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Early, concurrent palliative care interventions in chronic obstructive pulmonary disease (COPD) are limited. Project EPIC (Early Palliative Care In COPD) is a multiphase mixed methods study working to fill this gap.To conduct a formative and summative evaluation of EPIC, a telephonic nurse coach-led early palliative care intervention for COPD adapted from the ENABLE intervention in cancer.Phase I Formative Evaluation: Patients with moderate-to-very-severe COPD, family caregivers, and pulmonary and palliative care clinicians rated the acceptability and feasibility of EPIC (≥4 out of 5 on a Likert-scale survey). Phase II Summative Evaluation: Patients and family caregivers in Phase I participated in a pilot of the 3-month EPIC prototype to evaluate intervention and data collection feasibility (≥70% completion) and to seek qualitative feedback.Phase I Formative Evaluation: Patients (n=10), family caregivers (n=10), pulmonary clinicians (n=6), and palliative care clinicians (n=6) found EPIC acceptable and feasible to support adaptation, while priority early palliative care needs in COPD from our prior research mapped well to the EPIC prototype. Phase II Summative Evaluation: Patients (n=5; ages 49-72, 40% moderate COPD, 40% Black) and their family caregivers (n=5; ages 51-73, 40% Black) completed 100% of EPIC prototype components, including weekly telephone sessions, a 1-month follow-up call, Advance Directive, palliative care clinic attendance, and 95% of monthly phone data collection sessions. Feedback from participants about EPIC was all positive.EPIC was acceptable and feasible in patients with COPD and their family caregivers. Larger feasibility and effectiveness trials are warranted.

Datasets and R scripts for the COVID anthropause case study sites for the publication entitled "Lessons learned from the COVID-19 anthropause in the Netherlands on urban aquatic ecosystem services provisioning and management" When using the .csv files for Figure 2B (bathing waters, file: Zwemmen buiten) and Figure 2C (national parks; files: De Alde Feanen, De Biesbosch, De Groote Peel, Dwingelderveld, Lauwersmeer and Weerribben-Wieden), make sure the dates are in the following format: dd-mm-yyyy When running the Figure 2C codes (in R script "COVID_GoogleTrends_Script"), set the working directory to a folder containing only the national parks .csv files.

Mine planning optimization aims at maximizing the profit obtained from extracting valuable ore. Beyond its theoretical complexity—the open-pit mining problem with capacity constraints reduces to a knapsack problem with precedence constraints, which is NP-hard—practical instances of the problem usually involve a large to very large number of decision variables, typically of the order of millions for large mines. Additionally, any comprehensive approach to mine planning ought to consider the underlying geostatistical uncertainty as only limited information obtained from drill hole samples of the mineral is initially available. In this regard, as blocks are extracted sequentially, information about the ore grades of blocks yet to be extracted changes based on the blocks that have already been mined. Thus, the problem lies in the class of multi-period large scale stochastic optimization problems with decision-dependent information uncertainty. Such problems are exceedingly hard to solve, so approximations are required. This paper presents an adaptive optimization scheme for multi-period production scheduling in open-pit mining under geological uncertainty that allows us to solve practical instances of the problem. Our approach is based on a rolling-horizon adaptive optimization framework that learns from new information that becomes available as blocks are mined. By considering the evolution of geostatistical uncertainty, the proposed optimization framework produces an operational policy that reduces the risk of the production schedule. Our numerical tests with mines of moderate sizes show that our rolling horizon adaptive policy gives consistently better results than a non-adaptive stochastic optimization formulation, for a range of realistic problem instances.

Background Leprosy is rare in the United Kingdom (UK), but migration from endemic countries results in new cases being diagnosed each year. We documented the clinical presentation of leprosy in a non-endemic setting. Methods Demographic and clinical data on all new cases of leprosy managed in the Leprosy Clinic at the Hospital for Tropical Diseases, London between 1995 and 2018 were analysed. Results 157 individuals with a median age of 34 (range 13–85) years were included. 67.5% were male. Patients came from 34 different countries and most contracted leprosy before migrating to the UK. Eighty-two (51.6%) acquired the infection in India, Sri Lanka, Bangladesh, Nepal and Pakistan. 30 patients (19.1%) acquired leprosy in Africa, including 11 from Nigeria. Seven patients were born in Europe; three acquired their leprosy infection in Africa, three in South East Asia, and one in Europe. The mean interval between arrival in the UK and symptom onset was 5.87 years (SD 10.33), the longest time to diagnosis was 20 years. Borderline tuberculoid leprosy (n = 71, 42.0%), and lepromatous leprosy (n =, 53 33.1%) were the commonest Ridley Jopling types. Dermatologists were the specialists diagnosing leprosy most often. Individuals were treated with World Health Organization recommended drug regimens (rifampicin, dapsone and clofazimine). Conclusion Leprosy is not a disease of travellers but develops after residence in an leprosy endemic area. The number of individuals from a leprosy endemic country reflect both the leprosy prevalence and the migration rates to the United Kingdom. There are challenges in diagnosing leprosy in non-endemic areas and clinicians need to recognise the symptoms and signs of leprosy.

Datasets and R scripts for the COVID anthropause case study sites for the publication entitled "Lessons learned from the COVID-19 anthropause for water quality management"

SUMMARY: As human mobility decreased in 2020, the interaction between humans and nature changed significantly. On one hand, water clarity improved in the Amsterdam canals because boat traffic was reduced. On the other hand increased use of fishing water and national parks formed potential threats to the aquatic ecosystems. It is important to use these experiences to foster a more eco-centric mindset, building up to handling handling climate change and future pandemics. ABSTRACT: The anomalous past two years of the COVID-19 pandemic have been a test of human response to global crisis management as typical human activities were significantly altered. The COVID-instigated anthropause has illustrated the influence that humans and the biosphere have on each other, especially given the variety of national mobility interventions that have been implemented globally. These local COVID-19-era restrictions influenced human-ecosystem interactions through changes in accessibility of water systems and changes in ecosystem service demand. Four urban aquatic case studies in the Netherlands demonstrated shifts in human demand during the anthropause. For instance, reduced boat traffic in Amsterdam canals led to improved water clarity. In comparison, ongoing service exploitation from increased recreational fishing, use of bathing waters and national parks visitation are heightening concerns about potential ecosystem degradation. We distilled management lessons from both the case studies as well as from recent literature pertaining to ecological intactness and social relevance. Equally important to the lessons themselves, however, is the pace at which informed management practices are established after the pandemic ends, particularly as many communities currently recognize the importance of aquatic ecosystems and are amenable to their protection.

