Search

An abstract of the paper "An Update of Observed Stratospheric Temperature Trends" from the 19th Conference on Climate Variability and Change is presented.

Objectives: Assisted dying has been legally available in Oregon in the USA for 25 years, since when official reports have been published each year detailing the number of people who have used this option as well as sociodemographic and information about the process. The aim of this study was to examine changes over time in these data., Methods: We collated and reviewed data on 2454 assisted deaths included in annual reports on assisted deaths published by the Oregon Health Authority from 1998 to 2022. Descriptive statistics were used to describe time trends., Results: The number of assisted deaths in Oregon increased from 16 in 1998 to 278 in 2022. Over this time, patients' health funding status changed from predominantly private (65%) to predominantly government support (79.5%), and there was an increase in patients feeling a burden and describing financial concerns as reasons for choosing an assisted death. There has been a reduction in the length of the physician-patient relationship from 18 weeks in 2010 to 5 weeks in 2022, and the proportion referred for psychiatric assessment remains low (1%). Data are frequently missing, particularly around complications., Conclusions: The number and characteristics of people accessing assisted deaths, and the process, have changed since data collection started in 1998. Prospective studies are needed to examine the relationship between socioeconomic factors and the desire for an assisted death in Oregon., Competing Interests: Competing interests: CR provides content for the website ‘Keep Assisted Dying Out of Healthcare’. IF is a board member of Living & Dying Well and is co-chair of the All Party Parliamentary Group for Dying Well. AW was a part-time paid researcher for Living and Dying Well from June 2021 to June 2022., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

We examined whether a community engagement approach and jurisdictional attributes were associated with local action to restrict the sale of flavored tobacco products in Los Angeles County during 2019-2022. We estimated crude and adjusted risk ratios to examine these associations. Jurisdictions that used an active community engagement approach to adopt a flavored tobacco ban ordinance, those with previous experience adopting other tobacco-related ordinances, and those located next to communities that have an existing tobacco retail license ordinance were more likely than jurisdictions without these attributes to adopt a new ordinance to restrict the sale of flavored tobacco products. Efforts to adopt such an ordinance were generally more successful in jurisdictions where community members were engaged and policy makers were familiar with the adoption of public health ordinances.

