Relevant Threshold Research Articles

Efficacy and Safety of Vonoprazan-Based Quadruple Therapy for the Eradication of Helicobacter pylori in Patients with Peptic Ulcers: A Pooled Analysis of Two Randomized, Double-Blind, Double-Dummy, Phase 3 Trials.

Helicobacter pylori eradication is crucial in the treatment of peptic ulcers caused by H. pylori infection, a disease highly prevalent in Asia. We present a pooled analysis of two randomized, double-blind, double-dummy, phase 3 studies evaluating the efficacy and safety of vonoprazan-based bismuth-containing quadruple therapy for H. pylori eradication. Patients aged ≥18 years with endoscopically confirmed duodenal or gastric ulcers were randomized 1 : 1 to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 6 (duodenal ulcers) or 8 weeks (gastric ulcers). H. pylori-positive patients received vonoprazan- or lansoprazole-based bismuth-containing quadruple therapy for the first 2 weeks. H. pylori eradication was determined using the carbon-13 urea breath test at a follow-up visit 4 weeks post-treatment. The H. pylori eradication rate was 90.6% with vonoprazan vs. 85.2% with lansoprazole (difference: 5.4%; 95% confidence interval (CI): -0.1, 10.8). H. pylori eradication rates were 7.1% (95% CI: 1.4, 12.8) and 12.6% (95% CI: 3.9, 22.0) higher in patients aged <65 years and current smokers, respectively, with vonoprazan vs. lansoprazole. In the Chinese subpopulation, the H. pylori eradication rate was 92.0% with vonoprazan vs. 86.0% with lansoprazole (difference: 6.1%; 95% CI: 0.5, 11.7). Treatment-emergent adverse events occurred in 72.7 vs. 62.6% of H. pylori-positive patients at baseline in the vonoprazan vs. lansoprazole arm. H. pylori eradication with vonoprazan-based quadruple therapy was noninferior to lansoprazole-based quadruple therapy and exceeded 90%, a clinically relevant threshold for determining the efficacy of H. pylori eradication regimens (ClinicalTrials.gov identifier: NCT03050359; NCT03050307).

The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.

To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

Self-employment, financial access and economic welfare: empirical evidence from Africa

Purpose This study aims to investigate the empirical linkages between self-employment, financial access and economic welfare in Africa. It particularly examines the moderating role of financial access in the self-employment-economic welfare nexus and determines relevant thresholds. Design/methodology/approach The paper samples 52 African economies from 2000 to 2018 and deploys the fixed effects and bootstrap quantile regression estimators. Findings The results show that self-employment has a negative and significant relationship with economic welfare, while access to finance has a positive and significant relationship with welfare. More notably, the conditional effect of self-employment and finance is significant and positive, confirming a synergetic effect. The result suggests that pushing more people into self-employment does not necessarily enhance economic welfare, other than the avoidance of unemployment, due to the large number of replicative and necessity entrepreneurs. However, granting the self-employed more access to affordable finance that boosts entrepreneurial activities enhances economic welfare. Practical implications African governments and relevant policymakers must recognize that deepening the financial sector is crucial in creating sustainable opportunity entrepreneurs and boosting general economic welfare. Originality/value The uniqueness of this paper centers on the exposé of the relevance of financial access/development in promoting the economic welfare of self-employed persons and entrepreneurs. It also determines relevant thresholds at which finance is most significant in procuring positive impacts on economic welfare. In addition, the simultaneous quantile regression is used to show snapshots of human development index at which this impact is paramount.