The purpose of this case study series was to assess improvement in the quality of life, function, and colonic motility before and after visceral and neural manipulation in five children with cerebral palsy and chronic constipation who had Gross Motor Function Classification System (GMFCS) levels of IV and V. Quality of life and function were assessed using the CPCHILD and the WeeFIM respectively. The CPCHILD and WeeFIM were administered at baseline before the intervention, after the intervention, and again at least three months post intervention. Colonic motility was assessed radiographically at baseline and post-intervention utilizing ingested radiopaque markers (Sitz markers). Bowel movement number and quality were assessed through family diaries. All subjects showed some degree of improved quality of life and function on the CPCHILD and WeeFIM at the end of the intervention. Colonic motility assessed radiographically before and after treatment was not statistically significant due to the small number of participants; however, the number of bowel movements increased during the study for 100% of the participants. Visceral and neural manipulation modalities may provide clinicians and families with an alternative to medications and/or other more invasive interventions.

The Samarco tailings dam broke on 5 November 2015, sending a wall of mud into the Bento Rodrigues township and killing 19 people. From there the mud made its way to the Rio Doce river system, killing fish and frogs, and causing massive pollution down to the mouth 650 km away. A year later a yellow fever outbreak occurred in the same state in Brazil, with 450 confirmed cases and about 150 deaths. After newspapers reported the yellow fever cases, online blogs started suggesting that the outbreak might have been caused by the Samarco disaster and citing comments by well-known scientists. Twelve months later another yellow fever outbreak occurred, and the online bloggers repeated the same claims, but the wording changed. In this paper we analyze the timing of the online activity, using Google search to find all the postings in the press and in social media with the two terms, “Samarco” and “Febre Amarela” (yellow fever, in Portuguese). In 2017, most postings faithfully reported what the scientists had said, but in 2018, some postings started making stronger claims than the scientists originally had. After analyzing the content of the postings, we construct two directed networks, one for 2017 and the other for 2018, to show to which scientists the postings refer and to illustrate the subtle and not so subtle distortions that started to creep in. In the conclusion we ask how the rise in hostility to mining expressed in some of these blogs should be interpreted. Is it just the usual low-level dislike of the extractive industries or are these the precursor symptoms of a more general refusal to accept mining in Brazil?

This research project developed an adaptive stochastic optimisation approach for multi-period production scheduling in open-pit mines under geological uncertainty, and compared it to an existing two-stage optimisation method. This new rolling-horizon optimisation approach updates the geological model each time period as new information becomes available. Numerical tests carried out earlier on open-pits of different sizes showed that, on average, the rolling-horizon adaptive policy gave better results than the non-adaptive two-stage approach. The metric used was the percentage gap between the results for each policy and those that would be obtained if the true block grades were perfectly known. This paper extends this earlier work in two ways: firstly, by introducing a second metric — the dollar-value difference between the NPV generated with perfect knowledge of the orebody and those given by the other two optimisation methods. The rolling-horizon approach is better on average than the two-stage approach, but not for all of the geostatistical simulations used to model the geological uncertainty. The second innovation in this paper is to analyse when the new rolling-horizon approach outperforms the non-adaptive one. This depends on the drill-hole spacing. For widely spaced grids, the rolling-horizon approach statistically outperforms the two-stage approach at the 95% confidence level. For very close spacings, both approaches converge toward the results for perfect knowledge.

Summary Introduction Determining the cause of eosinophilia in patients returning from the tropics continues to present a diagnostic challenge. The history, symptoms and degree of eosinophilia are often poor predictors of eventual diagnosis, but helminths are an important cause. The current British Infection Association recommendations use travel history to guide investigation of eosinophilia. However the global burden of helminth disease and travel patterns have changed over the last 3 decades and guidelines based on previous epidemiology need to be reviewed in the light of current data. Methods Consecutive patients presenting with, or referred for, investigation of eosinophilia were identified prospectively. Case notes, laboratory results and electronic records were reviewed for demographic and clinical data. Patients with an eosinophil count ≥0.50 × 10 9 /L were included, and grouped based on lifetime history of travel to: West Africa, elsewhere in Africa, and the rest of the world. Results were compared to published data from 1997 to 2002 collected at the same centre. Results Of 410 patients who met the inclusion criteria, 407 had a documented travel history. Average yearly referrals for eosinophilia fell from 58 per year between 1997 and 2002, to 33 per year (2002–2015). The proportion of eosinophilia cases diagnosed with a parasitic cause fell from 64% to 50%, and yields for all parasitological investigations fell, the largest reduction in stool microscopy (20% yield to 9%) and day bloods for microfilariae (14% yield to 3%). Strongyloides stercoralis was the commonest diagnosis overall in our cohort, accounting for 50% of the total parasites diagnosed, and was present in 38% of patients from West Africa, 19% from rest of Africa, and 34% from rest of world; a relative increase compared to previous data. Schistosomiasis is slightly less common in those who had travelled to West Africa than the rest of Africa, and overall point prevalence has fallen from 33% (1997–2002) to 17% (2002–2015). Travellers were significantly less likely than patients who had immigrated to the UK to be diagnosed with any parasite (OR 0.54 95% CI 0.378–0.778 p = 0.0009). Discussion A parasitic cause will still be found in half of people returning from the tropics with an eosinophilia, but we observed a fall in the overall prevalence of parasitic diagnoses when compared with the earlier data. This may, in part, be explained by the impact of control programmes on the prevalence of parasites globally, especially filarial disease. S. stercoralis now represents the majority of parasites diagnosed in our cohort from all continents. We identified significantly higher rates of strongyloidiasis in immigrants than returning travellers. Despite the falling yields of stool microscopy and filarial serology the current guidelines based on travel history remain relevant with adequate yield.

