State estimation for nonlinear state-space transmission models of tuberculosis.

Given the high prevalence of tuberculosis (TB) and the mortality rate associated with the disease, numerous models, such as the Gammaitoni and Nucci (GN) model, were developed to model the risk of transmission. These models typically rely on a quanta generation rate as a measurement of infectivity. Since the quanta generation rate cannot be measured directly, the unique contribution of this work is to develop state estimators to estimate the quanta generation rate from available measurements. To estimate the quanta generation rate, the GN model is adapted into an augmented single-room GN model and a simplified two-room GN model. Both models are shown to be observable, i.e., it is theoretically possible to estimate the quanta generation rate given available measurements. Kalman filters are used to estimate the quanta generation rate. First, a continuous-time extended Kalman filter is used for both adapted models using a simulation and measurement sampling rate of 60 s. Accurate quanta generate rate estimates are achieved in both cases. A more realistic scenario is also considered with a measurement sampling rate of one day. For these estimates, a hybrid extended Kalman filter (HEKF) is used. Accurate quanta generation rate estimates are achieved for the more realistic scenario. Future work could potentially use the HEKFs, the adapted models, and real-time measurements in a control system feedback loop to reduce the transmission of TB in confined spaces such as hospitals.

Collaborative Assessment of Molecular Geometries and Energies from the Open Force Field.

Force fields form the basis for classical molecular simulations, and their accuracy is crucial for the quality of, for instance, protein-ligand binding simulations in drug discovery. The huge diversity of small-molecule chemistry makes it a challenge to build and parameterize a suitable force field. The Open Force Field Initiative is a combined industry and academic consortium developing a state-of-the-art small-molecule force field. In this report, industry members of the consortium worked together to objectively evaluate the performance of the force fields (referred to here as OpenFF) produced by the initiative on a combined public and proprietary dataset of 19,653 relevant molecules selected from their internal research and compound collections. This evaluation was important because it was completely blind; at most partners, none of the molecules or data were used in force field development or testing prior to this work. We compare the Open Force Field "Sage" version 2.0.0 and "Parsley" version 1.3.0 with GAFF-2.11-AM1BCC, OPLS4, and SMIRNOFF99Frosst. We analyzed force-field-optimized geometries and conformer energies compared to reference quantum mechanical data. We show that OPLS4 performs best, and the latest Open Force Field release shows a clear improvement compared to its predecessors. The performance of established force fields such as GAFF-2.11 was generally worse. While OpenFF researchers were involved in building the benchmarking infrastructure used in this work, benchmarking was done entirely in-house within industrial organizations and the resulting assessment is reported here. This work assesses the force field performance using separate benchmarking steps, external datasets, and involving external research groups. This effort may also be unique in terms of the number of different industrial partners involved, with 10 different companies participating in the benchmark efforts.

Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease (ESRD) in the USA and worldwide. Recent experimental and clinical data suggest that the non-specific phosphodiesterase inhibitor pentoxifylline (PTX) may decrease progression of chronic kidney disease. However, a large-scale randomised clinical trial is needed to determine whether PTX can reduce ESRD and death in DKD. METHODS AND ANALYSIS: Veterans Affairs (VA) PTXRx is a pragmatic, randomised, placebo-controlled multicentre VA Cooperative Study to test the hypothesis that PTX, when added to usual care, leads to a reduction in the time to ESRD or death in patients with type 2 diabetes with DKD when compared with usual care plus placebo. The study aims to enrol 2510 patients over a 4-year period with an additional up to 5-year follow-up to generate a total of 646 primary events. The primary objective of this study is to compare the time until ESRD or death (all-cause mortality) between participants randomised to PTX or placebo. Secondary endpoints will be: (1) health-related quality of life, (2) time to doubling of serum creatinine, (3) incidence of hospitalisations for congestive heart failure, (4) incidence of a three-point major adverse cardiovascular events composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), (5) incidence of peripheral vascular disease, (6) change in urinary albumin-to-creatinine ratio from baseline to 6 months and (7) rate of annual change in estimated glomerular filtration rate (eGFR) during the study period. ETHICS AND DISSEMINATION: This study was approved by the VA Central Institutional Review Board (cIRB/18-36) and will be conducted in compliance with the Declaration of Helsinki and the Guidelines for Good Clinical Practice. The Hines Cooperative Studies Programme will finalise the study results, which will be published in accordance with the Consolidated Standards of Reporting Trials statement in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT03625648.

