A cross-sectional study of the prevalence of intensity of infection with Schistosoma japonicum in 50 irrigated and rain-fed villages in Samar Province, the Philippines

BACKGROUND: Few studies have described heterogeneity in Schistosoma japonicum infection intensity, and none were done in Philippines. The purpose of this report is to describe the village-to-village variation in the prevalence of two levels of infection intensity across 50 villages of Samar Province, the Philippines. METHODS: This cross-sectional study was conducted in 25 rain-fed and 25 irrigated villages endemic for S. japonicum between August 2003 and November 2004. Villages were selected based on irrigation and farming criteria. A maximum of 35 eligible households were selected per village. Each participant was asked to provide stool samples on three consecutive days. All those who provided at least one stool sample were included in the analysis. A Bayesian three category outcome hierarchical cumulative logit regression model with adjustment for age, sex, occupation and measurement error of the Kato-Katz technique was used for analysis. RESULTS: A total of 1427 households and 6917 individuals agreed to participate in the study. A total of 5624 (81.3%) participants provided at least one stool sample. The prevalences of those lightly and at least moderately infected varied from 0% (95% Bayesian credible interval (BCI): 0%–3.1%) to 45.2% (95% BCI: 36.5%–53.9%) and 0% to 23.0% (95% BCI: 16.4%–31.2%) from village-to-village, respectively. Using the 0–7 year old group as a reference category, the highest odds ratio (OR) among males and females were that of being aged 17–40-year old (OR = 8.76; 95% BCI: 6.03–12.47) and 11–16-year old (OR = 8.59; 95% BCI: 4.74–14.28), respectively. People who did not work on a rice farm had a lower prevalence of infection than those working full time on a rice farm. The OR for irrigated villages compared to rain-fed villages was 1.41 (95% BCI: 0.50–3.21). DISCUSSION: We found very important village-to-village variation in prevalence of infection intensity. This variation is probably due to village-level variables other than that explained by a crude classification of villages into the irrigated and non-irrigated categories. We are planning to capture this spatial heterogeneity by updating our initial transmission dynamics model with the data reported here combined with 1-year post-treatment follow-up of study participants

Does the early frog catch the worm? Disentangling potential drivers of a parasite age–intensity relationship in tadpoles

The manner in which parasite intensity and aggregation varies with host age can provide insights into parasite dynamics and help identify potential means of controlling infections in humans and wildlife. A significant challenge is to distinguish among competing mechanistic hypotheses for the relationship between age and parasite intensity or aggregation. Because different mechanisms can generate similar relationships, testing among competing hypotheses can be difficult, particularly in wildlife hosts, and often requires a combination of experimental and model fitting approaches. We used field data, experiments, and model fitting to distinguish among ten plausible drivers of a curvilinear age–intensity relationship and increasing aggregation with host age for echinostome trematode infections of green frogs. We found little support for most of these proposed drivers but did find that the parsimonious explanation for the observed age–intensity relationship was seasonal exposure to echinostomes. The parsimonious explanation for the aggregated distribution of parasites in this host population was heterogeneity in exposure. A predictive model incorporating seasonal exposure indicated that tadpoles hatching early or late in the breeding season should have lower trematode burdens at metamorphosis, particularly with simulated warmer climates. Application of this multi-pronged approach (field surveys, lab experiments, and modeling) to additional parasite–host systems could lead to discovery of general patterns in the drivers of parasite age–intensity and age–distribution relationships

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Accurate DMBE Potential Energy Surface For the N(2D) + H2(1S g+ ) Reaction Using an Improved Switching Function Formalism

Abstract A single-sheeted double many-body expansion (DMBE) potential energy surface is reported for the 1 2 A'' state of NH2. To approximate its true multi-sheeted nature, a novel switching function that imposes the correct behavior at the H2(X 1S g +)+ N(2 D) and NH(X 3S-) + H(2 S) dissociation limits has been suggested. The new DMBE form is shown to fit with high accuracy an extensive set of new ab initio points (calculated at the multi-reference configuration interaction level using the full valence complete active space as reference and aug-cc-pVQZ and aug-cc-pV5Z basis sets) that have been semiempirically corrected at the valence regions by scaling the n-body dynamical correlation terms such as to account for the finite basis set size and truncated configuration interaction expansion. A detailed study of the N(2 D) ... H2(X 1S g +) van der Waals region has also been carried out. These calculations predict a nearly free rigid-rotor with two shallow van der Waals wells of C 2v and C 8 v symmetries. Such a result contrasts with previous cc-pVTZ calculations which predict a single T-shaped van der Waals structure. Except in the vicinity of the crossing seam, which is replaced by an avoided intersection, the fit shows the correct physical behavior over the entire configurational space. The topographical features of the new DMBE potential energy surface are examined in detail and compared with those of other potential functions available in the literature. Amongst such features, we highlight the barrier for linearization (11,802 cm-1) which is found to overestimate the most recent empirical spectroscopic estimate by only 28 cm-1. Additionally, the T-shaped N(2 D) ... H2 van der Waals minimum is predicted to have a well depth of 90 cm-1, being 11 cm-1 deeper than the C 8 v minimum. The title DMBE form is therefore recommendable for dynamics studies of both non-reactive and reactive N(2 D)+H2 collisions

Can extrapolation to the basis set limit be an alternative to the counterpoise correction? A study on the helium dimer

Abstract Configuration interaction and coupled cluster calculations are reported for He2 using various orbital basis sets of the d-aug-AVXZ type, with the results being extrapolated to the one electron basis set limit both with counterpoise and without counterpoise correction. A generalized uniform singlet- and triplet-pair extrapolation scheme has been utilized for such a purpose. Using appropriate corrections to mimic full configuration interaction, the energies were predicted in excellent agreement with the best available estimates. The results also suggest that extrapolation to the complete basis set limit may be a general alternative to the counterpoise correction that yields a more accurate potential energy while being more economical