This study describes the clinical features of a cohort of imported cases of strongyloidiasis and the performance of standard diagnostic techniques for this condition. A total of 413 cases were identified, of whom 86 had microscopically proven infection. In proven cases, 23% had normal eosinophil counts, 19% had negative Strongyloides-specific serology, and 9.3% had normal blood counts and were seronegative. Serological testing was less sensitive for returning travelers (46.2%) than for migrants (89.7%). Immunosuppression, including human T-cell lymphotropic virus 1, was significantly associated with proven infection after controlling for age, presence of symptoms, duration of infection, and eosinophilia (OR 5.60, 95% CI 1.54–20.4). Patients with proven infection had lower serology values than those diagnosed with strongyloidiasis on the basis of positive serology and eosinophilia alone (P = 0.016). Symptomatic patients were significantly younger, had a shorter presumed duration of infection, and lower serology values. These data suggest a correlation between immunologic control of strongyloidiasis and the amplitude of the humoral response.

1. Frailty is a common syndrome affecting 25% of the population aged 70+ in Australia, equating to approximately 26,000 people residing in Northern Sydney. People living with frailty have 2-3 times the healthcare utilisation and poorer outcomes in hospital compared to their non-frail counterparts.2. Sydney North Health Network is working collaboratively with Northern Sydney Local Health District, health professionals and consumers, to co-design and implement targeted interventions to identify and reduce frailty, avoid inappropriate hospital admissions and improve health outcomes for our elderly population. Phase one includes delivery of education and support to health professionals, to increase understanding and implementation of:• The concept of frailty• Appropriate screening using the FRAIL scale• Preventive and reablement management plans in primary care.This included consultation with clinicians and consumers to understand existing knowledge and screening practices, co-design of resources, including protocols to support handover of care and development of pathways to support appropriate referral and management.Phase two will identify service gaps in the community and develop a co-commissioning strategy to shape service delivery to meet local need.3. Implement recommendations from the Asia Pacific Clinical Practice Guidelines for the Management of Frailty.4. The target populations for phase one are health professionals from primary care, community and acute settings.5. Phase one, 2 years. Phase two, 3-years.6. Education and awareness events were implemented in both settings:- 82 LHD health professionals and 79 general practice and allied health professionals have participated to date. - 53 general practices have received intensive, in-practice training on use of FRAIL scale and resources available to help them navigate service and management options. A trial of screening has been implemented in 2 acute hospitals. Screening of 387 patients identified high prevalence of frailty and pre-frailty (82-93%)Screening results and management plans have been included in patient discharge summaries to improve handover to primary care.7. Primary care is most likely the more appropriate setting to continue screening on an ongoing basis and likely to yield more sustainable, long term results, particularly on hospital avoidance.8. This framework includes a multi-disciplinary team approach to care and encourages screening at any point during the patient journey, in any care setting.9. Screening for frailty and implementing management plans to improve patient outcomes is possible in both the inpatient and community setting.Further data is required in primary care to measure impact and outcomes.10 & 11. Hospital screening is feasible, but capacity for intervention is limited. With some patients receiving appropriate intervention in hospital, aiming to prevent deterioration, analysis in progress will confirm impact and gaps.A vendor has been engaged to develop a screening app that integrates with GP clinical software systems, to support data collection in primary care.Next steps include:- development and implementation of primary care data app- follow up with general practices, to gauge acceptance of interventions and tools provided- utilise data from screening and mapping of community services to inform development of commissioning strategy.

Objectives: Prednisolone and thalidomide are commonly used in the management of erythema nodosum leprosum (ENL) and bring relief to patients with this condition worldwide. However, both ENL and its treatments can cause significant morbidity. This study describes the spectrum of ENL seen at The Hospital for Tropical Diseases, London (HTD), the use of steroids and thalidomide in its management and the complications of their use. Study Design: We conducted a retrospective audit of patients diagnosed with ENL between 1996 and 2013. Data were obtained from hospital records including severity and length of disease, together with treatments received and adverse effects. Results: Between 1996 and 2013, 30 patients were diagnosed with ENL. The median bacillary index (BI) at diagnosis was 4·65, higher than in previous studies. Most patients developed ENL during leprosy treatment (67%) and had chronic ENL (57%). The median length of ENL was 60 months (range 9 – 192); patients with BI . 4·5 had significantly longer duration of disease. 87% patients received prednisolone for median nine months; 35% developed adverse effects including diabetes and hypertension. 87% patients received thalidomide for median 16 months; 65% complained of side effects. There were no pregnancies or venous thromboembolisms. 77% patients stopped prednisolone within two months of starting thalidomide. There were no deaths in our cohort. Conclusion: We describe the clinical course of ENL in a non-endemic country with access to thalidomide and prednisolone. ENL may last far longer than previously described and has significant impact on a patient’s health. In the UK, thalidomide is essential as a steroid-sparing agent, to prevent the adverse effects and mortality of long-term steroids which have been documented elsewhere.

Securing stable long-term supplies of raw materials is vital for industrialized nations. China, Japan and South Korea are three countries in East Asia which import large quantities of raw material, especially metals and petroleum products. Unlike the other two, China has large mines and oilfields and so can use this expertise to exploit resources overseas. In contrast Japan and South Korea are resource-poor countries that lack domestic petroleum and mining industries. This paper compares the ways in which these two countries secure supplies. Japanese trading companies and industrial groups invest in mining and petroleum projects run by international groups with the active support from the Japanese government through the Japan Bank for International Cooperation (JBIC). In contrast, the Korean government has set up two state run corporations: the Korea Resource Corporation, KORES, for minerals, and the Korean National Oil Corporation KNOC for oil and LNG, which usually take a leading role in choosing projects, though they do work in partnership with large Korean private sector groups. After his election in 2008, President Lee Myung-bak put pressure on public sector entities to speed up investments in mining and petroleum projects, which resulted in unsuitable projects being financed and public money being wasted. We argue that three lessons can be learned from this: firstly, building up a solid basis of natural resources takes decades and should not be rushed; secondly, project finance in the sense of non-recourse funding provides better checks and balances than direct acquisitions do and thirdly more transparency is required when spending taxpayers' money.