The Functioning Assessment Short Test (FAST): Clinically meaningful response threshold in patients with major depressive disorder receiving antidepressant treatment

BackgroundFunctional impairment is common in patients with major depressive disorder (MDD). The Functioning Assessment Short Test (FAST) provides a detailed clinician-rated assessment of functioning across multiple aspects of daily life. This study aimed to establish clinically relevant response thresholds for the FAST in patients with MDD receiving antidepressant treatment. MethodsData were derived from three 8-week clinical trials of antidepressant therapy in patients with MDD that included assessment of functioning using the FAST as a pre-specified endpoint. The minimal clinically important difference (MCID) and threshold for response in terms of change in FAST total score were determined using anchor-based methods. ResultsAfter 8 weeks of antidepressant treatment, the mean reduction in FAST total score in patients considered clinically minimally improved (Clinical Global Impression–Improvement [CGI-I] score of 3) was 7–9 points (~20 % reduction). The threshold for functional response (reduction in FAST total score from baseline in patients with a CGI-I score of ≤2 at week 8) was 16–19 points (~50 % reduction). The threshold for functional response was higher in patients with MDD and comorbid generalized anxiety disorder than in those with MDD alone (mean reduction in FAST total score at 8 weeks: 26 points [63 %]). LimitationsShort-term studies. ConclusionsThese results provide further validation of the FAST for assessing functioning in patients with MDD. In patients with MDD, the suggested MCID for FAST total score is 7–9 points and the proposed threshold for response is a reduction from baseline of approximately 50 %.

Validation of an objective assessment tool for velopharyngeal insufficiency in cleft lip and palate children

The nasalance scores of 42 children aged 8 to 10 years old, born with a cleft lip and palate, were collected and compared with 50 control children. The scores were then analyzed in relation to 31 verbal stimuli from the French corpus created for this study (sentences and syllables). The most relevant threshold values were determined by receiver operating characteristic curves, which exhibited the highest sensitivity and specificity. The results demonstrated statistically significant differences (p < 0.05) in the mean nasalance scores of the control and cleft groups for all verbal stimuli containing oral phonemes. Threshold values with good diagnostic accuracy were defined, and 15 verbal stimuli were selected for use in clinical practice. The nasalance threshold values defined in this study can be utilized for the objective diagnosis of velopharyngeal insufficiency (VPI) and the subsequent monitoring of French children aged 8 to 10 years old, born with a cleft lip and palate.

Random survival forest for predicting the combined effects of multiple physiological risk factors on all-cause mortality

Understanding the combined effects of risk factors on all-cause mortality is crucial for implementing effective risk stratification and designing targeted interventions, but such combined effects are understudied. We aim to use survival-tree based machine learning models as more flexible nonparametric techniques to examine the combined effects of multiple physiological risk factors on mortality. More specifically, we (1) study the combined effects between multiple physiological factors and all-cause mortality, (2) identify the five most influential factors and visualize their combined influence on all-cause mortality, and (3) compare the mortality cut-offs with the current clinical thresholds. Data from the 1999–2014 NHANES Survey were linked to National Death Index data with follow-up through 2015 for 17,790 adults. We observed that the five most influential factors affecting mortality are the tobacco smoking biomarker cotinine, glomerular filtration rate (GFR), plasma glucose, sex, and white blood cell count. Specifically, high mortality risk is associated with being male, active smoking, low GFR, elevated plasma glucose levels, and high white blood cell count. The identified mortality-based cutoffs for these factors are mostly consistent with relevant studies and current clinical thresholds. This approach enabled us to identify important cutoffs and provide enhanced risk prediction as an important basis to inform clinical practice and develop new strategies for precision medicine.

Extracorporeal cardiopulmonary resuscitation versus standard treatment for refractory out-of-hospital cardiac arrest: a Bayesian meta-analysis

