Subsequent Intervals Research Articles

Genetic parameters of functional longevity and associated traits in Italian Charolais and Limousine breeds.

This study aimed to estimate the genetic parameters of Stay-ability (STAY) at different calvings using a single-step genomic best linear unbiased prediction (ssGBLUP) approach, comparing Gaussian-linear and threshold models in Italian Charolais and Limousine beef cattle. It also examined the genetic relationship between STAY and other traits to identify potential indicators of longevity and assessed the impact of STAY selection on economically important traits. Stay-ability, a key trait for farm profitability, is defined as the probability of a cow surviving and remaining productive in the herd until a determined age. We evaluated STAY from the second to third calving and subsequent intervals (e.g., STAY23, STAY78), along with two fertility traits and several conformation traits. Data included 47,362 Limousine cows and 9,174 Charolais cows from 2,471 and 1,774 herds, respectively, born between 1977 and 2023. Analyses were performed fitting univariate threshold and Gaussian-linear animal models to estimate genetic parameters for STAY traits (STAY2 to STAY8) using ssGBLUP. Also, bivariate models were used to estimate genetic correlations between STAY and fertility and conformation traits. Heritabilities for STAY ranged from 0.13 to 0.11 and from 0.21 to 0.14 for Limousine, and from 0.14 to 0.11 and from 0.21 to 0.19 for Charolais, using Gaussian-linear and threshold models, respectively. Significant re-ranking of genotyped sires based on STAY traits was observed, particularly for more distant calvings (STAY8) compared to earlier ones (STAY3), indicating that STAY traits are genetically distinct. Genetic correlations were positive between STAY and conformation traits for Limousine. In Charolais, many traits were uncorrelated, but some conformation traits showed positive correlations, except for rump convexity, which had negative correlations with STAY. In conclusion, the heritability estimates of STAY suggests that genetic improvement for longevity in Limousine and Charolais herds is feasible. Selecting sires with consistently high genomic breeding values for STAY across early and late calvings highlights the importance of long-term longevity. Genetic correlations indicate that selection based on conformation traits could enhance herd survival by improving cow resilience for the Limousine. Instead for the Charolais some conformation traits showed positive correlations with STAY, while rump convexity had negative association, potentially affecting longevity.

Impact of Therapeutic Inertia on Patient-Reported Outcomes in Moderate-to-Severe Atopic Dermatitis: A 12-Month Longitudinal Study from the TARGET-DERM AD Registry

Background: Therapeutic inertia, the delay or reluctance to modify treatment when goals are unmet, is a significant challenge in managing chronic diseases, including atopic dermatitis (AD). This inertia can lead to suboptimal disease control and affect patient outcomes. Objectives: This study evaluates the effect of therapeutic inertia on patient-reported outcomes (PROs) in moderate-to-severe AD patients undergoing systemic treatment over 3 to 12 months. Methods: We analyzed longitudinal data from the TARGET-DERM AD registry, which includes 3,457 patients with moderate-to-severe AD from 39 centers across the U.S. and Canada. Eligible patients had documented patient-reported outcomes (PROs) at the initiation of systemic therapy and at subsequent 3-month intervals up to 12 months of follow-up. We assessed the proportion of patients not meeting treatment targets based on expert consensus. Patients had a validated Investigator Global Assessment (vIGA-AD) score of 3 or more at initiation of either an advanced systemic therapy (AST) such as biologics or JAK inhibitors or a conventional systemic therapy (CST) such as cyclosporine, methotrexate, or prednisone. PROs were evaluated at 3-month intervals up to 12 months, assessing achievement against the predefined treatment targets. PRO measures included Worst-Itch (PROMIS Itch-Severity), POEM, PO-SCORAD, NRS-sleep, and NRS-pain with specific moderate and optimal target levels established for each. Itch-Severity (range: 0–10; moderate target: ≥4-point reduction, optimal target: score ≤1), POEM (range: 0-28; moderate target: ≥4-point reduction, optimal target: score ≤2), PO-SCORAD (range: 0-103; moderate target: score ≤24; optimal target: score ≤10), NRS-sleep and NRS-pain (range: 0-10; moderate target: reduction ≥3-points; optimal target: score ≤1). Results: Out of 2107 patients with moderate-to-severe AD, 445 qualifying participants were included (63.8% adult, 62.0% female, 45.4% Non-Hispanic White, mean age of 31 years). Most patients (88.8%) initiated AST, with dupilumab being the most common (86.5%). At 6 months, significant proportions of AST-treated patients failed to reach moderate and optimal targets for itch (67% and 79%, respectively), POEM (46% and 69%), and NRS-sleep (59% and 47%). By 12 months, these figures were similar, with 66% and 88% failing to meet itch targets, 53% and 73% failing to meet POEM targets, and 62% and 45% failing to meet NRS-sleep targets, respectively. A similar pattern was observed for other PROs. CST-treated patients exhibited similar trends. Conclusions: The study highlights the profound impact of therapeutic inertia on the quality of life of patients with moderate-to-severe AD. Despite systemic therapy, a considerable proportion failed to meet treatment targets over a 12-month period, underscoring the need for more proactive and responsive treatment strategies in AD management.