Recent data from Rio de Janeiro shows a sharp drop in the number of notified cases of Zika in the summer of 2016-17, compared to the previous summer. This is probably due to herd immunity built up after the previous year's epidemic. There is still a much higher incidence among women than men, almost certainly due to sexual transmission. An unexpected feature of the new data is that there are proportionally far more cases in children under 15 months than in older age classes. By comparing the incidence for 2016-17 with that of 2015-16, we can deduce the proportion of reported cases for men and women, and also verify that the disparity of incidence between them is still present. Women and children still represent risk groups with regard to Zika infection, even during a non-epidemic season.

Giardia intestinalis is the commonest gastrointestinal protozoal pathogen worldwide, and causes acute and chronic diarrhoea with malabsorption. First-line treatment is with a nitroimidazole, with a reported efficacy rate of 89%. Failure of treatment can occur in patients with hypogammaglobulinaemia or human immunodeficiency virus (HIV), or be due to nitroimidazole-resistant organisms. There is little evidence to guide the clinical management of nitroimidazole-refractory disease. We performed a retrospective audit of nitroimidazole-refractory giardiasis in returned travellers at the Hospital for Tropical Diseases, London between 2011 and 2013. Seventy-three patients with microscopy-proven or PCR-proven giardiasis in whom nitroimidazole treatment had failed were identified, and their management was investigated. In 2008, nitroimidazole treatment failed in 15.1% of patients. This increased to 20.6% in 2011 and to 40.2% in 2013. Patient demographics remained stable during this period, as did routes of referral. Of patients with giardiasis, 39.0% had travelled to India; this rose to 69.9% in patients with nitroimidazole-refractory disease. Of the patients with refractory disease, 44.6% had HIV serological investigations performed and 36.5% had immunoglobulin levels determined. Patients with refractory disease were treated with various agents, including albendazole, nitazoxanide, and mepacrine, alone or in combination. All 20 patients who received a mepacrine-containing regimen were cured. This data shows a worrying increase in refractory disease, predominantly in travellers from India, which is likely to represent increasing nitroimidazole resistance. Improved tools for the diagnosis of resistant G. intestinalis are urgently needed to establish the true prevalence of nitroimidazole-resistant giardiasis, together with clinical trials to establish the most effective second-line agent for empirical treatment regimens.

The number of major tailings dam failures has doubled over the past 20 years, culminating in the tragic accident at Brumadinho in Brazil where about 300 people lost their lives. In this context, there is a growing demand from mining companies, institutional investors and policymakers alike for updated mining project assessment tools taking account of such risks. As part of this research, this paper develops a real option framework for evaluating mining projects involving tailings dams and their associated risk. Two options are considered beyond standard business-as-usual safety measures: reinforced dam maintenance, and retrofitting a treatment process that reduces the volume of unconsolidated tailings. A closed-form expression was obtained for the expected value of the business-as-usual case; semi-analytic formulas were obtained for the two options for evaluation by dynamic programming with quantization of the price factor. When applied to an iron ore deposit with characteristics similar to the Samarco deposit, the method shows that both options are financially superior to business-as-usual for the mining company, with the dry processing retrofitting option being the most attractive. The sensitivity of the expected values was evaluated over a range of values of the key parameters. This research provides senior decision-makers with tools to evaluate different options regarding tailings dam safety from a financial point of view, and provides financial evidence in favour of safer treatment processes for mining waste.

The number of tailings dam failures has doubled in the past 20 years. Advances in mining technology have made it possible to exploit lower grade deposits despite decreasing commodity prices, which means disposing of more rejects and putting more pressure on tailings facilities. Our analysis of four recent tailings dam failures in countries with a strong mining tradition (Los Frailes in Spain, Mt Polley in Canada, Samarco and Brumadinho in Brazil), showed that production had been increased and/or cost cutting measures had been put in place before the accidents. In this paper, we postulate that the compensation packages offered to middle management which actively encourage managers to cut costs and increase production so as to increase their annual bonuses are a key factor in the rising number of serious accidents. Newmont Mining's compensation package contains a component that is equivalent to the options in traders' bonuses. As is well known, this led to excessive risk-taking in banks and hence to the subprime crisis and the global financial crisis. We argue that year after year managers keep taking risks with a low probability of occurrence but with potentially catastrophic consequences. These risks are compounded by shortages of experienced staff due to the cyclic nature of the industry and the retirement of the baby-boomer generation.

This paper addresses the question of evaluating how much the different stakeholders stand to gain from a mining project. By carefully analysing the breakdown of the cash-flows generated, we were able to estimate the amounts received by the local community and by the national community (outside the mining area), the taxes and royalties received by the government and the profits made by the mining company. A real options framework was used to take account of the inherent uncertainty on the commodity price and the reserves, and the operating flexibility (that is, the possibility for the company to stop mining if the commodity price drops and/or the reserves prove to be lower than that had been envisaged). A synthetic case-study of a gold mine in West Africa was used to illustrate how this procedure could be applied in practice. By using the real option framework we were able to envisage scenarios for developing an extension to a deposit as a function of future values of the commodity price. The procedure proposed should provide governments and NGOs with more objective data for making policy decisions.

By analogy with Social Licence to Operate, Social Licence to Finance refers to the pressure put by society as a whole on the finance industry not to fund projects that are considered as socially undesirable/irresponsible. Because of coal’s contribution to greenhouse gas emissions and hence to global warming, many environmentally active NGOs want to put an end to coal-fired power plants and are putting pressure on the finance industry to stop funding coal-mining. There have been three main impacts: firstly some banks involved in project finance (non-recourse funding of large projects) now refuse coal projects and other restrict funding to them; secondly, socially responsible pension funds no longer invest in coal companies (e.g. the Norwegian Sovereign Fund recently divested investments in thermal coal companies worth $8 billion), and finally the Financial Stability Board now requires international banks and insurance companies to evaluate the potential impact of climate change measures on their business. Going further, the Securities and Exchange Commission (SEC) and the New York Attorney General are putting pressure on mining and oil companies listed on the NYSE to provide much more explicit warnings to investors.

