of this study was to investigate the cross-sectional associations of modelled residential road traffic noise with cardiovascular disease risk factors [systolic (SBP) and diastolic blood pressure (DBP), C-reactive protein, triglycerides, glycated haemoglobin, and self-reported hypertension] in UK Biobank. METHODS AND RESULTS: The UK Biobank recruited 502 651 individuals aged 40-69 years across the UK during 2006-10. Road traffic noise (Lden and Lnight) exposure for 2009 was estimated at baseline address using a simplified version of the Common Noise Assessment Methods model. We used multivariable linear and logistic regression models, adjusting for age, sex, body mass index (BMI), smoking, alcohol intake, area- and individual-level deprivation, season of blood draw, length of time at residence, and nitrogen dioxide (main model), in an analytical sample size of over 370 000 participants. Exposure to road-traffic Lden >65 dB[A], as compared to ≤55 dB[A], was associated with 0.77% [95% confidence interval (CI) 0.60%, 0.95%], 0.49% (95% CI 0.32%, 0.65%), 0.79% (95% CI 0.11%, 1.47%), and 0.12% (95% CI -0.04%, 0.28%) higher SBP, DBP, triglycerides, and glycated haemoglobin, respectively. Removing BMI from the main model yielded significant positive associations with all five markers with elevated percent changes. The associations with SBP or DBP did not appear to be impacted by hypertension medication while a positive association with prevalent self-reported hypertension was seen in the non-medicated group who exposed to a Lden level of 60-65 dB[A] (odds ratio 1.07, 95% CI 1.00, 1.15). CONCLUSION: Exposure to road traffic noise >65 dB[A], independent of nitrogen dioxide, was associated with small but adverse changes in blood pressure and cardiovascular biochemistry.


Assuntos
Doenças Cardiovasculares , Ruído dos Transportes , Bancos de Espécimes Biológicos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Exposição Ambiental , Humanos , Ruído dos Transportes/efeitos adversos , Fatores de Risco , Reino Unido/epidemiologia
7.
Environ Health ; 20(1): 32, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766056

RESUMO

BACKGROUND: Both physical and psychological health outcomes have been associated with exposure to environmental noise. Noise sensitivity could have the same moderating effect on physical and psychological health outcomes related to environmental noise exposure as on annoyance but this has been little tested. METHODS: A cohort of 2398 men between 45 and 59 years, the longitudinal Caerphilly Collaborative Heart Disease study, was established in 1984/88 and followed into the mid-1990s. Road traffic noise maps were assessed at baseline. Psychological ill-health was measured in phase 2 in 1984/88, phase 3 (1989/93) and phase 4 (1993/7). Ischaemic heart disease was measured in clinic at baseline and through hospital records and records of deaths during follow up. We examined the longitudinal associations between road traffic noise and ischaemic heart disease morbidity and mortality using Cox Proportional Hazard Models and psychological ill-health using Logistic Regression; we also examined whether noise sensitivity and noise annoyance might moderate these associations. We also tested if noise sensitivity and noise annoyance were longitudinal predictors of ischaemic heart disease morbidity and mortality and psychological ill-health. RESULTS: Road traffic noise was not associated with ischaemic heart disease morbidity or mortality. Neither noise sensitivity nor noise annoyance moderated the effects of road traffic noise on ischaemic heart disease morbidity or mortality. High noise sensitivity was associated with lower ischaemic heart disease mortality risk (HR = 0.74, 95%CI 0.57, 0.97). Road traffic noise was associated with Phase 4 psychological ill-health but only among those exposed to 56-60dBA (fully adjusted OR = 1.82 95%CI 1.07, 3.07). Noise sensitivity moderated the association of road traffic noise exposure with psychological ill-health. High noise sensitivity was associated longitudinally with psychological ill-health at phase 3 (OR = 1.85 95%CI 1.23, 2.78) and phase 4 (OR = 1.65 95%CI 1.09, 2.50). Noise annoyance predicted psychological ill-health at phase 4 (OR = 2.47 95%CI 1.00, 6.13). CONCLUSIONS: Noise sensitivity is a specific predictor of psychological ill-health and may be part of a wider construct of environmental susceptibility. Noise sensitivity may increase the risk of psychological ill-health when exposed to road traffic noise. Noise annoyance may be a mediator of the effects of road traffic noise on psychological ill-health.


