Potential changes in disease patterns and pharmaceutical use in response to climate change

This is the final version of the article. Available from Taylor & Francis via the DOI in this record.As climate change alters environmental conditions, the incidence and global patterns of human diseases are changing. These modifications to disease profiles and the effects upon human pharmaceutical usage are discussed. Climate-related environmental changes are associated with a rise in the incidence of chronic diseases already prevalent in the Northern Hemisphere, for example, cardiovascular disease and mental illness, leading to greater use of associated heavily used Western medications. Sufferers of respiratory diseases may exhibit exacerbated symptoms due to altered environmental conditions (e.g., pollen). Respiratory, water-borne, and food-borne toxicants and infections, including those that are vector borne, may become more common in Western countries, central and eastern Asia, and across North America. As new disease threats emerge, substantially higher pharmaceutical use appears inevitable, especially of pharmaceuticals not commonly employed at present (e.g., antiprotozoals). The use of medications for the treatment of general symptoms (e.g., analgesics) will also rise. These developments need to be viewed in the context of other major environmental changes (e.g., industrial chemical pollution, biodiversity loss, reduced water and food security) as well as marked shifts in human demographics, including aging of the population. To identify, prevent, mitigate, and adapt to potential threats, one needs to be aware of the major factors underlying changes in the use of pharmaceuticals and their subsequent release, deliberately or unintentionally, into the environment. This review explores the likely consequences of climate change upon the use of medical pharmaceuticals in the Northern Hemisphere.The European Centre for Environment and Human Health (part of the University of Exeter Medical School) is partly financed by the European Regional Development Fund Programme 2007 to 2013 and European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

New Holocene grey whale (Eschrichtius robustus) material from North Carolina: the most complete North Atlantic grey whale skeleton to date

Skeletal remains and historical accounts indicate that grey whales (Eschrichtius robustus) existed in the North Atlantic Ocean from the Pleistocene into the seventeenth century. Fossil and sub-fossil occurrences in this basin are rare, distributed from the east coast of the United States to Iceland and Europe. Here, we report an incomplete skeleton of a Holocene grey whale from Pender County, North Carolina, USA. This specimen represents a physically immature individual and is the most complete North Atlantic grey whale specimen reported to date. It comprises 42 cranial and postcranial elements, including the cranium, parts of the rostrum, both mandibles, both scapulae, humeri, radii and ulnae, most of the vertebral column anterior to the lumbar region and numerous ribs. Its provenance near the inlet of a large estuary is consistent with previous findings from the southeastern USA and parallels the species' habitat use in Baja California breeding and calving grounds in the North Pacific Ocean. Radiocarbon dating indicates an age of 827 ± 172 years before present. Cut marks on multiple skeletal elements indicate that the animal was butchered, suggesting some level of human exploitation of the species in the southeastern USA in the twelfth century, approximately 500 years prior to its extirpation in the North Atlantic

Geographical inequalities in drinking water in the Solomon Islands

Sustainable Development Goal 6.1 seeks to “by 2030, achieve universal and equitable access to safe and affordable drinking water”, which is challenging particularly in Small Island Developing States (SIDS) and Pacific Island Countries (PIC). We report drinking water sources and services in the Solomon Islands and examine geographical inequalities. Based on two quantitative baseline datasets of n = 1,598 rural and n = 1,068 urban households, we analyzed different drinking water variables (source type, collection time, amount, use, perceived quality, storage, treatment) and a composite index, drinking water service level. We stratified data by urban and rural areas and by province, mapped, and contextualized them. There are substantive rural–urban drinking water inequalities in the Solomon Islands. Overall, urban households are more likely to: use improved drinking water sources, need less time to collect water, collect more water, store their water more safely, treat water prior to consumption, perceive their water quality as better and have an at least basic drinking water service than rural households. There are also provincial and center-periphery inequalities in drinking water access, with more centrally located provinces using piped water supplies and more distant and remote provinces using rainwater and surface water as their primary source. There are also inter-national inequalities. Out of all PICs, the Solomon Islands have among the lowest access to basic drinking water services: 92% of urban and 55% of rural households. Of all SIDS, PICs are least serviced. This study shows that drinking water inequality is a critical issue, and highlights that all identified dimensions of inequality - rural–urban, provincial, center-periphery and inter-national - need to be explicitly recognized and addressed and included in pro-equity monitoring, policy and programming efforts by the Solomon Islands Government and stakeholders to reduce inequalities as per the Agenda 2030