Objectives: Most clinical teams and organisations have not openly or formally discussed how they would react if physician-assisted suicide were to be legalised. This paper aims to discuss some of the potential challenges of introducing 'assisted dying' into medical care and produces a table of questions and considerations in light of such evidence so as to promote necessary discussion., Methods: An analysis of recent quantitative and qualitative studies from jurisdictions where 'assisted dying' is practised was conducted, with particular attention paid to studies which focus on the impact of legalising 'assisted dying' on clinical care., Results: 'Assisted dying' can have a significant impact on clinical practice by complicating patient care and increasing clinician workload, potentially causing stress on patient care., Conclusions: If physician-assisted suicide was to be legalised as part of existing healthcare, there are many questions that healthcare organisations must consider. Such considerations are tabulated in order to encourage awareness and discussion on the topic., Competing Interests: Competing interests: IF is on the board of Living and Dying Well, a think tank that researches and analyses evidence surrounding the ‘assisted dying’ debate. AW declares paid employment with Living and Dying Well for whom she works as a temporary researcher., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Routine health facility data provides the opportunity to monitor progress in quality and uptake of health care continuously. Our study aimed to assess the reliability and usefulness of emergency obstetric care data including temporal and regional variations over the past five years in Tanzania Mainland., Methods: Data were compiled from the routine monthly district reports compiled as part of the health management information systems for 2016-2020. Key indicators for maternal and neonatal care coverage, emergency obstetric and neonatal complications, and interventions indicators were computed. Assessment on reliability and consistency of reports was conducted and compared with annual rates and proportions over time, across the 26 regions in of Tanzania Mainland and by institutional delivery coverage., Results: Facility reporting was near complete with 98% in 2018-2020. Estimated population coverage of institutional births increased by 10% points from 71.2% to 2016 to 81.7% in 2020 in Tanzania Mainland, driven by increased use of dispensaries and health centres compared to hospitals. This trend was more pronounced in regions with lower institutional birth rates. The Caesarean section rate remained stable at around 10% of institutional births. Trends in the occurrence of complications such as antepartum haemorrhage, premature rupture of membranes, pre-eclampsia, eclampsia or post-partum bleeding were consistent over time but at low levels (1% of institutional births). Prophylactic uterotonics were provided to nearly all births while curative uterotonics were reported to be used in less than 10% of post-partum bleeding and retained placenta cases., Conclusion: Our results show a mixed picture in terms of usefulness of the District Health Information System(DHIS2) data. Key indicators of institutional delivery and Caesarean section rates were plausible and provide useful information on regional disparities and trends. However, obstetric complications and several interventions were underreported thus diminishing the usefulness of these data for monitoring. Further research is needed on why complications and interventions to address them are not documented reliably., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Official data reports from countries where assisted suicide and euthanasia is legal are an important resource for discerning participation rates, patient safety and transparency in the way that assisted dying is legal. We aimed to identify what information is published in official data reports on assisted suicide and euthanasia across jurisdictions., Methods: We searched for official data reports from every jurisdiction where assisted suicide or euthanasia is legal. Searches were conducted on these countries' official health authority websites as well as on mainstream search engines. The data measures included within each report were described in four categories: participation data, patient characteristics, clinician characteristics, and drugs and dying process., Results: We found that 16 jurisdictions where assisted suicide or euthanasia is currently legal regularly publish data reports regarding its practice. The information included within these official reports varies greatly, with few measures published across all or most jurisdictions., Conclusions: Differences in the kinds of information published within official reports on assisted suicide and euthanasia makes comparing the practice of assisted suicide and euthanasia across jurisdictions challenging. Many jurisdictions fail to report data measures, which could be valuable to the understanding of assisted suicide and euthanasia practices within that country. Improving data reporting across jurisdictions where assisted suicide and euthanasia is legal, for example, through establishing minimum requirements for data collection and reporting, is an important step towards ensuring patient safety and the transparent practice of assisted suicide and euthanasia., Competing Interests: Competing interests: IF is on the board of Living and Dying Well, a think tank that researches and analyses evidence surrounding the ‘assisted dying’ debate. AW declares paid employment with Living and Dying Well for whom she works as a temporary researcher., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tanzania has made remarkable progress in reducing malaria burden and aims to transition from malaria control to sub-national elimination. In 2013, electronic weekly and monthly reporting platforms using the District Health Information System 2 (DHIS2) were introduced. Weekly reporting was implemented through the mobile phone-based Integrated Disease Surveillance and Response (eIDSR) platform and progressively scaled-up from 67 to 7471 (100%) public and private health facilities between 2013 and 2020. This study describes the roll-out and large-scale implementation of eIDSR and compares the consistency between weekly eIDSR and monthly DHIS2 malaria indicator data reporting, including an assessment of its usefulness for malaria outbreak detection and case-based surveillance (CBS) in low transmission areas., Methods: The indicators included in the analysis were number of patients tested for malaria, number of confirmed malaria cases, and clinical cases (treated presumptively for malaria). The analysis described the time trends of reporting, testing, test positivity, and malaria cases between 2013 and 2021. For both weekly eIDSR and monthly DHIS2 data, comparisons of annual reporting completeness, malaria cases and annualized incidence were performed for 2020 and 2021; additionally, comparisons were stratified by malaria epidemiological strata (parasite prevalence: very low < 1%, low 1 ≤ 5%, moderate 5 ≤ 30%, and high > 30%)., Results: Weekly eIDSR reporting completeness steadily improved over time, with completeness being 90.2% in 2020 and 93.9% in 2021; conversely, monthly DHIS2 reporting completeness was 98.9% and 98.7% in 2020 and 2021, respectively. Weekly eIDSR reporting completeness and timeliness were highest in the very low epidemiological stratum. Annualized malaria incidence as reported by weekly eIDSR was 17.5% and 12.4% lower than reported by monthly DHIS2 in 2020 and 2021; for both 2020 and 2021, annualized incidence was similar across weekly and monthly data in the very low stratum., Conclusion: The concurrence of annualized weekly eIDSR and monthly DHIS2 reporting completeness, malaria cases and incidence in very low strata suggests that eIDSR could be useful tool for early outbreak detection, and the eIDSR platform could reliably be expanded by adding more indicators and modules for CBS in the very low epidemiological stratum., (© 2022. The Author(s).)