Summary Objectives To establish the clinical reasons for inpatient admissions among injecting drug users. To determine the frequency of behavioural issues during their care and to estimate the financial implications of injecting drug use to the health service. Methods Retrospective cohort study at University College London Hospital. Clinical, laboratory and financial data were extracted from case notes and electronic records. The cost of each admission was compared to the income received for the period of care. Results 124 injecting drug users required 191 admissions between 2005 and 2009. Skin and soft tissue infections (58%) and pneumonia (18%) were the commonest reasons for admission. Bacteraemia at admission was often not accompanied by an inflammatory response. Exposure to HIV (4%), hepatitis B (49%) and C (84%) was common. Drug misuse (16%) during admission was frequent. The cost to the NHS of treating soft tissue infections in drug users was approximately £77 million per annum. After a median follow-up of 40 months, 10 patients (8%) had died. All deaths were attributable to drug use. Conclusions Bacterial and viral infections are largely responsible for the significant mortality and morbidity of injecting drug users presenting to secondary care. The financial burden to the NHS is substantial.

International audience; Objectives: The recent emergence of Zika in Brazil and its association with an increased rate of congenital malformations has raised concerns over its impact on the birth rate in the country. Using data on the incidence of Zika in 2015-2016 and dengue in 2013 and 2015-2016 for the city of Rio de Janeiro (population 6.4 million), a massive increase of Zika in women compared to men was documented.Methods: The age-adjusted incidence was compared between men and women. A negative binomial Poisson generalized linear model was fitted to the Zika incidence data to determine the significance of sexual transmission statistically.Results: Even after correcting for the bias due to the systematic testing of pregnant women for Zika, there were found to be 90% more registered cases per 100 000 women than men in the sexually active age group (15-65 years); this was not the case for age groups < 15 years and > 65 years. Assuming that infected men transmit the disease to women in their semen, but that the converse is not true, some extra incidence in women is to be expected. An alternate hypothesis would be that women visit doctors more often than men. To test this, the incidence of dengue fever was compared in men and women in 2015 and in 2013 (before Zika reached Rio de Janeiro): in both years, women were 30% more likely to be reported with dengue.Conclusion: Women in the sexually active age group are far more likely to get Zika than men (+ 90% increase); sexual transmission is the most probable cause. Women in the 15-65 years age group are also 30% more likely to be reported with dengue than men, which is probably due to women being more careful with their health.

This paper studies the impact of virtual power plant (VPP) contracts on the French day-ahead market. Holders of VPPs have the right to access electric power at a predetermined strike price per MWh in 30-minute slices 24 hours per day, 7 days a week during the delivery period, after paying an upfront premium, which is fixed at the auction. So VPPs are call options. Recent work on market power in Nordic countries suggests that subtle mechanisms such as transfers from one time period to another may be involved, rather than short-run manipulations. To assess the effect VPPs have on market power we need to understand precisely how they function. In this paper we show that the structure of the market allows holders of VPPs to sell power on the exchange when the day-ahead price is above the VPP strike (if they do not need the power) and conversely to buy power when the price is below the strike. By documenting the strike prices of VPPs that were active at different times and by carefully examining the structure of day-ahead prices we demonstrate that they are doing this.

This paper estimates the value of information for highly uncertain projects whose decisions have long-term impacts. We present a mathematically consistent framework using decision trees, Bayesian updating, and Monte Carlo simulation to value future information today, even when that future information is imperfect. One drawback of Monte Carlo methods in multivariate cases is the large number of samples required, which may result in prohibitive run times when considerable computer time is required to obtain each sample, as it is in our example. A polynomial chaos approach suitable for black-box functions is used to reduce these computations to manageable proportions. To our knowledge, this is the first exposition of polynomial chaos in the valuation literature. In our example it provides a speed-up of more than two orders of magnitude. We demonstrate the approach with an oilfield example involving a future decision on where to place a new injection well relative to a fault. The example considers the value to the asset holder of a measurement, to be made in the future, that reveals the degree of reservoir compartmentalization caused by this fault. In conditions of high demand for rigs and other scarce capital-intensive oilfield equipment, it may be appropriate for the asset holder to agree to a forward contract for this critical measurement to be taken at a future date at some specified price. The service provider would be contractually bound to provide this measurement at this pre-agreed price within a specified time window, regardless of the prevailing price and availability of rigs and equipment. Despite the presence of financial uncertainty on future oil price and private uncertainty on reservoir variables that are largely unresolved by the measurement, our methodology provides a computationally efficient valuation framework, possibly leading to novel ways of setting up contract terms.

Summary Background: The probability that a returned traveller with a history of fever has malaria is likely to vary by geographical area, but this has not been quantified in travellers. Aim: To collect data on prevalence of malaria in outpatients returning with a fever or history of fever from malaria-endemic countries, at the point of presentation for a malaria test. Design: Observational retrospective study. Consecutive patients presenting to an unselected ‘walk-in’ clinic for returned travellers. Results: Of 2867 patients meeting inclusion criteria, 337 (11.8%) had malaria, 89.5% originating in sub-Saharan Africa. Of travellers returning from sub-Saharan Africa excluding South Africa with fever/ history of fever, 291/1497 had malaria (19.4%, 95% CI 17–21%). A high proportion was visiting friends and relatives. In those from other areas the proportions were: 16/707 (2.3%, 95% CI 1.5–3.8) from Indian subcontinent/Southeast Asia; 2/143 (1.4%) from Southern America; 4/129 (3.1%) from South Africa; 1/44 (2.3%) from North Africa; and 8/41 (19.5%) from Oceania. Compared to other malaria-endemic regions, African travel gave an adjusted odds ratio of 7.8 (95% CI 5.4–11.2, P < 0.0001). Only 45.1% of malaria cases had a fever (37.58C) at the time of presentation. Only 3% of all diagnoses of malaria had no history of fever. In 28% of cases parasite count increased in the initial 24 h of antimalarial treatment. Conclusions: The likelihood that a patient with fever returning from Africa has malaria is high (around 1 in 5), and is significantly lower from other areas. Absence of fever at presentation does not exclude malaria.