OAS1 Polymorphisms Are Associated with Susceptibility to West Nile Encephalitis in Horses

West Nile virus, first identified within the United States in 1999, has since spread across the continental states and infected birds, humans and domestic animals, resulting in numerous deaths. Previous studies in mice identified the Oas1b gene, a member of the OAS/RNASEL innate immune system, as a determining factor for resistance to West Nile virus (WNV) infection. A recent case-control association study described mutations of human OAS1 associated with clinical susceptibility to WNV infection. Similar studies in horses, a particularly susceptible species, have been lacking, in part, because of the difficulty in collecting populations sufficiently homogenous in their infection and disease states. The equine OAS gene cluster most closely resembles the human cluster, with single copies of OAS1, OAS3 and OAS2 in the same orientation. With naturally occurring susceptible and resistant sub-populations to lethal West Nile encephalitis, we undertook a case-control association study to investigate whether, similar to humans (OAS1) and mice (Oas1b), equine OAS1 plays a role in resistance to severe WNV infection. We identified naturally occurring single nucleotide mutations in equine (Equus caballus) OAS1 and RNASEL genes and, using Fisher's Exact test, we provide evidence that mutations in equine OAS1 contribute to host susceptibility. Virtually all of the associated OAS1 polymorphisms were located within the interferon-inducible promoter, suggesting that differences in OAS1 gene expression may determine the host's ability to resist clinical manifestations associated with WNV infection

Detection of distant metastases in patients with oesophageal or gastric cardia cancer: a diagnostic decision analysis

Computed tomography (CT) is presently a standard procedure for the detection of distant metastases in patients with oesophageal or gastric cardia cancer. We aimed to determine the additional diagnostic value of alternative staging investigations. We included 569 oesophageal or gastric cardia cancer patients who had undergone CT neck/thorax/abdomen, ultrasound (US) abdomen, US neck, endoscopic ultrasonography (EUS), and/or chest X-ray for staging. Sensitivity and specificity were first determined at an organ level (results of investigations, i.e., CT, US abdomen, US neck, EUS, and chest X-ray, per organ), and then at a patient level (results for combinations of investigations), considering that the detection of distant metastases is a contraindication to surgery. For this, we compared three strategies for each organ: CT alone, CT plus another investigation if CT was negative for metastases (one-positive scenario), and CT plus another investigation if CT was positive, but requiring that both were positive for a final positive result (two-positive scenario). In addition, costs, life expectancy and quality adjusted life years (QALYs) were compared between different diagnostic strategies. CT showed sensitivities for detecting metastases in celiac lymph nodes, liver and lung of 69, 73, and 90%, respectively, which was higher than the sensitivities of US abdomen (44% for celiac lymph nodes and 65% for liver metastases), EUS (38% for celiac lymph nodes), and chest X-ray (68% for lung metastases). In contrast, US neck showed a higher sensitivity for the detection of malignant supraclavicular lymph nodes than CT (85 vs 28%). At a patient level, sensitivity for detecting distant metastases was 66% and specificity was 95% if only CT was performed. A higher sensitivity (86%) was achieved when US neck was added to CT (one-positive scenario), at the same specificity (95%). This strategy resulted in lower costs compared to CT only, at an almost similar (quality adjusted) life expectancy. Slightly higher specificities (97–99%) were achieved if liver and/or lung metastases found on CT, were confirmed by US abdomen or chest X-ray, respectively (two-positive scenario). These strategies had only slightly higher QALYs, but substantially higher costs. The combination of CT neck/thorax/abdomen and US neck was most cost-effective for the detection of metastases in patients with oesophageal or gastric cardia cancer, whereas the performance of CT only had a lower sensitivity for metastases detection and higher costs. The role of EUS seems limited, which may be due to the low number of M1b celiac lymph nodes detected in this series. It remains to be determined whether the application of positron emission tomography will further increase sensitivities and specificities of metastases detection without jeopardising costs and QALYs

