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We present in this work an economic analysis of ransomware, a relatively new form of cyber-enabled extortion. We look at how the illegal gains of the criminals will depend on the strategies they use, examining uniform pricing and price discrimination. We also explore the welfare costs to society of such strategies. In addition, we present the results of a pilot survey which demonstrate proof of concept in evaluating the costs of ransomware attacks. We discuss at each stage whether the different strategies we analyse have been encountered already in existing malware, and the likelihood of them being implemented in the future. We hope this work will provide some useful insights for predicting how ransomware may evolve in the future.

We present laboratory experiments on the growth of a tubular ice structure surrounding a plume of cold brine that descends under gravity into water with a higher freezing point. Brinicles are geological analogues of these structures found under sea ice in the polar regions on Earth. Brinicles are hypothesized to exist in the oceans of other celestial bodies, and being environments rich in minerals, serve a potentially analogous role as an ecosystem on icy-ocean worlds to that of submarine hydrothermal vents on Earth.

Abstract The Strytan Hydrothermal Field (SHF) in basaltic terrain in Iceland is one of the extant alkaline submarine hydrothermal vent systems favoured as analogues for where life on Earth may have begun. To test this hypothesis we analyse the composition, structure, and mineralogy of samples from hydrothermal chimneys generated at the SHF. We find that the chimney precipitates are composed of Mg-silicates including clays of the saponite-stevensite group (high Mg and Si, low Fe and Al), Ca-carbonates and Ca-sulfates. The chimneys comprise permeable structures with pores sizes down to 1 µm or less. Their complex interiors as observed with SEM (Scanning Electron Microscopy) and X-ray CT (computed tomography scanning), exhibit high internal surface areas. EDX (energy-dispersive X-ray spectroscopy) analysis reveals an increase in the Mg/Si ratio toward the chimney exteriors. Chemical garden analogue experiments produce similar Mg–silicate chimneys with porous internal structures, indicating that injection-precipitation experiments can be high-fidelity analogues for natural hydrothermal chimneys at the SHF. We conclude that SHF chimneys could have facilitated prebiotic reactions comparable to those proposed for clays and silica gels at putative Hadean to Eoarchean alkaline vents. Analysis of the fluid dynamics shows that these chimneys are intermediate in growth rate compared to faster black smokers though slower than those at Lost City. The SHF is proposed as a prebiotic alkaline vent analogue for basaltic terrains on the early Earth.

Abstract Tubular structures self‐assemble from precipitating magnesium salts under the chemical garden chemobrionic growth process. Two experimental procedures, the dissolution of magnesium salt pellets and the injection of magnesium salt solutions into silicate solutions, were explored to reproduce in the laboratory the geochemical conditions under which similar structures may form from mineral‐rich fluids at some seafloor hydrothermal vents driven by serpentinization. X‐ray diffraction and Raman microspectroscopy applied to the materials formed indicated the presence of layers of magnesium silicate and magnesium oxide/hydroxide. Quantum mechanical calculations based on density functional theory were performed on models of hydrated magnesium silicate surfaces and related minerals to explain the Raman spectroscopy results. We examine the precipitate morphology, chemical structure, and crystal or mineral structure in our experiments and how these change with the reaction conditions. This is a fascinating example in geochemistry of a self‐organizing nonequilibrium process that creates complex structures.

We carry out a nonlinear time series analysis motivated by dynamical systems theory to investigate the links between temperatures on the eastern South Pacific coast, influenced by the Humboldt Current System, and El Niño–Southern Oscillation (ENSO) events. To this aim, we use a set of 16 oceanic and atmospheric temperature time series from Chilean coastal stations distributed between 18 and 45 ∘ S. The spectral analysis indicates periodicities that can be related to both internal and external forcing, involving not only ENSO, but also the Pacific Decadal Oscillation, the Southern Annual Mode, the Quasi-Biennial Oscillation and the lunar nodal cycle. The asymptotic neural network test for chaos based on the largest global Lyapunov exponent indicates that the temperature dynamics along the Chilean coast is not chaotic. We use local Lyapunov exponents to characterize the short-term stability of the series. Using a cross-entropy test, we find that two stations in northern Chile, one oceanic (Iquique) and one atmospheric (Arica), present a significant positive cross-dependence between local Lyapunov exponents and ENSO. Iquique is the station that presents the greater number of regional characteristics and correlates with ENSO differently from the rest. The unique large-scale study area, combined with time series from hitherto unused sources (Chilean naval records), reveals the nonlinear dynamics of climate variability in Chile. [ABSTRACT FROM AUTHOR]

Large methane hydrates reserves are found in mud volcanoes, but climate change may lead to methane release. Here, the authors show that methane adsorption creates overpressures leading to rapid recirculation of seawater, thus reducing the melting timescales of methane hydrates from millennia to decades.

