Longer Intervals Research Articles

Dose Intervals and Time since Final Dose on Changes in Metabolic Indices after COVID-19 Vaccination.

The rapid development and implementation of COVID-19 vaccines merit understanding its effects on metabolic indices. This retrospective longitudinal study investigated the influence of first-to-second-dose intervals and time since the final dose on the metabolic indices of individuals receiving COVID-19 vaccinations. A total of 318 Saudi subjects (59.7% females) aged 12-60 years received COVID-19 vaccines via the national vaccination program. We collected the anthropometric data and fasting blood samples at specific time points before vaccination and after the final vaccination dose, and biochemical metabolic indices, including glucose and lipid profile, were measured. We also collected the dates of vaccination and COVID-19 history during the study period. The participants were stratified into groups based on first-to-second-dose intervals and time since the final dose to compare pre-and post-vaccination changes in metabolic indices between the groups. Logistic regression analysis revealed no differences in pre- to post-vaccination metabolic status between groups based on first-to-second-dose intervals in either adolescents or adults. However, shorter intervals (≤6 months) between the final dose and follow-up were associated with a decrease in total cardiometabolic components, especially triglyceride levels (OR = 0.39, 95% CI: (0.22-0.68), p < 0.001) than longer intervals (>6 months) in adults. In conclusion, time duration since final dose was associated with pre- to post-vaccination changes in metabolic indices, especially triglyceride levels, indicating that post-vaccination improvements wane over time. Further research is needed to validate the observed relationship, as it may contribute to optimizing vaccine effectiveness and safety in the future.

No difference between using short and long intervals for distributed proficiency-based laparoscopy simulator training: a randomized trial

BackgroundSimulation-based training is increasingly used to acquire basic laparoscopic skills. Multiple factors can influence training, e.g., distributed practice is superior to massed practice in terms of efficiency. However, the optimal interval between training sessions is unclear. The objective of this trial was to investigate if shorter intervals between sessions are more efficient than longer intervals during proficiency-based laparoscopy simulator training.MethodsA randomized simulation-based trial where medical students (n = 39) were randomized to proficiency-based training with either 1–2 days (intervention group) or 6–8 days (control group) between training sessions. Both groups practiced a series of basic tasks and a procedural module until proficiency level on the LapSim® simulator. Both groups were given instructor feedback upon request. After reaching proficiency, participants were invited back for a retention test 3–5 weeks later and practiced the same tasks to proficiency again.ResultsThe mean time to reach proficiency during training was 291 (SD 89) and 299 (SD 89) min in the intervention and control group, respectively (p = 0.81). During the retention test, the mean time to reach proficiency was 94 (SD 53) and 96 (SD 39) minutes in the intervention and control groups, respectively (p = 0.91).ConclusionWe found no difference whether practicing with shorter intervals or longer intervals between training sessions when examining time to proficiency or retention.

Using Instrumental Variables to Measure Causation over Time in Cross-Lagged Panel Models

Cross-lagged panel models (CLPMs) are commonly used to estimate causal influences between two variables with repeated assessments. The lagged effects in a CLPM depend on the time interval between assessments, eventually becoming undetectable at longer intervals. To address this limitation, we incorporate instrumental variables (IVs) into the CLPM with two study waves and two variables. Doing so enables estimation of both the lagged (i.e., “distal”) effects and the bidirectional cross-sectional (i.e., “proximal”) effects at each wave. The distal effects reflect Granger-causal influences across time, which decay with increasing time intervals. The proximal effects capture causal influences that accrue over time and can help infer causality when the distal effects become undetectable at longer intervals. Significant proximal effects, with a negligible distal effect, would imply that the time interval is too long to estimate a lagged effect at that time interval using the standard CLPM. Through simulations and an empirical application, we demonstrate the impact of time intervals on causal inference in the CLPM and present modeling strategies to detect causal influences regardless of the time interval in a study. Furthermore, to motivate empirical applications of the proposed model, we highlight the utility and limitations of using genetic variables as IVs in large-scale panel studies.

Effect of nitrogen-modulated laminar burning velocity on duct-vented hydrogen-air explosions

To investigate the combined effect of venting and dilution on flame behavior and pressure evolution, nitrogen gas was used to modulate the laminar burning velocity (LBV) of stoichiometric hydrogen/air mixtures. The results reveal that the coupling of the relief duct and LBV affects the flame dynamic, e.g., at LBV = 114 cm/s, the flame front becomes planar at the end of the enclosure. Lowering the LBV extends the time of the flame front into the vent, and the second peak pressure in the enclosure decreases with longer time intervals. There is a notable reduction in both the duration and magnitude of the negative pressure at the lower LBVs. The original equation is modified to achieve a greater degree of applicability. At lower LBVs, the interaction between the maximum pressure in the duct and the maximum pressure in the enclosure is weak, the correlation is probably variable for different fuel types.