Delays in Cardiopulmonary Resuscitation, Defibrillation, and Epinephrine Administration in Out-of-Hospital Cardiac Arrest - Composite Time-Dependent Effects of Prehospital Interventions on 30-Day Favorable Neurological Outcomes and Social Implications From a Prospective Nationwide Population-Based Cohort Study.

Our study investigated the prognostic impacts of the interval between collapse and the initiation of cardiopulmonary resuscitation (CPR), and subsequent intervals to defibrillation or epinephrine administration, on 30-day favorable neurological outcomes following out-of-hospital cardiac arrest (OHCA). This nationwide population-based cohort study used the All Japan Utstein Registry, encompassing OHCA patients in Japan between January 2006 and December 2021. The primary outcome was 30-day favorable neurological outcomes, defined as Cerebral Performance Category 1 or 2. Three-dimensional plots and multivariable logistic regression models were used to assess the time-dependent prognostic impacts of prehospital CPR interventions. In all, 184,731 OHCA patients (86,246 with shockable rhythm and 98,485 with non-shockable rhythm) were included in the study. Three-dimensional plots revealed that the interval between collapse and initiation of CPR, and subsequent intervals to defibrillation or epinephrine, were independently associated with 30-day favorable neurological outcomes in the groups with shockable and non-shockable rhythms, respectively (P<0.05 for all). Among patients with witnessed OHCA, there was a dose-response relationship between delays in the collapse-CPR initiation interval, and subsequent intervals to defibrillation or epinephrine administration, and 30-day favorable neurological outcomes. Our findings provide valuable insights into OHCA management.

In vitro anthelmintic activity of Chaetomorpha vieillardii ethanolic extract against adult worm motility and egg-hatching of Haemonchus contortus from sheep

This study aimed to evaluate the potential of macroalgae Chaetomorpha vieillardii as an in vitro candidate for bio-anthelmintic. Adult Worm Motility Test (AWMT) was conducted at concentration levels of 2 mg/mL, 4 mg/mL, and 6 mg/mL of C. vieillardii ethanol extract on 150 female H. contortus worms, randomly divided into 6 treatments with 5 replications, using a two way completely randomized factorial design. 0.9% sodium chloride was used as a negative control, and albendazole at 0.5 and 2 mg/mL served as positive controls. Worm motility observations were performed at 0, 0.25, 0.5, 1, 2, and subsequent time intervals until 100% of the worms were deceased. The identical treatment was applied to the egg hatching inhibiting test (EHIT) using a completely randomized design in a one-way pattern by observing the number of eggs at 0 and 24 hours. The results showed that the concentration level of C. vieillardii ethanol extract and the observation time significantly influenced (P&lt;0.01) the motility of H. contortus, and there was an interaction between them (P&lt;0.01). All three levels were able to decrease the motility of H. contortus, but they were unable to match albendazole. Despite of this result, the three levels were equally effective (P&lt;0.01) as albendazole in terms of inhibiting the egg-hatching of H. contortus. The 2 mg/mL level was sufficient to inhibit the motility and egg-hatching of H. contortus. These findings indicated that the ethanol extract of C. vieillardii has the potential to be developed as a bio-anthelmintic for ruminants.

Delaying post-exercise carbohydrate intake impairs next-day exercise capacity but not muscle glycogen or molecular responses.

