Action Threshold Research Articles

Abstract 4140126: Comparison of Clinical Risk Calculators for Atherosclerotic Cardiovascular Diseases: PREVENT, Pooled Cohort Equations, and QRISK3

Introduction: The cardio-kidney-metabolic pathway has a crucial role in ASCVD, motivating development of the PREVENT equation. There is a need for external validation of the PREVENT equation and assessment of its performance in independent cohorts to assess generalizability across diverse populations. Aim: To compare predictive performance of the PREVENT equation with previously developed risk calculators; pooled cohort equations (PCE), and QRISK3. Methods: We used data from 500k participants of the United Kingdom Biobank (UKB). ASCVD was defined as the composite outcome of fatal and non-fatal myocardial infarction, coronary revascularization, and stroke. We ascertained demographic and clinical covariates required to calculate ASCVD risk, using the base model of PREVENT, PCE, and QRISK3, at the time of recruitment. Those with a diagnosis of ASCVD at the time of recruitment or missing data on age, sex, or ethnicity were excluded. We used the area under the ROC curve (AUC) and calibration plots for analysis. Results: Of 459,681 participants (mean age 56.3±8.1 years, 44.4% male, and 94.7% White), 24,514 (5.4%) participants had a new diagnosis of ASCVD during a 10-year follow-up. The median [interquartile range] of estimated 10-y ASCVD risk was 3.7% [1.9% - 6.1%] for PREVENT, 5.6% [2.4% - 11.3%] for PCE, and 8.0% [3.9% - 13.8%] for QRISK3 (Figure 1A). The calibration slope (95% CI) was 1.71 (1.66 – 1.76) for PREVENT, 0.64 (0.63 – 0.66) for PCE, and 0.66 (0.64 – 0.67) for QRISK3 (Figure 1B). The AUC for ASCVD prediction was 0.741 (0.738 - 0.744) for PREVENT, 0.744 (0.741 – 0.747) for PCE, and 0.751 (0.749 – 0.755) for QRISK3 (Figure 1C). Conclusion: In the UKB cohort, the PREVENT equation underpredicted while the PCE and QRISK3 overpredicted ASCVD risk, with a similar discrimination. Consequently, fewer individuals would be eligible for primary prevention with statins, based on the actionable thresholds of 7.5% or 10% when considering ASCVD risk based on PREVENT. Therefore, the external application of the PREVENT equation requires recalibration and context-specific interpretation.

Recommendations for monitoring adherence and fidelity in pragmatic trials based on experience in the Pain Management Collaboratory.

Most pragmatic trials follow the PRagmatic Explanatory Continuum Indicator Summary (PRECIS-2) criteria. The criteria specify unobtrusive measurement of participants' protocol adherence and practitioners' intervention fidelity but suggest no special monitoring strategies to assure trial integrity. We present experience with adherence/fidelity monitoring in the Pain Management Collaboratory (PMC) and provide recommendations for their monitoring in pragmatic trials to preserve inferences of treatment comparisons. In November 2021, we surveyed 10 of 11 originally funded PMC pragmatic trials to determine the extent to which adherence and fidelity data were being monitored. Of the 10 PMC trials, 8 track adherence/fidelity. The electronic health record is the most frequent source for monitoring adherence (7/10) and fidelity (5/10). Most adherence data are used to monitor participant engagement with the trial intervention (4/10) and are reviewed by study teams (8/10) and often with a data and safety monitoring board (DSMB) (5/10). Half of the trials (5/10) reported using fidelity data for feedback/training; such data are not shared with a DSMB (0/10). Only 2 of 10 trials reported having prespecified guidance or rules around adherence/fidelity (eg, stopping rules or thresholds for corrective action, such as retraining). As a best practice for pragmatic trials, we recommend early and regular adherence/fidelity monitoring to determine whether intervention delivery is as intended. We propose a 2-stage process with thresholds for intervening and triggers for conducting a formal futility analysis if adherence and fidelity are not maintained. The level of monitoring should be unobtrusive for both participants and those delivering the intervention; resulting data should be reviewed by an independent DSMB.