Stochasticity-driven weekly fluctuations distinguished the temporal pattern of particle-associated microorganisms from its free-living counterparts in temperate coastal seawater

Microbial community dynamics directly determine their ecosystem functioning. Despite the well-known annual recurrence pattern, little is known how different lifestyles affect the temporal variation and how community assembly mechanisms change over different temporal scales. Here, through a high-resolution observation of size fractionated samples over 60 consecutive weeks, we investigate the distinction in weekly distribution pattern and assembly mechanism between free-living (FL) and particle-associated (PA) communities in highly dynamic coastal environments. A clear pattern of annual recurrence was observed, which was more pronounced in FL compared to PA, resulting in higher temporal specificity in the former samples. Both the two size fractions displayed significant temporal distance-decay patterns, yet the PA community showed a higher magnitude of community variation between adjacent weeks, likely caused by sudden, drastic and long-lived blooms of heterotrophic bacteria. Generally, determinism (environmental selection) had a greater effect on the community assembly than stochasticity (random birth, death, and dispersal events), with significant contributions from temperature and inorganic nutrients. However, a clear shift in the temporal assembly pattern was observed, transitioning from a prevalence of stochastic processes driving short-term (within a month) fluctuations to a dominance of deterministic processes over longer time intervals. Between adjacent weeks, stochasticity was more important in the community assembly of PA than FL. This study revealed that stochastic processes can lead to rapid, dramatic and irregular PA community fluctuations, indicating weak resistance and resilience to disturbances, which considering the role of PA microbes in carbon processing would significantly affect the coastal carbon cycle. Our results provided a new insight into the microbial community assembly mechanisms in the temporal dimension.

Abstract 420: The Association Between Ventricular Fibrillation Duration and Successful Termination After the First Shock in Witnessed Out-of-Hospital Cardiac Arrest Patients

Introduction: In OHCA patients with an initial shockable rhythm, a longer time interval between onset of VF and the first shock decreases the likelihood of survival. The exact mechanism to explain this decrease is not clear. We investigated the time interval between delay to the first shock and outcomes VF termination, return of organized rhythm (ROOR), ROSC and survival. Methods: We studied witnessed OHCA patients with VF as an initial rhythm using the prospective ARREST registry. Patient- and resuscitation data, including time-synchronized AED and manual defibrillator data, were analysed to determine VF termination at 5 seconds after the first shock. Shock delay was defined as the time from initial emergency call till first shock by any defibrillator. Outcomes were rates of termination of VF, ROOR 5 seconds after the first shock, ROSC before transport, and survival to discharge, all in relation to the delay to the first shock. A logistic regression corrected for age, sex and basic life support before EMS arrival was used to analyse the association between VF duration and outcomes. Results: A total of 3676 cases were analysed. VF termination rates declined from 95% when the first shock was delivered &lt;2 minutes after the call to 75% when delivered after &gt;16 minutes (Figure 1). Rates of ROOR (49% to 23%), ROSC before transport (86% to 33%), and survival to discharge (79% to 23%) all declined significantly. Every additional minute in VF was associated with a 9% increased odds of failure to terminate VF (OR 1.09 [95% CI 1.07-1.12]), a 7% reduced odds of ROOR (OR 0.93 [95% CI 0.91-0.95]), a 12% reduced odds of acquiring ROSC before transport (OR 0.88 [95% CI 0.86-0.90]), and a 15% reduced odds of surviving to discharge (OR 0.85 [95% CI 0.83-0.87]). Conclusions: Every additional minute of delay to the first shock was associated with significant decreases in rates of VF termination, ROOR, and ROSC during transportation. This may explain the worse outcomes in patients with a long delay to defibrillation.

Abstract 18200: Prognostic Importance of Serial NT-proBNP Measurements Following High-Risk Mi: The PARADISE-MI Trial

