Variation In Duration Research Articles

Producing Nasal Vowels Without Nasalization? Perceptual Judgments and Acoustic Measurements of Nasal/Oral Vowels Produced by Children With Cochlear Implants and Typically Hearing Peers.

The objective of the present study is to investigate nasal and oral vowel production in French-speaking children with cochlear implants (CIs) and children with typical hearing (TH). Vowel nasality relies primarily on acoustic cues that may be less effectively transmitted by the implant. The study investigates how children with CIs manage to produce these segments in French, a language with contrastive vowel nasalization. The children performed a task in which they repeated sentences containing a consonant-vowel-consonant-vowel-type pseudoword, the vowel being a nasal or oral vowel from French. Thirteen children with CIs and 25 children with TH completed the task. Among the children with CIs, the level of exposure to Cued Speech (CS) was either occasional (CS-) or intense (CS+). The productions were analyzed through perceptual judgments and acoustic measurements. Different acoustic cues related to nasality were collected: segmental durations, formant values, and predicted values of nasalization. Multiple regression analyses were conducted to examine which acoustic features are associated with perceived nasality in perceptual judgments. The perceptual judgments realized on the children's speech productions indicate that children with sustained exposure to CS (CS+) exhibited the best identified and most distinct oral/nasal productions. Acoustic measures revealed different production profiles among the groups: Children in the CS+ group seem to differentiate between nasal and oral vowels by relying on segmental duration cues and variations in oropharyngeal configurations (associated with formant differences) but less through nasal resonance. The study highlights (a) a benefit of sustained CS practice for CI children for the intelligibility of nasal-oral segments, (b) privileged exploitation of temporal (segmental duration) and salient acoustic cues (oropharyngeal configuration) in the CS+ group, and (c) difficulties among children with CI in distinguishing nasal-oral segments through nasal resonance. https://doi.org/10.23641/asha.27744768.

PitRSDNet: Predicting intra‐operative remaining surgery duration in endoscopic pituitary surgery

AbstractAccurate intra‐operative Remaining Surgery Duration (RSD) predictions allow for anaesthetists to more accurately decide when to administer anaesthetic agents and drugs, as well as to notify hospital staff to send in the next patient. Therefore, RSD plays an important role in improved patient care and minimising surgical theatre costs via efficient scheduling. In endoscopic pituitary surgery, it is uniquely challenging due to variable workflow sequences with a selection of optional steps contributing to high variability in surgery duration. This article presents PitRSDNet for predicting RSD during pituitary surgery, a spatio‐temporal neural network model that learns from historical data focusing on workflow sequences. PitRSDNet integrates workflow knowledge into RSD prediction in two forms: (1) multi‐task learning for concurrently predicting step and RSD; and (2) incorporating prior steps as context in temporal learning and inference. PitRSDNet is trained and evaluated on a new endoscopic pituitary surgery dataset with 88 videos to show competitive performance improvements over previous statistical and machine learning methods. The findings also highlight how PitRSDNet improves RSD precision on outlier cases utilising the knowledge of prior steps.

Evolution of Rice Cultivar Performance Across China: A Multi-Dimensional Study on Yield and Agronomic Characteristics over Three Decades

Rice (Oryza sativa L.) is a staple food crop for over half of the world’s population, with China being the largest producer. However, the growth rate of rice yield per hectare has slowed in recent years, emphasizing the need for in-depth studies on the evolution of rice cultivar performance. This study presents a comprehensive analysis of the yield and key agronomic traits of rice cultivars across China over three decades, utilizing data from 11,811 cultivar trials conducted between 1990 and 2023. We assessed the spatial distribution and temporal evolution of rice cultivar performance, exploring regional differences and the interplay between agronomic traits and environmental factors. Our results reveal significant variations in growth duration, plant height, grains per panicle, thousand-grain weight, effective panicle number, and seed setting rate across different regions. Temporal trends showed diverse patterns of improvement, with some regions experiencing rapid advancements (up to 1.42% annual yield increase in Jiangxi Province of Central China) and others nearing yield plateaus (0.16% in Jilin Province and 0.45% in Heilongjiang Province of Northeast China). Correlation analysis between agronomic traits and grain yield highlighted the complex relationships and potential for further genetic gains through targeted breeding. This study underscores the importance of region-specific breeding strategies to optimize rice production in the face of environmental challenges and yield ceilings. The insights gained provide a scientific basis for future rice cultivar development and regional agricultural policies aimed at enhancing sustainability and efficiency in China’s diverse rice-growing regions.