This study of the bidding strategies used by electricity producers in the day-ahead and intraday markets in Spain-Portugal shows that they clearly do respect the merit order. They offer their production at a range of prices which vary from one hour of the day to another, and from one day of the week to another. We show that on average over a quarter producers received about the same revenue per MWh sold irrespective of fuel type. The average dropped from 70–75 euro per MWh in 2008 to as low as 25 euro in 2010 because of the global crisis then rose to about 50 euro in 2012 despite the increasing quantity of renewal energy and the stagnation of the demand.

Often studies on the impact of demand side management on GHG emissions assume that power plants respect the merit order when bidding on electricity markets. By analyzing bidding patterns in Sicily from 2006 to 2012 we show that this is not the case. Generators offer their production at prices ranging from zero upwards. Going further we estimate the GHG emissions of the power plants that were actually dispatched compared to those that would have been dispatched if producers respected the merit order rule. This highlights the need for in-depth studies of actual bidding strategies.

Just more than 2,000 cases of Plasmodium falciparum malaria are reported in the United Kingdom annually, with a mortality rate of approximately 1%. Some studies suggest that patients with malaria who originate from disease-endemic areas are less likely to develop severe disease; such patients are often treated at home. We have prospectively examined 99 patients with imported P. falciparum malaria and categorized them according to severity as defined by World Health Organization criteria. There was no significant difference between those who developed severe disease and those who did not in terms of their ethnicity, residence in a malaria-endemic area, or history of previous episodes of malaria. To assume a patient has clinical immunity to malaria simply because they originate from or have lived for a long time in a malaria-endemic area may be inappropriate and unsafe.

Use of parenteral pentavalent antimonials to treat leishmaniasis is associated with a range of cardiological, biochemical and haematological adverse effects. The most serious of these is the development of ventricular tachyarrhythmias associated with prolongation of the electrocardiographic rate-corrected QT interval (QTc). Whereas some studies have reported that serious cardiological and biochemical adverse effects are common and often require treatment interruption or discontinuation, others have reported the drugs to be well tolerated. We conducted a detailed retrospective analysis of adverse events among British returned travellers (n=65) with New World cutaneous or mucosal leishmaniasis who received i.v. sodium stibogluconate (SbV) for >or=21 days. The mean+/-SEM QTc progressively increased from 389+/-3.1 msec to 404+/-2.9 msec during 3 weeks of treatment and the QTc reached the threshold for potential cardiac toxicity among 6 (10%) patients during the third week of treatment. Marked QTc prolongation and ventricular tachyarrhythmias occurred in one elderly patient with hypokalaemia and pre-existing cardiovascular morbidity. Although increased serum concentrations of amylase and hepatic transaminases were observed among 67% and 85% of patients respectively, none developed clinical pancreatitis or hepatitis and treatment modification was not required. SbV can be used safely in this population with adequate monitoring and the need for treatment interruption is uncommon. Identification of factors before and during treatment that may increase the risk of QTc prolongation and arrhythmias is important.

In many industrial applications, the option to acquire information instead of simply waiting for conditions to improve can add considerable value to projects. As one example, most oil wells require periodic “workovers” to maintain production at satisfactory levels, and acquiring up-to-date information on the reservoir using a production logging tool (PLT) generally improves the efficiency of such workovers. This article presents a case study of oil production enhancement in which Bayesian analysis is incorporated into a real options framework to determine whether the additional cost of acquiring information is justified. This case is different from most applications of real options in that there are two main sources of uncertainty: the oil price and the reservoir. Bayesian analysis was used to update the reservoir model, using the PLT data together with prior knowledge about the reservoir. The updated reservoir model was then incorporated into a real options valuation framework.

Problem Introduction and evaluation of evidence based medicine (EBM) into routine hospital practice. Strategy for change Routine EBM meetings introduced in 1997. Design Review of outcomes of meetings from 1997 to 2004, focusing on their effect on clinical practice. Setting Referral centre for tropical and domestic infectious diseases. Key measure for improvement Outcome of meetings, classified as resulting in a change in practice; confirmation or clarification of existing practice; identification of a need for more evidence; and outcome unclear. Effects of change Examples include a change from inpatient to day case treatment of New World cutaneous leishmaniasis; development of guidelines on the treatment of coinfection with visceral leishmaniasis and HIV; and identification of the need for more data on the efficacy and toxicity of atovaquone-proguanil (Malarone) compared with quinine plus sulfadoxine-pyrimethamine (Fansidar) in the treatment of uncomplicated falciparum malaria, which resulted in a clinical trial being set up. Lessons learnt Incorporation of EBM meetings into our routine practice has resulted in treatment guidelines being more closely based on published evidence and improvements to care of patients. Written summaries of the meetings are important to facilitate change.

Real options are a way of valuing projects such as oil fields, which involve irreversible investment decisions subject to uncertainty. Whereas discounted cash flow (DCF) analysis is based on fixed estimates of costs and revenues, and a predetermined development scenario, real options focus on project flexibility (e.g., being able to defer starting a project, or conversely, to accelerate its development, etc.). Early applications concentrated on flexibility to overcome uncertainty on financial parameters and tended to ignore uncertainty on technical parameters (such as recoverable reserves). In some cases, companies can reduce the latter by acquiring additional information and sequentially updating parameter values and then the estimate of the project's value. This paper addresses the question of how to evaluate the option to acquire more information. The natural way to incorporate the new data is by Bayesian analysis. Choosing a multivariate normal framework for this analysis considerably simplifies the computations but this distribution has symmetric upper and lower tail dependence. To overcome this limitation, we have developed a novel form of Bayesian updating based on Archimedean copulas. We present a case study on production enhancement that shows how to combine Bayesian updating and real options. In this study, the oil company has the option to gather information from a production logging tool (PLT) before carrying out a workover.