Assessment of tangible coastal inundation damage related to critical infrastructure and buildings: The case of Mauritius Island

Storm tides, which combine sea level rise (SLR), astronomical tides, and storm surges generated by tropical cyclones, pose significant threats to coastal zones, leading to flooding and substantial damage to property and infrastructure.There is a clear upward trend in the frequency of storms reaching tropical cyclone strength. A notable example is Cyclone Belal, which struck Mauritius on January 2024, during high tide, causing extensive infrastructure damage. This underscores the importance of conducting risk assessments to identify vulnerable areas and develop risk reduction strategies. However, quantitative risk assessments of storm tides are often challenging due to the lack of long-term projections. To address this, we developed a GIS-based flood model for Mauritius to simulate inundation areas and quantify the assets exposed to flooding. Under current conditions, the estimated damage exposure from extreme coastal flood events with return periods of 50 to 500 years is significant, with 6.2% and 27.1% of the area inundated, respectively. By 2100, damage exposure associated with these events is projected to increase by a factor of 1.1, with minimal variation between sea-level rise scenarios (0.3m). However, by 2200 and 2300, damage exposure is expected to rise by factors of 3.1 and 6.6, respectively. In the worst-case scenario for 2500, Mauritius could experience maximum inundation of 66.3 km2, with buildings covering 5.02 km2 submerged. Additionally, this study presents a detemporalized inundation scenario to assess impacts from any coastal flood event. This approach enables the identification of critical thresholds ( 1.5 m and 4.5 m) and , beyond which significant increases in damage exposure are likely, and allows for evaluating adaptation strategies against user-defined levels of change, rather than relying solely on predefined scenarios. These findings highlight the urgent need for strategic sectoral interventions to address the widespread consequences of coastal inundation, especially in light of critical thresholds for remedial action.

Nuclear-excited source of coherent and incoherent radiation with direct nuclear pumping

Uranium fission fragments, as well as the products of 3He(n,p)3H and 10B(n,α)7Li nuclear reactions were utilized in the nuclear reactor for gas ionization and excitation. However, the 6Li(n,α)3H nuclear reaction was less examined. The use of lithium-6 as a surface source of excitation of the gas medium, due to the long path length of tritium nuclei in the gas, allows to excite large volumes of gas as opposed to using 235U or 10B.While investigating the luminescence of noble gases in the core of the IVG.1M research reactor, we noted an appearance of alkali metal lines and a sharp increase in the intensity of these lines at temperatures above 570 K. It was determined that the population of levels of lithium atoms has practically no effect on the population of the 2p-levels of atoms of noble gases. The selectivity of p- and s-levels deactivation by lithium atoms implies the possibility of creating inversion of population at 2p-1s transitions of noble gas atoms. Successful experiments to study the luminescence of gases upon excitation by 6Li(n,α)3H nuclear reaction products allow us to proceed to experiments to achieve the laser action threshold and study the lasing characteristics of gas mixtures at the IGR pulsed nuclear reactor with thermal neutron flux density up to 7∙1016 n/cm2s. For this purpose, an experimental device designs were proposed to perform experiments on the IGR reactor. A step-by-step procedure of fabrication of a nuclear-excited source for excitation of gas mixtures is provided. The results of reactor experiments aimed at determining the spectral and temporal characteristics of optical radiation during excitation of gas mixtures by 6Li(n,α)3H nuclear reaction products are presented.

Development of a sequential sampling plan for classifying Thrips tabaci (Thysanoptera: Thripidae) populations in onion fields.

Onion thrips, Thrips tabaci Lindeman, is a global pest of onion crops, causing substantial economic damage by diminishing bulb yields and transmitting plant pathogens. Insecticides are used to manage T. tabaci infestations with control decisions traditionally based on action thresholds that require visually counting thrips on a fixed, predetermined number of onion plants per field. However, this approach for treatment decisions is inefficient when thrips populations are well above or below the action threshold. The aim of this research was to develop a sequential sampling plan that would provide a rapid and reliable classification of thrips populations in commercial onion fields above or below prespecified management thresholds. The study was conducted in a total of 24 commercial onion fields in New York in 2021 and 2022. Taylor's power law and Wald's Sequential Probability Ratio Test were used in concert to develop each sampling plan. Simulated and historical field data of thrips populations were used to further validate the efficacy of each sampling plan. Results demonstrated the sequential sampling plan required an average of 78% fewer samples to make a control decision compared with the traditional fixed-sampling approach. Treatment decisions were reached in 72% of cases after inspecting only 10 plants, while only 6% of the cases required examining more than 25 plants. Comparisons with fixed-sample sizes ranging from 23 to 68 plants revealed a 96% agreement in decision-making and a 78% reduction in sampling effort when using the sequential sampling plans.