To investigate how delayed post-exercise carbohydrate intake affects muscle glycogen, metabolic- and mitochondrial-related molecular responses, and subsequent high-intensity interval exercise (HIIE) capacity. In a double-blind cross-over design, nine recreationally active men performed HIIE (10 × 2-min cycling, ~94% W˙peak) in the fed state, on two occasions. During 0-3 h post-HIIE, participants drank either carbohydrates ("Immediate Carbohydrate" [IC], providing 2.4 g/kg) or water ("Delayed Carbohydrate" [DC]); total carbohydrate intake over 24 h post-HIIE was matched (~7 g/kg/d). Skeletal muscle (sampled pre-HIIE, post-HIIE, +3 h, +8 h, +24 h) was analyzed for whole-muscle glycogen and mRNA content, plus signaling proteins in cytoplasmic- and nuclear-enriched fractions. After 24 h, participants repeated the HIIE protocol until failure, to test subsequent HIIE capacity; blood lactate, heart rate, and ratings of perceived effort (RPE) were measured throughout. Muscle glycogen concentrations, and relative changes, were similar between conditions throughout (p > 0.05). Muscle glycogen was reduced from baseline (mean ± SD mmol/kg dm; IC: 409 ± 166; DC: 352 ± 76) at post-HIIE (IC: 253 ± 96; DC: 214 ± 82), +3 h (IC: 276 ± 62; DC: 269 ± 116) and + 8 h (IC: 321 ± 56; DC: 269 ± 116), returning to near-baseline by +24 h. Several genes (PGC-1ɑ, p53) and proteins (p-ACCSer79, p-P38 MAPKThr180/Tyr182) elicited typical exercise-induced changes irrespective of condition. Delaying carbohydrate intake reduced next-day HIIE capacity (5 ± 3 intervals) and increased RPE (~2 ratings), despite similar physiological responses between conditions. Molecular responses to HIIE (performed in the fed state) were not enhanced by delayed post-exercise carbohydrate intake. Our findings support immediate post-exercise refueling if the goal is to maximize next-day HIIE capacity and recovery time is ≤24 h.

Patient-Reported Outcomes Between Whole-Breast Plus Regional Irradiation and Whole-Breast Irradiation Only in pN1 Breast Cancer After Breast-Conserving Surgery and Taxane-Based Chemotherapy: A Randomized Phase 3 Clinical Trial (KROG 17-01)

BackgroundThe role of regional node irradiation (RNI) with whole-breast irradiation (WBI) in patients with pN1 breast cancer receiving taxane-based adjuvant chemotherapy is not well defined. The KROG 1701 trial, a phase III, multicenter, non-inferiority study, aimed to compare the disease-free survival between WBI+RNI and WBI alone in this patient cohort. Comprehensive patient-reported outcomes (PROs) collected at multiple time points are reported. MethodsThe trial (NCT03269981) enrolled patients with pN1 breast cancer after breast-conserving surgery and taxane-based adjuvant chemotherapy, allocating them to receive either WBI +RNI or WBI only. PROs were assessed using EORTC QLQ-C30 and QLQ-BR23 modules at baseline, during RT, and at subsequent follow-up intervals of 3-6 months, and annually up to 4years. ResultsFrom April 2017 to December 2021, 840 patients were enrolled; 777 received intervention as assigned, and 750 completed baseline PRO questionnaires (387 in WBI+RNI, 363 in WBI only). All PRO domains showed improvements over time (p<0.001). During RT, the WBI+RNI group reported greater fatigue and nausea. Higher arm symptom scores were observed in the WBI+RNI group 3 months post-treatment (p=0.030). No other significant PRO domain differences, including arm/breast symptoms, were observed between the two groups. ConclusionIn patients with pN1 breast cancer treated with taxane-based chemotherapy, adding RNI to WBI resulted in minor, temporary declines in specific PRO domains, but these differences were not clinically significant. This indicates that overall patient experience between WBI+RNI and WBI is comparable, supporting the safety and patient tolerability of both treatments.

Adapting the percentage intensity method to assess accelerations and decelerations in football: moving beyond absolute and arbitrary thresholds.

We adapted the percentage intensity approach to monitor accelerations and decelerations allowing players' individualisation. Forty-two players were monitored during four microcycles via global navigation satellite system devices. Raw velocity and time data were collected to calculate acceleration and deceleration magnitudes according to specific starting speed intervals, and the efforts intensities were established as very low (<25% of the maximal effort), low (25-50%), moderate (50-75%) and high (>75%). Linear regressions and Pearson correlation (r) analysed the relationship between maximal efforts and starting speeds; additionally, mean paired differences compared efforts magnitudes between subsequent starting speed intervals. Most very low intensity accelerations (86%) and decelerations (79%) started from <5 km.h-1. Correlation between maximal efforts and starting speeds were r = -0.97 (p < .001) for acceleration, and r = -0.94 (p < .01) for deceleration. Maximal acceleration decreased as starting speed increases (very large effect sizes), but deceleration is less starting speed dependent (unclear to large effect sizes). This adaptation allows practitioners to individualise accelerations and decelerations classification during real-life scenarios, leading to a more precise training prescription. The very low intensity interval could be excluded to consider only relevant efforts. Maximal acceleration should be collected for each starting speed interval because accelerations are starting speed dependents.