Equine chorionic gonadotrophin (eCG) is a placental glycoprotein critical for early equine pregnancy and used therapeutically in a number of species to support reproductive activity. The factors in trophoblast that transcriptionally regulate eCGβ-subunit (LHB), the gene which confers the hormones specificity for the receptor, are not known. The aim of this study was to determine if glial cells missing 1 regulates LHB promoter activity. Here, studies of the LHB proximal promoter identified four binding sites for glial cells missing 1 (GCM1) and western blot analysis confirmed GCM1 was expressed in equine chorionic girdle (ChG) and surrounding tissues. Luciferase assays demonstrated endogenous activity of the LHB promoter in BeWo choriocarcinoma cells with greatest activity by a proximal 335 bp promoter fragment. Transactivation studies in COS7 cells using an equine GCM1 expression vector showed GCM1 could transactivate the proximal 335 bp LHB promoter. Chromatin immunoprecipitation using primary ChG trophoblast cells showed GCM1 to preferentially bind to the most proximal GCM1-binding site over site 2. Mutation of site 1 but not site 2 resulted in a loss of endogenous promoter activity in BeWo cells and failure of GCM1 to transactivate the promoter in COS-7 cells. Together, these data show that GCM1 binds to site 1 in the LHB promoter but also requires the upstream segment of the LHB promoter between −119 bp and −335 bp of the translation start codon for activity. GCM1 binding partners, ETV1, ETV7, HOXA13, and PITX1, were found to be differentially expressed in the ChG between days 27 and 34 and are excellent candidates for this role. In conclusion, GCM1 was demonstrated to drive the LHB promoter, through direct binding to a predicted GCM1-binding site, with requirement for another factor(s) to bind the proximal promoter to exert this function. Based on these findings, we hypothesize that ETV7 and HOXA13 act in concert with GCM1 to initiate LHB transcription between days 30 and 31, with ETV1 partnering with GCM1 to maintain transcription.

Organisations like the International Cartographic Association champion programmes that develop and deliver education and training to cartographers and geospatial scientists, globally. This can be in the form of traditional university and training college programmes, short courses for professional and technical members of mapping agencies and as outreach initiatives to transfer knowledge about the discipline and its contemporary practices. Through its international community, the ICA undertakes the transfer of knowledge about cartography and GI Science by publishing books and special editions of journals and running workshops. Colleagues from the ICA community conduct these workshops on a volunteer basis, generally with the support of the national member organisation of ICA or the national mapping body. For example, the ICA promotes the generation of extensive publications, generally through its Commissions and Working Groups. The publications include books, journals and the ICA Newsletter. Outreach activities are especially pertinent to up skill colleagues from developing countries. Specialist programmes can be offered for professional and 'everyday' map users (from adults to children). The ICA can assist with its current programmes, designed to embrace professional and non-professional cartographers alike. This paper will address how education and outreach programmes can be supported by international associations, by offering programmes independently, or in partnership with sister associations and national and regional organisations and societies. As well, the paper will address the need to deliver education and outreach programmes not to just the professional international community, but also to map users and citizen map publishers.

Mixing fluid in a container at low Reynolds number--in an inertialess environment--is not a trivial task. Reciprocating motions merely lead to cycles of mixing and unmixing, so continuous rotation, as used in many technological applications, would appear to be necessary. However, there is another solution: movement of the walls in a cyclical fashion to introduce a geometric phase. We show using journal-bearing flow as a model that such geometric mixing is a general tool for using deformable boundaries that return to the same position to mix fluid at low Reynolds number. We then simulate a biological example: we show that mixing in the stomach functions because of the "belly phase," peristaltic movement of the walls in a cyclical fashion introduces a geometric phase that avoids unmixing.

In human pregnancy, successful placentation and remodelling of the uterine vasculature require the integration of a number of stages, which are crucial for a healthy pregnancy. As the demands of the developing fetus for nutrients and oxygen increase, the capacity of the maternal blood vessels to supply this must be altered radically, with deficiencies in this process implicated in a number of dangerous pregnancy complications. The complex signalling networks that regulate these tightly co-ordinated events are becoming clearer as more studies of early pregnancy are performed. It is the aim of this review to draw together our knowledge of events that occur to facilitate a successful pregnancy ranging from the preparation for implantation, through the invasion and differentiation of the trophoblast and the regulation of these processes by other cells within the decidual environment, to the active role that the trophoblast and maternal immune cells play in facilitating the remodelling of the uterine spiral arteries. The events involved in a healthy pregnancy will then be compared to aberrant placentation and remodelling, which are characteristics of many pregnancy disorders, and recent advances in detection of abnormal placental development will also be discussed. [ABSTRACT FROM AUTHOR]