The clinical impact of estimating low-density lipoprotein cholesterol (LDL-C) using different equations in the general population

BackgroundLow-density lipoprotein cholesterol (LDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD). Friedewald, Sampson, and Martin-Hopkins equations are used to calculate LDL-C. This study compares the impact of switching between these equations in a large geographically defined population.Materials and methodsData for individuals who had a lipid panel ordered clinically between 2010 and 2019 were included. Comparisons were made across groups using the two-sample t-test or chi-square test as appropriate. Discordances between LDL measures based on clinically actionable thresholds were summarized using contingency tables.ResultsThe cohort included 198,166 patients (mean age 54 years, 54% female). The equations perform similarly at the lower range of triglycerides but began to diverge at a triglyceride level of 125 mg/dL. However, at triglycerides of 175 mg/dL and higher, the Martin-Hopkins equation estimated higher LDL-C values than the Samson equation. This discordance was further exasperated at triglyceride values of 400 to 800 mg/dL. When comparing the Sampson and Friedewald equations, at triglycerides are below 175 mg/dL, 9% of patients were discordant at the 70 mg/dL cutpoint, whereas 42.4% were discordant when triglycerides are between 175 and 400 mg/dL. Discordance was observed at the clinically actionable LDL-C cutpoint of 190 mg/dL with the Friedewald equation estimating lower LDL-C than the other equations. In a high-risk subgroup (ASCVD risk score > 20%), 16.3% of patients were discordant at the clinical cutpoint of LDL-C < 70 mg/dL between the Sampson and Friedewald equations.ConclusionsDiscordance at clinically significant LDL-C cutpoints in both the general population and high-risk subgroups were observed across the three equations. These results show that using different methods of LDL-C calculation or switching between different methods could have clinical implications for many patients.

A Rate of Change and Center of Gravity Approach to Calculating Composite Indicator Thresholds: Moving from an Empirical to a Theoretical Perspective

A composite indicator (CI) is the mathematical aggregation of sub-dimension (local) indicators used to provide an overall score for the multidimensional concept being measured. CIs are widely used to assess the benefits or risks in human endeavors, such as by creating life satisfaction indices or disaster risk indicators. One important aspect of the development of CIs is setting up value thresholds for taking action, such as in determining the minimum acceptable level of life satisfaction in a community or the maximum acceptable flood risk value beyond which people should be ordered to evacuate from the area in danger. The analytic hierarchy/network process (AHNP) is widely used for the development of CIs. In a review of 111 AHP/ANP CI studies, fewer than 10% discussed any threshold. This means that about 90% of the developed CIs were theoretically sound but lacked the actionable thresholds necessary to be of practical use. Furthermore, for the few studies that set thresholds, the values were typically set arbitrarily or using inadequate statistical approaches. To address this important concern, this study first discusses the most commonly used approaches to setting up thresholds, as well as their inadequacies, and proposes the development of AHP/ANP CI thresholds using a mathematical approach based on the rate of change and center of gravity (RCCG) concepts. Using this approach, a virtual reference alternative, i.e., a threshold profile (TP) made up of the local thresholds of each indicator, is calculated. The key advantage of the proposed method is that it not only provides a non-arbitrary way to set up a CI threshold; more importantly, it is independent of the data and/or alternatives to be evaluated; that is, a threshold calculated with the proposed approach constitutes an absolute reference value, outside the dataset.