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a potent predictor of heart failure (HF) and death following myocardial infarction (MI). NT-proBNP levels change post MI. Hypothesis: Serial measurements of NT-proBNP add prognostic information. Aims: To investigate the prognostic importance of NT-proBNP two weeks after MI in PARADISE-MI and to identify predictors of week 2 NT-proBNP. Methods: Patients with MI and LVEF ≤40% and/or pulmonary congestion (n=5661) were randomized to sacubitril/valsartan or ramipril. Patients with NT-proBNP measured at week 2 (n=1057) were analyzed. Associations of week 2 NT-proBNP with subsequent clinical outcomes were evaluated with Cox models adjusted for baseline NT-proBNP, age, sex, atrial fibrillation (AF), LVEF, STEMI presentation, BMI, eGFR, high-sensitivity troponin T (hs-cTnT), time from presentation to randomization and treatment assignment. Results: Median NT-proBNP was 1425 [685, 2598] ng/L at week 2, declining 23% (95% CI, 20-26%) from baseline. Patients in the highest NT-proBNP quartile at week 2 (≥2616 ng/L) were older, had lower LVEF and eGFR, higher Killip class, more AF, and higher baseline NT-proBNP (all p≤0.05). Higher NT-proBNP at week 2 was independently associated with greater risk of CV death or incident HF (adjusted HR [aHR] 1.62 per log2; 95% CI, 1.30-2.03), HF hospitalization (aHR 1.96; 95% CI, 1.46-2.62) and all-cause death (aHR 1.86; 95% CI, 1.40-2.47). Higher baseline NT-proBNP and hs-cTnT, longer interval between presentation and randomization and female sex were associated with higher week 2 NT-proBNP levels while sacubitril/valsartan was associated with lower levels (Table). Conclusions: Patients with elevated NT-proBNP two weeks after high-risk MI are at greater risk of subsequent death or incident HF, even after adjusting for baseline level. Higher baseline NT-proBNP and hs-cTnT are predictive of higher week 2 NT-proBNP while sacubitril/valsartan decreases levels.

Phonological acquisition depends on the timing of speech sounds: Deconvolution EEG modeling across the first five years

The late development of fast brain activity in infancy restricts initial processing abilities to slow information. Nevertheless, infants acquire the short-lived speech sounds of their native language during their first year of life. Here, we trace the early buildup of the infant phoneme inventory with naturalistic electroencephalogram. We apply the recent method of deconvolution modeling to capture the emergence of the feature-based phoneme representation that is known to govern speech processing in the mature brain. Our cross-sectional analysis uncovers a gradual developmental increase in neural responses to native phonemes. Critically, infants appear to acquire those phoneme features first that extend over longer time intervals—thus meeting infants’ slow processing abilities. Shorter-lived phoneme features are added stepwise, with the shortest acquired last. Our study shows that the ontogenetic acceleration of electrophysiology shapes early language acquisition by determining the duration of the acquired units.

Effectiveness of BNT162b2 Vaccine Against Omicron-SARS-CoV-2 Subvariants in Children 5-11 Years of Age in Quebec, Canada, January 2022 to January 2023.

In premarketing clinical trials conducted before Omicron emergence, BNT162b2 vaccine efficacy against COVID-19 was 90% in children. We conducted postmarketing evaluation of 1- and 2-dose vaccine effectiveness (VE) against Omicron BA.1, BA.2 and BA.4/5 subvariants in 5- to 11-year olds. We estimated VE against SARS-CoV-2 infection using a test-negative design. Specimens collected between January 9, 2022, and January 7, 2023, from children 5-11 years old in Quebec, Canada, and tested by nucleic acid amplification test were eligible. We estimated VE by time since last vaccine dose, interval between doses and by period of Omicron subvariant predominance. A total of 48,826 NAATs were included in overall analysis. From 14-55 to 56-385 days postvaccination, 2-dose VE against symptomatic infection decreased from 68% (95% CI, 62-74) to 25% (95% CI, 11-36). Two-dose VE with restriction to specimens collected from acute care hospitals (emergency rooms or wards) did not decline but was stable at ~40%. VE against symptomatic infection remained comparable at any interval between doses but increased with longer interval among children tested in acute care settings, from 18% (95% CI, -17 to 44) with 21- to 55-day interval to 69% (95% CI, 43-86) with ≥84-day interval. Two-dose VE against symptomatic infection dropped from 70% (95% CI, 63-76) during BA.1, to 32% (95% CI, 13-47) with BA.2 and to nonprotective during BA.4/5 dominance. In children 5-11 years of age, VE against symptomatic infection was stable at any interval between doses but decreased with time since the last dose and against more divergent omicron subvariants.