Abstract In this paper we report on the design and validation process for the profiled corrugated horn antennas, which feed the bolometer array of a cosmology experiment known as QUaD located at the South Pole. This is a cosmic background radiation polarization project, which demands precise knowledge and control of the optical coupling to the signal in order to map the feeble E- and B-polarization mode structure. The system will operate in two millimeter wavelength bands at 100 and 150 GHz. The imaging horn array collects the incoming signal via on-axis front-end optics and a Cassegrain telescope, with a cold stop in front of the array to terminate side-lobe structure at an edge taper of -20dB. The corrugated horn design process was undertaken using in-house analytical software tools, based on modal scattering, specially developed for millimeter -wave profiled horn antennas. An important part of the instrument development was the validation of the horn design, in particular to verify low edge taper levels and the required well-defined band edges. Suitable feed horn designs were measured and were found to be in excellent agreement with theoretical predictions. [ABSTRACT FROM AUTHOR]

We carry out a nonlinear time series analysis motivated by dynamical systems theory to investigate the links between temperatures on the eastern South Pacific coast, influenced by the Humboldt Current System, and El Niño–Southern Oscillation (ENSO) events. To this aim, we use a set of 16 oceanic and atmospheric temperature time series from Chilean coastal stations distributed between 18 and 45∘ S. The spectral analysis indicates periodicities that can be related to both internal and external forcing, involving not only ENSO, but also the Pacific Decadal Oscillation, the Southern Annual Mode, the Quasi-Biennial Oscillation and the lunar nodal cycle. The asymptotic neural network test for chaos based on the largest global Lyapunov exponent indicates that the temperature dynamics along the Chilean coast is not chaotic. We use local Lyapunov exponents to characterize the short-term stability of the series. Using a cross-entropy test, we find that two stations in northern Chile, one oceanic (Iquique) and one atmospheric (Arica), present a significant positive cross-dependence between local Lyapunov exponents and ENSO. Iquique is the station that presents the greater number of regional characteristics and correlates with ENSO differently from the rest. The unique large-scale study area, combined with time series from hitherto unused sources (Chilean naval records), reveals the nonlinear dynamics of climate variability in Chile.

Abstract Methane‐rich water moves through conduits beneath the seafloor whose surfaces are formed through precipitation reactions. To understand how such submarine fluid conduit and venting systems form and grow, we develop a detailed mathematical model for this reaction‐advection system and we quantify the evolution of an ensemble of similar filaments. We show that this growth can be described by a superposition of advection and dispersion. We analyze analog laboratory experiments of chemical‐garden type to study the growth of a single filament undergoing a precipitation reaction with the surrounding environment. We apply these findings to geological fluid conduit and venting systems, showing that their irregular trajectories can lead to very effective spreading within the surrounding seabed, thus enhancing contact and exchanges of chemicals between the conduit and external fluids. We discuss how this methane venting leads to the formation of marine authigenic carbonate rocks, and for confirmation, we analyze two field samples from the Gulf of Cadiz for composition and mineralogy of the precipitates. We note the implications of this work for hydrate melting and methane escape from the seabed.

We derive from kinetic theory, fluid mechanics and thermodynamics the minimal continuum-level equations governing the flow of a binary, non-electrolytic mixture in an isotropic porous medium with osmotic effects. For dilute mixtures, these equations are linear and in this limit provide a theoretical basis for the widely used semi-empirical relations of Kedem & Katchalsky (Kedem & Katchalsky 1958 Biochim. Biophys. Acta 27, 229–246 (doi:10.1016/0006-3002(58)90330-5), which have hitherto been validated experimentally but not theoretically. The above linearity between the fluxes and the driving forces breaks down for concentrated or non-ideal mixtures, for which our equations go beyond the Kedem–Katchalsky formulation. We show that the heretofore empirical solute permeability coefficient reflects the momentum transfer between the solute molecules that are rejected at a pore entrance and the solvent molecules entering the pore space; it can be related to the inefficiency of a Maxwellian demi-demon.