Predicting construction schedule performance with last planner system and machine learning

Construction project schedules deviate due to uncertainty and variability unless timely actions are implemented. While the limitations of traditional management practices help to facilitate such assessments have been widely covered, quantitative LPS research has shown empirical relations between its indicators, performance, and outcome. This paper creates a model to predict the schedule outcome during early execution using the LPS metrics and the Design Science approach. 18 solution artifacts were evaluated to predict three schedule outcome variables using 15 indicators in 1464 sample points collected from nine subsequent execution intervals from 164 projects. The selected artifact predicted the schedule outcome, which is a combination of the schedule performance at planned completion and the actual schedule deviation at completion, with a MAE of 1.24% and R2 = 0.96 averaged across the nine execution intervals, using solely LPS indicators. The model can be applied as an early warning mechanism in LPS IT-Support software.

Relationship between Countermovement Jump and Sprint Performance in Professional Football Players.

Objectives: The aim of this study was to assess the relationship between the countermovement jump (CMJ) and sprint performance of professional football players, and to determine which strength and speed elements assessed by the CMJ translate into effective running. Methods: The research sample comprised 87 male professional football players (age 23.7 ± 4.20 years; body mass 82.33 ± 6.56 kg; body height 1.86 ± 0.05 m) who performed the CMJ on a dual-force platform, as well as the 30 m sprint test. The time and velocity of the run were recorded by photocells at 0, 5, 10, and 30 m of the distance. Results: No significant differences were noted in the time or velocity of the sprint over the initial 5 m between the groups of football players with a higher and lower braking rate of force development (RFD) in the CMJ (p > 0.05). However, at subsequent intervals (5-10 m and 10-30 m), players with a higher braking RFD achieved significantly better time and velocity than those with a lower RFD. Significant correlations in the group with a lower braking RFD between the CMJ and sprint variables occurred in the propulsion phase of the CMJ and most of them were in the first interval (0-5 m). In the group with a higher braking RFD, significant relationships were visible in both the propulsion (concentric) and braking (eccentric) phases of the CMJ, mainly during the second and third intervals of the sprint test. Conclusions: The noted observations may suggest that the relationship between strength and running performance is more complex than previously indicated, and that higher strength in the CMJ does not fully correlate with better sprinting. Therefore, it has been hypothesized that training aimed at generally increasing strength may not always be fully beneficial for running performance in football players and hence specific training guidelines are suggested for targeted strengthening of the required muscle performance characteristics. This may possibly contribute to reducing the unnecessary muscle overload during both training and matches, thereby preventing sports-related injuries.

Impact of selective serotonin reuptake inhibitors on weight loss after vertical sleeve gastrectomy

BackgroundMental health disorders, such as depression, are prominent within the bariatric population, with antidepressants ranking among the most frequently prescribed medications. ObjectivesOur surgery aimed to investigate selective serotonin reuptake inhibitor (SSRI) effects on weight loss in patients undergoing vertical sleeve gastrectomy (VSG). SettingUniversity affiliated Community Hospital, United States. MethodsWe performed a retrospective chart review at a single bariatric center, involving multiple bariatric surgeons, on adults (>18 years of age) who underwent VSG between 2011 and 2018. The patients were followed for a total of 2 years. Exclusion criteria included revisional surgery during the 2-year follow-up period, SSRI prescription initiated after the index surgery or within 2 years following surgery, and individuals who missed 3 or more postoperative visits. A total of 267 patients met the criteria and were categorized into 2 groups: those prescribed an SSRI prior to surgery and those not on an SSRI. Statistical analysis was performed using T-tests and chi-square tests, with significance set at P < .05. ResultsThe preoperative weight in the SSRI group averaged 118.57 kg (±20.59), whereas in the non-SSRI group, it averaged 129.60 kg (±24.39) (P < .0001). Similarly, the preoperative body mass index (BMI) in the SSRI group averaged 43.34 (±6.14), while in the non-SSRI group, it averaged 46.13 (±6.82) (P = .001). At the 1-month, 3-month, and 6-month follow-ups, the average BMI and weight were lower in the SSRI group compared to the non-SSRI group. However, at the 1-year and 2-year follow-ups, the weight and BMI were no longer statistically different. There was no significant difference in the percentage total weight change (%TWC) between the groups; the %TWC was 22.17 in the SSRI group and 23.35 in the non-SSRI group (P = .324). Follow-up attendance significantly decreased at each subsequent interval, with 65.41% in the SSRI group and 29.27% in the non-SSRI group at the 2-year follow-up. ConclusionsBased on our analysis, we suggest that VSG can be an effective option for weight loss in patients taking SSRIs. However, due to the limitations, particularly with follow-up of this study, further research is needed to support this conclusion.

Preoperative Impella therapy in patients with ventricular septal rupture and cardiogenic shock: haemodynamic and organ function outcomes.

