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Many rail services around the world continue to use diesel as the primary fuel source and enclosed railway stations have been identified as a possible hotspot for exposure to harmful diesel exhaust exposures. Little is known about the occupational exposure to air pollution for railway station workers due to their mobility around the station and variations in station design. A detailed understanding of the concentration of black carbon (BC), a diesel exhaust tracer, inside railway stations and the factors driving occupational exposures is required to minimize occupational exposure. Real-time personal exposure to BC was measured during 60 work-shifts encompassing different roles at three large enclosed railway stations of different design in London, Birmingham and Edinburgh (UK). Sampling was conducted by the train station workers over a period of 27 days between January 2017 to October 2018. Worker shift-mean BC exposures ranged 0.6–20.8 μg m−3 but 1-min peak exposures reached 773 μg m−3, with train dispatchers experiencing the highest BC exposures. Station design, job role, and frequency of diesel trains were the main drivers of occupational BC exposure. Elevated exposures for some station workers indicate that mitigation measures to reduce their exposure should be implemented to lower the risk of occupational health impacts. These could include improving ventilation and reducing engine emissions. Funding for open access charge: CRUE-Universitat Jaume I

While biological treatments for chronic plaque psoriasis should be administered continuously to maximize and maintain efficacy, interruptions in therapy may be necessary for a number of reasons. We reviewed the evidence from clinical trials on efficacy, safety and immunogenicity in clinical trials for approved biologic agents for chronic plaque psoriasis. A systematic search of three major medical databases was performed and a total of 35 articles were included into the analysis, including 13 controlled trials. Trials assessing continuous therapy against dosing as-needed therapy (including infliximab, etanercept and secukinumab) have demonstrated superior efficacy for continuous regimes. However, randomized withdrawal trials for etanercept, adalimumab, ixekizumab, brodalumab, guselkumab, risankizumab and tildrakizumab, showed no significant impact on skin clearance rates in patients who are interrupted once and then re-treated. With the possible exception of infliximab, temporary interruption in biologic therapy appears to be safe and most agents will regain efficacy after re-introduction. J Drugs Dermatol. 2021;20(10):1063-1071. doi:10.36849/JDD.5716.

Floodplains are particularly important in the semi-arid region of the Sub-Sahelian Africa. In this region, water governance is still being developed, often without adequate information and technical capacity for good, sustainable water resource management. However, water resources are being allocated for use with minimal sustainability considerations. Environmental flows (e-flows) include the quantity and timing of flows or water levels needed to meet the sustainable requirements of freshwater and estuarine ecosystems. Holistic regional scale e-flows linked to floodplain management can make a noticeable contribution to sustainable floodplain management. The Inner Niger Delta (IND) in Mali is an example of a vulnerable, socio-ecologically important floodplain in the Sahel region of North Africa that is being developed with little understanding of sustainability requirements. Although integrally linked to the Upper Niger River catchment, the IND sustains a million and half people within the region and exports food to surrounding areas. The flooding of the Delta is the engine of the socio-economic development as well as its ecological integrity. This paper aims to demonstrate the contribution that holistic regional e-flow assessment using the PROBFLO approach has to achieving floodplain sustainability. This can be achieved through the determining the e-flow requirements to maintain critical requirements of the ecosystems and associated services used by local vulnerable human communities for subsistence and describing the socio-ecological consequences of altered flows. These outcomes can contribute to the management of the IND. In this study, the socio-ecological consequences of altered flows have been evaluated by assessing the risk of alterations in the volume, duration, and timing of flows, to a number of ecological and social endpoints. Based on the risk posed to these endpoints by each scenario of change, an e-flow of 58% (26,685 million cubic meters (MCM) of water annually) was determined that would protect the ecosystem and maintain indicator components at a sustainable level. These e-flows also provide sustainable services to local communities including products for subsistence and limit any abnormal increases in diseases to the vulnerable African communities who live in the basin. Relative risk outputs for the development scenarios result in low-to-high-risk probabilities for most endpoints. The future development scenarios include insufficient flows to maintain sustainability during dry or low-flow periods with an increase in zero flow possibilities. Although unsuitable during the low-flow or dry periods, sufficient water is available through storage in the basin to meet the e-flows if these scenarios were considered for implementation. The IND is more vulnerable to changes in flows compared to the rivers upstream of the IND. The e-flow outcomes and consequences of altered flow scenarios has contributed to the management of vulnerable IND floodplains and the requirements and trade-off considerations to achieve sustainability.