Efficacy and Safety of Belantamab Mafodotin Monotherapy in Patients with Relapsed or Refractory Light Chain Amyloidosis: A Phase 2 Study By the European Myeloma Network

Introduction Belantamab mafodotin (belamaf) targets B-cell maturation antigen (BCMA) expressing plasma cells (PCs) and is approved for heavily pretreated patients (pts) with relapsed/refractory (RR) multiple myeloma. Clonal PCs in light-chain (AL) amyloidosis also express BCMA; thus, belamaf could be a treatment option for RRAL amyloidosis pts. We present an interim analysis of the prospective EMN27 study assessing efficacy and safety of belamaf monotherapy in RRAL amyloidosis pts. Methods The ongoing prospective, open-label, multinational, phase 2 EMN27 study (NCT04617925) aims to enroll 36 adult pts with RR (defined as ≥2 cycles of therapy directed against PC clone) AL amyloidosis, adequate hematologic, hepatic, renal, and cardiac function, and ECOG ≤2. Pts at Mayo cardiac stage 3B or with previous exposure to anti-BCMA agents are excluded. Monotherapy with belamaf at a starting dose of 2.5 mg/kg (or 1.92 mg/kg for toxicity) is administered by intravenous infusion every 6 weeks for up to 8 cycles. Pre-planned study analyses included an interim safety (after first 6 pts received ≥1 treatment cycle) and an efficacy analysis (after 13 pts were enrolled). Outcomes of both were favorable and study enrollment is ongoing. This descriptive analysis included pts initiating treatment ≥3 months before 31/05/2023 (cutoff date). Results Twenty-eight pts have been included in this analysis (median [range] age: 66 years [46-80]; male: 16 [57%]). At screening, 5 (18%), 15 (54%), and 8 (29%) pts were rated as Mayo stages I, II, and IIIA, respectively. Most pts had cardiac involvement (22, 79%), followed by those with renal (17, 61%) and peripheral nerve (6, 21%) involvement. Most pts (21, 75%) had New York Heart Association class II symptoms and the median N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T, and difference in involved and uninvolved free light chain (dFLC) were 1,393 ng/L (90-7,270), 34 ng/L (3-116), and 119 mg/L (38-2,791), respectively. The median number of prior treatment lines was 4 (1-10). Twenty-one (75%) pts had previously received daratumumab (dara) (12 [42.9%] dara refractory pts), while 24 (86%) pts had previously received bortezomib, both with median of 4 (1-10) prior treatment lines. At cutoff, 4 (14%) pts were continuing therapy, 21 (75%) pts discontinued (disease progression/inadequate response: 9 [32%]; adverse events [AE]: 8 [29%]; withdrew consent: 1 [4%]; death 3 [11%]), and 3 (11%) pts completed treatment. Median belamaf cycles administered were 3 (1-8). Ninety-five belamaf doses were given (2.5 mg/kg: 72, 1.92 mg/kg: 23). Eleven (39%) pts had 23 belamaf dose holds due to AE/SAE, with median delay of 21 (7-128) days from planned administration. At a median follow up of 16 months (4-26), the overall hematologic response (≥partial response [PR]) and very good partial response (VGPR) rates were 54% (15 pts) and 32% (9 pts), respectively ( Table). Median times to first hematologic response and VGPR were 15 (7-148) and 43 (15-106) days, respectively ( Table). Median duration of hematologic response (time from first response to hematologic progression or treatment/disease-related death) was not reached either for all pts or for pts pre-treated with dara. At 1 and 3 months, the respective overall hematologic responses were 39% (11 pts) and 50% (14 pts). Respective rates for pts with prior dara exposure were 29% (6 pts) and 43% (9 pts). For all pts, 3-month organ response rate was 14% (4 pts; Table). All pts experienced &amp;gt;1 AE (ocular AEs: 27 [96%] pts; hematologic toxicity: 8 [30%] pts; cardiac disorders: 7 [25%] pts); no new cardiac or renal toxicity observed. Three (11%) pts had a fatal AE, all considered unrelated to belamaf. Twenty-two (79%) pts had visual acuity reduced (grade [Gr]1: 3 (11%); Gr2: 8 [29%]; Gr3: 10 [36%]; Gr4: 1 [4%]), 22 (79%) keratopathy (Gr1: 10 [36%]; Gr2: 8 [29%]; Gr3: 4 [14%]; Gr4: 0 [0%]), and 7 (25%) visual impairment (Gr1: 1 [4%]; Gr2: 4 [14%]; Gr3: 1 [4%]; Gr4: 1 [4%]). Conclusions In heavily pretreated pts with RRAL and limited treatment options, belamaf monotherapy achieved an overall hematologic response of 54% without unexpected toxicity. Results suggest belamaf could be a treatment option for RRAL amyloidosis, a difficult to treat population. Further evaluation of belamaf in combination with other active agents could allow longer intervals (i.e., 8-12 weeks) between belamaf doses, which has shown to reduce ocular toxicity, while maintaining efficacy.

Effects of treatment delays on lung cancer survival.