Improving approaches to hygienic rationing of antimicrobial drugs

Introduction. Currently, the production of medicines, including those with antimicrobial properties, is expanding at chemical and pharmaceutical enterprises. However, scientific approaches to hygienic regulation of the content of specific antimicrobials in the air of the work area are not yet available. The study aims to substantiate approaches to predicting approximate safe levels of exposure (ASLE) to substances with a specific antimicrobial effect. Materials and methods. The scientists have carried out the research in two stages. The first stage is an experimental study of the single inhalation effect of an antibiotic clarithromycin at concentrations of 54.2; 25.4; 15.3; 9.1; 2.8 and 0.9 mg/m3 on mongrel female rats weighing 230–250 g. The authors have evaluated the indicators of toxic (morphological and functional parameters of the nervous, cardiovascular and respiratory systems, biochemical parameters of the liver and kidneys, as well as the composition of peripheral blood) and specific effects (qualitative and quantitative composition of the microbiota of the large intestine of rats). The second stage was the analysis of the database on hygienic rationing of chemicals, which consisted in searching for hygienic standards (ASLE, MPC), threshold concentrations for the general toxic (Limint) and specific (Limbact) effects of antimicrobials. Results. During the experiment, experts have established the threshold of acute inhalation exposure (Limac int) of clarithromycin at a concentration of 25.4 mg/m3 according to the total toxic effects (peripheral blood counts, liver and kidney function). When exposed to an antibiotic at a concentration of 2.8 mg/m3, there was an imbalance of the intestinal microflora in the absence of a general toxic effect, which indicated a specific and selective antimicrobial effect of the drug. Based on the analysis of literature data, the parameters of toxicometry of 21 substances with antimicrobial effect were determined, their representative sample was justified and its regression analysis was carried out. Conclusion. Based on experimental and literary data, the authors established a significantly strong correlation (r=0.729) between the values of MPC (ASLE) and the threshold of antimicrobial action (Limbact). They also developed a mathematical equation to predict safe levels of antimicrobials based on their specific and selective activity.

Alfaxalone is an effective anesthetic for the electrophysiological study of anoxia-tolerance mechanisms in western painted turtle pyramidal neurons.

Anoxia in the mammalian brain leads to hyper-excitability and cell death; however, this cascade of events does not occur in the anoxia-tolerant brain of the western painted turtle, Chrysemys picta belli. The painted turtle has become an important anoxia-tolerant model to study brain, heart, and liver function in the absence of oxygen, but being anoxia-tolerant likely means that decapitation alone is not a suitable method of euthanasia. Many anesthetics have long-term effects on ion channels and are not appropriate for same day experimentation. Using whole-cell electrophysiological techniques, we examine the effects of the anesthetic, Alfaxalone, on pyramidal cell action potential amplitude, threshold, rise and decay time, width, frequency, whole cell conductance, and evoked GABAA receptors currents to determine if any of these characteristics are altered with the use of Alfaxalone for animal sedation. We find that Alfaxalone has no long-term impact on action potential parameters or whole-cell conductance. When acutely applied to naïve tissue, Alfaxalone did lengthen GABAA receptor current decay rates by 1.5-fold. Following whole-animal sedation with Alfaxalone, evoked whole cell GABAA receptor current decay rates displayed an increasing trend with 1 and 2 hours after brain sheet preparation, but showed no significant change after a 3-hour washout period. Therefore, we conclude that Alfaxalone is a suitable anesthetic for same day use in electrophysiological studies in western painted turtle brain tissue.

Evaluation of the groundwater radon concentration in the Al Jahra Governorate, Kuwait

The importance of groundwater as a necessary and vital water supply has been increasing worldwide. With the overpopulation and improving living standards in the Al Jahra Governorate, Kuwait, the demand for these products has risen quickly in recent years. Significant activity has recently emerged in relation to the inherent radon concentration in water. Fifteen groundwater samples from various locations in the Al Jahra Governorate region of Kuwait were tested for radon (Rn-222) concentrations using a RAD 7 device, which is an electronic radon detector linked to a RAD 7- H2O accessory. The obtained concentrations of Rn-222 in the ground water samples examined in our investigation ranged from 3.51 Bq.l−1 to 19.35 Bq.l−1, with a mean of 9.01 Bq.l−1. The dose of Rn-222 to the stomach caused by drinking water varied from 6.76 to 37.24 μSv/y (average: 17.35 μSv/y), and the Rn-222 dose to the lungs varied from 8.85 to 48.75 μSv/y. (average: 22.71 μSv/y). The range of the total yearly effective dosage, with a mean of 40.06 μSv/y, was 15.62–85.99 μSv/y. The annual effective dose (AED) due to intake corresponded to the concentration of one Bq. l−1 was 4.445 μSv/y. The results of the present study showed that the AED concentrations of Rn-222 in many of the groundwater samples collected from around the Al Jahra Governorate were less than the actionable thresholds advised by the USEPA, UNSCEAR, the EU Council, and the WHO (0.1 mSv/y).