Trifluoromethyloxadiazoles: inhibitors of histone deacetylases for control of Asian soybean rust.

BACKGROUND: Trifluoromethyloxadiazoles (TFMOs) are selective inhibitors of class II histone deacetylases (HDACs). To date, class II HDACs have not been addressed as target enzymes by commercial fungicides. RESULTS: Antifungal testing of a broad variety of TFMOs against several important plant pathogens showed activity against only rusts, and especially Phakopsora pachyrhizi, the cause of Asian soybean rust. A structure-activity relationship was established, leading to highly active fungicides that inhibit fungal class II and HOS3-type HDACs of Aspergillus nidulans. Studies of the enzyme-inhibitor binding mode using protein structural information based on the crystal structure of human HDAC4 argue that TFMOs inhibit these enzymes only after undergoing hydration. CONCLUSION: Fungal class II HDACs are potential target enzymes for the control of at least some biotrophic crop diseases, in particular Asian soybean rust. As with any novel mode-of-action, class II HDAC fungicides would offer the potential to control fungal isolates that show reduced sensitivity toward existing commercial fungicides.

Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action.

Importance: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. Observations: In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. Conclusions and Relevance: By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.

Optimized Lockdown Strategies for Curbing the Spread of COVID-19: A South African Case Study.

To curb the spread of COVID-19, many governments around the world have implemented tiered lockdowns with varying degrees of stringency. Lockdown levels are typically increased when the disease spreads and reduced when the disease abates. A predictive control approach is used to develop optimized lockdown strategies for curbing the spread of COVID-19. The strategies are then applied to South African data. The South African case is of interest as the South African government has defined five distinct levels of lockdown, which serves as a discrete control input. An epidemiological model for the spread of COVID-19 in South Africa was previously developed, and is used in conjunction with a hybrid model predictive controller to optimize lockdown management under different policy scenarios. Scenarios considered include how to flatten the curve to a level that the healthcare system can cope with, how to balance lives and livelihoods, and what impact the compliance of the population to the lockdown measures has on the spread of COVID-19. The main purpose of this article is to show what the optimal lockdown level should be given the policy that is in place, as determined by the closed-loop feedback controller.

A Novel Single-Site Mutation in the Catalytic Domain of Protoporphyrinogen Oxidase IX (PPO) Confers Resistance to PPO-Inhibiting Herbicides.

Protoporphyrinogen oxidase (PPO)-inhibiting herbicides are used to control weeds in a variety of crops. These herbicides inhibit heme and photosynthesis in plants. PPO-inhibiting herbicides are used to control Amaranthus palmeri (Palmer amaranth) especially those with resistance to glyphosate and acetolactate synthase (ALS) inhibiting herbicides. While investigating the basis of high fomesafen-resistance in A. palmeri, we identified a new amino acid substitution of glycine to alanine in the catalytic domain of PPO2 at position 399 (G399A) (numbered according to the protein sequence of A. palmeri). G399 is highly conserved in the PPO protein family across eukaryotic species. Through combined molecular, computational, and biochemical approaches, we established that PPO2 with G399A mutation has reduced affinity for several PPO-inhibiting herbicides, possibly due to steric hindrance induced by the mutation. This is the first report of a PPO2 amino acid substitution at G399 position in a field-selected weed population of A. palmeri. The mutant A. palmeri PPO2 showed high-level in vitro resistance to different PPO inhibitors relative to the wild type. The G399A mutation is very likely to confer resistance to other weed species under selection imposed by the extensive agricultural use of PPO-inhibiting herbicides.

Modeling the Airborne Infection Risk of Tuberculosis for a Research Facility in eMalahleni, South Africa.