Assuntos
Saúde Mental , Isquemia Miocárdica/epidemiologia , Ruído dos Transportes/efeitos adversos , Adulto , Exposição Ambiental , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Isquemia Miocárdica/mortalidade , País de Gales/epidemiologia
8.
J Acoust Soc Am ; 150(5): 3362, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34852585

RESUMO

The robust assessment of noise annoyance is of key importance given that it is the most prevalent community response in populations exposed to environmental noise. In 1993, the International Commission on Biological Effects of Noise Community Response to Noise team began formalizing a standardized methodology for assessing noise annoyance which resulted in reporting guidelines and recommendations later published as a Technical Specification (TS) in 2003 by the International Standards Organization (ISO) [(2003). ISO/TS 15666]. This TS, intended to inform the international community on the quantification of the exposure-response relationship between noise exposure and annoyance, has been in circulation for nearly two decades and was updated in 2021 by ISO [(2021). ISO/TS 15666] by an international working group (ISO TC43/SC1/WG62). This paper reviews use of the 2003 TS, identifies common adaptations in use, and summarizes the revisions. Methodological issues arising from the use of the 5-point verbal and the 11-point numeric scale questions and the scoring of "highly annoyed" are discussed. The revisions are designed to encourage further standardization in noise annoyance research. The paper highlights research needs that, if addressed, would strengthen the methodology underlying the assessment of noise annoyance including multidimensional assessments of annoyance.


Assuntos
Exposição Ambiental , Ruído , Ruído/efeitos adversos , Padrões de Referência , Inquéritos e Questionários
9.
Am J Epidemiol ; 187(3): 474-483, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28595334

RESUMO

Public expenditure on large events such as the London 2012 Olympic Games is often justified by the potential legacy of urban regeneration and its associated health and well-being benefits for local communities. In the Olympic Regeneration in East London Study, we examined whether there was an association between urban regeneration related to the 2012 Games and improved mental health in young people. Adolescents aged 11-12 years attending schools in the Olympic host borough of Newham in London or in 3 adjacent comparison London boroughs completed a survey before the 2012 Games and 6 and 18 months after the Games (in 2013 and 2014, respectively). Changes in depressive symptoms and well-being between baseline and each follow-up were examined. A total of 2,254 adolescents from 25 randomly selected schools participated. Adolescents from Newham were more likely to have remained depressed between baseline and the 6- and 18-month follow-up surveys (for 6-month follow-up, relative risk = 1.78, 95% confidence interval: 1.12, 2.83; for 18-month follow-up, relative risk = 1.93, 95% confidence interval: 1.01, 3.70) than adolescents from the comparison boroughs. No differences in well-being were observed. There was little evidence that urban regeneration had any positive influence on adolescent mental health and some suggestion that regeneration may have been associated with maintenance of depressive symptoms. Such programs may have limited short-term impact on the mental health of adolescents.


Assuntos
Aniversários e Eventos Especiais , Depressão/epidemiologia , Estudantes/psicologia , Reforma Urbana/história , Adolescente , Depressão/etiologia , Depressão/história , Feminino , História do Século XXI , Humanos , Londres/epidemiologia , Masculino , Instituições Acadêmicas , Esportes/história , Inquéritos e Questionários
10.
Phys Chem Chem Phys ; 19(11): 7877-7885, 2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-28262897