Neurocognitive adverse events (NAEs) have been reported in up to 60% of patients on lorlatinib, a potent central nervous system-active ALK inhibitor. Manifestations may include psychotic, mood, speech, and cognitive symptoms. Current guidance recommends permanent discontinuation of lorlatinib in cases of grade IV NAEs. Here, we report a case of successful rechallenge of dose-reduced lorlatinib after recovery of grade IV psychosis in a patient with ALK-positive NSCLC., Competing Interests: Mrs. Vick reports receiving honoraria from Amgen, AstraZeneca, Pfizer, and Takeda. Mrs. Middleton reports receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Takeda. Dr. McMahon reports receiving travel fees from Takeda. Prof. Popat reports receiving consulting fees and honoraria from Amgen, AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi EQRx, Sankyo, GlaxoSmithKline, Guardant Health, Incyte, Janssen, Lilly, Merck Serono, SD, Novartis, Roche, Takeda, Pfizer, Seattle Genetics, and Turning Point Therapeutics. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Background: Most oesophagogastric adenocarcinomas (OGAs) and colorectal cancers (CRCs) are mismatch repair proficient (MMRp), responding poorly to immune checkpoint inhibition. We evaluated the safety and efficacy of domatinostat (histone deacetylase inhibitor) plus avelumab (anti-PD-L1 antibody) in patients with previously treated inoperable, advanced/metastatic MMRp OGA and CRC., Patients and Methods: Eligible patients were evaluated in a multicentre, open-label dose escalation/dose expansion phase II trial. In the escalation phase, patients received escalating doses of domatinostat [100 mg once daily (OD), 200 mg OD, 200 mg twice daily (BD)] orally for 14 days followed by continuous dosing plus avelumab 10 mg/kg administered intravenously 2-weekly (2qw) to determine the recommended phase II dose (RP2D). The trial expansion phase evaluated the best objective response rate (ORR) during 6 months by RECIST version 1.1 using a Simon two-stage optimal design with 2/9 and 1/10 responses required to proceed to stage 2 in the OGA and CRC cohorts, respectively., Results: Patients (n = 40) were registered between February 2019 and October 2021. Patients in the dose escalation phase (n = 12) were evaluated to confirm the RP2D of domatinostat 200 mg BD plus avelumab 10 mg/kg. No dose-limiting toxicities were observed. Twenty-one patients were treated at the RP2D, 19 (9 OGA and 10 CRC) were assessable for the best ORR; 2 patients with CRC did not receive combination treatment and were not assessable for the primary endpoint analysis. Six patients were evaluated in the dose escalation and expansion phases. In the OGA cohort, the best ORR was 22.2% (95% one-sided confidence interval lower bound 4.1) and the median duration of disease control was 11.3 months (range 9.9-12.7 months). No responses were observed in the CRC cohort. No treatment-related grade 3-4 adverse events were reported at the RP2D., Conclusions: Responses in the OGA cohort met the criteria to expand to stage 2 of recruitment with an acceptable safety profile. There was insufficient signal in the CRC cohort to progress to stage 2., Trial Registration: NCT03812796 (registered 23 rd January 2019)., Competing Interests: Disclosure DC received research funding from Clovis, Eli-Lilly, 4SC, Bayer, Celgene, Leap and Roche and sits on the scientific advisory board for OVIBIO. IC is on the advisory board of Eli-Lilly, Bristol Myers Squibb (BMS), MSD, Roche, Merck, AstraZeneca, OncXerna, Boehringer Ingelheim, Incyte, Astella, GSK, SOTIO, Eisai, Daiichi-Sankyo, Taiho, Servier, Seagen, Turning Point Therapeutics, Novartis, BioNTech, Takeda and Elevation Oncology; received research funding from Eli-Lilly and Janssen-Cilag; and honoraria from Eli-Lilly, Eisai, Servier and Roche. NS has served on advisory boards for Pfizer, Servier, AstraZeneca, MSD Oncology, Novartis, Guardant, GSK, Gilead, Seagen and Janssen; received research funding from Merck, AstraZeneca, BMS, Pfizer and Guardant Health; and honoraria from Merck, Novartis, MSD Oncology, Eli-Lilly, Pierre Fabre, Amgen, Eli-Lilly Bangladesh, GSK, Seagen, BMS, AstraZeneca and Servier. SR receives financial support from Boehringer, Merck, Servier and Bayer; has served on advisory boards for HOOKIPA, Bayer, BeiGene, AstraZeneca, Merck, Seagen and Servier. CF has received financial support from AAA and Servier. ES receives financial support from the NIHR Biomedical Research Centre in Oxford; receives grants and personal fees from Bristol Myers Squibb and AstraZeneca; receives personal fees from Amgen, Daiichi Sankyo, Mirati, Merck, Viracta, Astellas, Novartis, Pfizer, Zymeworks and BeiGene, outside the submitted work; receives nonfinancial support from Mirati; and is the European Organisation for Research and Treatment of Cancer Gastric Cancer Taskforce Chair and an Ireland Oesophagogastric Cancer Group Trustee. WM has consulting and advisory roles with Ipsen, Novartis, Pfizer, MSD, BMS and Servier; has been involved in the speakers’ bureau with Ipsen, Novartis, MSD and Servier; has travel grants from MSD, Ipsen, BMS and Servier; and institutional grants from Nordic and MSD. The other authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Several artificial intelligence (AI) systems for diabetic retinopathy screening have been validated but there is limited evidence on their performance in real-world settings. This study aimed to assess the performance of an AI software deployed within the diabetic retinopathy screening programme in Dominica., Methods and Analysis: We conducted a prospective, cross-sectional clinical validation study. Patients with diabetes aged 18 years and above attending the diabetic retinopathy screening in primary care facilities in Dominica from 5 June to 3 July 2021 were enrolled.Grading was done at the point of care by the field grader, followed by counselling and referral to the eye clinic. Images were then graded by an AI system. Sensitivity, specificity with 95% CIs and area under the curve (AUC) were calculated for comparing the AI to field grader as gold standard., Results: A total of 587 participants were screened. The AI had a sensitivity and specificity for detecting referable diabetic retinopathy of 77.5% and 91.5% compared with the grader, for all participants, including ungradable images. The AUC was 0.8455. Excluding 52 participants deemed ungradable by the grader, the AI had a sensitivity and specificity of 81.4% and 91.5%, with an AUC of 0.9648., Conclusion: This study provides evidence that AI has the potential to be deployed to assist a diabetic screening programme in a middle-income real-world setting and perform with reasonable accuracy compared with a specialist grader., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