Learn to flap: foil non-parametric path planning via deep reinforcement learning

To optimize flapping foil performance, in the current study we apply deep reinforcement learning (DRL) to plan foil non-parametric motion, as the traditional control techniques and simplified motions cannot fully model nonlinear, unsteady and high-dimensional foil–vortex interactions. Therefore, a DRL training framework is proposed based on the proximal policy optimization algorithm and the transformer architecture, where the policy is initialized from the sinusoidal expert display. We first demonstrate the effectiveness of the proposed DRL-training framework, learning the coherent foil flapping motion to generate thrust. Furthermore, by adjusting reward functions and action thresholds, DRL-optimized foil trajectories can gain significant enhancement in both thrust and efficiency compared with the sinusoidal motion. Last, through visualization of wake morphology and instantaneous pressure distributions, it is found that DRL-optimized foil can adaptively adjust the phases between motion and shedding vortices to improve hydrodynamic performance. Our results give a hint of how to solve complex fluid manipulation problems using the DRL method.

Feeding Damage Evaluation of the Mirid Bug, Helopeltis bakeri Poppius on Cacao Pods

Actual observations and documentation of cacao pests feeding on the pods in the field are very few. The cacao mirid bug, Helopeltis bakeri Poppius, was laboratory-reared and released [21 pairs = Tree 1; 17 pairs = Tree 2; 21 pairs = Tree 3] in three randomly chosen cacao trees under controlled settings from October 2019–March 2020 with the aim of observing and documenting cacao pests feeding on the pods in the field to have insights into the proper pest action threshold. A coefficient score of 4.93 on a 0–5 rating scale described “heavy damage” as &gt; 50% of feeding lesion marks on 28 out of 30 pods (93%) were visible. The first feeding lesions were observed in an average of 37 days but came as early as 10 d upon release of H. bakeri. Within this time of observing the initial feeding lesions, there would only be 39 d before the whole pod is scorched due to black pod disease. The study shows the harmfulness of this cacao pest and highlights the need for integrated pest management to reduce the reliance on chemical control, which has been the default strategy for too long.

Liver toxicity in oncology trials and beyond: a simplified concept for management of hepatocellular drug-induced liver injury in patients with abnormal baseline liver tests

ABSTRACT Background Management of side effects in clinical trials has to balance generation of meaningful data with risk for patients. A toxicity area requiring detailed management guidelines is drug-induced liver injury (DILI). In oncology trials, patients are often included despite baseline liver test abnormalities, for whom there is no consensus yet on levels of liver test changes that should trigger action, such as drug interruption or discontinuation. Methods We provide an innovative approach to manage hepatocellular DILI in oncology trials for patients with abnormal baseline alanine aminotransferase (ALT) levels. The algorithm proposed is based on mathematical derivation of action thresholds from those generally accepted for patients with normal baselines. Results The resulting algorithm is grouped by level of baseline abnormality and avoids calculation of baseline multiples. Suggested layered action levels are 4, 6, and 11 × Upper Limit of Normal (ULN) for patients with baseline ALT between 1.5 and 3 × ULN, and 6, 8, and 12 × ULN for patients with baseline ALT between 3 and 5 × ULN, respectively. Conclusions Our concept and resulting algorithm are consistent, transparent, and easy to follow, and the method for derivation from consensus-based thresholds may also be applicable to other drug toxicity areas.