RESUMO

Understanding what influences the formation and lifetime of charge-separated states is key to developing photoelectrochemical devices. This paper describes the use of time-resolved infrared absorption spectroscopy (TRIR) to determine the structure and lifetime of the intermediates formed on photoexcitation of two organic donor-π-acceptor dyes adsorbed to the surface of NiO. The donor and π-linker of both dyes is triphenylamine and thiophene but the acceptors differ, maleonitrile (1) and bodipy (2). Despite their structural similarities, dye 1 outperforms 2 significantly in devices. Strong transient bands in the fingerprint region (1 and 2) and nitrile region (2300-2000 cm-1) for 1 enabled us to monitor the structure of the excited states in solution or adsorbed on NiO (in the absence and presence of electrolyte) and the corresponding kinetics, which are on a ps-ns timescale. The results are consistent with rapid (<1 ps) charge-transfer from NiO to the excited dye (1) to give exclusively the charge-separated state on the timescale of our measurements. Conversely, the TRIR experiments revealed that multiple species are present shortly after excitation of the bodipy chromophore in 2, which is electronically decoupled from the thiophene linker. In solution, excitation first populates the bodipy singlet excited state, followed by charge transfer from the triphenylamine to the bodipy. The presence and short lifetime (τ ≈ 30 ps) of the charge-transfer excited state when 2 is adsorbed on NiO (2|NiO) suggests that charge separation is slower and/or less efficient in 2|NiO than in 1|NiO. This is consistent with the difference in performance between the two dyes in dye-sensitized solar cells and photoelectrochemical water splitting devices. Compared to n-type materials such as TiO2, less is understood regarding electron transfer between dyes and p-type metal oxides such as NiO, but it is evident that fast charge-recombination presents a limit to the performance of photocathodes. This is also a major challenge to photocatalytic systems based on a "Z-scheme", where the catalysis takes place on a µs-s timescale.

11.
Noise Health ; 19(87): 41-50, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29192612

RESUMO

Noise is defined as "unwanted sound." Aircraft noise is one, if not the most detrimental environmental effect of aviation. It can cause community annoyance, disrupt sleep, adversely affect academic performance of children, and could increase the risk for cardiovascular disease of people living in the vicinity of airports. In some airports, noise constrains air traffic growth. This consensus paper was prepared by the Impacts of Science Group of the Committee for Aviation Environmental Protection of the International Civil Aviation Organization and summarizes the state of the science of noise effects research in the areas of noise measurement and prediction, community annoyance, children's learning, sleep disturbance, and health. It also briefly discusses civilian supersonic aircraft as a future source of aviation noise.


Assuntos
Aeronaves , Aeroportos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/prevenção & controle , Humor Irritável , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/prevenção & controle , Ruído dos Transportes/efeitos adversos , Ruído dos Transportes/prevenção & controle , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/prevenção & controle , Guias como Assunto , Humanos
12.
Lancet Oncol ; 17(12): 1720-1731, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27838224

RESUMO

BACKGROUND: Aberrant hedgehog signalling underlies the development of basal-cell carcinomas. We previously reported the interim analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial in patients with the basal-cell nevus (Gorlin) syndrome indicating that the smoothened inhibitor vismodegib reduces basal-cell carcinoma tumour burden and prevents new basal-cell carcinoma growth in patients with basal-cell nevus syndrome. We report the final results of this 36 month trial. METHODS: In our multicentre, randomised, double-blind, placebo-controlled, phase 2 trial we enrolled patients aged 35-75 years with basal-cell nevus syndrome with at least ten surgically eligible basal-cell carcinomas at the Children's Hospital Oakland, Columbia University outpatient dermatology clinic (NY, USA) and a private practice outpatient dermatology office in Newport Beach (CA, USA). Patients were assigned to vismodegib or placebo (2:1) according to a randomisation sequence generated by computer code. The primary endpoint of the trial of 41 patients was to compare the effect of oral vismodegib (150 mg/day) versus placebo on the incidence of new surgically eligible basal-cell carcinomas after 3 months of treatment. In the subsequent, open-label phase (n=37) patients continued vismodegib at two sites for as long as month 36 (n=25) and at the third site were monitored up to month 36 (n=12). Additional endpoints for this phase were: whether continuous versus interrupted dosing differentially affected tumour burden; time to reach various levels of reduction in tumour burden; reduction in tumour size in patients who took less than 50% of the expected number of vismodegib tablets; reduction in the number of surgical excisions required per year before, during, and after treatment; and the effect of vismodegib on hedgehog target gene expression. We monitored patients at visits every 3 months for up to 36 months. The primary endpoint was analysed on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00957229. FINDINGS: Between Sept 22, 2009, and Jan 24, 2011, 41 patients were monitored for a median of 36 months (IQR 36-36). Patients treated with vismodegib (n=26) had a mean reduced rate of new surgically eligible basal-cell carcinomas compared with patients randomly assigned to placebo (n=15; two [SD 0·12] new surgically eligible basal-cell carcinomas per patient per year vs 34 [1·32] new surgically eligible basal-cell carcinomas per patient per year, p<0·0001). In the 11 patients initially assigned to placebo, mean cross over to vismodegib reduced the development of new surgically eligible basal-cell carcinomas compared with placebo (0·4 [SD 0·2] new surgically eligible basal-cell carcinomas per patient per year vs 30·0 [7·8] new surgically eligible basal-cell carcinomas per patient per year, p<0·0001). Only three (17%) of 18 patients tolerated vismodegib continuously for the full 36 months. Fewer new surgically eligible basal-cell carcinomas developed in patients receiving vismodegib continuously than in those who interrupted dosing (mean 0·6 [0·72] new surgically eligible basal-cell carcinomas per patient per year vs 1·7 [1·8] new surgically eligible basal-cell carcinomas per patient per year, p<0·0001). Treatment-related grade 3-4 adverse events included weight loss of 20% or more (n=6) and muscle cramps (n=2). Two patients died during the course of the trial, one each from laryngeal and metastatic prostate cancer, deemed probably unrelated to drug. INTERPRETATION: Vismodegib reduces basal-cell carcinoma tumour burden in patients with basal-cell nevus syndrome. Adverse events associated with vismodegib frequently led to interruption of treatment, which is followed by basal-cell carcinoma recurrence. FUNDING: Genentech investigator-initiated trial funding, Clinical and Translational Science Award from the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Cancer Institute, Damon Runyon Cancer Research Foundation Clinical Investigator Award, Swim across America Foundation, and Michael J Rainen Family Foundation.