We examined the effects of preoperative Impella treatment on haemodynamic stability, organ recovery and postoperative outcomes in patients with postinfarction ventricular septal rupture (PIVSR) and cardiogenic shock (CS). Between April 2018 and February 2024, the data of 10 of 15 patients with PIVSR and CS who underwent Impella therapy were analysed. Emergency surgery was contingent on haemodynamic stability with the Impella/ECpella, except in the presence of organ failure. We utilized a generalized linear mixed model to evaluate organ ischaemia through changes in blood parameters upon admission and at subsequent intervals post-Impella insertion. Preoperative Impella or combined Impella and ECpella (5 patients each) support was provided, with diagnoses and operations occurring at an average of 4 days (interquartile range: 2-5) and 8 days (interquartile range: 2-14) after myocardial infarction, respectively. Treatment significantly reduced lactate, alanine aminotransferase, creatine kinase-MB and troponin I levels (P ≤ 0.05 for all). Conversely, no significant change was noted in the aspartate aminotransferase level or the estimated glomerular filtration rate. Haemoglobin and platelet counts decreased despite transfusions (P < 0.001). No surgical deaths occurred; however, 70% of the patients required prolonged mechanical ventilation, and 80% were transferred to other facilities for rehabilitation. Impella or ECpella treatment can improve haemodynamic and organ failure outcomes in patients with PIVSR and CS. However, the risks of prolonged support, including haemorrhagic events and the need for extended rehabilitation, point to a need for comparative studies to optimize support duration.

PSA Levels and Mortality in Prostate Cancer Patients

IntroductionProstate cancer (PC) is the second most common cancer among men around the world. Several smaller studies have explored the relationship between elevated PSA and mortality, but results have been conflicting. Additionally, studies have shown that Black men are more likely to be diagnosed with PC at late-stages and may have a twofold increase in mortality risk. This study aims to evaluate the relationship between PSA levels and mortality in patients with PC and differences between Black versus White patients. MethodsIn this retrospective study, the TriNetX database, was used to extract de-identified EMRs of 198,083 patients. Patients were included if they were diagnosed with PC and had obtained a PSA level (measured in ng/mL) within 6 months prior to diagnosis. Cohorts were separated into 7 groups based on intervals of PSA, ranging from < 2 to ≥ 500 and compared to a control cohort with a PSA of 4 to 20 for differing 2-year mortality rates. A subgroup analysis was performed to compare mortality differences between Black and White patients. A posthoc analysis evaluated 5- and 10-year mortality amongst all patients with PC. ResultsAfter propensity matching, mortality risk was significantly lower for patients with PSA < 2 (5.9% vs. 7.5%; RR 0.784; P < .001) when compared to the control cohort. Mortality was significantly higher for all other subsequent PSA intervals > 20, with the lowest risk ratios at PSA 20-100 (24.1% vs. 10.0%; RR 2.419; P < .001) and highest at PSA 200 to 500 (50.4% vs. 10.8%; RR 4.673; P < .001). The sub-group analysis showed that when compared to White patients, Black patients with PSA < 20 had similar mortalities, but had significantly lower 2-year mortality rates at PSA levels ≥ 20. The posthoc analysis of PSA levels and 5- and 10-year mortality of all patients with PC showed similar trends to the 2-year outcomes. ConclusionThis study found that prostate cancer patients with significantly elevated PSA levels have a greater mortality, and Black patients have lower 2-year mortality rates than their White counterparts when matched for PSA levels greater than 20.

Effects of Center Based vs. Telerehabilitation using an Interval and Continuous Aerobic Training among Post-Coronary Revascularization Patients-A Randomized Controlled Trial

Background: This investigation used continuous aerobic and high-intensity interval training to compare the differences between centre-based and telerehabilitation. This study seeks to identify the most efficient rehabilitation strategy positioned to empower patients on their path to recovery and well-being in the contemporary era of cardiac care. Methodology: The study was a single-blinded, randomized controlled trial involving 80 patients who had undergone coronary revascularization procedures, were enrolled in the cardiac rehabilitation department, and were eligible for Phase-III CR. Patients were divided into Group A, receiving centre-based Continuous Moderate-Intensity Aerobic Exercise, 3–4 days a week, at 50%-70% of MHR. Group B received high-intensity interval-based training for 3–4 days and at four subsequent intervals. Telerehabilitation was conducted with Group C following the same protocol as Group A and Group D following the same protocol as Group B, while each group had n=20 participants. Results: The within-group analysis showed significant improvements in the 6-Minute Walk Test (6MWT) and Self-reported Seven-Day Physical Activity Questionnaire (PAR) across all groups (p&lt;0.001). Significant improvements in the Rate of Perceived Exertion (RPE) were found in Groups A and B (p&lt;0.05). ANOVA results indicated that centre-based rehabilitation was significantly more effective than telerehabilitation in improving 6MWT and RPE scores (p&lt;0.05). Conclusion: Centre-based intervention is more effective than telerehabilitation in Phase-III Cardia Rehabilitation patients. However, high-intensity interval-based training was more effective in centre-based, while continuous moderate-intensity aerobic exercise was effective in telerehabilitation. Keywords: Aerobic Exercises, Cardiac Rehabilitation, Coronary Artery, Physical Activity.