BackgroundThe outcomes of several randomized trials on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out-of-hospital cardiac arrest were examined using frequentist methods, resulting in a dichotomous interpretation of results based on p-values rather than in the probability of clinically relevant treatment effects. To determine such a probability of a clinically relevant ECPR-based treatment effect on neurological outcomes, the authors of these trials performed a Bayesian meta-analysis of the totality of randomized ECPR evidence.MethodsA systematic search was applied to three electronic databases. Randomized trials that compared ECPR-based treatment with conventional CPR for refractory out-of-hospital cardiac arrest were included. The study was preregistered in INPLASY (INPLASY2023120060). The primary Bayesian hierarchical meta-analysis estimated the difference in 6-month neurologically favorable survival in patients with all rhythms, and a secondary analysis assessed this difference in patients with shockable rhythms (Bayesian hierarchical random-effects model). Primary Bayesian analyses were performed under vague priors. Outcomes were formulated as estimated median relative risks, mean absolute risk differences, and numbers needed to treat with corresponding 95% credible intervals (CrIs). The posterior probabilities of various clinically relevant absolute risk difference thresholds were estimated.ResultsThree randomized trials were included in the analysis (ECPR, n = 209 patients; conventional CPR, n = 211 patients). The estimated median relative risk of ECPR for 6-month neurologically favorable survival was 1.47 (95%CrI 0.73–3.32) with a mean absolute risk difference of 8.7% (− 5.0; 42.7%) in patients with all rhythms, and the median relative risk was 1.54 (95%CrI 0.79–3.71) with a mean absolute risk difference of 10.8% (95%CrI − 4.2; 73.9%) in patients with shockable rhythms. The posterior probabilities of an absolute risk difference > 0% and > 5% were 91.0% and 71.1% in patients with all rhythms and 92.4% and 75.8% in patients with shockable rhythms, respectively.ConclusionThe current Bayesian meta-analysis found a 71.1% and 75.8% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favorable survival in patients with all rhythms and shockable rhythms. These results must be interpreted within the context of the reported credible intervals and varying designs of the randomized trials.RegistrationINPLASY (INPLASY2023120060, December 14th, 2023, https://doi.org/10.37766/inplasy2023.12.0060).

Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis: The Swedish CardioPulmonary BioImage Study.

Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.

Feasibility and Clinical Utility of Patient-Reported Outcome Measurement Information System-29 in a Newly Established Adolescent and Young Adult Oncology Program.

Purpose: Despite improvements in survival, adolescent and young adult (AYA) oncology patients are at high risk for experiencing negative health-related quality of life (HRQOL) outcomes. AYA cancer programs have attempted to develop assessment tools to identify areas of need. We aimed to demonstrate the feasibility/utility of the Patient-Reported Outcome Measurement Information System®-29 (PROMIS®-29) within an AYA oncology program clinic. Methods: AYA patients were referred by oncologists to the AYA oncology program at Prisma Health. The PROMIS-29 v2.0 survey was administered to AYAs at point of care. Feasibility of distribution and completion rate of surveys were determined. PROMIS surveys were self-reported and subsequently scored using standardized methods. The domains assessed included physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles/activities, pain interference, and pain intensity. Qualitative descriptions of AYA care delivery based on survey responses at the patient level and programmatic level are also presented. Results: Between May 2017 and 2019, 134 AYAs who were newly diagnosed or in treatment completed the survey. Distribution and completion rates for the PROMIS-29 were both 100%, and meaningful changes in program-level services were implemented as a result of PROMIS-29 score patterns. Within the entire cohort, T-scores for anxiety, fatigue, and physical function reached clinically relevant thresholds. Conclusion: PROMIS offers a feasible opportunity for AYA programs to measure clinically useful HRQOL outcomes in AYAs. The survey can be used to deliver real-time AYA care to recently diagnosed and in-treatment AYAs and make programmatic changes within AYA oncology programs.

Detection of genetically modified organisms using highly multiplexed amplicon sequencing