We examine the influence of the COVID-19 pandemic on medical occupation preference, focusing on Wuhan, China. We conducted a survey of 5686 respondents in China regarding the influence of the COVID-19 pandemic on medical occupation preference. We also conducted a complimentary survey in the UK with 1198 respondents, as well as a field experiment in Wuhan with 428 first and second-year medical students. We find a significant negative impact of the pandemic on the willingness to let a loved one choose a medical occupation. Individuals who were heavily influenced by the pandemic, that is, Wuhan residents, especially medical workers, express significantly lower medical occupation preference. Further analysis from Sobel-Goodman mediation tests reveals that around half of the total negative effect can be mediated by enhanced risk aversion and reduced altruism. The UK survey and the field experiment with medical students in Wuhan reinforce these findings. Our results suggest a shift in medical workers' risk- and altruistic-preferences has led to a reduced medical occupation preference. Non-medical workers and students who are more altruistic and risk-seeking are more likely to choose a medical occupation., (© 2023 John Wiley & Sons Ltd.)

Circulating tumour DNA (ctDNA) has potential applications in gastric cancer (GC) with respect to screening, the detection of minimal residual disease (MRD) following curative surgery, and in the advanced disease setting for treatment decision making and therapeutic monitoring. It can provide a less invasive and convenient method to capture the tumoural genomic landscape compared to tissue-based next-generation DNA sequencing (NGS). In addition, ctDNA can potentially overcome the challenges of tumour heterogeneity seen with tissue-based NGS. Although the evidence for ctDNA in GC is evolving, its potential utility is far reaching and may shape the management of this disease in the future. This article will review the current and future applications of ctDNA in GC.

Oesophago-gastric adenocarcinoma remains a leading cause of cancer-related morbidity and mortality worldwide. Although there has been an enormous progress in the multimodality management of resectable oesophago-gastric adenocarcinoma, most patients still develop a recurrent disease that eventually becomes resistant to systemic therapy. Currently, there is no global consensus on the optimal multimodality approach and there are variations in accepted standards of care, ranging from preoperative chemoradiation to perioperative chemotherapy and, more recently, adjuvant immune checkpoint inhibitors. Ongoing clinical trials are aimed to directly compare multimodal treatment options as well as the additional benefit of targeted therapies and immunotherapies. Furthermore, our understanding of the molecular and genetic features of oesophago-gastric cancer has improved significantly over the last decade and these data may help inform the best approach for the individual patient, utilising biomarker selection and precision medicine.

This review assessed the effects of environmental labels on consumers' demand for more sustainable food products. Six electronic databases were searched for experimental studies of ecolabels and food choices. We followed standard Cochrane methods and results were synthesized using vote counting. Fifty-six studies ( N  = 42,768 participants, 76 interventions) were included. Outcomes comprised selection ( n  = 14), purchase ( n  = 40) and consumption ( n  = 2). The ecolabel was presented as text ( n  = 36), logo ( n  = 13) or combination ( n  = 27). Message types included: organic ( n  = 25), environmentally sustainable ( n  = 27), greenhouse gas emissions ( n  = 17), and assorted "other" message types ( n  = 7). Ecolabels were tested in actual ( n  = 15) and hypothetical ( n  = 41) environments. Thirty-nine studies received an unclear or high RoB rating. Sixty comparisons favored the intervention and 16 favored control. Ecolabeling with a variety of messages and formats was associated with the selection and purchase of more sustainable food products., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: This study uses machine learning techniques to identify sociodemographic and clinical predictors of progression through the hepatitis C (HCV) cascade of care for patients in the 1945-1965 birth cohort in the Southern United States., Methods: We compared sociodemographic and clinical variables between groups of patients for three care outcomes: linkage to care, initiation of antiviral treatment, and virologic cure. A decision tree model and random forest model were built for each outcome., Results: Patients were primarily male, African American/Black or Caucasian/White, non-Hispanic or Latino, and insured. The average age at first HCV screening was 60 years old, and common medical diagnoses included chronic kidney disease, fibrosis and/or cirrhosis, transplanted liver, diabetes mellitus, and liver cell carcinoma. Variables used in predicting linkage to care included age at first HCV screening, insurance at first HCV screening, race, fibrosis and/or cirrhosis, other liver disease, ascites, and transplanted liver. Variables used in predicting initiation of antiviral treatment included insurance at first HCV screening, gender, other liver cancer, steatosis, and liver cell carcinoma. Variables used in predicting virologic cure included insurance at first HCV screening, transplanted liver, and ethnicity., Conclusion: These patients have a high hepatic health burden, likely reflecting complications of untreated HCV and highlighting the urgency to cure HCV in this birth cohort. We found differences in HCV care outcomes based on sociodemographic and clinical variables. More work is needed to understand the mechanisms of these differences in care outcomes and to improve HCV care., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Health-related fear is a normal and common response in the face of the global pandemic of COVID-19. Children and young people are frequently being exposed to messages about the threat to health, including from the media and authorities. Whilst for most, their anxiety will be proportionate to the threat, for some, existing pre-occupation with physical symptoms and illness will become more problematic. There is a growing body of evidence that health anxiety may occur in childhood, however much of the literature is taken from research using adult samples. This practitioner review aims to give an overview of the assessment and treatment of health-related worries in children and young people in the context of the COVID-19 pandemic. This review is based on the limited existing evidence in this population and the more substantial evidence base for treating health anxiety in adults. We consider the adaptations needed to ensure such interventions are developmentally appropriate.