Social Support Buffers the Effect of Social Deprivation on Comorbidity Burden in Adults with Cancer.

Adults with cancer have higher rates of comorbidity compared to those without cancer, with excess burden in people from lower socioeconomic status (SES). Social deprivation, based on geographic indices, broadens the focus of SES to include the importance of "place" and its association with health. Further, social support is a modifiable resource found to have direct and indirect effects on health in adults with cancer, with less known about its impact on comorbidity. We prospectively examined associations between social deprivation and comorbidity burden and the potential buffering role of social support. Our longitudinal sample of 420 adults (Mage = 59.6, SD = 11.6; 75% Non-Hispanic White) diagnosed with cancer completed measures at baseline (~6 months post-diagnosis) and four subsequent 3-month intervals for 1 year. Adjusting for age, cancer type, and race/ethnicity, we found a statistically significant interaction between social support and the effect of social deprivation on comorbidity burden (β = -0.11, p = 0.012), such that greater social support buffered the negative effect of social deprivation on comorbidity burden. Implementing routine screening for social deprivation in cancer care settings can help identify patients at risk of excess comorbidity burden. Clinician recognition of these findings could trigger a referral to social support resources for individuals high on social deprivation.

Dating post-LGM aeolian sedimentation and the Late Palaeolithic in Central Yakutia (northeastern Siberia)

Central Yakutia is a large region in northeastern Siberia characterized by extensive permafrost, large river valleys, mountain glaciers, and large massifs of aeolian sands; the geological history of the region is complex and, at present, poorly constrained. In recent years, it has been shown that aeolian sands cover up to 60% of large parts of Central Yakutia. This paper presents the results of luminescence dating of aeolian sedimentation at the Diring Yuriakh Palaeolithic site located in the middle reaches of the Lena River. Field studies identified several thick units of aeolian sand, which cover an old deflation surface with Late (Duktai culture) and Early Palaeolithic (Diring culture) artefacts. The reliability of the OSL chronology was assessed by comparison of ages based on the optically stimulated luminescence from quartz and the infra-red stimulated luminescence from potassium-rich feldspars; these age pairs are in good agreement, implying that at least the quartz grains were sufficiently bleached before sedimentation. We obtained OSL ages that reflect three periods of accumulation between the LGM and the Holocene: ∼21 ka, 15-14 ka, and 12.5–10 ka. These periods of accumulation broadly coincide with global cooling episodes during the Last Glacial Maximum, the Older Dryas, and the Younger Dryas, with some extension into subsequent warmer intervals, whereas the intervening intervals without preserved sediments are taken to reflect dune stability during warmer periods. The sand on the terraces, sourced from alluvial bars in the river channel, was blown up the valley slope during cold and dry periods when the vegetation cover was sparse. When the climate warmed, the vegetation took some time to spread, and so the accumulation of aeolian sand on the high terraces continued into the warm periods. We also infer periods of deflation (wind erosion) that occurred before 21 ka and between 20 and 15 ka, presumably due to increased aeolian activity and localized remobilization of sediment. The new OSL chronology shows that the younger artefacts located at the cape of Diring Yuriakh, belonging to the Late Palaeolithic Duktai culture, are older than 15 ka. The new ages also show that the post-LGM aeolian sand sequences at Diring Yuriakh are correlated with the regionally developed subaerial Dolkuma Formation.

Effectiveness of ferritin-guided donation intervals in whole-blood donors in the Netherlands (FIND'EM): a stepped-wedge cluster-randomised trial