Double Non-Global Logarithms In-N-Out of Jets

We derive the leading non-global logarithms (NGLs) of ratios of jet masses m_{1,2} and a jet energy veto \Lambda due to soft gluons splitting into regions in and out of jets. Such NGLs appear in any exclusive jet cross section with multiple jet measurements or with a veto imposed on additional jets. Here, we consider back-to-back jets of radius R produced in e^+e^- collisions, found with a cone or recombination algorithm. The leading NGLs are of the form \alpha_s^2 \ln^2(\Lambda/m_{1,2}) or \alpha_s^2\ln^2(m_1/m_2). Their coefficients depend both on the algorithm and on R. We consider cone, \kt, anti-\kt, and Cambridge-Aachen algorithms. In addition to determining the full algorithmic and R dependence of the leading NGLs, we derive new relations among their coefficients. We also derive to all orders in \alpha_s a factorized form for the soft function S(k_L,k_R,\Lambda) in the cross section \sigma(m_1,m_2,\Lambda) in which dependence on each of the global logs of \mu/k_L, \mu/k_R and \mu/\Lambda determined by the renormalization group are separated from one another and from the non-global logs. The same kind of soft function, its associated non-global structure, and the algorithmic dependence we derive here will also arise in exclusive jet cross sections at hadron colliders, and must be understood and brought under control to achieve precise theoretical predictions.Comment: 19 pages, 10 figures. v2: minor edits, additional discussion in Introduction. v3: version published in JHE

Initial Evaluation of the Effects of Aerosolized Florida Red Tide Toxins (Brevetoxins) in Persons with Asthma

Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tides. Anecdotal reports indicate that persons with underlying respiratory diseases may be particularly susceptible to adverse health effects from these aerosolized toxins. Fifty-nine persons with physician-diagnosed asthma were evaluated for 1 hr before and after going to the beach on days with and without Florida red tide. Study participants were evaluated with a brief symptom questionnaire, nose and throat swabs, and spirometry approved by the National Institute for Occupational Safety and Health. Environmental monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate size distribution), and personal monitoring (for toxins) were performed. Brevetoxin concentrations were measured by liquid chromatography mass spectrometry, high-performance liquid chromatography, and a newly developed brevetoxin enzyme-linked immunosorbent assay. Participants were significantly more likely to report respiratory symptoms after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in forced expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak expiratory flow after exposure, particularly those regularly using asthma medications. Similar evaluation during nonexposure periods did not significantly differ. This is the first study to show objectively measurable adverse health effects from exposure to aerosolized Florida red tide toxins in persons with asthma. Future studies will examine the possible chronic effects of these toxins among persons with asthma and other chronic respiratory impairment

Standing genetic variation and compensatory evolution in transgenic organisms: a growth-enhanced salmon simulation

Genetically modified strains usually are generated within defined genetic backgrounds to minimize variation for the engineered characteristic in order to facilitate basic research investigations or for commercial application. However, interactions between transgenes and genetic background have been documented in both model and commercial agricultural species, indicating that allelic variation at transgene-modifying loci are not uncommon in genomes. Engineered organisms that have the potential to allow entry of transgenes into natural populations may cause changes to ecosystems via the interaction of their specific phenotypes with ecosystem components and services. A transgene introgressing through natural populations is likely to encounter a range of natural genetic variation (among individuals or sub-populations) that could result in changes in phenotype, concomitant with effects on fitness and ecosystem consequences that differ from that seen in the progenitor transgenic strain. In the present study, using a growth hormone transgenic salmon example, we have modeled selection of modifier loci (single and multiple) in the presence of a transgene and have found that accounting for genetic background can significantly affect the persistence of transgenes in populations, potentially reducing or reversing a “Trojan gene” effect. Influences from altered life history characteristics (e.g., developmental timing, age of maturation) and compensatory demographic/ecosystem controls (e.g., density dependence) also were found to have a strong influence on transgene effects. Further, with the presence of a transgene in a population, genetic backgrounds were found to shift in non-transgenic individuals as well, an effect expected to direct phenotypes away from naturally selected optima. The present model has revealed the importance of understanding effects of selection for background genetics on the evolution of phenotypes in populations harbouring transgenes