478 Background: Previous studies have established a link between treatment initiation delays and reduced overall survival in individuals diagnosed with lung cancer. These delays are often influenced by diagnostic complexities, logistical hurdles, and patient-related factors. However, the association between treatment delays and survival outcomes has yet to be extensively investigated using data from a large national cohort. This study aims to fill this research gap and provide unique insights into the relationship between treatment delays and lung cancer survival by utilizing data from a substantial national cohort. Methods: The study population consisted of 3,723 lung cancer patients participating in the NCI PLCO Cancer Screening Trial. Cox Proportional Hazards (PH) Regression analyses examined the time between cancer diagnosis and treatment initiation using several measures including intervals from tumor doubling/stage progression time models by Spratt et al. (1964) and Detterbeck et al. (2008). Analyses controlled for patient and clinical characteristics including age, sex, race/ethnicity, smoking status, histopathologic type, cancer stage, and treatment modality. Data analysis was conducted using Microsoft Excel, STATA, and IBM SPSS software. Results: PH Regression analyses demonstrated a clear association between longer time intervals from diagnosis to treatment initiation and increased risk of mortality. Patients with time intervals exceeding 20 days exhibited a hazard ratio (HR) for mortality of 1.21 (p &lt; 0.001, 95% confidence interval [CI] 1.1158-1.3176).The Spratt tumor progression model, considering intervals exceeding 88 days, revealed a HR of 1.22 (p = 0.03, 95% CI 1.0146-1.4885). On the other hand, the Detterbeck model, which considered intervals exceeding 118 days, did not show a statistically significant association with increased mortality risk. Furthermore, PH analysis identified cigarette smoking status, marital status, and tumor grade as significant predictors of mortality risk. Conclusions: Data from a large national cohort study indicate that delays in lung cancer treatment initiation have detrimental impacts on survival. Treatment initiation shortly after diagnosis had the most significant differential impact on mortality risk. Timely initiation of treatment is of utmost importance and should be prioritized in lung cancer care. By addressing factors contributing to treatment delays, it is likely possible to improve the survival rates of patients with lung cancer.

23 Developmental Outcomes and Educational Service Utilization for Pediatric Brain Tumor Survivors Treated with Proton Radiotherapy Prior to Four Years of Age

Objective:Pediatric brain tumor survivors treated with proton radiation therapy (PRT) prior to 4 years of age are at high risk for poor cognitive and developmental outcomes. This cross-sectional study examined developmental outcomes and educational service utilization at follow-up in a cohort of pediatric survivors treated with PRT before the age of 4 years.Participants and Methods:A total of 46 patients (58.7% female, 93.5% White) were assessed using age-appropriate measures for executive, behavioral, and adaptive functioning. Mean age at PRT was 2.4 years (SD=0.9, range 1.0-3.9 years); mean age at follow-up was 7.0 years (SD=4.8, range 2.0-18.6 years). Mean follow-up interval was 4.57 years (SD=4.52, range 0.9-16.2 years). Diagnoses included ependymoma (n=26, 54.2%), medulloblastoma (n=7, 14.6%), craniopharyngioma (n=4, 8.3%), and a few other tumor types. Infratentorial tumors were most common (69.6%). Treatment included prior surgical resection (93.5%) and chemotherapy (60.9%). Posterior fossa syndrome was present in 10.9% (n=5). PRT field consisted of focal (n=41, 89.1%) or craniospinal irradiation (CSI) (n=5, 10.9%). The impact of demographic, diagnostic, and treatment-related factors was examined, including age at PRT, gender, time interval since PRT, radiation field, and tumor location, on intelligence quotient (IQ), adaptive skills, and executive functioning. Rates of impairment (T-scores &gt;65) were calculated. The utilization of educational services was determined.Results:Mean IQ (SS = 97.6, SD=16.3), as well as mean global executive functioning (Mean T=53.4, SD=11.1) and adaptive skills (Mean SS = 92.5, SD=21.4), as assessed by parent rating scales (BRIEF; SIB), were in the average range. Despite mean scores being within the average range, a large proportion of patients demonstrated difficulties with social withdrawal (28.3%) and activities of daily living (28.3%) (BASC), and global executive dysfunction (17.4%) (BRIEF). Younger age at PRT was associated with lower global adaptive skills at follow-up (r=.39, p=.005), better activities of daily living (r=.53, p&lt;.001), lower social skills (r=.43, p=.002), and more hyperactivity (r=-.37, p=.008), but not aggression, anxiety, depression, somatization, atypical behaviors, withdrawal, or attention problems. Longer follow-up interval was correlated with better activities of daily living (r=.46, p&lt;.001), but more anxiety (r=.39, p=.006). Gender, SES, radiation field, history of hydrocephalus, and location of tumor were not significantly related to primary outcome variables. Posterior fossa syndrome was associated with lower adaptive skills (t=2.90, p=.003) and IQ (t=2.02, p=.026). Of those enrolled in school, 59% received special education services and/or accommodations (IEP n=18, Early Intervention n=6; 504 Plan n=3).Conclusions:Overall, PRT before age 4 years was associated with difficulties with withdrawal, adaptive skills, and executive functioning. Younger age at PRT was associated with lower adaptive functioning, lower social skills, and higher hyperactivity, but not with IQ, attention, mood, or anxiety. While a longer time interval since treatment was associated with improvement in activities of daily living, anxiety was increased, suggesting some late emotional effects. Furthermore, posterior fossa syndrome after surgery was related to lower adaptive skills and IQ. Attention problems were not indicated. Approximately half received school services/accommodations. Young children treated with PRT require proactive support and services to foster their developmental outcomes.