Background: 'Assisted dying' is practiced in some European countries and US states. Legislation suggests that there exists an easily prescribed drug which consistently brings about death quickly and painlessly. Evidence from jurisdictions where 'assisted dying' is practiced, however, reveals that hastening patient death is not so simple., Sources of Data: This report is a collation of assisted suicide and euthanasia drug protocols published by the Canadian Association of MAiD Assessors and Providers and the Royal Dutch Medical Association, annual data reports from the USA and Canada and relevant academic publications pertaining to methods of 'assisted dying' in the USA, Belgium, Canada and Switzerland., Areas of Agreement: A wide variety of lethal drug combinations are used for people who want their life ended, and the prevalence of complications and failures in intentionally ending life suggest that 'assisted dying' applicants are at risk of distressing deaths., Areas of Controversy: The efficacy and safety of 'assisted dying' drugs are currently difficult to assess, as clinician reporting is often very low., Growing Points: The findings from this report reveal that little attention has been given to the problem of unmonitored prescribing and administering of lethal drug combinations, whose mode of action is unclear., Areas Timely for Developing Research: In order to properly assess the efficacy and safety of 'assisted dying', a more thorough means of data collection regarding the drugs used must be implemented and research is urgently needed into their mode of action., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Tanzania introduced District Health Information Software (version 2; DHIS2) in 2013 to support existing health management information systems and to improve data quality and use. However, to achieve these objectives, it is imperative to build human resource capabilities to address the challenges of new technologies, especially in resource-constrained countries., Objective: This study aimed to determine the perceived usefulness, competency, and associated factors in using DHIS2 data among district health managers (DHMs) in Tanzania., Methods: This descriptive cross-sectional study used a quantitative approach, which involved using a self-administered web-based questionnaire. This study was conducted between April and September 2019. We included all core and co-opted members of the council or district health management teams (DHMTs) from all 186 districts in the country. Frequency and bivariate analyses were conducted, and the differences among categories were measured by using a chi-square test. P values of <.05 were considered significant., Results: A total of 2667 (77.96%) of the expected 3421 DHMs responded, of which 2598 (97.41%) consented and completed the questionnaires. Overall, the DHMs were satisfied with DHIS2 (2074/2596, 79.83%) because of workload reduction (2123/2598, 81.72%), the ease of learning (1953/2598, 75.17%), and enhanced data use (2239/2598, 86.18%). Although only half of the managers had user accounts (1380/2598, 53.12%) and were trained on DHIS2 data analysis (1237/2598, 47.61%), most claimed to have average to advanced skills in data validation (1774/2598, 68.28%), data visualization (1563/2598, 60.16%), and DHIS2 data use (1321/2598, 50.85%). The biggest challenges facing DHMs included the use of a paper-based system as the primary data source (1890/2598, 72.75%) and slow internet speed (1552/2598, 59.74%). Core members were more confident in using DHIS2 compared with other members (P=.004), whereas program coordinators were found to receive more training on data analysis and use (P=.001) and were more confident in using DHIS2 data compared with other DHMT members (P=.001)., Conclusions: This study showed that DHMs have appreciable competencies in using the DHIS2 and its data. However, their skill levels have not been commensurate with the duration of DHIS2 use. This study recommends improvements in the access to and use of DHIS2 data. More training on data use is required and should involve using cost-effective approaches to include both the core and noncore members of the DHMTs. Moreover, enhancing the culture and capacity of data use will ensure the better management and accountability of health system performance., (©Daudi Simba, Felix Sukums, Claud Kumalija, Sarah Eden Asiimwe, Sai Kumar Pothepragada, Patrick Warui Githendu. Originally published in JMIR Formative Research (https://formative.jmir.org), 23.05.2022.)

Biomarkers are needed in muscle-invasive bladder cancer (MIBC). We previously reported that high tumor aurora kinase (AURK) A expression identifies patients with MIBC with poor prognosis. Aberrant p53 expression has also been associated with poor outcomes in MIBC, though to the best of our knowledge, co-expression rates of p53 and aurora kinases have not been previously described in MIBC. As aurora kinase and p53 family members may co-regulate each other, the present study investigated whether tumor p53 or p63 protein expression influenced the prognostic value of AURKA in a pilot study of 50 patients with MIBC treated with curative intent. Immunohistochemistry for AURKA, AURKB, p53 and p63 were performed on archival pre-treatment tumor specimens and correlated with clinical outcomes in patients with MIBC who received neoadjuvant chemotherapy (NAC) prior to cystectomy. Baseline p53 [hazard ratio (HR) 1.46; 95% confidence interval (CI)=0.55-3.9; P=0.448) and p63 (HR 2.02; 95% CI=0.51-8.1; P=0.313) protein expression did not predict for overall survival (OS). Low p53 protein expression did not correlate with high AURKA (φ=0.190) or AURKB (φ=0.075) expression. However, in tumors with low p53 expression (n=17), the presence of either high AURKA or AURKB expression levels predicted an increased risk for relapse (HR 27.1; 95% CI=2.7-270.1; P=0.005) and mortality (HR 14.9; 95% CI=2.3-95.6; P=0.004) compared to tumors with both low AURKA and AURKB levels. The relationship between p63 and AURKA/B expression levels was not tested due to the prevalence (80%) of high p63 expression in the present cohort. In tumors with low AURKA expression, p53 status did not predict for OS (HR 0.62; 95% CI 0.2-3.2; P=0.572). In multivariable analysis, only high baseline AURKA expression predicted for inferior OS (HR 4.9; 95% CI 1.7-14.1; P=0.003). To the best of our knowledge, the present study was the first to report co-expression of p53 and aurora kinase family members in MIBC, and although wild-type p53 may regulate the aurora kinases in preclinical models, the adverse prognostic value of tumor AURKA overexpression was independent from baseline tumor p53 protein expression in the present cohort. AURKA remains an important prognostic biomarker in patients with MIBC and warrants further evaluation in prospective studies to validate whether baseline AURKA can identify patients that are unlikely to benefit from standard of care with NAC., Competing Interests: The authors declare they have no competing interests., (Copyright: © Burgess et al.)

