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

Leptoproduction of J/psi

We study leptoproduction of $J/\psi$ at large $Q^2$ within the nonrelativistic QCD (NRQCD) factorization formalism. The cross section is dominated by color-octet terms that are of order $\alpha_s$. The color-singlet term, which is of order $\alpha^2_s$, is shown to be a small contribution to the total cross section. We also calculate the tree diagrams for color-octet production at order $\alpha^2_s$ in a region of phase space where there is no leading color-octet contribution. We find that in this regime the color-singlet contribution dominates. We argue that non-perturbative corrections arising from diffractive leptoproduction, higher twist effects, and higher order terms in the NRQCD velocity expansion should be suppressed as $Q^2$ is increased. Therefore, the color-octet matrix elements $$and$$ can be reliably extracted from this process. Finally, we point out that an experimental measurement of the polarization of leptoproduced $J/\psi$ will provide an excellent test of the NRQCD factorization formalism.Comment: 33 pages latex. 10 figures. Uses revtex, epsf, and rotate macros. This paper is also available via the UW phenomenology archives at http://phenom.physics.wisc.edu/pub/preprints

Assessing the benefits of five years of different approaches to treatment of urogenital schistosomiasis: A SCORE project in Northern Mozambique.

BACKGROUND: In Mozambique, schistosomiasis is highly endemic across the whole country. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinates a five-year study that has been implemented in various African countries, including Mozambique. The overall goal of SCORE was to better understand how to best apply preventive chemotherapy with praziquantel (PZQ) for schistosomiasis control by evaluating the impact of alternative treatment approaches. METHODS: This was a cluster-randomised trial that compared the impact of different treatment strategies in study areas with prevalence among school children of ≥21% S. haematobium infection by urine dipstick. Each village was randomly allocated to one of six possible combinations of community-wide treatment (CWT), school-based treatment (SBT), and/or drug holidays over a period of four years, followed by final data collection in the fifth year. The most intense intervention arm involved four years of CWT, while the least intensive arm involved two years of SBT followed by two consecutive years of PZQ holiday. Each study arm included 25 villages randomly assigned to one of the six treatment arms. The primary outcome of interest was change in prevalence and intensity of S. haematobium among 100 children aged 9-to-12-years that were sampled each year in every village. In addition to children aged 9-to-12 years, 100 children aged 5-8 years in their first-year of school and 50 adults (aged 20-55 years) were tested in the first and final fifth year of the study. Prevalence and intensity of S. haematobium infection was evaluated by two filtrations, each of 10mL, from a single urine specimen. PRINCIPAL FINDINGS: In total, data was collected from 81,167 individuals across 149 villages in ten districts of Cabo Delgado province, Northern Mozambique. Overall PZQ treatment resulted in a significant reduction in the prevalence of S. haematobium infection from Year 1 to Year 5, where the average prevalence went from 60.5% to 38.8%, across all age groups and treatment arms. The proportion of those heavily infected also reduced from 17.6% to 11.9% over five years. There was a significantly higher likelihood of males being infected than females at baseline, but no significant difference between the sexes in their response to treatment. The only significant response based on a study arm was seen in both the 9-to-12-year-old and first-year cross sections, where two consecutive treatment holidays resulted in a significantly higher final prevalence of S. haematobium than no treatment holidays. When the arms were grouped together, four rounds of treatment (regardless of whether it was CWT or SBT), however, did result in a significantly greater reduction in S. haematobium prevalence than two rounds of treatment (i.e. with two intermittent or consecutive holiday years) over a five-year period. CONCLUSIONS: Although PC was successful in reducing the burden of active infection, even among those heavily infected, annual CWT did not have a significantly greater impact on disease prevalence or intensity than less intense treatment arms. This may be due to extremely high starting prevalence and intensity in the study area, with frequent exposure to reinfection, or related to challenges in achieving high treatment coverage More frequent treatment had a greater impact on prevalence and intensity of infection when arms were grouped by number of treatments, however, cost efficiency was greater in arms only receiving two treatments. Finally, a significant reduction in prevalence of S. haematobium was seen in adults even in the SBT arms implying the rate of transmission in the community had been decreased, even where only school children have been treated, which has significant logistical and cost-saving implications for a national control programme in justifying CWT

The impact of current CH4 and N2O atmospheric loss process uncertainties on calculated ozone abundances and trends