Whole-blood donors are at increased risk for iron deficiency and anaemia. The current standard of haemoglobin monitoring is insufficient to ensure the maintenance of proper iron reserves and donor health. We aimed to determine the effects of ferritin-guided donation intervals for blood donor health and blood supply in the Netherlands. In this stepped-wedge cluster-randomised trial (FIND'EM), the 138 fixed and mobile donation centres in the Netherlands are organised into 29 geographical clusters and the clusters were randomly assigned to four treatment groups, with two groups being further split into two per a protocol amendment. Eligible donors were whole-blood donors who consented for use of their leftover material in the study. Each group was sequentially crossed over from the existing policy (haemoglobin-based screening; control) to a ferritin-guided donation interval policy over a 3-year period. In the intervention groups, in addition to the existing haemoglobin screening, ferritin was measured in all new donors and at every fifth donation in repeat donors. Subsequent donation intervals were extended to 6 months if ferritin concentrations were 15-30 ng/mL and to 12 months if they were less than 15 ng/mL. Outcomes were measured cross-sectionally across all donation centres at four timepoints. Primary outcomes were ferritin and haemoglobin concentrations, iron deficiency, and haemoglobin-based deferrals. We assessed all outcomes by sex and menopausal status and significance for primary outcomes was indicated by a p value of less than 0·0125. This trial is registered in the Dutch trial registry, NTR6738, and is complete. Between Sept 11, 2017, and Nov 27, 2020, 412 888 whole-blood donors visited a donation centre, and we did measurements on samples from 37 621 donations from 36 099 donors. Over 38 months, ferritin-guided donation intervals increased mean ferritin concentrations (by 0·18 log10 ng/mL [95% CI 0·15-0·22; p<0·0001] in male donors, 0·10 log10 ng/mL [0·06-0·15; p<0·0001] in premenopausal female donors, and 0·17 log10 ng/mL [0·12-0·21; p<0·0001] in postmenopausal female donors) and mean haemoglobin concentrations (by 0·30 g/dL [95% CI 0·22-0·38; p<0·0001] in male donors, 0·12 g/dL [0·03-0·20; p<0·0074] in premenopausal female donors, and 0·16 g/dL [0·05-0·27; p<0·0044] in postmenopausal female donors). Iron deficiency decreased by 36-38 months (odds ratio [OR] 0·24 [95% CI 0·18-0·31; p<0·0001] for male donors, 0·49 [0·37-0·64; p<0·0001] for premenopausal female donors, and 0·24 [0·15-0·37; p<0·0001] for postmenopausal female donors). At 36-38 months, haemoglobin-based deferral decreased significantly in male donors (OR at 36-38 months 0·21 [95% CI 0·10-0·40, p<0·0001]) but not significantly in premenopausal or postmenopausal female donors (0·81 [0·54-1·20; p=0·29] and 0·50 [95% CI 0·25-0·98; p=0·051], respectively). Ferritin-guided donation intervals significantly improved haemoglobin and ferritin concentrations and significantly decreased iron deficiency over the study period. Haemoglobin-based deferrals decreased significantly for male donors, but not female donors. Although this intervention is overall beneficial for maintenance of iron and haemoglobin concentrations in donors, increased efforts are needed to recruit and retain donors. The Sanquin Research Programming Committee.

Event Analysis for Automated Estimation of Absent and Persistent Medication Alerts: Novel Methodology.

Event analysis is a promising approach to estimate the acceptance of medication alerts issued by computerized physician order entry (CPOE) systems with an integrated clinical decision support system (CDSS), particularly when alerts cannot be interactively confirmed in the CPOE-CDSS due to its system architecture. Medication documentation is then reviewed for documented evidence of alert acceptance, which can be a time-consuming process, especially when performed manually. We present a new automated event analysis approach, which was applied to a large data set generated in a CPOE-CDSS with passive, noninterruptive alerts. Medication and alert data generated over 3.5 months within the CPOE-CDSS at Heidelberg University Hospital were divided into 24-hour time intervals in which the alert display was correlated with associated prescription changes. Alerts were considered "persistent" if they were displayed in every consecutive 24-hour time interval due to a respective active prescription until patient discharge and were considered "absent" if they were no longer displayed during continuous prescriptions in the subsequent interval. Overall, 1670 patient cases with 11,428 alerts were analyzed. Alerts were displayed for a median of 3 (IQR 1-7) consecutive 24-hour time intervals, with the shortest alerts displayed for drug-allergy interactions and the longest alerts displayed for potentially inappropriate medication for the elderly (PIM). Among the total 11,428 alerts, 56.1% (n=6413) became absent, most commonly among alerts for drug-drug interactions (1915/2366, 80.9%) and least commonly among PIM alerts (199/499, 39.9%). This new approach to estimate alert acceptance based on event analysis can be flexibly adapted to the automated evaluation of passive, noninterruptive alerts. This enables large data sets of longitudinal patient cases to be processed, allows for the derivation of the ratios of persistent and absent alerts, and facilitates the comparison and prospective monitoring of these alerts.

Cochlear Implantation: Long-Term Effect of Early Activation on Electrode Impedance.