Enhancing climate change planning and adaptive management in marine protected areas through targets, thresholds, and social-ecological objectives

Marine Protected Areas (MPAs) are being deployed globally to protect the Earth’s biodiversity in rapidly changing oceans. Nesting climate change considerations within adaptive MPA management and monitoring is becoming a more common approach, and while climate change is increasingly addressed in MPA planning, implementation gaps remain. This study applied the climate robustness index (CRI) to MPA monitoring plans to assess how climate change is outlined within site- and regional-level plans. Previously developed to assess MPA management plans, the CRI scores plans based on their degree of incorporation of climate change adaptation principles, including core elements of adaptive management. We supplemented our CRI findings for monitoring plans by associating index scores of MPAs in the United States with selected MPA traits, as well as by examining specific physical, ecological, and sociological climate change impacts that were being considered within the monitoring scope of a subset of monitoring plans. We found considerable gaps in actionable targets and thresholds in MPA monitoring plans, consistent with a previous study evaluating MPA management plans, demonstrating that the adaptive management cycle is incomplete in many cases. We consider the importance of completing the adaptive management cycle as a core climate adaptation strategy, and explore the roles of social-ecological objectives and local partnerships as avenues to continue to improve MPA outcomes in a changing world.

Enduring Consensus Guidelines for Cervical Cancer Screening and Management: Introduction to the Scope and Process.

The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

Modeling the Airborne Inoculum of Polystigma amygdalinum to Optimize Fungicide Programs Against Almond Red Leaf Blotch.

Red leaf blotch (RLB) of almond, caused by the ascomycete Polystigma amygdalinum, is a severe foliar disease endemic in the Mediterranean Basin and Middle East. Airborne ascospores of P. amygdalinum were monitored from 2019 to 2021 in two almond orchards in Lleida, Spain, and a Bayesian beta regression was used to model its seasonal dynamics. The selected model incorporated accumulated degree-days (ADD), ADD considering both vapor pressure deficit and rainfall as fixed effects, and a random effect for the year and location. The performance of the model was evaluated in 2022 to optimize RLB fungicide programs by comparing the use of model predictions and action thresholds with the standard program. Two variants were additionally considered in each program to set the frequency between applications, based on (i) a fixed frequency of 21 days or (ii) specific meteorological criteria (spraying within 7 days after rainfalls greater than 10 mm, with daily mean temperatures between 10 and 20°C, and with a minimum frequency of 21 days between applications). Programs were evaluated in terms of RLB incidence and number of applications. The program based on the model with periodic fungicide applications was similarly effective as the standard program, resulting only in a 2.6% higher RLB incidence but with fewer applications (three to four, compared with seven in the standard program). When setting the frequency between applications by using the meteorological criteria, a higher reduction in the number of applications (two to three) was observed, while RLB incidence increased by roughly 16% in both programs. Therefore, the model developed in this study may represent a valuable tool toward a more sustainable fungicide schedule for the control of almond RLB in northeast Spain.

Insights and Challenges for the Development of Mosquito Control Action Thresholds Using Historical Mosquito Surveillance and Climate Datasets.

Strategies to advance action threshold development can benefit both civilian and military vector control operations. The Anastasia Mosquito Control District (AMCD) has curated an extensive record database of surveillance programs and operational control activities in St. Johns County, Florida, since 2004. A thorough exploratory data analysis was performed on historical mosquito surveillance and county-wide climate data to identify climate predictors that could be used in constructing proactive threshold models for initiating control of Aedes, Culex, and Anopheles vector mosquitoes. Species counts pulled from Centers for Disease Control and Prevention (CDC) light trap (2004-2019) and BG trap (2014-2019) collection records and climate parameters of temperature (minimum, maximum, average), rainfall, and relative humidity were used in two iterations of generalized linear models. Climate readings were incorporated into models 1) in the form of continuous measurements, or 2) for categorization into number of "hot," "wet," or "humid" days by exceedance of selected biological index threshold values. Models were validated with tests of residual error, comparison of model effects, and predictive capability on testing data from the two recent surveillance seasons 2020 and 2021. Two iterations of negative binomial regression models were constructed for 6 species groups: container Aedes (Ae. aegypti, Ae. albopictus), standing water Culex (Cx. nigripalpus, Cx. quinquefasciatus), floodwater Aedes (Ae. atlanticus, Ae. infirmatus), salt-marsh Aedes (Ae. taeniorhyncus, Ae. sollicitans), swamp water Anopheles (An. crucians), and a combined Total Mosquitoes group. Final significant climate predictors varied substantially between species groups. Validation of models with testing data displayed limited predictive abilities of both model iterations. The most significant climate predictors for floodwater Aedes, the dominant and operationally influential species group in the county, were either total precipitation or frequency of precipitation events (number of "wet" days) at two to four weeks before trap collection week. Challenges hindering the construction of threshold models were discussed. Insights gained from these models provide initial feedback for streamlining the AMCD mosquito control program and analytical recommendations for future modelling efforts of interested mosquito control programs, in addition to generalized guidance for deployed armed forces personnel with needs of mosquito control but lacking active surveillance programs.