The circulation of products based on genetically modified (GM) organisms is highly regulated by some governments with strict implementation rules for the breeding, planting, marketing, labelling, and trading of such products. To ensure compliance, accurate detection methods for GM events are necessary, along with assurance that GM material falls within relevant threshold levels. The increasing complexity and potential of undocumented GM are a growing challenge for genetic screening. Here, we developed and assessed a highly multiplexed amplicon sequencing assay for the detection of GM events based on a microfluidics platform and next-generation sequencing (NGS). To probe GM events comprehensively, we designed a total of 230 new amplicons to cover flanking, promoter, junction, and coding sequences of GM sequences. In addition, we designed and implemented parallel amplification of ribosomal and chloroplast markers to define crop species identity from potentially mixed samples. Using reference GM material of 11 crop species and multiple amplicons, we successfully detected the presence of 10 known modifications per GM event. We also find that reported flanking sequences of GM events may not be all useful for diagnostic. We assessed the assay's potential to detect GM events in mixed samples as well as in highly diluted DNA. Finally, we performed a prospective search of potentially undocumented GM events in plant material. Our microfluidics-based amplicon GM detection approach fills important gaps in detecting potentially undocumented and complex GM events by recovering a wide range of specific amplicon sequences for evaluation. Integrating highly parallel amplicon assays in GM screening efforts should be an effective complement to aid post-market monitoring and regulatory compliance efforts.

Philosophy of Religion and the Future of Religion

No religion is more deserving of philosophical attention than all others, and philosophy of religion should reflect a broad understanding of the religious experience of humanity. The field should also include within its purview these topics: future directions religion might and should take; whether religion can make progress; what this progress might consist in and how it might be facilitated; whether we human beings may be at an early stage in our religious development; and whether there may be skills or capacities or dispositions or the like we do not possess now but could possess in the future, and that might help us to make religious progress. So part of the focus of this essay is on expanding the scope of the field. However, as we pursue religious progress we should narrow our focus somewhat and pay special attention to traditions that are above a certain normative threshold, some elements of which I introduce. Drawing on recent work by John Bishop, I propose that a religion merits special attention in this context when moral progress is reflected in its metaphysical posits. Avoiding excessive confidence in our assertions about religious matters and avoiding denigrating attitudes to religious outsiders are also elements that may reasonably be considered essential for being above this threshold. Being above the relevant threshold and therefore qualifying for special attention as we pursue religious progress will be a matter of scoring highly in terms of all relevant elements.

Commission Calling: “Call-in” of transactions under the Foreign Subsidies Regulations – uncertainty and unpredictable risks?

Abstract Focusing on the Commission’s power to call-in transactions prior to their implementation, this article explores the broad prerequisites provided for in Art. 21 (5) FSR and the far-reaching consequences for parties involved in transactions which do not exceed the relevant FSR thresholds.

Informing optimal treatment (tx) sequences for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in the United States: Results of a clinical simulation modeling exercise.

e13514 Background: Platinum-based chemotherapy (PBT) followed by avelumab (AVE) as first-line (1L) maintenance for patients with nonprogressive disease (PBT ± AVE) is the standard of care in la/mUC. This study compared the overall survival (OS) and cost-effectiveness of the tx sequence of PBT ± AVE followed by enfortumab vedotin (EV) or other therapies, including immuno-oncology (IO), in second line (2L; ie, PBT + 2L EV/IO or PBT + AVE + 2L EV/IO) vs 1L EV + pembrolizumab (PEM) for PBT-eligible patients (PBTp) from a US commercial payer perspective. Methods: A partitioned survival model compared outcomes with PBT ± AVE and EV + PEM among PBTp. Inputs included progression-free survival and OS, time to tx discontinuation, adverse event (AE) incidence, and health utilities and costs. Efficacy inputs were sourced and extrapolated from patient data in JAVELIN Bladder 100 (data cut: Jun 4, 2021), AVENANCE real-world study (1), and published data (EV-302 trial). Safety data were sourced from US prescribing information. Drug, subsequent tx, disease management, and AE management costs (2023 USD) were calculated. The optimal tx sequencing scenario assumed 80% of patients starting PBT were eligible to receive AVE (2023 Flatiron data cut; (2)), 70% of patients progressing on PBT ± AVE would start 2L, and 70% of those would be eligible for EV. Outcomes included life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Scenarios and probabilistic sensitivity analyses (PSAs) were conducted to assess uncertainty. Results: LY, QALY, costs, and ICER modeling outcomes are shown in the Table. Use of EV in 2L after PBT ± AVE is associated with 0.76 lower QALYs, but given the large cost saving, it represents a cost-effective use of resources at the $150,000/QALY willingness to pay (WTP) threshold. PSAs showed that PBT ± AVE is likely to be more cost-effective over a broad and relevant WTP threshold range ($0-500,000/QALY). Results were sensitive to drug acquisition costs and eligibility to receive AVE and 2L EV. Conclusions: Based on this simulation exercise, the use of 2L EV after PBT ± AVE achieves considerable survival benefit at substantially lower costs vs 1L EV + PEM in PBTp with la/mUC. Given the shift toward value-based care in oncology, such analyses are becoming increasingly relevant to guide clinical decision-making. There is a need to assess tx alternatives that balance healthcare costs while optimizing outcomes in patients with la/mUC. 1. Barthélémy et al, J Clin Oncol 2024;42[suppl 4]: Abstract 561. 2. Moon et al, J Clin Oncol 2023;41[suppl 16]: Abstract 4567. [Table: see text]