A detailed mathematical modeling framework for the risk of airborne infectious disease transmission in indoor spaces was developed to enable mathematical analysis of experiments conducted at the Airborne Infections Research (AIR) facility, eMalahleni, South Africa. A model was built using this framework to explore possible causes of why an experiment at the AIR facility did not produce expected results. The experiment was conducted at the AIR facility from August 31, 2015 to December 4, 2015, in which the efficacy of upper room germicidal ultraviolet (GUV) irradiation as an environmental control was tested. However, the experiment did not produce the expected outcome of having fewer infections in the test animal room than the control room. The simulation results indicate that dynamic effects, caused by switching the GUV lights, power outages, or introduction of new patients, did not result in the unexpected outcomes. However, a sensitivity analysis highlights that significant uncertainty exists with risk of transmission predictions based on current measurement practices, due to the reliance on large viable literature ranges for parameters.

Effect of cytochrome CYP2C19 metabolizing activity on antidepressant response and side effects: Meta-analysis of data from genome-wide association studies.

Cytochrome (CYP) P450 enzymes have a primary role in antidepressant metabolism and variants in these polymorphic genes are targets for pharmacogenetic investigation. This is the first meta-analysis to investigate how CYP2C19 polymorphisms predict citalopram/escitalopram efficacy and side effects. CYP2C19 metabolic phenotypes comprise poor metabolizers (PM), intermediate and intermediate+ metabolizers (IM; IM+), extensive and extensive+ metabolizers (EM [wild type]; EM+) and ultra-rapid metabolizers (UM) defined by the two most common CYP2C19 functional polymorphisms (rs4244285 and rs12248560) in Caucasians. These polymorphisms were genotyped or imputed from genome-wide data in four samples treated with citalopram or escitalopram (GENDEP, STAR*D, GenPod, PGRN-AMPS). Treatment efficacy was assessed by standardized percentage symptom improvement and by remission. Side effect data were available at weeks 2-4, 6 and 9 in three samples. A fixed-effects meta-analysis was performed using EM as the reference group. Analysis of 2558 patients for efficacy and 2037 patients for side effects showed that PMs had higher symptom improvement (SMD = 0.43, CI = 0.19-0.66) and higher remission rates (OR = 1.55, CI = 1.23-1.96) compared to EMs. At weeks 2-4, PMs showed higher risk of gastro-intestinal (OR = 1.26, CI = 1.08-1.47), neurological (OR = 1.28, CI = 1.07-1.53) and sexual side effects (OR = 1.52, CI = 1.23-1.87; week 6 values were similar). No difference was seen at week 9 or in total side effect burden. PMs did not have higher risk of dropout at week 4 compared to EMs. Antidepressant dose was not different among CYP2C19 groups. CYP2C19 polymorphisms may provide helpful information for guiding citalopram/escitalopram treatment, despite PMs being relatively rare among Caucasians (∼2%).

Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP).

A key feature of major depressive disorder (MDD) is anhedonia, which is a predictor of response to antidepressant treatment. In order to shed light on its genetic underpinnings, we conducted a genome-wide association study (GWAS) followed by investigation of biological pathway enrichment using an anhedonia dimension for 759 patients with MDD in the GENDEP study. The GWAS identified 18 SNPs associated at genome-wide significance with the top one being an intronic SNP (rs9392549) in PRPF4B (pre-mRNA processing factor 4B) located on chromosome 6 (P = 2.07 × 10-9) while gene-set enrichment analysis returned one gene ontology term, axon cargo transport (GO: 0008088) with a nominally significant P value (1.15 × 10-5). Furthermore, our exploratory analysis yielded some interesting, albeit not statistically significant genetic correlation with Parkinson's Disease and nucleus accumbens gray matter. In addition, polygenic risk scores (PRSs) generated from our association analysis were found to be able to predict treatment efficacy of the antidepressants in this study. In conclusion, we found some markers significantly associated with anhedonia, and some suggestive findings of related pathways and biological functions, which could be further investigated in other studies.

The sensitivity of 38 heart rate variability measures to the addition of artifact in human and artificial 24-hr cardiac recordings.