Assuntos
Anilidas/uso terapêutico , Síndrome do Nevo Basocelular/tratamento farmacológico , Proteínas Hedgehog/antagonistas & inibidores , Piridinas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Anilidas/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piridinas/efeitos adversos
13.
Environ Sci Technol ; 50(19): 10653-10660, 2016 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-27552529

RESUMO

Flame retardant (FR) chemicals have often been added to polyurethane foam to meet required state and federal flammability standards. However, some FRs (e.g., PBDEs and TDCIPP) are associated with health hazards and are now restricted from use in some regions. In addition, California's residential furniture flammability standard (TB-117) has undergone significant amendments over the past few years, and TDCIPP has been added to California's Proposition 65 list. These events have likely led to shifts in the types of FRs used, and the products to which they are applied. To provide more information on the use of FRs in products containing polyurethane foam (PUF), we established a screening service for the general public. Participants residing in the US were allowed to submit up to 5 samples from their household for analysis, free of charge, and supplied information on the product category, labeling, and year and state of purchase. Between February 2014 and June 2016, we received 1141 PUF samples for analysis from various products including sofas, chairs, mattresses, car seats and pillows. Of these samples tested, 52% contained a FR at levels greater than 1% by weight. Tris(1,3-dichloroisopropyl)phosphate (TDCIPP) was the most common FR detected in PUF samples, and was the most common FR detected in all product categories. Analysis of the data by purchasing date suggests that the use of TDCIPP decreased in recent years, paralleled with an increase in the use of TCIPP and a nonhalogenated aryl phosphate mixture we call "TBPP." In addition, we observed significant decreases in FR applications in furniture products and child car seats, suggesting the use of additive FRs in PUF may be declining, perhaps as a reflection of recent changes to TB-117 and Proposition 65. More studies are needed to determine how these changes in FR use relate to changes in exposure among the general population.


Assuntos
Retardadores de Chama , Decoração de Interiores e Mobiliário , Poeira , Éteres Difenil Halogenados , Habitação , Humanos
14.
Phys Chem Chem Phys ; 18(16): 10727-38, 2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-26734947

RESUMO

We investigated a range of different mesoporous NiO electrodes prepared by different research groups and private firms in Europe to determine the parameters which influence good quality photoelectrochemical devices. This benchmarking study aims to solve some of the discrepancies in the literature regarding the performance of p-DSCs due to differences in the quality of the device fabrication. The information obtained will lay the foundation for future photocatalytic systems based on sensitized NiO so that new dyes and catalysts can be tested with a standardized material. The textural and electrochemical properties of the semiconducting material are key to the performance of photocathodes. We found that both commercial and non-commercial NiO gave promising solar cell and water-splitting devices. The NiO samples which had the two highest solar cell efficiency (0.145% and 0.089%) also gave the best overall theoretical H2 conversion.