Cerebrovascular Pressure Reactivity Measures: Index Comparison and Clinical Outcome in Patients With Traumatic Brain Injury Treated According to an Intracranial Pressure-Focused Management: Rejection of the Null Hypothesis.

The aim was to investigate whether the pressure reactivity indices PRx, long-PRx (L-PRx), and pressure reactivity (PR) are interchangeable as measures of vascular reactivity, and whether they correlate with clinical outcome when an intracranial pressure (ICP)-targeted treatment regimen is applied in patients with traumatic brain injury (TBI). Patients with TBI (n = 29) that arrived at the hospital within 24 h of injury were included. PRx and L-PRx were derived from Pearson correlations between mean arterial pressure (MAP) and ICP over a short- and long-time interval. PR was the regression coefficient between the hourly mean values of ICP and MAP. Indices were compared to each other, parameters at admission, and outcome assessed by the extended Glasgow Outcome Scale-Extended (GOSE) at 6 and 12 months. PRx and L-PRx had the strongest correlation with each other (R = 0.536, p < 0.01). A correlation was also noted between L-PRx and PR (R = 0.475, p < 0.01), but not between PRx and PR. A correlation was found between age and PRx (R = 0.482, p = 0.01). No association with outcome for any of the indices was found. PRx/L-PRx and L-PRx/PR were moderately correlated with each other. Age was associated with PRx. None of the indices correlated with outcome when our ICP treatment regime was applied. Part of our null hypothesis, that the three indices are associated with outcome, must be rejected. There was, however, an association between some of the indices. To further understand the relation of treatment regimes and pressure reactivity indices, a larger, randomized study is warranted.

Rapid but incomplete degradation of residual visual representations over time.

While visual working memory has a short lifetime, residual representations can persist and disrupt currently maintained information. This phenomenon is known as proactive interference (PI), and the present study investigated whether the representations underpinning item-specific PI lose details over time. This would be expected if the memories underlying PI are susceptible to temporal processes such as decay, which is strongly disputed. In four experiments, a modified version of the recent probes task was used, requiring participants to determine whether a probe matched one of two recently presented targets. The probe sometimes matched an untested target from a previous trial, or varied in its resemblance to it, and the amount of time separating trials varied. Results revealed that PI was specific and highly disruptive at very short intervals, but its effect diminished over time. At longer intervals, a milder form of PI was present and produced by probes that were only similar to a recently encountered target. In summary, residual visual representations may remain accurate for a few seconds after encoding, before losing precise details and continuing to endure in an inexact state. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

44 A Case Study of Non-Alcoholic Wernicke’s Encephalopathy in a Young Man with Intractable Vomiting

Objective:Wernicke’s encephalopathy (WE) is an acute neurological condition caused by thiamine deficiency. The typical presentation is characterized by a triad of oculomotor abnormalities, gait ataxia, and altered mental status, though patients rarely present with all three symptoms. WE is a serious medical condition that is associated with high rates of morbidity and mortality if left untreated. It is most commonly seen in patients with severe alcohol use disorder; however, it has also been found in patients with thiamine deficiency due to other causes of malnutrition such as prolonged starvation, hyperemesis, dialysis, cancer, and geriatric surgery. Despite growing research demonstrating WE in non-alcoholic populations, it is frequently misdiagnosed in patients without an extensive alcohol-use history, particularly when they do not present with the typical clinical triad of symptoms. Thus, more knowledge about non-alcoholic WE is needed to improve diagnostic accuracy.Participants and Methods:We present a case of a 26-year-old male with an unremarkable alcohol use history, who was diagnosed with WE following a 6-week period of excessive nausea and vomiting of unclear etiology. He presented to the ED three times prior to his diagnosis, and was treated with intravenous hydration, Zofran, and Pepcid. He presented to the ED for the fourth time with altered mental status and gait ataxia and was diagnosed with WE based on MRI findings. He was admitted and treated with high doses of IV thiamine and folate. His clinical course was tracked over time via outpatient neurology examinations, and his cognitive functioning was assessed with an outpatient neuropsychological evaluation approximately six months post-discharge. Record review, including clinical notes, lab tests, and imaging results supplement his outpatient neuropsychological evaluation performance.Results:Data from a comprehensive outpatient neuropsychological evaluation approximately six months after WE diagnosis is presented. His cognitive profile was characterized by impaired performance on measures of verbal fluency and memory, including encoding and retention of verbal and visual information (with minimal benefit from cueing). Given these impairments and continued functional declines related to cognitive deficits, he met criteria for a Major Neurocognitive Disorder. These results demonstrate persistent cognitive deficits beyond the acute WE period.Conclusions:WE is a serious neurological condition that can have lasting cognitive effects if left untreated. This case demonstrates persistent cognitive impairments six months after WE diagnosis in a young patient with an unremarkable alcohol history. These findings highlight the necessity of increased diagnostic efficiency of WE in non-alcoholic patients, as immediate thiamine treatment is essential to the recovery process. Neuropsychological functioning at a longer interval will be useful in further elucidating cognitive prognosis as well as providing quality of life recommendations.