Deep learning nomogram for predicting neoadjuvant chemotherapy response in locally advanced gastric cancer patients

PurposeDeveloped and validated a deep learning radiomics nomogram using multi-phase contrast-enhanced computed tomography (CECT) images to predict neoadjuvant chemotherapy (NAC) response in locally advanced gastric cancer (LAGC) patients.MethodsThis multi-center study retrospectively included 322 patients diagnosed with gastric cancer from January 2013 to June 2023 at two hospitals. Handcrafted radiomics technique and the EfficientNet V2 neural network were applied to arterial, portal venous, and delayed phase CT images to extract two-dimensional handcrafted and deep learning features. A nomogram model was built by integrating the handcrafted signature, the deep learning signature, with clinical features. Discriminative ability was assessed using the receiver operating characteristics (ROC) curve and the precision-recall (P-R) curve. Model fitting was evaluated using calibration curves, and clinical utility was assessed through decision curve analysis (DCA).ResultsThe nomogram exhibited excellent performance. The area under the ROC curve (AUC) was 0.848 [95% confidence interval (CI), 0.793–0.893)], 0.802 (95% CI 0.688–0.889), and 0.751 (95% CI 0.652–0.833) for the training, internal validation, and external validation sets, respectively. The AUCs of the P-R curves were 0.838 (95% CI 0.756–0.895), 0.541 (95% CI 0.329–0.740), and 0.556 (95% CI 0.376–0.722) for the corresponding sets. The nomogram outperformed the clinical model and handcrafted signature across all sets (all P < 0.05). The nomogram model demonstrated good calibration and provided greater net benefit within the relevant threshold range compared to other models.ConclusionThis study created a deep learning nomogram using CECT images and clinical data to predict NAC response in LAGC patients undergoing surgical resection, offering personalized treatment insights.Graphical abstract

Development and Validation of a Prediction Model for 1-Year Mortality in Patients With a Hematologic Malignancy Admitted to the ICU.

To develop and validate a prediction model for 1-year mortality in patients with a hematologic malignancy acutely admitted to the ICU. A retrospective cohort study. Five university hospitals in the Netherlands between 2002 and 2015. A total of 1097 consecutive patients with a hematologic malignancy were acutely admitted to the ICU for at least 24 h. None. We created a 13-variable model from 22 potential predictors. Key predictors included active disease, age, previous hematopoietic stem cell transplantation, mechanical ventilation, lowest platelet count, acute kidney injury, maximum heart rate, and type of malignancy. A bootstrap procedure reduced overfitting and improved the model's generalizability. This involved estimating the optimism in the initial model and shrinking the regression coefficients accordingly in the final model. We assessed performance using internal-external cross-validation by center and compared it with the Acute Physiology and Chronic Health Evaluation II model. Additionally, we evaluated clinical usefulness through decision curve analysis. The overall 1-year mortality rate observed in the study was 62% (95% CI, 59-65). Our 13-variable prediction model demonstrated acceptable calibration and discrimination at internal-external validation across centers (C-statistic 0.70; 95% CI, 0.63-0.77), outperforming the Acute Physiology and Chronic Health Evaluation II model (C-statistic 0.61; 95% CI, 0.57-0.65). Decision curve analysis indicated overall net benefit within a clinically relevant threshold probability range of 60-100% predicted 1-year mortality. Our newly developed 13-variable prediction model predicts 1-year mortality in hematologic malignancy patients admitted to the ICU more accurately than the Acute Physiology and Chronic Health Evaluation II model. This model may aid in shared decision-making regarding the continuation of ICU care and end-of-life considerations.