Purpose: The purpose of this qualitative ethnographic case study was to explore the perceptions of a team of interprofessional healthcare providers regarding how oral health care was integrated into health care provided within a Federally Qualified Health Center (FQHC) in Brighton, Colorado. Methods: Data were gathered through one-on-one, semi-structured personal interviews, which were recorded and professionally transcribed for evaluation. Purposive sampling included physicians, physician assistants, dentists, and dental hygienists. Descriptive analysis was used to describe the sample demographics. An inductive and deductive approach was utilized to assess the qualitative data and subsequently develop themes. Validity was established using triangulation, member checks, and peer review of data and themes by co-investigators. Results: Eight participants (n=8) were interviewed. Subjects were between the ages of 31 and 58 and had been practicing between 5 and 30 years with an average of 13.6 years and had been employed by the FQHC an average of 6.8 years. Thematic analysis revealed seven themes: interprofessional collaboration supports patient care, immediate consultations lead to improved outcomes for all, shared expertise to optimize care delivery, oral health is health, increased communication through collocation, role clarity does not impede team functioning, and mission driven to provide excellent care. These themes support the domains of patient centered care, communication, and the role clarity of the Interprofessional Care Competency Framework and Team Assessment Toolkit (ICCFTAT). Conclusion: Findings from this study can aid FQHC's in the implementation of integrated oral health care delivery systems. Further research is needed to understand how interprofessional health care collaboration (IPHC) affects the team dynamic in FQHC settings., (Copyright © 2020 The American Dental Hygienists’ Association.)

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. Since there is no cure for OA and no effective treatment to slow its progression, current pharmacologic treatments, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), only alleviate symptoms, such as pain and inflammation, but do not inhibit the disease process. Moreover, chronic intake of these drugs may result in severe adverse effects. For these reasons, patients have turned to the use of various complementary and alternative approaches, including diverse dietary supplements and nutraceuticals, in an effort to improve symptoms and manage or slow disease progression. The present study was conducted to evaluate the anti-osteoarthritic effects of FlexPro MD ® (a mixture of krill oil, astaxanthin, and hyaluronic acid; FP-MD) in a rat model of OA induced by monosodium iodoacetate (MIA). FP-MD significantly ameliorated joint pain and decreased the severity of articular cartilage destruction in rats that received oral supplementation for 7 days prior to MIA administration and for 21 days thereafter. Furthermore, FP-MD treatment significantly reduced serum levels of the articular cartilage degeneration biomarkers cartilage oligomeric matrix protein (COMP) and crosslinked C-telopeptide of type II collagen (CTX-II), and the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as mRNA expression levels of inflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and matrix-degrading enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, in the knee joint tissue. Our findings suggest that FP-MD is a promising dietary supplement for reducing pain, minimizing cartilage damage, and improving functional status in OA, without the disadvantages of previous dietary supplements and medicinal agents, including multiple adverse effects.

Background: Altering the availability of healthier or less-healthy products may increase healthier purchases, but evidence is currently limited. The current study aimed to investigate the impact of altering the absolute-and-relative availability of healthier and less-healthy products - i.e. simultaneously altering the number of options available and the proportion of healthier options - in hospital vending machines., Methods: An adapted multiple treatment reversal design was used, altering products available in ten vending machines serving snack foods and/or cold drinks in one English hospital. Machines were randomised to one of two sequences for the seven 4-week study periods: ABCADEA or ADEABCA. In Condition A (study periods 1, 4 and 7) the proportions of healthier products were standardised across all machines, so that 25% of all snack slots and 75% of drink slots were healthier. In Condition B, 20% of vending machine slots were emptied by removing less-healthy products. In Condition C, the empty slots created in Condition B were filled with healthier products. Conditions D and E were operationalised in the same way as B and C, except healthier products were removed in D, and then less-healthy products added in E. Sales data were obtained from machine restocking records. Separate linear mixed models were conducted to examine the impact of altering availability on energy purchased (kcal) from (i) snacks or (ii) drinks each week, with random effects for vending machine., Results: The energy purchased from drinks was reduced when the number of slots containing less-healthy drinks was decreased, compared to standardised levels (- 52.6%; 95%CI: - 69.3,-26.9). Findings were inconclusive for energy purchased from snacks when less-healthy snack slots were reduced (- 17.2%; 95%CI: - 47.4,30.5). Results for altering the number of slots for healthier drinks or snacks were similarly inconclusive, with no statistically significant impact on energy purchased., Conclusions: Reducing the availability of less-healthy drinks could reduce the energy purchased from drinks in vending machines. Further studies are needed to establish whether any effects might be smaller for snacks, or found with higher baseline proportions of healthier options.