BACKGROUND: Artifact is common in cardiac RR interval data derived from 24-hr recordings and has a significant impact on heart rate variability (HRV) measures. However, the relative impact of progressively added artifact on a large group of commonly used HRV measures has not been assessed. This study compared the relative sensitivity of 38 commonly used HRV measures to artifact to determine which measures show the most change with increasing increments of artifact. A secondary aim was to ascertain whether short-term and long-term HRV measures, as groups, share similarities in their sensitivity to artifact. METHODS: Up to 10% of artifact was added to 20 artificial RR (ARR) files and 20 human cardiac recordings, which had been assessed for artifact by a cardiac technician. The added artifact simulated deletion of RR intervals and insertion of individual short RR intervals. Thirty-eight HRV measures were calculated for each file. Regression analysis was used to rank the HRV measures according to their sensitivity to artifact as determined by the magnitude of slope. RESULTS: RMSSD, SDANN, SDNN, RR triangular index and TINN, normalized power and relative power linear measures, and most nonlinear methods examined are most robust to artifact. CONCLUSION: Short-term time domain HRV measures are more sensitive to added artifact than long-term measures. Absolute power frequency domain measures across all frequency bands are more sensitive than normalized and relative frequency domain measures. Most nonlinear HRV measures assessed were relatively robust to added artifact, with Poincare plot SD1 being most sensitive.

Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals.

BackgroundDepression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.ResultsIn the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (ß = 0.12, P = 2.7 × 10-4) and with the Han/Eskin random effects method (P = 1.4 × 10-7) but not with traditional random effects (ß = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (ß = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10-8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTOConclusionsThis meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.

Design of the Familial Hypercholesterolaemia Australasia Network Registry: Creating Opportunities for Greater International Collaboration.

Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprotein metabolism that leads to premature coronary heart disease. There are over 65,000 people estimated to have FH in Australia, but many remain undiagnosed. Patients with FH are often under-treated, but with early detection, cascade family testing and adequate treatment, patient outcomes can improve. Patient registries are key tools for providing new information on FH and enhancing care worldwide. The development and design of the FH Australasia Network Registry is a crucial component in the comprehensive model of care for FH, which aims to provide a standardized, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. Informed by stakeholder engagement, the FH Australasia Network Registry was collaboratively developed by government, patient and clinical networks and research groups. The open-source, web-based Rare Disease Registry Framework was the architecture chosen for this registry owing to its open-source standards, modular design, interoperability, scalability and security features; all these are key components required to meet the ever changing clinical demands across regions. This paper provides a high level blueprint for other countries and jurisdictions to help inform and map out the critical features of an FH registry to meet their particular health system needs.

Pharmacogenetics of antidepressant response: A polygenic approach.

BACKGROUND: Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. METHODS: Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756). RESULTS: No significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results. DISCUSSION: We identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.

Association between weekend admission and mortality for upper gastrointestinal hemorrhage: an observational study and meta-analysis.

Higher in-hospital mortality for weekend vs. weekday admissions has been described. We performed a retrospective study and accompanying meta-analysis to examine the association between weekend admission for upper gastrointestinal hemorrhage (UGIH) and in-hospital mortality. We identified adult admissions to United States (US) hospitals for acute variceal and nonvariceal UGIH between 1/2010 and 12/2012 from the National Inpatient Sample (NIS). We used multivariable logistic regression to compare the odds of in-hospital mortality (adjusting for hospital- and patient-level factors) for weekend vs. weekday admissions. For our meta-analysis, we searched MEDLINE and SCOPUS to identify NIS studies. Using cumulative meta-analysis, we calculated the adjusted odds ratio (aOR) of in-hospital mortality for variceal and nonvariceal UGIH weekend admission. From 2010 to 2012, we identified 119,353 admissions for UGIH. After multivariable adjustment, there was no difference in the odds of mortality for weekend admissions with variceal (aOR 1.00; 95 % CI 0.81-1.23) or nonvariceal UGIH (aOR 1.10; 95 % CI 0.99-1.22); although, a decreased use of endoscopy in weekend admissions for all-cause UGIH (adjusted hazard ratio 0.91; 95 % CI 0.89-0.92) was observed. Meta-analysis of five studies (including our own) shows no association between weekend admission and mortality for variceal UGIH (aOR 1.02; 95 % CI 0.86-1.21). Weekend admission for nonvariceal UGIH is associated with an increased odds of mortality (aOR 1.09; 95 % CI 1.04-1.15). Weekend admission for UGIH is not associated with a higher odds of in-hospital mortality in our observational study. However, we observed a 9.0 % increase in nonvariceal UGIH mortality for weekend admissions in our meta-analysis.