Factors Associated with Symptom Persistence in PANS: Part I-Access to Care.

Objective: Pediatric acute-onset neuropsychiatric syndrome (PANS) presents with abrupt neuropsychiatric symptoms, often after an immunologic trigger. A 2017 survey of 698 subjects found diagnostic delays to be associated with recurrences, suggesting that timely care impacts course. This secondary analysis explores the impact of barriers to care on symptom persistence. Methods: A 146-question online survey gathered history, symptomatology, intervention, and outcome data from subjects with PANS. Multivariate analyses examined associations between symptom persistence over the entire reported disease course, measured as % days symptom-free over reporting periods averaging approximately 4 years, and access-to-care history, reflected in availability of medical expertise and affordability of care. The impacts of time from symptom onset to treatment and effectiveness of initial antibiotics were also examined. Results: Among the 646 subjects analyzed, greater symptom persistence was associated with longer intervals between symptom onset and treatment (F = 4.43, p = 0.002). Thirty-four percent of subjects with the least symptom persistence (>75% symptom-free days), versus 13% of those with the most (symptoms every day), had been diagnosed by the first practitioner seen (likelihood ratio [L-R] χ2 = 36.55, p < 0.0001, for comparison across all groups). Diagnosis and treatment had not been impeded by lack of access to expertise for 52% of subjects with the least persistent symptoms, versus 22% of those with the most (L-R χ2 = 22.47, p < 0.0001). Affordability had not impacted diagnosis and treatment for 76% of subjects with the least persistent symptoms, versus 42% of those with the most (L-R χ2 = 27.83, p < 0.0001). The subjects whose PANS symptoms resolved with antibiotic treatment of the inciting infection experienced less symptom persistence than others (χ2 = 23.27, p = 0.0001). More persistently symptomatic subjects were more likely to have discontinued intravenous immunoglobulin (IVIG) treatment for access-to-care reasons. Conclusions: Unimpeded access to care for PANS is associated with more symptom-free days over reporting periods averaging approximately 4 years. Difficulty reaching expert providers, missed opportunities for diagnoses, and financial limitations may worsen outcomes. Practitioners, particularly primary providers, should adhere to published diagnostic and treatment guidelines promptly upon presentation.

Study of the variability and components of the pulsar B0823+26 at a frequency of 111 MHz

ABSTRACT Studies of the pulsar B0823+26 have been carried out using the Large Phased Array (LPA) radio telescope. At a time span of 5.5 yr, the amplitudes of the main pulse (MP), postcursor (PC), and interpulse (IP) were evaluated in daily sessions lasting 3.7 min. It is shown that the ratio of the average amplitudes of MP in the bright (B) and quiet (Q) modes is 60. For B-mode, the average ratio of MP amplitudes to IP amplitudes is 65, and the ratio of MP amplitudes to PC amplitudes is 28. The number of sessions with a nulling is 4 per cent of the total number of sessions. Structure function (SF) and correlation function analysis of MP, IP, and PC amplitude variations of over a long-time interval allowed us to detect typical time scales 37 ± 5 d and one year. The analysis of time variations shows that the time scale of 37 d is well explained by refraction on inhomogeneities of interstellar plasma, which is distributed mostly quasi-uniformly in the line of sight. This scintillation makes the main contribution to the observed variability. Analysis of the structure function showed that there may be a few days variability. This time scale does not have an unambiguous interpretation but is apparently associated with the refraction of radio waves on the interstellar medium. One-year variability time scale has not been previously detected. We associate its appearance with the presence of a scattering layer on a closely located screen at a distance of about 50–100 pc from the Earth.