In this article, we consider the arguments for and against physician-assisted suicide (AS) and physician-assisted euthanasia (Eu). We assess the evidence around law and practice in three jurisdictions where one or both are legal, with emphasis on data from Oregon. We compare the eligibility criteria in these different regions and review the range of approved disorders. Cancer is the most common cause for which requests are granted, with neurodegenerative diseases, mostly motor neurone disease, ranking second. We review the issues that may drive requests for a physician-assisted death, such as concerns around loss of autonomy and the possible role of depression. We also review the effectiveness and tolerability of some of the life-ending medications used. We highlight significant variation in regulatory oversight across the different models. A large amount of data are missing or unavailable. We explore physician-AS and physician-assisted Eu within the wider context of end-of-life practice., Competing Interests: Competing interests: CR and ML are the members of the Association of Palliative Medicine. CR manages the KADOH website (www.kadoh.uk)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

For the spectroscopic assessment of brain disorders that require large-volume coverage, the requirements of RF performance and field homogeneity are high. For epilepsy, this is also challenging given the inter-patient variation in location, severity and subtlety of anatomical identification and its tendency to involve the temporal region. We apply a targeted method to examine the utility of large-volume MR spectroscopic imaging (MRSI) in surgical epilepsy patients, implementing a two-step acquisition, comprised of a 3D acquisition to cover the fronto-parietal regions, and a contiguous parallel two-slice Hadamard-encoded acquisition to cover the temporal-occipital region, both with T R /T E = 2000/40 ms and matched acquisition times. With restricted (static, first/second-order) B 0 shimming in their respective regions, the Cramér-Rao lower bounds for creatine from the temporal lobe two-slice Hadamard and frontal-parietal 3D acquisition are 8.1 ± 2.2% and 6.3 ± 1.9% respectively. The datasets are combined to provide a total 60 mm axial coverage over the frontal, parietal and superior temporal to middle temporal-occipital regions. We applied these acquisitions at a nominal 400 mm 3 voxel resolution in n = 27 pre-surgical epilepsy patients and n = 20 controls. In controls, 86.6 ± 3.2% voxels with at least 50% tissue (white + gray matter, excluding CSF) survived spectral quality inclusion criteria. Since all patients were clinically followed for at least 1 year after surgery, seizure frequency outcome was available for all. The MRSI measurements of the total fractional metabolic dysfunction (characterized by the Cr/NAA metric) in FreeSurfer MRI gray matter segmented regions, in the patients compared with the controls, exhibited a significant Spearman correlation with post-surgical outcome. This finding suggests that a larger burden of metabolic dysfunction is seen in patients with poorer post-surgical seizure control., (© 2021 John Wiley & Sons, Ltd.)