15.
Angew Chem Int Ed Engl ; 55(11): 3580-5, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26846616

RESUMO

Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.


Assuntos
Benzeno/química , Idoso , Animais , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID
16.
Lancet ; 383(9925): 1325-1332, 2014 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-24183105

RESUMO

Noise is pervasive in everyday life and can cause both auditory and non-auditory health effects. Noise-induced hearing loss remains highly prevalent in occupational settings, and is increasingly caused by social noise exposure (eg, through personal music players). Our understanding of molecular mechanisms involved in noise-induced hair-cell and nerve damage has substantially increased, and preventive and therapeutic drugs will probably become available within 10 years. Evidence of the non-auditory effects of environmental noise exposure on public health is growing. Observational and experimental studies have shown that noise exposure leads to annoyance, disturbs sleep and causes daytime sleepiness, affects patient outcomes and staff performance in hospitals, increases the occurrence of hypertension and cardiovascular disease, and impairs cognitive performance in schoolchildren. In this Review, we stress the importance of adequate noise prevention and mitigation strategies for public health.


Assuntos
Dispositivos de Proteção das Orelhas , Perda Auditiva Provocada por Ruído/etiologia , Perda Auditiva Provocada por Ruído/prevenção & controle , Saúde Pública , Atividades Cotidianas , Fatores Etários , Animais , Doenças Cardiovasculares/etiologia , Transtornos Cognitivos/etiologia , Exposição Ambiental/efeitos adversos , Perda Auditiva Provocada por Ruído/diagnóstico , Humanos , Ruído Ocupacional/efeitos adversos , Exposição Ocupacional/efeitos adversos , Fatores de Risco
17.
Inorg Chem ; 54(24): 11697-708, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26630550

RESUMO

The photophysical properties of a number of ruthenium complexes of the general structure [Ru(L1)(L2)(NCS)2], related to the prominent solar cell dye [Ru(dcb)2(NCS)2] (dcb = 4,4'-dicarboxylato-2,2'-bipyridine) are investigated. For L1 = dcb and dmb (dmb = 4,4'-dimethyl-2,2'-bipyridine), several variations of L2 show very little difference in the lowest energy absorption peak. Resonance Raman and density functional theory calculations have been used to assign the corresponding transitions as {Ru(NCS)2} → dcb with significant contributions of the NCS ligands. Transient absorption, time-resolved infrared, and transient resonance Raman spectroscopic techniques were used to probe the photophysics of the complexes and relatively short-lived {Ru(NCS)2} → dcb/dpb (dpb = 4,4'-diphenylethenyl-2,2'-bipyridine) excited states were observed with the exception of [Ru(dcb)(dab)(NCS)2] (dab = 4,4'-dianthracenethenyl-2,2'-bipyridine), which showed a long-lived excited state assigned as ligand centered charge separated.

18.
BMC Public Health ; 15: 150, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25884502

RESUMO

BACKGROUND: Populations living in urban areas experience greater health inequalities as well as higher absolute burdens of illness. It is well-established that a range of social and environmental factors determine these differences. Less is known about the relative importance of these factors in determining adolescent health within a super diverse urban context. METHODS: A cross-sectional sample of 3,105 adolescent participants aged 11 to 12 were recruited from 25 schools in the London boroughs of Newham, Tower Hamlets, Hackney and Barking & Dagenham. Participants completed a pseudo-anonymised paper-based questionnaire incorporating: the Warwick-Edinburgh Mental Well-being Scale used for assessing positive mental well-being, the Short Moods and Feelings Questionnaire based on the DSM III-R criteria for assessment of depressive symptoms, the Youth-Physical Activity Questionnaire and a self-assessment of general health and longstanding illness. Prevalence estimates and unadjusted linear models estimate the extent to which positive well-being scores and time spent in physical/sedentary activity vary by socio-demographic and environmental indicators. Logistic regression estimated the unadjusted odds of having fair/(very)poor general health, a long standing illness, or depressive symptoms. Fully adjusted mixed effects models accounted for clustering within schools and for all socio-demographic and environmental indicators. RESULTS: Compared to boys, girls had significantly lower mental well-being and higher rates of depressive symptoms, reported fewer hours physically active and more hours sedentary, and had poorer general health after full adjustment. Positive mental well-being was significantly and positively associated with family affluence but the overall relationship between mental health and socioeconomic factors was weak. Mental health advantage increased as positive perceptions of the neighbourhood safety, aesthetics, walkability and services increased. Prevalence of poor health varied by ethnic group, particularly for depressive symptoms, general health and longstanding illness suggesting differences in the distribution of the determinants of health across ethnic groups. CONCLUSIONS: During adolescence perceptions of the urban physical environment, along with the social and economic characteristics of their household, are important factors in explaining patterns of health inequality.