Anthropological research can provide the time depth needed for a rich understanding of the health effects of atmospheric and ocean warming, shifting weather patterns, and the breakdown of biological and social systems large and small. Medical anthropologists are poised to document the human costs of floods, fires, droughts and other catastrophic events, as well as the slowly shifting supplies of fresh water, clean air, and adequate food. Our anthropological eyes on the ground are needed for contextual, local, and critical understandings of how human lifestyles of the twenty-first century are creating climate change.

Introduction: Reducing meat consumption could contribute towards preventing some chronic conditions and protecting the natural environment. This study will examine the effectiveness of a behavioural intervention to reduce meat consumption., Methods and Analyses: Replacing meat with alternative plant-based product is a randomised controlled trial comparing a behavioural intervention to reduce meat consumption with a no intervention control condition. Eligible volunteers will be recruited from the general public through advertisement and randomised in a 1:1 ratio to receive no intervention or a 4-week intervention comprising the provision of free plant-based meat alternatives, written information on the health and environmental benefits of eating less meat, success stories of people who reduced their meat consumption and recipes. The primary outcome is the change in meat consumption at 4 weeks (T1) from baseline. Secondary and exploratory outcomes include changes in meat consumption at 8 weeks (T2) from baseline and changes from the baseline to both follow-up in other aspects of participants diet, putative psychosocial determinants of eating a low meat diet and of using meat substitutes and biomarkers of health risk, including blood lipid profiles, blood pressure, weight and body composition. Linear models will be employed to explore whether the changes in each of the aforementioned outcomes differ significantly between the control and intervention group. Qualitative interviews on a subsample of participants receiving the intervention will evaluate their experiences of the intervention and help to identify the mechanisms through which the intervention reduced meat consumption or the barriers preventing the intervention to aid this dietary transition., Ethics and Dissemination: The trial has been granted ethical approval by the Medical Sciences Interdivisional Research Ethics Committee (IDREC) of the University of Oxford (Ref: R54329/RE001). All results originating from this study will be submitted for publication in scientific journals and presented at meetings and through the media., Trial Registration Number: ISRCTN13180635;Pre-recruitment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Increasing the proportion of healthier foods available could encourage healthier consumption, but evidence to date is limited in scope and quality. The current study aimed to: (a) examine the feasibility and acceptability of intervening to change product availability in worksite cafeterias; and (b) estimate the impact on energy purchased of increasing the proportion of healthier (i.e. lower energy) cooked meals, snacks, cold drinks and sandwiches. Six English worksite cafeterias increased the proportion of healthier foods available, aiming to keep the total number of options constant, in a stepped wedge randomized controlled pilot trial conducted between January and May 2017. The intervention was generally successfully implemented and acceptable to clientele. Generalized linear mixed models showed a reduction of 6.9% (95%CI: -11.7%, -1.7%, p = 0.044) in energy (kcal) purchased from targeted food categories across all sites. However, impact varied across sites, with energy purchased from targeted categories significantly reduced in two sites (-10.7% (95%CI: -18.1% to -2.6%, p = 0.046); -18.4% (95%CI: -26.9% to -8.8%, p = 0.013)), while no significant differences were seen in the other four sites. Overall, increasing the proportion of healthier options available in worksite cafeterias seems a promising intervention to reduce energy purchased but contextual effects merit further study., (Copyright © 2018 University of Cambridge. Published by Elsevier Ltd.. All rights reserved.)