Hydraulic fracturing is used to access oil and natural gas reserves. This process involves the high-pressure injection of fluid to fracture shale. Fracking fluid contains approximately 95% water, chemicals and 4.5% fracking sand. Workers may be exposed to fracking sand dust (FSD) during the manipulation of the sand, and negative health consequences could occur if FSD is inhaled. In the absence of any information about its potential toxicity, a comprehensive rat animal model study (see Fedan et al., 2020) was designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems. The goal of this study was to assess the effects of inhalation of one FSD, i.e., FSD 8, on factors and tissues that affect cardiovascular function. Male rats were exposed to 10 or 30 mg/m 3 FSD (6 h/d for 4 d) by whole body inhalation, with measurements made 1, 7 or 27 d post-exposure. One day following exposure to 10 mg/m 3 FSD the sensitivity to phenylephrine-induced vasoconstriction in tail arteries in vitro was increased. FSD exposure at both doses resulted in decreases in heart rate (HR), HR variability, and blood pressure in vivo. FSD induced changes in hydrogen peroxide concentrations and transcript levels for pro-inflammatory factors in heart tissues. In kidney, expression of proteins indicative of injury and remodeling was reduced after FSD exposure. When analyzed using regression analysis, changes in proteins involved in repair and remodeling were correlated. Thus, it appears that inhalation of FSD does have some prolonged effects on cardiovascular, and, possibly, renal function. The findings also provide information regarding potential mechanisms that may lead to these changes, and biomarkers that could be examined to monitor physiological changes that could be indicative of impending cardiovascular dysfunction., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest in relation to this publication., (Copyright © 2020. Published by Elsevier Inc.)

Background: Recent malaria control efforts in mainland Tanzania have led to progressive changes in the prevalence of malaria infection in children, from 18.1% (2008) to 7.3% (2017). As the landscape of malaria transmission changes, a sub-national stratification becomes crucial for optimized cost-effective implementation of interventions. This paper describes the processes, data and outputs of the approach used to produce a simplified, pragmatic malaria risk stratification of 184 councils in mainland Tanzania., Methods: Assemblies of annual parasite incidence and fever test positivity rate for the period 2016-2017 as well as confirmed malaria incidence and malaria positivity in pregnant women for the period 2015-2017 were obtained from routine district health information software. In addition, parasite prevalence in school children (PfPR 5to16 ) were obtained from the two latest biennial council representative school malaria parasitaemia surveys, 2014-2015 and 2017. The PfPR 5to16 served as a guide to set appropriate cut-offs for the other indicators. For each indicator, the maximum value from the past 3 years was used to allocate councils to one of four risk groups: very low (< 1%PfPR 5to16 ), low (1- < 5%PfPR 5to16 ), moderate (5- < 30%PfPR 5to16 ) and high (≥ 30%PfPR 5to16 ). Scores were assigned to each risk group per indicator per council and the total score was used to determine the overall risk strata of all councils., Results: Out of 184 councils, 28 were in the very low stratum (12% of the population), 34 in the low stratum (28% of population), 49 in the moderate stratum (23% of population) and 73 in the high stratum (37% of population). Geographically, most of the councils in the low and very low strata were situated in the central corridor running from the north-east to south-west parts of the country, whilst the areas in the moderate to high strata were situated in the north-west and south-east regions., Conclusion: A stratification approach based on multiple routine and survey malaria information was developed. This pragmatic approach can be rapidly reproduced without the use of sophisticated statistical methods, hence, lies within the scope of national malaria programmes across Africa.

Objectives: Overexpression of aurora kinase A (AURKA) confers a poor prognosis in patients with urothelial carcinoma of the bladder. The prognostic value of high aurora kinase B (AURKB) expression in local bladder cancer is not well defined, and whether the prognostic value of either AURKA or AURKB is affected by the use of chemotherapy is unknown. We sought to characterize the impact of high AURKA and AURKB expression on clinical outcome in patients with muscle-invasive bladder cancer (MIBC) who received neoadjuvant chemotherapy (NAC)., Materials and Methods: Immunohistochemistry for AURKA and AURKB was performed on pretreatment diagnostic transurethral resection of bladder tumor (TURBT) and matched cystectomy specimens in 50 subjects with MIBC who received NAC. Receiver operator characteristic curves (ROC) were calculated to assess the impact of AURKA and AURKB expression on pathologic response rate. Kaplan-Meier techniques and Cox proportional hazards models were used to assess the association with relapse-free survival (RFS) and overall survival (OS)., Results: Twenty-two of 50 [44%] patients had residual muscle-invasive (ypT2-4) urothelial carcinoma after NAC. Neither baseline tumor expression of AURKA (ROC = 0.57, P = 0.46) nor AURKB (ROC = 0.56, P = 0.87) predicted for ypT2-4 status. However, baseline expression of AURKA above the 75th percentile for this cohort was associated with an inferior RFS, (HR = 3.88, P = 0.008) and OS, (HR = 6.10, P < 0.001). Similar trends for worse survival outcomes were also observed for high AURKB levels (RFS, [HR = 2.2, P = 0.13] and OS, (HR = 2.25, P = 0.09)., Conclusions: High baseline tumor AURKA and AURKB expression identified MIBC patients with inferior RFS and OS despite the use of NAC and may identify patients who should be prioritized for clinical trial enrollment rather than standard cisplatin-based chemotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Biological invasions are among the main drivers of biodiversity losses. As threats from biological invasions increase, one of the most urgent tasks is to identify areas of high vulnerability. However, the lack of comprehensive information on the impacts of invasive alien species (IAS) is a problem especially on islands, where most of the recorded extinctions associated with IAS have occurred. Here we provide a global, network-oriented analysis of IAS on islands. Using network analysis, we structured 27,081 islands and 437 threatened vertebrates into 21 clusters, based on their profiles in term of invasiveness and shared vulnerabilities. These islands are mainly located in the Southern Hemisphere and many are in biodiversity hotspots. Some of the islands share similar characteristics regarding their connectivity that could be useful for understanding their response to invasive species. The major invaders found in these clusters of islands are feral cats, feral dogs, pigs and rats. Our analyses reveal those IAS that systematically act alone or in combination, and the pattern of shared IAS among threatened species, providing new information to implement effective eradication strategies. Combined with further local, contextual information this can contribute to global strategies to deal with IAS.