Defining the Cost of Arthroscopic Rotator Cuff Repair

Background: Rotator cuff repair (RCR) is a frequently performed outpatient orthopaedic surgery, with substantial financial implications for health-care systems. Time-driven activity-based costing (TDABC) is a method for nuanced cost analysis and is a valuable tool for strategic health-care decision-making. The aim of this study was to apply the TDABC methodology to RCR procedures to identify specific avenues to optimize cost-efficiency within the health-care system in 2 critical areas: (1) the reduction of variability in the episode duration, and (2) the standardization of suture anchor acquisition costs. Methods: Using a multicenter, retrospective design, this study incorporates data from all patients who underwent an RCR surgical procedure at 1 of 4 academic tertiary health systems across the United States. Data were extracted from Avant-Garde Health’s Care Measurement platform and were analyzed utilizing TDABC methodology. Cost analysis was performed using 2 primary metrics: the opportunity costs arising from a possible reduction in episode duration variability, and the potential monetary savings achievable through the standardization of suture anchor costs. Results: In this study, 921 RCR cases performed at 4 institutions had a mean episode duration cost of $4,094 ± $1,850. There was a significant threefold cost variability between the 10th percentile ($2,282) and the 90th percentile ($6,833) (p < 0.01). The mean episode duration was registered at 7.1 hours. The largest variability in the episode duration was time spent in the post-acute care unit and the ward after the surgical procedure. By reducing the episode duration variability, it was estimated that up to 640 care-hours could be saved annually at a single hospital. Likewise, standardizing suture anchor acquisition costs could generate direct savings totaling $217,440 across the hospitals. Conclusions: This multicenter study offers valuable insights into RCR cost as a function of care pathways and suture anchor cost. It outlines avenues for achieving cost-savings and operational efficiency. These findings can serve as a foundational basis for developing health-economics models. Level of Evidence: Economic and Decision Analysis Level III. See Instructions for Authors for a complete description of levels of evidence.

Anticoagulation with warfarin for paediatric cardiac indications: a retrospective study.

Warfarin is used as anticoagulation for children for a wide range of cardiac indications but carries the disadvantage of requiring international normalised ratio monitoring and dose adjustment. Management of warfarin therapy is challenging due to its narrow therapeutic window and is further complicated in children by dietary changes, frequent illnesses, and developing systems of metabolism and haemostasis.A retrospective review was performed of patients' medical records to assess the indication for warfarin use, percentage of international normalised ratio values in target range (%ITR), and frequency of phlebotomy.Twenty-six patients were identified. The most common indication for warfarin use was in patients post-total cavo-pulmonary connection (n = 19, 73%). We demonstrated a variability in duration of warfarin therapy following total cavo-pulmonary connection (median of 11.1 months). Nineteen (73%) patients had used the CoaguChek machine for home measurement of international normalised ratio. The median frequency of phlebotomy for all indications was once every 10 days, and the median %ITR was 55.4 % (29.7-86.4%). Of note, the percentage under target range in the patients with mechanical mitral (n = 2) and aortic valves (n = 1) was found to be 23% and 33%, respectively.These data demonstrate a high frequency of international normalised ratio values outside of the target range as seen in previous studies of warfarin in children. This necessitates frequent phlebotomy and dose changes, which can have a significant effect on the quality of life of these patients and their families highlighting the need to focus on quality improvement in the area of anticoagulation in paediatric cardiac patients.

Interconnection between adolescents’ and family members’ sleep

Deficient sleep has been linked to a broad range of physical, cognitive and mental health impacts, in particular during adolescence. It is thus essential to understand its underlying mechanisms, including family factors. The goal of our study was to assess through combined subjective and objective assessments, how family members’ daily variations in sleep are interconnected, between parents and siblings of adolescents. A total of 111 participants within 30 families were included, of whom 30 adolescents (14.5 years +/− 2.1 years, 46.7% boys), 30 siblings (12.8 years + /− 3.8, 40% boys), 30 mothers (43.5 years +/− 5.5) and 21 fathers (47.5 years +/− 7.6). Sleep was objectively assessed using parallel actigraphy recordings during a single week for all family members. Adolescents’ daily variation in sleep duration and timing displayed many concordances with their siblings’ and their mothers’ sleep, but not with their fathers’ sleep. Adolescents whose parents did not set limits on sleep time or screen use went to bed over an hour later (p < 0.001) and slept over 30 min less on school nights. Our study demonstrates the important role of family sleep on adolescent sleep, through rule-setting and congruence between each family members sleep, in particular regarding sleep duration and timing.

Gain-of-Function and Loss-of-Function Mutations in the RyR2-Expressing Gene Are Responsible for the CPVT1-Related Arrhythmogenic Activities in the Heart.

Mutations in the ryanodine receptor (RyR2) gene have been linked to arrhythmia and possibly sudden cardiac death (SCD) during acute emotional stress, physical activities, or catecholamine perfusion. The most prevalent disorder is catecholaminergic polymorphic ventricular tachycardia (CPVT1). Four primary mechanisms have been proposed to describe CPVT1 with a RyR2 mutation: (a) gain-of-function, (b) destabilization of binding proteins, (c) store-overload-induced Ca2+ release (SOICR), and (d) loss of function. The goal of this study was to use computational models to understand these four mechanisms and how they might contribute to arrhythmia. To this end, we have developed a local control stochastic model of a ventricular cardiac myocyte and used it to investigate how the Ca2+ dynamics in the mutant RyR2 are responsible for the development of an arrhythmogenic episode under the condition of β-adrenergic (β-AR) stimulation or pauses afterward. Into the model, we have incorporated 20,000 distinct cardiac dyads consisting of stochastically gated L-type Ca2+ channels (LCCs) and ryanodine receptors (RyR2s) and the intervening dyadic cleft to analyze the alterations in Ca2+ dynamics. Recent experimental findings were incorporated into the model parameters to test these proposed mechanisms and their role in triggering arrhythmias. The model could not find any connection between SOICR and the destabilization of binding proteins as the arrhythmic mechanisms in the mutant myocyte. On the other hand, the model was able to observe loss-of-function and gain-of-function mutations resulting in EADs (Early Afterdepolarizations) and variations in action potential amplitudes and durations as the precursors to generate arrhythmia, respectively. These computational studies demonstrate how GOF and LOF mutations can lead to arrhythmia and cast doubt on the feasibility of SOICR as a mechanism of arrhythmia.