Objectives: The growing adoption of cochlear implants (CIs) necessitates understanding the factors influencing long-term performance and improved outcomes. This work investigated the long-term effect of early activation of CIs on electrode impedance in a large sample of CI users at different time points. Methods: A retrospective study on 915 ears from CI patients who were implanted between 2015 and 2020. According to their CI audio processor activation time, the patients were categorized into early activation (activated 1 day after surgery, n = 481) and classical activation (activated 4 weeks after surgery, n = 434) groups. Then, the impact of the activation times on the electrode impedance values, along the electrode array contacts, at different time points up to two years was studied and analyzed. Results: The early activation group demonstrated lower impedance values across all the electrode array sections compared to the classical activation at 1 month, 1 year, and 2 years post-implantation. At 1 month, early activation was associated with a reduction of 0.34 kΩ, 0.46 kΩ, and 0.37 kΩ in the apical, middle, and basal sections, respectively. These differences persisted at subsequent intervals. Conclusions: Early activation leads to sustained reductions in the electrode impedance compared to classical activation (CA), suggesting that earlier activation might positively affect long-term CI outcomes.

Electrical rejuvenation of chronically implanted macroelectrodes in nonhuman primates

Objective. Electrodes chronically implanted in the brain undergo complex changes over time that can lower the signal to noise ratio (SNR) of recorded signals and reduce the amount of energy delivered to the tissue during therapeutic stimulation, both of which are relevant for the development of robust, closed-loop control systems. Several factors have been identified that link changes in the electrode-tissue interface (ETI) to increased impedance and degraded performance in micro- and macro-electrodes. Previous studies have demonstrated that brief pulses applied every few days can restore SNR to near baseline levels during microelectrode recordings in rodents, a process referred to as electrical rejuvenation. However, electrical rejuvenation has not been tested in clinically relevant macroelectrode designs in large animal models, which could serve as preliminary data for translation of this technique. Here, several variations of this approach were tested to characterize parameters for optimization. Approach. Alternating-current (AC) and direct-current (DC) electrical rejuvenation methods were explored in three electrode types, chronically implanted in two adult male nonhuman primates (NHP) (Macaca mulatta), which included epidural electrocorticography (ECoG) electrodes and penetrating deep-brain stimulation (DBS) electrodes. Electrochemical impedance spectroscopy (EIS) was performed before and after each rejuvenation paradigm as a gold standard measure of impedance, as well as at subsequent intervals to longitudinally track the evolution of the ETI. Stochastic error modeling was performed to assess the standard deviation of the impedance data, and consistency with the Kramers–Kronig relations was assessed to evaluate the stationarity of EIS measurement. Main results. AC and DC rejuvenation were found to quickly reduce impedance and minimize the tissue component of the ETI on all three electrode types, with DC and low-frequency AC producing the largest impedance drops and reduction of the tissue component in Nyquist plots. The effects of a single rejuvenation session were found to last from several days to over 1 week, and all rejuvenation pulses induced no observable changes to the animals’ behavior. Significance. These results demonstrate the effectiveness of electrical rejuvenation for diminishing the impact of chronic ETI changes in NHP with clinically relevant macroelectrode designs.

Bioactivation of Legacy Phosphorus in Calcareous Soil by P-Activators and Its Effect on Maize Growth

ABSTRACT Soil legacy phosphorus (P) accumulated due to the long-term continuous application of P fertilizers in agricultural fields accumulated in the soil for years, as sparingly soluble forms. This can be made as a possible soil P source using P-activators. In this study, a laboratory incubation and a pot experiment were conducted to evaluate the potential of some P activators (Phosphorus solubilizing bacteria, phytase, humic acid, oxalic acid) in increasing the availability of residual phosphorus in calcareous soil. For the incubation experiment, the P activators were applied alone and in combination. Soil samples were analyzed at subsequent intervals for soil available P, alkaline phosphatase activity, and sequential P fractions. The results showed that phytase application with humic acid (HA) increased the available soil P (12.4 kg ha−1) and alkaline phosphatase activity (47.42 µg p-nitrophenol released g−1 soil hr−1) followed by phosphorus solubilizing Bacteria (PSB) with humic acid and PSB with phytase treatments. All treatments have a significant effect on different soil P-fractions. A greater reduction in calcium phosphate fraction was noted in phytase and humic acid application. The combined application of P-activators performed better than their sole application. The best three treatments selected from the laboratory incubated experiment were used for the pot experiment with maize, along with the different dosages of P fertilizer. The morphological parameters were observed on the 30th and 60th days of the maize crop. The results of plant height, chlorophyll index, and dry matter production showed that the application of phytase and HA with 100% recommended dose of P was statistically comparable with phytase and HA with 75% recommended dose of P. The findings have illustrated the extent of P release by different P activators in increasing the legacy P availability. The application of phytase and HA with 25% reduced dose of P fertilizers will promote the availability of legacy P in calcareous soils through solubilization.