Talimogene laherparepvec (T-Vec) is the first live virus to be approved by the US Food and Drug Administration for the treatment of cancer. This engineered version of herpes simplex virus type 1 (HSV-1) is the product of decades of preclinical work aimed at identifying and modifying aspects of the viral genome involved in virulence and immunogenicity. T-Vec preferentially infects and lyses tumor cells and, in some cases, induces a systemic immune response against the tumor. These properties have translated into significant and durable clinical responses, particularly in advanced melanoma. Many unanswered questions remain, including how to augment these clinical responses and which other tumor types may respond to oncolytic therapy. Here, we review the development of T-Vec, our current understanding of its impact on the tumor immune micro-environment, and its safety and efficacy in clinical trials for melanoma and other cancers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Research in cancer immunology is currently accelerating following a series of cancer immunotherapy breakthroughs during the last 5 years. Various monoclonal antibodies which block the interaction between checkpoint molecules PD-1 on immune cells and PD-L1 on cancer cells have been used to successfully treat non-small cell lung cancer (NSCLC), including some durable responses lasting years. Two drugs, nivolumab and pembrolizumab, are now FDA approved for use in certain patients who have failed or progressed on platinum-based or targeted therapies while agents targeting PD-L1, atezolizumab and durvalumab, are approaching the final stages of clinical testing. Despite impressive treatment outcomes in a subset of patients who receive these immune therapies, many patients with NSCLC fail to respond to anti-PD-1/PD-L1 and the identification of a biomarker to select these patients remains highly sought after. In this review, we discuss the recent clinical trial results of pembrolizumab, nivolumab, and atezolizumab for NSCLC, and the significance of companion diagnostic testing for tumor PD-L1 expression.

Schools are increasingly seen as key sites for support to HIV-affected and other vulnerable children, and teachers are assigned the critical role of identifying and providing psychosocial support. Drawing on the life-work history narratives of 12 teachers in Zimbabwe, this paper explores the psychosocial processes underpinning teachers' conceptualisations of these caring roles. The influence of prolonged adversity, formative relationships, and broader patterns of social and institutional change in teacher identity formation processes speak to the complex and embodied nature of understandings of 'care'. In such extreme settings teachers prioritise the material and disciplinary aspects of 'care' that they see as essential for supporting children to overcome hardship. This focus not only means that emotional support as envisaged in international policy is commonly overlooked, but also exposes a wider ideological clash about childrearing. This tension together with an overall ambivalence surrounding teacher identities puts further strain on teacher-student relationships. We propose the current trainings on providing emotional support are insufficient and that more active focus needs to be directed at support to teachers in relation with their students. © 2015 The Authors. Journal of Community & Applied Social Psychology published by John Wiley & Sons Ltd.

Objective: The aim of this study was to use an established model of vibration-induced injury to assess frequency-dependent changes in transcript expression in skin, artery, and nerve tissues., Methods: Transcript expression in tissues from control and vibration-exposed rats (4 h/day for 10 days at 62.5, 125, or 250 Hz; 49 m/s, rms) was measured. Transcripts affected by vibration were used in bioinformatics analyses to identify molecular- and disease-related pathways associated with exposure to vibration., Results: Analyses revealed that cancer-related pathways showed frequency-dependent changes in activation or inhibition. Most notably, the breast-related cancer-1 pathway was affected. Other pathways associated with breast cancer type 1 susceptibility protein related signaling, or associated with cancer and cell cycle/cell survivability were also affected., Conclusion: Occupational exposure to vibration may result in DNA damage and alterations in cell signaling pathways that have significant effects on cellular division.