Background: Reducing the portion sizes of foods available in restaurants and cafeterias is one promising approach to reducing energy intake, but there is little evidence of its impact from randomised studies in field settings. This study aims to i. examine the feasibility and acceptability, and ii. estimate the impact on energy purchased, of reducing portion sizes in worksite cafeterias., Methods: Nine worksites in England were recruited to reduce by at least 10% the portion sizes of foods available in their cafeterias from targeted categories (main meals, sides, desserts, cakes). In a stepped wedge randomised controlled pilot trial, each site was randomised to a date of implementation, staggered fortnightly, following a baseline period of four weeks. Impact on energy purchased was analysed using generalised linear mixed modelling. We also assessed feasibility, acceptability, and fidelity of intervention implementation., Results: Data from six of the nine randomised sites were analysed, with three sites excluded for not providing sufficient data and/or not implementing the intervention. The extent to which the intervention was implemented varied by site, with between 6 and 49% of products altered within targeted categories. Feedback following the intervention suggested it was broadly acceptable to customers and cafeteria staff. For the primary outcome of daily energy (kcal) purchased from intervention categories, there was no statistically significant change when data from all six sites were pooled: percentage change - 8.9% (95% CI: -16.7, - 0.4; p = 0.081). Each of these six sites showed reductions in energy purchased, ranging from - 15.6 to - 0.3%, which were borderline statistically significant at two sites (respective percentage changes (95% CIs): - 15.6% (- 26.7, - 2.8); - 14.0% (- 25.0, - 1.2)). Secondary outcome data are suggestive of a compensatory increase in energy purchased from food categories not targeted by the intervention, with no overall effect observed on energy purchased across all categories., Conclusions: The results of this pilot trial suggest that reducing portion sizes could be effective in reducing energy purchased and consumed from targeted food categories, and merits investigation in a larger trial. Future studies will need to address factors that prevented optimal implementation including site dropout and application across a limited range of products., Trial Registration: ( ISRCTN52923504 ). Registered on 20th September 2016.

Esophagogastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis for patients with locally advanced disease is poor and the majority of patients with operable tumors treated with surgery alone will have recurrent disease. A multimodal approach to treatment with adjunctive chemotherapy or chemoradiotherapy is therefore the standard of care for these patients. However, there is no global consensus on the optimal treatment strategy and international guidelines vary. National clinical trials inform local practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy combinations are all possible treatment options in the management of resectable esophagogastric cancer. A number of clinical trials are ongoing, which seek to directly compare multimodal treatment options and hope to provide clarity in this area. Furthermore, increased understanding of the molecular and genetic features of esophagogastric cancer may help to guide management of operable disease by determining optimal patient selection through identification of predictive biomarkers of response and the application of novel targeted agents.

Background: For working adults, about one-third of energy is consumed in the workplace making this an important context in which to reduce energy intake to tackle obesity. The aims of the current study were first, to identify barriers to the feasibility and acceptability of implementing calorie labelling in preparation for a larger trial, and second, to estimate the potential impact of calorie labelling on energy purchased in worksite cafeterias., Methods: Six worksite cafeterias were randomised to the intervention starting at one of six fortnightly periods, using a stepped wedge design. The trial was conducted between August and December 2016, across 17 study weeks. The intervention comprised labelling all cafeteria products for which such information was available with their calorie content (e.g. "250 Calories") displayed in the same font style and size as for price. A post-intervention survey with cafeteria patrons and interviews with managers and caterers were used to assess the feasibility and acceptability of the intervention. Intervention impact was assessed using generalised linear mixed modelling. The primary outcome was the total energy (kcal) purchased from intervention items in each cafeteria each day., Results: Recruitment and retention of worksite cafeterias proved feasible, with post-intervention feedback suggesting high levels of intervention acceptability. Several barriers to intervention implementation were identified, including chefs' discretion at implementing recipes and the manual recording of sales data. There was no overall effect of the intervention: -0.4% (95%CI -3.8 to 2.9, p = .803). One site showed a statistically significant effect of the intervention, with an estimated 6.6% reduction (95%CI -12.9 to - 0.3, p = .044) in energy purchased in the day following the introduction of calorie labelling, an effect that diminished over time. The remaining five sites did not show robust changes in energy purchased when calorie labelling was introduced., Conclusions: A calorie labelling intervention was acceptable to both cafeteria operators and customers. The predicted effect of labelling to reduce energy purchased was only evident at one out of six sites studied. Before progressing to a full trial, the calorie labelling intervention needs to be optimised, and a number of operational issues resolved., Trial Registration: ISRCTN52923504 ; Registered: 22/09/2016; retrospectively registered.

Competing Interests: Competing interests: I have read and understood BMJ policy on declaration of interests and declare the following: None.

Bucket chlorination (where workers stationed at water sources manually add chlorine solution to recipients' water containers during collection) is a common emergency response intervention with little evidence to support its effectiveness in preventing waterborne disease. We evaluated a bucket chlorination intervention implemented during a cholera outbreak by visiting 234 recipients' homes across five intervention villages to conduct an unannounced survey and test stored household drinking water for free chlorine residual (FCR). Overall, 89 per cent of survey respondents reported receiving bucket chlorination, and 80 per cent reported receiving the intervention in the previous 24 hours. However, only 8 per cent of stored household water samples that were reportedly treated only with bucket chlorination in the previous 24 hours had FCR ≥0.2 mg/l. Current international guidelines for bucket chlorination recommend an empirically derived dosage determined 30 minutes after chlorine addition, and do not account for water storage in the home. In controlled investigations we conducted, an initial FCR of 1.5 mg/l resulted in FCR ≥0.5 mg/l for 24 hours in representative household plastic and clay storage containers. To ensure reduction of the risk of waterborne disease, we recommend revising bucket chlorination protocols to recommend a chlorine dosage sufficient to maintain FCR ≥0.2 mg/l for 24 hours in recipients' household stored drinking water.