Association of Lipoprotein(a) with Progression of Coronary Artery Calcification: Retrospective Longitudinal Study.

Atherosclerotic cardiovascular disease (ASCVD) is a major health concern, and lipoprotein(a) (Lp(a)) is an independent risk factor. However, there is limited evidence regarding Lp(a) and the risk of ASCVD in Asian populations. This study aimed to assess the predictive value of changes in coronary artery calcification (CAC) for ASCVD risk associated with Lp(a) level. Participants (n=2,750) were grouped according to their Lp(a) levels, and the association between Lp(a) and CAC progression was examined. CAC progression was defined as the occurrence of incident CAC or a difference ≥2.5 between the square root (√) of baseline and follow-up coronary artery calcium scores (CACSs) (Δ√transformed CACS). To adjust for differences in follow-up periods, Δ√transformed CACS was divided by the follow- up period (in years). Over an average follow-up of 3.07 years, 18.98% of participants experienced CAC progression. Those with disease progression had notably higher Lp(a) levels. Higher Lp(a) tertiles correlated with increased baseline and follow-up CACS, CAC progression (%), and Δ√transformed CACS. Even after adjustment, higher Lp(a) levels were associated with CAC progression. However, annualized Δ√transformed CACS analysis yielded no significant results. This study demonstrated an association between elevated Lp(a) levels and CAC progression in a general population without ASCVD. However, longer-term follow-up studies are needed to obtain meaningful results regarding CAC progression. Further research is necessary to utilize Lp(a) level as a predictor of cardiovascular disease and to establish clinically relevant thresholds specific to the Korean population.

Native myocardial T1 and right ventricular size by CMR predict outcome in systemic sclerosis-associated pulmonary hypertension.

Measures of right heart size and function are prognostic in systemic sclerosis-associated pulmonary hypertension (SSc-PH), but the importance of myocardial tissue characterisation remains unclear. We aimed to investigate the predictive potential and interaction of cardiovascular magnetic resonance (CMR) myocardial tissue characterisation and right heart size and function in SSc-PH. A retrospective, single-centre, observational study of 148 SSc-PH patients confirmed by right heart catheterization who underwent clinically indicated CMR including native myocardial T1 and T2 mapping from 2016 to 2023 was performed. Sixty-six (45%) patients died during follow-up (median 3.5 years, range 0.1-7.3). Patients who died were older (65 vs 60 years, P = 0.035) with more dilated (P < 0.001), hypertrophied (P = 0.013) and impaired (P < 0.001) right ventricles, more dilated right atria (P = 0.043) and higher native myocardial T1 (P < 0.001).After adjustment for age, indexed right ventricular end-systolic volume (RVESVi, P = 0.0023) and native T1 (P = 0.0024) were independent predictors of all-cause mortality. Both RVESVi and native T1 remained independently predictive after adjusting for age and PH subtype (RVESVi P < 0.001, T1 P = 0.0056). Optimal prognostic thresholds for RVESVi and native T1 were ≤38 mL/m2 and ≤1119 ms, respectively (P < 0.001). Patients with RVESVi ≤ 38 mL/m2 and native T1 ≤ 1119 ms had significantly better outcomes than all other combinations (P < 0.001). Furthermore, patients with RVESVi > 38mL/m2 and native T1 ≤ 1119 ms had significantly better survival than patients with RVESVi > 38mL/m2 and native T1 > 1119ms (P = 0.017). We identified prognostically relevant CMR metrics and thresholds for patients with SSc-PH. Assessing myocardial tissue characterisation alongside right ventricular function confers added value in SSc-PH and may represent an additional treatment target.