Repeated exposure to hand-transmitted vibration through the use of powered hand tools may result in pain and progressive reductions in tactile sensitivity. The goal of the present study was to use an established animal model of vibration-induced injury to characterize changes in sensory nerve function and cellular mechanisms associated with these alterations. Sensory nerve function was assessed weekly using the current perception threshold test and tail-flick analgesia test in male Sprague-Dawley rats exposed to 28 d of tail vibration. After 28 d of exposure, Aβ fiber sensitivity was reduced. This reduction in sensitivity was partly attributed to structural disruption of myelin. In addition, the decrease in sensitivity was also associated with a reduction in myelin basic protein and 2',3'- cyclic nucleotide phosphodiasterase (CNPase) staining in tail nerves, and an increase in circulating calcitonin gene-related peptide (CGRP) concentrations. Changes in Aβ fiber sensitivity and CGRP concentrations may serve as early markers of vibration-induced injury in peripheral nerves. It is conceivable that these markers may be utilized to monitor sensorineural alterations in workers exposed to vibration to potentially prevent additional injury.

Exposure to hand-transmitted vibration in the work-place can result in the loss of sensation and pain in workers. These effects may be exacerbated by pre-existing conditions such as diabetes or the presence of primary Raynaud's phenomena. The goal of these studies was to use an established model of vibration-induced injury in Zucker rats. Lean Zucker rats have a normal metabolic profile, while obese Zucker rats display symptoms of metabolic disorder or Type II diabetes. This study examined the effects of vibration in obese and lean rats. Zucker rats were exposed to 4h of vibration for 10 consecutive days at a frequency of 125 Hz and acceleration of 49 m/s(2) for 10 consecutive days. Sensory function was checked using transcutaneous electrical stimulation on days 1, 5 and 9 of the exposure. Once the study was complete the ventral tail nerves, dorsal root ganglia and spinal cord were dissected, and levels of various transcripts involved in sensorineural dysfunction were measured. Sensorineural dysfunction was assessed using transcutaneous electrical stimulation. Obese Zucker rats displayed very few changes in sensorineural function. However they did display significant changes in transcript levels for factors involved in synapse formation, peripheral nerve remodeling, and inflammation. The changes in transcript levels suggested that obese Zucker rats had some level of sensory nerve injury prior to exposure, and that exposure to vibration activated pathways involved in injury and re-innervation., (Published by Elsevier B.V.)

The Neuberger report failed to show that the Liverpool Care Pathway was the cause of poor end-of-life care and made it the scapegoat for poor communication and faulty decision-making. The report's discrediting of a quality assurance mechanism that had the potential for improvement is a disservice to dying patients. Several of the report's recommendations are puzzling, but two consequences of the report, an excellent review of care pathways and a recommendation to establish a national end-of-life coalition, have the potential to improve care of the dying individual.

Work rotation schedules may be used to reduce the negative effects of vibration on vascular function. This study determined how long it takes vascular function to recover after a single exposure to vibration in rats (125 Hz, acceleration 5 g). The responsiveness of rat-tail arteries to the vasoconstricting factor UK14304, an α2C-adrenoreceptor agonist, and the vasodilating factor acetylcholine (ACh) were measured ex vivo 1, 2, 7, or 9 d after exposure to a single bout of vibration. Vasoconstriction induced by UK14304 returned to control levels after 1 d of recovery. However, re-dilation induced by ACh did not return to baseline until after 9 d of recovery. Exposure to vibration exerted prolonged effects on peripheral vascular function, and altered vascular responses to a subsequent exposure. To optimize the positive results of work rotation schedules, it is suggested that studies assessing recovery of vascular function after exposure to a single bout of vibration be performed in humans.