Early Action Error Processing Is Due to Domain-General Surprise, Whereas Later Processing Is Error Specific.

The ability to adapt behavior after erroneous actions is one of the key aspects of cognitive control. Error commission typically causes people to slow down their subsequent actions [post-error slowing (PES)]. Recent work has challenged the notion that PES reflects adaptive, controlled processing and instead suggests that it is a side effect of the surprising nature of errors. Indeed, human neuroimaging suggests that the brain networks involved in processing errors overlap with those processing error-unrelated surprise, calling into question whether there is a specific system for error processing in the brain at all. In the current study, we used EEG decoding and a novel behavioral paradigm to test whether there are indeed unique, error-specific processes that contribute to PES beyond domain-general surprise. Across two experiments in male and female humans (N = 76), we found that both errors and error-unrelated surprise were followed by slower responses when response-stimulus intervals were short. Furthermore, the early neural processes following error-specific and domain-general surprise showed significant cross-decoding. However, at longer intervals, which provided additional processing time, only errors were still followed by post-trial slowing. Furthermore, this error-specific PES effect was reflected in sustained neural activity that could be decoded from that associated with domain-general surprise, with the strongest contributions found at lateral frontal, occipital, and sensorimotor scalp sites. These findings suggest that errors and surprise initially share common processes, but that after additional processing time, unique, genuinely error-specific processes take over and contribute to behavioral adaptation.SIGNIFICANCE STATEMENT Humans typically slow their actions after errors (PES). Some suggest that PES is a side effect of the unexpected, surprising nature of errors, challenging the notion of a genuine error processing system in the human brain. Here, we used multivariate EEG decoding to identify behavioral and neural processes uniquely related to error processing. Action slowing occurred following both action errors and error-unrelated surprise when time to prepare the next response was short. However, when there was more time to react, only errors were followed by slowing, further reflected in sustained neural activity. This suggests that errors and surprise initially share common processing, but that after additional time, error-specific, adaptive processes take over.

Quantitative assessment of breast volume changes after whole-breast irradiation for breast cancer using breast auto-segmentation.

This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887-1.069) and 0.866 (interquartile range: 0.773-0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = -0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry.

Effect of pre- and postpartum supplementation of a pure glycerol product to dairy cows on feeding behavior, lying behavior, and reticulorumen pH

The objective of this study was to quantify the effects of supplementing a low level of dry glycerol product pre- and postpartum on the feeding behavior, lying behavior, and reticulorumen pH of dairy cows. Multiparous Holstein dairy cows (n = 60) were enrolled in a 2 × 2 factorial design study. Twenty-one days before expected parturition, cows individually received a dry cow diet with (1) 250 g/d glycerol supplementation (GLY; 66% pure glycerol, United States Pharmacopeia grade), or (2) no supplementation (CON). Following parturition, cows were individually assigned to either (1) 250 g/d glycerol product (GLY; 66% pure glycerol), or (2) no supplementation (CON) to their partial mixed ration (PMR) for the first 21 d in milk (DIM). All cows were milked by an automated milking system and offered a target of 5.4 kg/d pellet (23% of target total dry matter intake [DMI]). For both treatment periods, cows were individually assigned to automated feed bins to measure PMR feeding behavior. Rumination time and lying behavior were monitored with electronic sensors for the whole study (-21 to 21 DIM). Reticulorumen pH boluses were administered to a subset of cows (n = 40) where pH was recorded every 10 min from 21 d prepartum to 21 d postpartum. Prepartum, cows fed GLY had fewer, larger meals and spent 20.2% more time feeding than CON while consuming feed at a similar rate. Cows on the CON diet prepartum spent more time lying down in more frequent bouts in the 21 d before calving. Following parturition, cows that received GLY prepartum continued to devote more time to eating, while tending to spend less time ruminating per kilogram of DMI. Cows receiving CON postpartum had larger meals with longer intervals between meals. In the first 21 DIM, cows receiving CON prepartum tended to have shorter, but significantly more frequent, lying bouts than cows fed GLY prepartum. Glycerol supplementation pre- and postpartum resulted in less time spent lying down following parturition. Minimal differences between treatments were observed for pre- and postpartum sorting behavior or reticulorumen pH. Overall, supplementation of glycerol pre- and postpartum altered cow time budgets, with cows spending more time eating pre- and postpartum, less time lying pre- and postpartum, and having fewer, larger meals prepartum when receiving glycerol prepartum, and with cows having slower feeding rates and smaller meals following parturition with postpartum glycerol supplementation.