Background: Patients from malaria-endemic areas who present in non-endemic countries with Plasmodium falciparum malaria are often assumed to have some degree of immunity. If this were reliably true, it would simplify their management. Aim: To determine whether being born and resident in a malaria-endemic country is a predictor of clinical course in UK admissions for malaria. Design: Prospective observational study. Methods: We compared clinical and laboratory parameters between two groups of adult patients with acute P. falciparum malaria, admitted to the Hospital for Tropical Diseases in London: one born and resident in non-endemic countries ( n = 167); the other born and resident in malaria-endemic countries of Africa ( n = 93). Patients were excluded if they had taken prophylaxis or prior treatment. Results: There were no differences between these two groups in terms of peak parasitaemia or time to parasite clearance. There was a significantly higher risk of malaria-naive patients having peak parasitaemia >5% (OR 4.5, 95%CI 1.5–13.2). Of those usually resident in Africa, 31% required parenteral treatment compared to 41% of the malaria-naive group. Of the visitors from Africa, 4.3% needed admission to the Intensive Therapy Unit (ITU), although there was a tendency for more malaria-naive patients to require ITU care (OR 2.69, 95%CI 0.9–8.1). Discussion: While there are differences in presentation between those who are malaria-naive and those who live in malaria-endemic African countries, making assumptions about the immunity or clinical course of an individual patient with malaria presenting in the UK on the basis of presumed history of exposure is unwise.

Objectives: Patients with eosinophilia are an important clinical problem. This study aimed to assess the most efficient manner of investigating patients with peripheral eosinophilia (eosinophil count >0.5×10 9 ml −1 ) presenting from the tropics. Methods: Patients attending the Hospital for Tropical Diseases, London, from October 1997 to March 2002 for investigation of eosinophilia were identified prospectively. Laboratory, clinical and demographic data were recorded from laboratory and clinical records. An investigation set was proposed prospectively and assessed for all geographical areas (stool microscopy, strongyloides culture and serology), all of Africa (additional schistosomal serology, terminal urine microscopy and filarial serology) and West Africa (additional day-bloods for microfilaria). Results: Data was analysed for 261 patients. At least one helminthic cause for eosinophilia was found in 64% of patients (median eosinophilia 1.2×10 9 ml −1 ). Seventeen per cent of patients had more than one helminth species found. Median eosinophilia increased with number of diagnoses per patient. The proposed investigation sets were validated, with high yield for all proposed tests apart from filarial serology outside West Africa, and good sensitivity. Conclusions: Initial investigation of eosinophilia in patients presenting from the tropics may be guided by a simple investigation set depending on broad area of travel which has high sensitivity and yield. Patients frequently have more than one helminthic cause of eosinophilia.

Schistosomiasis is found in a significant proportion of returning travellers and immigrants to Britain. This study is a retrospective review of 1107 consecutive cases of schistosomiasis from Africa diagnosed by microscopy or serology presenting to the Hospital for Tropical Diseases, London, UK. 50·4% of cases were asymptomatic. The most common symptom which resolved on treatment was tiredness. Serology was positive in 951 (86%), and ova seen in 45%. Urine dipstick testing was positive for blood in 21% and protein in 15%, with eosinophilia in 44%. In this population urine dipstick, full blood count and serology were all insufficient screening tools used alone. Among patients with full follow-up data 3 months or more after treatment with praziquantel, definite treatment failure occured in 4 of 271 (1·5%), restricting the analysis to those with ova seen at diagnosis. There was no significant difference in treatment failure between 1 and 3 days of treatment. Antibody level was the same or higher than at treatment in 55% of cases seen after about 3 months and 38% after 1 year, confirming it is probably of limited clinical use in detecting treatment failure.

This paper (SPE 57894) was revised for publication from paper 52949, originally presented at the 1999 SPE Hydrocarbon Economics and Evaluation Symposium held in Dallas, 20–23 March. Original manuscript received 3 January 1999. This paper has not been peer reviewed. Summary Option pricing, decision trees, and Monte Carlo simulations are three methods used to evaluate projects. In this paper, we compare their similarities and differences from three points of view—how they handle uncertainty in the values of key parameters, such as reserves, oil price, and costs; how they incorporate the time value of money; and whether they allow for managerial flexibility. We show that, despite their obvious differences, they are in fact different facets of a general project-evaluation framework that has the static base-case scenario as its simplest form. Compromises have to be made when modeling the complexity of the real world. These three approaches can be obtained from the general framework by focusing on certainty aspects. Introduction Option pricing, decision trees, and Monte Carlo simulations are three methods for evaluating oil projects that seem at first radically different. Option pricing comes from the world of finance. In its most common form, it incorporates the Black and Scholes1 model for spot prices and expresses the value of the project as a stochastic differential equation. Decision trees, which come from operations research and games theory, neglect the time variations in prices but concentrate on estimating the probabilities of possible values of the project, sometimes with Bayes theorem and pre- and post-probabilities (see Ref. 2). In their simplest form, Monte Carlo simulations merely require the user to specify the marginal distributions of all the parameters appearing in the equation for the net present value (NPV) of the project. All three approaches seek to determine the expected value (or maximum expected value) of the project and possibly the histogram of project values; however, they make different assumptions about the underlying distributions, the variation with time of input variables, and the correlations between these variables. Another important difference is the way they handle the time value of money. Decision trees and Monte Carlo simulations use the traditional discount rate; option pricing makes use of the financial concept of risk-neutral probabilities. One of the difficulties in estimating the value of a project is that it usually is a nonlinear function of the input variables (for example, tax is treated differently in years with a profit than in years with a loss). Starting out from the NPV calculated on the base case, this paper shows how Monte Carlo simulations and decision trees build uncertainty and managerial flexibility into the evaluation method. Option pricing starts out by defining the options available to management and then models the uncertainty in key parameters. The three approaches are, in fact, different facets of a general framework. They can be obtained from this framework by focusing on certain aspects and simplifying or ignoring others. First Step-NPV for the base case The first step in evaluating any project is to set up a base-case scenario and to calculate its NPV with the parameter values that have been agreed upon. This assumes that the values of the input parameters are known: original oil in place, decline rate, oil prices for each year, costs for each year, discount rate, and tax structure, among others. It further assumes that the scenario and the project life are fixed and that management will not intervene because of changes in the oil price, new technological developments, and other such factors. In the real world, the values of the variables are uncertain and management does react to changing situations, so it is vital to incorporate these two factors into the evaluation procedure. Ideally, distributions of all the variables should be modeled together with the correlations over time and the complex links between variables should be modeled for a wide variety of management scenarios. However, as Smith and McCardle3 demonstrated, this rapidly becomes very unwieldy and the sheer complexity of the situation forces compromise. Monte Carlo simulations, decision trees, and option pricing address this problem in different ways; each focuses on certain aspects and simplifies or ignores others. We show how these methods build up from the NPV equation in the base case incorporating uncertainty in the input variables for all three methods and incorporating managerial flexibility for decision trees and option pricing.