Background: The utility of Mycobacterium tuberculosis direct nucleic acid amplification testing (MTD) for pulmonary tuberculosis disease diagnosis in the United States has not been well described., Methods: We analyzed a retrospective cohort of reported patients with suspected active pulmonary tuberculosis in 2008-2010 from Georgia, Hawaii, Maryland, and Massachusetts to assess MTD use, effectiveness, health-system benefits, and cost-effectiveness., Results: Among 2140 patients in whom pulmonary tuberculosis was suspected, 799 (37%) were M. tuberculosis-culture-positive. Eighty percent (680/848) of patients having acid-fast-bacilli-smear-positive specimens had MTD performed; MTD positive-predictive value (PPV) was 98% and negative-predictive value (NPV) was 94%. Nineteen percent (240/1292) of patients having smear-negative specimens had MTD; MTD PPV was 90% and NPV was 88%. Among patients suspected of tuberculosis but not having MTD, smear PPV for lab-confirmed tuberculosis was 77% and NPV 78%. Compared with no MTD, MTD significantly decreased time to diagnosis in patients with smear-positive/MTD-positive specimens, decreased respiratory isolation for patients having smear-positive/MTD-negative/culture-negative specimens, decreased outpatient days of unnecessary tuberculosis medications, and reduced resources expended on contact investigation. While MTD generally cost more than no MTD, incremental cost savings occurred in patients with human immunodeficiency virus (HIV) or homelessness to diagnose or to exclude tuberculosis, and in patients with substance abuse having smear-negative specimens to exclude tuberculosis., Conclusions: MTD improved diagnostic accuracy and timeliness and reduced unnecessary respiratory isolation, treatment, and contact investigations. It was cost saving in patients with HIV, homelessness, or substance abuse, but not in others.

This article takes a human rights perspective with a view to articulating the infant's perspective when the infant has been subjected to abuse, neglect, or both and is reliant on the state to ensure his or her health and well-being. When a young child is removed from parental care, important and often difficult decisions have to be made about subsequent contact between child and parent. We consider a number of dilemmas which may arise for practitioners when they are assisting child welfare decision makers in relation to contact, and acknowledge the limited empirical follow-up studies of the impact of child welfare practice and legal decisions on infant outcomes. We draw on the significant and substantive evidence base about infant emotional and cognitive development and infant-parent attachment relationships as well as infant mental health to illuminate the infant's subjective experience in these practice dilemmas. We describe innovations in practice from various countries, which seek to shed light on the challenges often associated with contact.

Research regarding the risk of developing hand-arm vibration syndrome after exposure to impact vibration has produced conflicting results. This study used an established animal model of vibration-induced dysfunction to determine how exposure to impact vibration affects peripheral blood vessels and nerves. The tails of male rats were exposed to a single bout of impact vibration (15 min exposure, at a dominant frequency of 30 Hz and an unweighted acceleration of approximately 345 m/s(2)) generated by a riveting hammer. Responsiveness of the ventral tail artery to adrenoreceptor-mediated vasoconstriction and acetylcholine-mediated re-dilation was measured ex vivo. Ventral tail nerves and nerve endings in the skin were assessed using morphological and immunohistochemical techniques. Impact vibration did not alter vascular responsiveness to any factors or affect trunk nerves. However, 4 days following exposure there was an increase in protein-gene product (PGP) 9.5 staining around hair follicles. A single exposure to impact vibration, with the exposure characteristics described above, affects peripheral nerves but not blood vessels.

Objective: There is a concern that pain is under-recognized in dementia. However, there may be other causes of distress. We wished to evaluate the utility of a distress tool and a pain tool., Methods: Nursing home residents with advanced dementia were observed using pain (Pain Assessment in Advanced Dementia scale (PAINAD)) and distress (Disability Distress Assessment Tool (DisDAT)) assessment tools. Those in pain were treated. Reassessment occurred at one and three months., Results: From 79 participants, 13 were assessed as being in pain. Psychosocial factors explained the behaviour of a false positive group. Both tools showed a significant decrease in pain following intervention (p = 0.008). Behaviours were similar in both groups., Conclusions: Both tools are useful. However, the pain tool also picks up distress, which is not caused by pain. It could potentially lead to false ascriptions of pain. The distress tool picks up a broader array of signs, which may be useful both in practice and in research.

Objective: Occupational exposure to hand-transmitted vibration can result in damage to nerves and sensory loss. The goal of this study was to assess the frequency-dependent effects of repeated bouts of vibration on sensory nerve function and associated changes in nerves., Methods: The tails of rats were exposed to vibration at 62.5, 125, or 250 Hz (constant acceleration of 49 m/s2) for 10 days. The effects on sensory nerve function, nerve morphology, and transcript expression in ventral tail nerves were measured., Results: Vibration at all frequencies had effects on nerve function and physiology. However, the effects tended to be more prominent with exposure at 250 Hz., Conclusion: Exposure to vibration has detrimental effects on sensory nerve function and physiology. However, many of these changes are more prominent at 250-Hz exposure than at lower frequencies.