This work aims to assess the efficacy of x-ray quality assurance tests undertaken on fluoroscopy units in the UK. Information was gathered on the results of image quality tests recommended by the reports of the Institute of Physics and Engineering in Medicine, and those additionally undertaken by medical physics departments. The assessment of efficacy considers the frequency with which a test result breaches the remedial level or other relevant threshold where applicable. The third quartile of those results exceeding the remedial level or threshold is used to estimate the severity of such a breach in terms of potential impact on patient dose and image quality. A risk assessment approach is then used to recommend to what degree, if any, the test should be included in an on-going test regimen. Data was analysed from 469 testing sessions to 337 unique fluoroscopy units throughout the UK. Across all tests, the rate with which the remedial level was exceeded varied from 0–10.6%, with severity ranging from little or none to major degradation to image quality or significant increase on population dose. Where possible, the data has also been used to produce representative ranges for the results of image quality tests. These could be useful as an up to date comparator for those sites considering the purchase of or commissioning new equipment. Overall the results indicate a wide range for the efficacy of those tests undertaken at present; this can be used to review local test protocols and to inform future changes to national guidance in the UK. The results also highlight some tests where measurement technique varies significantly throughout the UK, making any valid comparison difficult. This may indicate a need for further guidance on how best to undertake these tests.

Early modern Siam is usually portrayed as a predominantly rural, peasant society. This picture is assumed from the worldwide trend of rural-to-urban transition, rather than from study of Siam itself. The available sources have a striking lack of any evidence on rural society. This article explores the possibility that this absence may reflect a real-world difference, not just perception. Unlike in temperate zones, enough food could be produced without dedicating the efforts of a majority of the population to agriculture. Rice could be grown by part-time ‘commuter’ agriculture, and other foods found by everyday hunting and gathering. Cultural preference based on the instinct for survival may have reinforced an affinity for urban residence. The scant data on Siam's demography suggest the majority of the population lived in urban places. Descriptions of the capital portray a commercial and industrial centre, capable of employing many in non-agricultural pursuits. The state systems for raising resources were tailored to an urban rather than a rural society. While the scarcity of data on early Siam makes any ‘proof’ impossible, the thesis that Siam was a predominantly urban society is worth exploring. From the early eighteenth century on, Siam was subject to a process of ‘ruralization’ that created the familiar peasant society that historians have projected back into the past.

This chapter examines the space now defined as Thailand in the longue duree of a thousand years or more under five headings: landscape and resources; population and settlement; political organisation; language and identity; and belief and power. For most of the millennium, the key features were a low population constrained by disease and warfare, an economy based on low-intensity exploitation of the fecund tropical environment, a highly varied society from waves of immigration, and a loose political structure. Over the past century, the changes have been dramatic. A resource-rich territory with a sparse population has been transformed by medicine and by resource-hungry economic development. The prevailing landscape of forests has disappeared. The population, once clustered mainly in urban settlements, was first spread across the territory along a moving “land frontier” and is now being gathered back to the cities and towns. Colonial-style bureaucracy and the idea of the nation-state have imposed central control over the loose coalitions of city-states. The jumble of languages and ethnicities has been subsumed under a concept of Thai identity through mass education and media.

To determine how to optimize the delivery of machine learning techniques in a clinical setting to detect intracranial hemorrhage (ICH) on non-contrast-enhanced CT images to radiologists to improve workflow.In this study, a commercially available machine learning algorithm that flags abnormal noncontrast CT examinations for ICH was implemented in a busy academic neuroradiology practice between September 2017 and March 2019. The algorithm was introduced in three phases:Notification with a widget or flagging the examination had no effect on queue-adjusted image wait (The approach used to present flags from artificial intelligence and machine learning algorithms to the radiologist can reduce image wait time and turnaround times.© RSNA, 2021See also the commentary by O'Connor and Bhalla in this issue.

Thailand is the only country currently ruled by a coup-installed military government. The 2014 coup aimed not only to abolish the influence of Thaksin Shinawatra but also to shift Thailand’s politics in an authoritarian direction. While the army authored the coup, the professional and official elite played a prominent role in engineering the coup and shaping political reforms. This article examines some historical antecedents of this authoritarian turn, first in the broad trends of Thailand’s modern political history, and second in the emergence and political evolution of the Bangkok middle class.