A canine model to evaluate the effect of exercise intensity and duration on olfactory detection limits: the running nose.

Detection canines serve critical roles to support the military, homeland security and border protection. Some explosive detection tasks are physically demanding for dogs, and prior research suggests this can lead to a reduction in olfactory detection sensitivity. To further evaluate the effect of exercise intensity on olfactory sensitivity, we developed a novel olfactory paradigm that allowed us to measure olfactory detection thresholds while dogs exercised on a treadmill at two different exercise intensities. Dogs (n = 3) showed a decrement in olfactory detection for 1-bromooctane at 10-3 (v/v) dilutions and lower under greater exercise intensity. Dogs' hit rate for the lowest concentration dropped from 0.87 ± 0.04 when walking at low intensity to below 0.45 ± 0.06 when trotting at moderate intensity. This decline had an interaction with the duration of the session in moderate intensity exercise, whereby dogs performed near 100% detection in the first 10 min of the 8 km/h session, but showed 0% detection after 20 min. Hit rates for high odor concentrations (10-2) were relatively stable at both low (1 ± 0.00) and moderate (0.91 ± 0.04) exercise intensities. The paradigm and apparatus developed here may be useful to help further understand causes of operationally relevant olfactory detection threshold decline in dogs.

Residual canopy cover provides buffering of near-surface temperatures, but benefits are limited under extreme conditions

Increasing summer temperatures and higher probabilities of extreme heat events have led to concerns about tree damage and mortality. However, insufficient attention has been given to conditions leading to heat-related regeneration failures in temperate forests. To address this, managers need to understand how microclimate varies under a range of overstory conditions. We measured air temperatures at 2 cm above-ground underneath a gradient of canopy cover on south-facing slopes in recently thinned Douglas-fir stands in western Oregon, USA. To expand the ecological relevance of these data to impacts on regeneration, we created the stress degree hours (SDH) metric, representing the amount of time—and by how much—temperatures exceeded biologically relevant stress thresholds. Overall, for every 10% increase in canopy cover, maximum temperatures at 2 cm were 1.3 °C lower, the odds of temperatures exceeding stress thresholds for conifer regeneration declined by a multiplicative factor of 0.26, and the total of SDH decreased by 40%. These reductions are large enough to be worthy of attention when managing for tree regeneration. However, data collected during the Pacific Northwest Heat Dome in June 2021 indicate that with various climate change scenarios and heatwave occurrences, temperatures will be unfavorable for regeneration regardless of overstory cover.

Deriving ecological risk thresholds for soil molybdenum in China based on interspecies correlation estimation and quantitative ion character–activity relationship models

Soil molybdenum (Mo) levels can reach ecologically hazardous levels. China has not yet established the relevant thresholds, posing challenges for environmental management. Therefore, we present our data relevant to Mo toxicity for several important species. By normalizing soil properties, we obtained a correlation model of Mo toxicity to Hordeum vulgare, as well as 31 models for the toxicity of other elements including Cu and Ni to invertebrates and microbial processes. Using interspecies correlation estimation (ICE) extrapolation, the sensitivity coefficient (0.12–0.71) for five plants were found. For invertebrates and microbial processes lacking Mo data, we used regression analysis to establish Mo toxicity models based on the soil quantitative ion character–activity relationships (s–QICAR; R2 =0.70–0.95) and known toxicities of other metal elements to invertebrate and microbial processes. Furthermore, combining species sensitivity distribution calculations, the HC5 values for protecting 95% of soil species from Mo in three typical soil scenarios in China were calculated. After correction, the predicted no-effect concentrations were 6.8, 4.8, and 3.4 mg/kg, respectively. This study innovatively combined ICE and s − QICAR to derive soil Mo thresholds. Our results can provide a basis for decision-making in the assessment and management of soil Mo pollution.