The atmospheric loss processes of N2O and CH4, their estimated uncertainties, lifetimes, and impacts on ozone abundance and long-term trends are examined using atmospheric model calculations and updated kinetic and photochemical parameters and uncertainty factors from SPARC [2013]. The uncertainty ranges in calculated N2O and CH4 global lifetimes computed using the SPARC estimated uncertainties are reduced by nearly a factor of two compared with uncertainties from Sander et al. [2011]. Uncertainties in CH4 loss due to reaction with OH and O(1D) have relatively small impacts on present day global total ozone (±0.2-0.3%). Uncertainty in the Cl + CH4 reaction affects the amount of chlorine in radical vs. reservoir forms and has a modest impact on present day SH polar ozone (~±6%), and on the rate of past ozone decline and future recovery. Uncertainty in the total rate coefficient for the O(1D) + N2O reaction results in a substantial range in present day stratospheric odd nitrogen (±20-25%) and global total ozone (±1.5-2.5%). Uncertainty in the O(1D) + N2O reaction branching ratio for the O2 + N2 and 2*NO product channels results in moderate impacts on odd nitrogen (±10%) and global ozone (±1%),with uncertainty in N2O photolysis resulting in relatively small impacts (±5% in odd nitrogen, ±0.5% in global ozone). Uncertainties in the O(1D) + N2O reaction and its branching ratio also affect the rate of past global total ozone decline and future recovery, with a range in future ozone projections of ±1-1.5% by 2100, relative to present day

From Multiview Image Curves to 3D Drawings

Reconstructing 3D scenes from multiple views has made impressive strides in recent years, chiefly by correlating isolated feature points, intensity patterns, or curvilinear structures. In the general setting - without controlled acquisition, abundant texture, curves and surfaces following specific models or limiting scene complexity - most methods produce unorganized point clouds, meshes, or voxel representations, with some exceptions producing unorganized clouds of 3D curve fragments. Ideally, many applications require structured representations of curves, surfaces and their spatial relationships. This paper presents a step in this direction by formulating an approach that combines 2D image curves into a collection of 3D curves, with topological connectivity between them represented as a 3D graph. This results in a 3D drawing, which is complementary to surface representations in the same sense as a 3D scaffold complements a tent taut over it. We evaluate our results against truth on synthetic and real datasets.Comment: Expanded ECCV 2016 version with tweaked figures and including an overview of the supplementary material available at multiview-3d-drawing.sourceforge.ne

Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. We report lymphocytic DPD data concerning a group of 53 patients (23 men, 30 women, mean age 58, range 36–73), treated by 5-FU-based chemotherapy in different French institutions and who developed unanticipated 5-FU-related toxicity. Lymphocyte samples (standard collection procedure) were sent to us for DPD determination (biochemical method). Among the whole group of 53 patients, 19 had a significant DPD deficiency (DD; below 150 fmol min−1 mg−1 protein, i.e. less than 70% of the mean value observed from previous population study). There was a greater majority of women in the DD group (15 out of 19, 79%) compared with the remaining 34 patients (15 out of 34, 44%, P<0.014). Toxicity was often severe, leading to patient death in two cases (both women). The toxicity score (sum of WHO grading, theoritical range 0–20) was twice as high in patients with marked DD (below 100 pmol min−1 mg−1 protein, n = 11, mean score = 13.2) compared with patients with moderate DD (between 150 and 100 pmol min−1 mg−1 protein, n = 8, mean score = 6.8), P = 0.008. In the DD group, there was a high frequency of neurotoxic syndromes (7 out of 19, 37%). The two deceased patients both had severe neurotoxicity. The occurrence of cardiac toxicity was relatively rare (1 out of 19, 5%). These data suggest that women are particularly prone to DPD deficiency and allow a more precise definition of the DD toxicity profile. © 1999 Cancer Research Campaig

Field Induced Reduction of the Low Temperature Superfluid Density in YBa2Cu3O6.95

A novel high magnetic field (8 T) spectrometer for muon spin rotation has been used to measure the temperature dependence of the in-plane magnetic penetration depth in YBa2Cu3O6.95. At low H and low T, the penetration depth exhibits the characteristic linear T dependence associated with the energy gap of a d_x^2-y^2-wave superconductor. However, at higher fields the penetration depth is essentially temperature independent at low T. We discuss possible interpretations of this surprising new feature in the low-energy excitation spectrum.Comment: 8 pages, 4 figures, 1 RevTex file and 4 postscript figure

Lessons Learned in Conducting Mass Drug Administration for Schistosomiasis Control and Measuring Coverage in an Operational Research Setting

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created to conduct research that could inform programmatic decision-making related to schistosomiasis. SCORE included several large cluster randomized field studies involving mass drug administration (MDA) with praziquantel. The largest of these were studies of gaining or sustaining control of schistosomiasis, which were conducted in five African countries. To enhance relevance for routine practice, the MDA in these studies was coordinated by or closely aligned with national neglected tropical disease (NTD) control programs. The study protocol set minimum targets of at least 90% for coverage among children enrolled in schools and 75% for all school-age children. Over the 4 years of intervention, an estimated 3.5 million treatments were administered to study communities. By year 4, the median village coverage was at or above targets in all studies except that in Mozambique. However, there was often a wide variation behind these summary statistics, and all studies had several villages with very low or high coverage. In studies where coverage was estimated by comparing the number of people treated with the number eligible for treatment, denominator estimation was often problematic. The SCORE experiences in conducting these studies provide lessons for future efforts that attempt to implement strong research designs in real-world contexts. They also have potential applicability to country MDA campaigns against schistosomiasis and other NTDs, most of which are conducted with less logistical and financial support than was available for the SCORE study efforts