Assuntos
Disparidades nos Níveis de Saúde , Saúde Mental , Determinantes Sociais da Saúde , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Londres , Masculino , Características de Residência/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários , Saúde da População Urbana
19.
Soc Psychiatry Psychiatr Epidemiol ; 50(11): 1701-11, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26205126

RESUMO

PURPOSE: This study examines the extent to which in adolescent positive mental well-being and depressive symptoms vary across ethnic groups, and prospectively examines whether social support is protective against low/poor well-being and depression. METHODS: A longitudinal survey of 2426 adolescents from the Olympic Regeneration in East London study measured well-being and depressive symptoms at baseline at ages 11-12 and at follow-up two years later at ages 13-14. Social support was assessed at ages 11-12 years by the Multidimensional Scale of Perceived Social Support, by the level of parental support for school, by the frequency of family activities and by friendship choices. Ethnic differences in well-being and depression in Bangladeshi (N = 337) and Black African (N = 249) adolescents compared to their White UK counterparts (N = 380) were estimated adjusted stepwise for socio-demographic factors and domains of social support. RESULTS: Black African and Bangladeshi adolescents scored significantly higher for well-being than their White UK counterparts. There were no significant ethnic differences in the prevalence of depressive symptoms. Lower levels of social support were prospectively associated with lower well-being and higher rates of depression in all ethnic groups. Adjustment for multiple domains of social support did not account for ethnic differences in well-being. CONCLUSION: Bangladeshi and Black African adolescents in East London may have a positive mental health advantage over their White UK counterparts though social support did not fully explain this difference. Further investigation of the reasons for lower well-being in the White UK group is needed.


Assuntos
Povo Asiático/psicologia , População Negra/psicologia , Depressão/etnologia , Disparidades nos Níveis de Saúde , Saúde Mental/etnologia , Apoio Social , População Branca/psicologia , Adolescente , Povo Asiático/estatística & dados numéricos , População Negra/estatística & dados numéricos , Criança , Feminino , Humanos , Londres/epidemiologia , Masculino , Estudos Prospectivos , Reino Unido/epidemiologia , População Branca/estatística & dados numéricos
20.
Growth Factors ; 32(1): 11-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24471468

RESUMO

The non-canonical Wnt receptor, Ryk, promotes chemorepulsive axon guidance in the developing mouse brain and spinal cord in response to Wnt5a. Ryk has also been identified as a major suppressor of axonal regrowth after spinal cord injury. Thus, a comprehensive understanding of how growing axons and dendrites respond to Wnt5a-mediated Ryk activation is required if we are to overcome this detrimental activity. Here we undertook a detailed analysis of the effect of Wnt5a/Ryk interactions on axonal and dendritic growth in dissociated embryonic mouse cortical neuron cultures, focusing on callosal neurons known to be responsive to Ryk-induced chemorepulsion. We show that Ryk inhibits axonal growth in response to Wnt5a. We also show that Wnt5a inhibits dendrite growth independently of Ryk. However, this inhibition is relieved when Ryk is present. Therefore, Wnt5a-mediated Ryk activation triggers divergent responses in callosal axons and dendrites in the in vitro context.


Assuntos
Axônios/metabolismo , Dendritos/metabolismo , Neurogênese/fisiologia , Receptores Proteína Tirosina Quinases/metabolismo , Proteínas Wnt/metabolismo , Animais , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurogênese/genética , Receptores Proteína Tirosina Quinases/genética , Medula Espinal/embriologia , Medula Espinal/crescimento & desenvolvimento , Traumatismos da Medula Espinal/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/farmacologia , Via de Sinalização Wnt , Proteína Wnt-5a
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