Age-related changes in gap detection thresholds in adult cochlear-implant users: Effects of stimulus level and electrode-to-neural interface

Aging is associated with reduced sensitivity to brief temporal gaps in auditory stimuli. Although gap detection is a relative strength among late-deafened cochlear-implant users, aging and electrode-to-neural interface (ENI) factors may contribute to temporal processing difficulties. Because aging may negatively impact perception particularly at very low and very high input levels, we hypothesized larger gap detection thresholds (GDTs) at poor-ENI electrodes and an interaction between age and level such that GDT improvement with increased level would be less evident in older listeners. GDTs were measured on three electrodes selected to span a range of good-to-poor ENI based on electrically-evoked compound action potential amplitude growth or threshold sensitivity to increased pulse rate. GDTs were assessed using constant-amplitude single-electrode 1000-pps pulse trains presented at 40/60/80/100% dynamic range. In preliminary data (N = 4), GDTs averaged 3 ms at 100%DR and 40 ms at 40%DR. Listeners with better average ENI metrics displayed better GDTs. Within-subject, an advantage for best-ENI electrode over poorer-ENI electrodes was evident only at low levels. Finding an interaction between age and level such that temporal processing is impaired at both low and high (but not mid) levels for older listeners may help elucidate the contributions of peripheral versus central factors.

Ethnicity-specific blood pressure thresholds based on cardiovascular and renal complications: a prospective study in the UK Biobank.

The appropriateness of hypertension thresholds for triggering action to prevent cardiovascular and renal complications among non-White populations in the UK is subject to question. Our objective was to establish ethnicity-specific systolic blood pressure (SBP) cutoffs for ethnic minority populations and assess the efficacy of these ethnicity-specific cutoffs in predicting adverse outcomes. We analyzed data from UK Biobank, which included 444,418 participants from White, South Asian, Black Caribbean, and Black African populations with no history of cardiorenal complications. We fitted Poisson regression models with continuous SBP and ethnic groups, using Whites as the referent category, for the composite outcome of atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease. We determined ethnicity-specific thresholds equivalent to the risks observed in Whites at SBP levels of 120, 130, and 140mm Hg. We adjusted models for clinical characteristics, sociodemographic factors, and behavioral factors. The performance of ethnicity-specific thresholds for predicting adverse outcomes and associated population-attributable fraction (PAF) was assessed in ethnic minority groups. After a median follow-up of 12.5years (interquartile range, 11.7-13.2), 32,662 (7.4%) participants had incident composite outcomes. At any given SBP, the predicted incidence rate of the composite outcome was the highest for South Asians, followed by White, Black Caribbean, and Black African. For an equivalent risk of outcomes observed in the White population at an SBP level of 140mm Hg, the SBP threshold was lower for South Asians (123mm Hg) and higher for Black Caribbean (156mm Hg) and Black African (165mm Hg). Furthermore, hypertension defined by ethnicity-specific thresholds was a stronger predictor and resulted in a larger PAF for composite outcomes in South Asians (21.5% [95% CI, 2.4,36.9] vs. 11.3% [95% CI, 2.6,19.1]) and Black Africans (7.1% [95% CI, 0.2,14.0] vs. 5.7 [95% CI, -16.2,23.5]) compared to hypertension defined by guideline-recommended thresholds. Guideline-recommended blood pressure thresholds may overestimate risks for the Black population and underestimate risks for South Asians. Using ethnicity-specific SBP thresholds may improve risk estimation and optimize hypertension management toward the goal of eliminating ethnic disparities in cardiorenal complications.