Intratumoral (IT) delivery of plasmid IL-12 (tavokinogene telseplasmid; tavo) via electroporation (EP), collectively referred as IT-tavo-EP, generates immunologically-relevant levels of localized IL-12, triggering regression of both treated and distant tumors with minimal toxicity in preclinical and clinical studies. Our previous clinical trial data from melanoma patients treated with IT-tavo-EP identified a treatment-related increase of infiltrating T cells and transcripts related to immune activation, as well as a significant increase in the IFN-γ score of patients with a clinical benefit, suggesting that CD3+ tumor-infiltrating lymphocytes (TIL) may be critical in maximizing the anti-tumor effects of IT-tavo-EP. Furthermore, in-house biomarker data have identified an abundance of non-tumor reactive TIL that, if mobilized could additionally contribute to a clinical response. Accordingly, a plasmid-encoded membrane-bound polyclonal T cell-stimulating anti-CD3 (αCD3) hybrid antibody (scFv) was developed and used in combination with tavo (IT-tavo-αCD3-EP) to broaden the scope and depth of the T cell response. We previously demonstrated that membrane expression of αCD3 on neoplastic and stromal cells could activate CD3+ TIL, driving enhanced proliferation and cytotoxicity in a B16-OVA murine model. Here, using immune profiling of the tumor microenvironment (TME), we have demonstrated that this membrane-bound αCD3 therapeutic can significantly upregulate frequencies of CXCR3+CD8+ T cells and short-lived effector T cells, while reducing PD-1 expression on CD8+ T cells in vivo. Critically, naïve T cells, Treg cells, and exhausted T cells (subsets not typically associated with strong anti-tumor responses) displayed enhanced effector function (IFN-γ and granzyme B release) with engagement of membrane-bound αCD3 and IL-12. Furthermore, we found that this therapeutic approach could equally enhance proliferation of T cells regardless of the affinity for their cognate peptide:MHC, suggesting a TCR independent mechanism. Collectively, these observations demonstrate that IT-tavo-αCD3-EP can mobilize broad subsets of T cells beyond dominant anti-tumor effectors demonstrated. Thus, while enhanced cytolytic function is associated with this therapy, inclusion of additional atypical anti-tumor T cell subsets may also promote reshaping of the TME by production of effector cytokines upon engagement of surface-bound αCD3. Moreover, functional restoration of TIL isolated from a melanoma patient with active clinical progression on anti-PD-1 therapy, was possible with engagement of membrane-bound αCD3 in the presence of IL-12. Collectively, these data continue to support the utility of IT-tavo-αCD3-EP as a promising therapeutic approach for patients with melanoma and other accessible solid tumors. Citation Format: Mia Han, Anandaroop Mukhopadhyay, Bianca Nguyen, Jack Y. Lee, Erica Browning, Jon Salazar, Reneta Hermiz, Lauren Svenson, Chris Baker, Daniel O'Connor, Kellie Malloy, David A. Canton, Christopher G. Twitty. Intratumoral electroporation of plasmid-encoded IL-12 and membrane-bound anti-CD3 increases tumor immunogenicity and augments the function of T cell subsets [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-390.

Precision analog circuit accuracy in a microcontroller product was impacted by unmodeled behavior across the temperature range. Three critical analog circuits from the microcontroller were built and tested in discrete parametric test structures. It was shown that a process with reduced parasitic edge FET leakage dramatically improved the accuracy of the analog circuits, which were operating in the subthreshold region.

The threat, impact and management problems associated with alien plant invasions are increasingly becoming a major issue in environmental conservation. Invasive species cause significant damages, and high associated costs. Controlling them cost-effectively is an ongoing challenge, and mathematical models and optimizations are becoming increasingly popular as a tool to assist managers. The aim of this study is to develop a modelling approach for the optimal spatiotemporal control of invasive species in natural protected areas of high conservation value. Typically, control programs are either distributed uniformly across an area, or applied with a given fixed intensity, although there is no guarantee that such a strategy would be cost-effective at the conservation asset. The proposed approach, based on diffusion equations, is spatially explicit, and includes a functional response (Holling type II) which models the control rate as a function of the invasive species density. We apply a budget constraint to the control program and search for the optimal effort allocation for the minimisation of the invasive species density. Remote sensing derived input layers and expert knowledge have been assimilated in the model to estimate the initial species distribution and its habitat suitability, empirically extracted by a land cover map of the study area. Both the initial density map and the land cover map have been generated by using very high resolution satellite images and validated by means of ground truth data. The approach has been applied to the Alta Murgia National Park, where the EU LIFE Alta Murgia Project is underway with the aim to eradicate Ailanthus altissima, one of the most invasive alien plant species in Europe. The Alta Murgia National Park is one of the study site of the on-going H2020 project ECOPOTENTIAL which aims at the integration of modelling tools and Earth Observations for a sustainable management of protected areas. The H2020 project 'ECOPOTENTIAL: Improving Future Ecosystem Benefits Through Earth Observations' (http://www.ecopotential-project.eu) has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 641762. All ground data regarding Ailanthus altissima (Mill.) Swingle presence and distribution are from the EU LIFE Alta Murgia Project (LIFE12 BIO/IT/000213 titled "Eradication of the invasive exotic plant species Ailanthus altissima from the Alta Murgia National Park" funded by the LIFE+ financial instrument of the European Commission).