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

BACKGROUND: Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. METHODS: Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. RESULTS: We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. CONCLUSIONS: We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder.

Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia.

BACKGROUND: Cardiovascular outcomes trials of fibrates, niacin, or omega-3 fatty acids alone, or added to a statin, have not consistently demonstrated reduced risk, but larger, statistically significant clinical benefits have been reported in subgroups with elevated triglycerides (TG) and/or elevated TG plus low high-density lipoprotein cholesterol (HDL-C). OBJECTIVE: To perform a meta-analysis of the effects of therapies targeting TG and TG-rich lipoprotein cholesterol on cardiovascular disease event risk in subjects with elevated TG or elevated TG paired with low HDL-C. METHODS: Publications were identified using PubMed, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Internet Stroke Center. Random-effects meta-analysis models were used to generate summary relative risk estimates and 95% confidence intervals. Heterogeneity was assessed by χ(2) and I(2) statistics, and the impact of each trial was assessed in one study-removed sensitivity analyses. RESULTS: Six trials of fibrates, 2 of niacin, 1 of fibrate + niacin, and 1 of omega-3 eicosapentaenoic acid ethyl esters were identified. For the prespecified primary cardiovascular disease or coronary heart disease end point used in each trial, the summary relative risk estimate (95% confidence interval) for subjects with elevated TG was 0.82 (0.73-0.91), p-heterogeneity = 0.13, I(2) = 36.2, and for subjects with elevated TG and low-HDL-C, it was 0.71 (0.63-0.81), p-heterogeneity = 0.52, I(2) = 0.0. There was no evidence of publication bias, and the results remained statistically significant when each individual trial was removed. CONCLUSION: Drugs that substantially, but not exclusively, lower TG and TG-rich lipoprotein cholesterol may have cardiovascular benefits in individuals with elevated TG, particularly if accompanied by low HDL-C.

Washoff of Residual Photosystem II Herbicides from Sugar Cane Trash under a Rainfall Simulator.

Herbicides are often applied to crop residues, but their fate has not been well studied. We measured herbicide washoff from sugar cane trash during simulated rainfall, at 1, 8, and 40 days after spraying (DAS), to provide insight into herbicide fate and for use in modeling. Herbicides included are commonly used in the sugar industry, either in Australia or in Brazil. Concentrations of all herbicides and applied Br tracer in washoff declined exponentially over time. The rate of washoff during rainfall declined with increasing DAS. Cumulative washoff as a function of rainfall was similar for most herbicides, although the most soluble herbicides did have more rapid washoff. Some but not all herbicides became more resistant to washoff with increasing DAS. Of the total mass washed off, 80% washed off in the first 30 mm (∼40 min) of rainfall for most herbicides. Little herbicide remained on the trash after rainfall, implying nearly complete washoff.

A preprocessing tool for removing artifact from cardiac RR interval recordings using three-dimensional spatial distribution mapping.

Artifact is common in cardiac RR interval data that is recorded for heart rate variability (HRV) analysis. A novel algorithm for artifact detection and interpolation in RR interval data is described. It is based on spatial distribution mapping of RR interval magnitude and relationships to adjacent values in three dimensions. The characteristics of normal physiological RR intervals and artifact intervals were established using 24-h recordings from 20 technician-assessed human cardiac recordings. The algorithm was incorporated into a preprocessing tool and validated using 30 artificial RR (ARR) interval data files, to which known quantities of artifact (0.5%, 1%, 2%, 3%, 5%, 7%, 10%) were added. The impact of preprocessing ARR files with 1% added artifact was also assessed using 10 time domain and frequency domain HRV metrics. The preprocessing tool was also used to preprocess 69 24-h human cardiac recordings. The tool was able to remove artifact from technician-assessed human cardiac recordings (sensitivity 0.84, SD = 0.09, specificity of 1.00, SD = 0.01) and artificial data files. The removal of artifact had a low impact on time domain and frequency domain HRV metrics (ranging from 0% to 2.5% change in values). This novel preprocessing tool can be used with human 24-h cardiac recordings to remove artifact while minimally affecting physiological data and therefore having a low impact on HRV measures of that data.