Objectives We sought to identify chloroquine-resistant Plasmodium falciparum parasites among 66 travellers who presented in the UK with malaria. Methods A multiplex real-time PCR assay was devised to identify wild-type and two distinct chloroquine-resistance-associated alleles of the pfcrt gene. Results Those with documented use of chloroquine/proguanil prophylaxis were more likely to carry parasites with resistance-associated alleles of pfcrt than were patients who had been using antimalarials other than chloroquine (92.9% versus 37.5%; P = 0.011). We also found evidence that people reporting optimum compliance with chloroquine prophylaxis during malaria exposure were more common among malaria cases than were those reporting optimum compliance with other regimens (OR 3.85, 95% CI 1.61-9.69; P = 0.0008). Conclusions Chloroquine, known to be failing as therapy for falciparum malaria worldwide, is also failing to provide adequate malaria prophylaxis for travellers.

We report 79 cases of acute schistosomiasis. Most of these cases were young, male travelers who acquired their infection in Lake Malawi. Twelve had a normal eosinophil count at presentation and 11 had negative serology, although two had neither eosinophilia nor positive serology when first seen. Acute schistosomiasis should be considered in any febrile traveler with a history of fresh water exposure in an endemic area once malaria has been excluded.

Background: Few studies have investigated incidence rate and risk factors for giardiasis and strongyloidiasis in returning UK travellers. The clinical presentations of these two diseases are often similar and difficult to distinguish. This study was conducted to investigate the incidence rate and the risk factors for symptomatic giardiasis and strongyloidiasis in returned tropical travellers. Methods: We retrospectively analysed 3306 consecutive attendances presenting to the emergency clinic at the Hospital for Tropical Diseases in London, the UK from September 2008 to May 2010. Odds ratios between the diagnoses and patient variables were analysed by logistic regression. Results: Giardiasis was diagnosed in 92/3306 cases (2.8%, proportionate morbidity), and the incidence rate per 1000 person-months was 12.5. Multivariate analysis with logistic regression revealed that Caucasian ethnicity (adjusted odds ratio (aOR): 2.37, 95% confidence interval (CI): 1.12–5.03, P value = 0.025), travel length ≥32 days (aOR: 2.63, 95%CI: 1.43–4.83, P = 0.002), travelling to South or South East Asia (aOR: 4.90, 95%CI: 2.03–11.8, P

BACKGROUND: Early diagnosis of HIV infection reduces morbidity and mortality associated with late presentation. Despite UK guidelines, the HIV testing rate has not increased. We have introduced universal HIV screening in an open-access returning traveller clinic. METHODS: Data were prospectively recorded for all patients attending the open-access returning traveller clinic between August 2008 and December 2010. HIV testing was offered to all patients from May 2009; initially testing with laboratory samples (phase 1) and subsequently a point-of-care test (POCT) (phase 2). RESULTS: A total of 4965 patients attended the clinic; 1342 in phase 0, 792 in phase 1 and 2831 in phase 2. Testing rates for HIV increased significantly from 2% (38 of 1342) in phase 0 to 23.1% (183 of 792) in phase 1 and further increased to 44.5% (1261 of 2831) during phase 2 (P

Purpose - The purpose of this paper is to highlight the potentials offered by New Product Committees for the development of responsible innovation in the financial services industry; and to provide grounds for policy recommendations. Design/methodology/approach - The paper takes the form of collective, interdisciplinary reflection and experience within the industry. Findings - New Product Committees can serve a practical approach to responsible innovation in finance. Originality/value - The paper fills a gap in the empirical consideration of New Product Committees in the financial services industry and proposes original directions for policy orientations within organizations and at a regulatory level. Abstract - The paper first lists the multiple interpretations of responsibility that should be taken into account, then proceeds to an empirical description of New Products Committees and to an analysis of their potentials to meet the several interpretations of responsibility. The paper concludes with a series of policy implications. The role of New Product Committees could be better formalized in regulatory frameworks, but also more open to scrutiny and revision. They could also play a more central role within the internal culture of the investment bank.

This chapter describes how to calculate experimental variograms for the facies indicators and how to fit models to them. The relationship between the facies indicators and the underlying gaussian values has been given in Chap. 2. In this chapter we will give the variogram equations in the case when we only have constraints on facies but no other categorical variable or continuous function in the data set. The theoretical relation linking the variograms of the underlying gaussians and those of the indicators is described. From this link we use a specific fitting method: rather than invert it, we use an indirect iterative procedure to fit a variogram model. But first, we show how to calculate the experimental variograms for the facies indicators.

Simulation methods fall into two broad classes: pixel methods and object-based methods. Before presenting any practical examples, it is important to decide which method would be the most appropriate for the problem under study. So we first review the pros and cons of two classes of models, sequence-based pixel methods such as the truncated gaussian and plurigaussian simulations, and object-based methods, in particular boolean simulations. As this book focuses on plurigaussian simulations, we do not intend to present boolean simulations here. Interested readers can consult Matheron (1968, 1975), Lantuejoul (1997a, 1997b and 2002) Chiles and Delfiner (1999), and Molchanov (1997). Sequence-based pixel methods and boolean simulations can also be combined to get the best of both approaches. These are called nested simulations.

In truncated gaussian simulations, the lithofacies are not simulated directly: a stationary gaussian random function is simulated first, and is then transformed into the lithofacies variable by truncation. For example, if we want to simulate two lithofacies, F1 and F2, a very intuitive way to transform the simulated gaussian variable into facies values is to say “if the numerical value of the simulated gaussian is lower than the number t1, we obtain the first facies F1; otherwise, we obtain the second facies F2”. The value t1 is called a threshold.