Parametric Study of Rainfall-Induced Instability in Fine-Grained Sandy Soil

This study investigates the stability of fine-grained sandy soil slopes under varying rainfall intensities, durations, and geotechnical properties using a parametric analysis within GeoStudio. A total of 4416 unique parameter combinations were analyzed, incorporating variations in unit weight, cohesion, friction angle, slope inclination, slope height, rainfall intensity, and duration. Results reveal that rainfall intensity is the most influential variable on the factor of safety (FS), with higher intensities (e.g., 360 mm/h) on steeper slopes (e.g., 45°) leading to critical FS values below 1, indicating an imminent risk of failure. Under moderate conditions (e.g., 9 mm/h rainfall on slopes of 26.6°), the FS remains above 2. This dataset provides a valuable foundation for training machine learning models to predict slope stability under diverse environmental conditions, contributing to the development of early warning systems for rainfall-induced landslides.

Abstract 4136033: High-Dose Folic acid Supplementation in Acute Myocardial Infarction - A systematic review

Background: Folic acid, a B vitamin, is essential for DNA synthesis and repair, and its role in reducing homocysteine levels has been linked to cardiovascular health. Elevated homocysteine is a risk factor for cardiovascular diseases, including acute myocardial infarction (MI) and coronary artery disease (CAD). Despite evidence suggesting that folic acid supplementation may lower homocysteine levels, its clinical benefits in reducing cardiovascular events remain unclear. Methods: A comprehensive literature search was conducted in PubMed/Medline, Google Scholar, and Cochrane Library databases for studies published from 2000 to 2024 using MeSH terms related to “folic acid,” “B vitamin,” “acute myocardial infarction,” “cardiac arrest,” “heart attack,” and “coronary heart disease.” Only randomized controlled trials (RCTs) and observational studies in English involving adult patients with acute MI or CAD were included. Exclusion criteria were applied to poor-quality studies, irrelevant outcomes, overlapping populations, and non-English texts. Data on study characteristics and patient demographics were extracted, and study quality was assessed using the RoB2 tool. Outcomes were pooled using RevMan 5.3.4 software. Results: Fourteen studies on all-cause mortality showed a risk ratio (RR) of 0.99 [95% CI: 0.94-1.04], indicating no significant difference between folic acid and control groups. Eight studies on cardiovascular mortality yielded a RR of 0.90 [95% CI: 0.82-0.99], suggesting a significant reduction in cardiovascular deaths with folic acid supplementation. Analyses of sudden death, coronary artery bypass graft (CABG) events, revascularization procedures, stroke, and recurrent MI found no significant associations with folic acid supplementation. Conclusions: High-dose folic acid supplementation appears to reduce cardiovascular mortality in post-MI patients but shows no significant impact on other clinical outcomes. This meta-analysis’s limitations include potential publication bias, heterogeneity among included studies, and variability in folic acid dosages and treatment durations. Furthermore, the lack of comprehensive homocysteine level data constrained the analysis. Future large-scale RCTs are needed to fully ascertain the therapeutic potential of folic acid supplementation in secondary prevention of cardiovascular events.

Neighbor Density and Post‐Contact Immobility Duration as Antipredator Behavior: Antlion Larvae Do Not Fit the Selfish Prey Hypothesis

ABSTRACTRemaining immobile for an unpredictable period after being touched by a potential predator (post‐contact immobility, PCI) may favor survival. However, the factors that determine variation in PCI duration are poorly understood. We tested whether PCI duration depends on the surrounding conspecific density (the selfish prey hypothesis) in the tropical antlion larvae Myrmeleon crudelis. These insects avoid predation by being immobile or burying themselves. The selfish prey hypothesis predicts a reduction in the PCI duration as conspecific density increases because this high density of conspecifics around can stimulate the redirection of the predator's interest in other nearby potential prey. In the field, we measured PCI and found that its duration was independent of the conspecific density. In the lab, we also measured the PCI of a subset of the same larvae in the absence of neighbors. Using a paired design, we found that PCI duration was lower in the lab in the absence of neighbors than in the field. Our results suggest that the antlion larvae did not follow the selfish prey hypothesis. We propose two alternative explanations. First, the larvae have a limited ability to detect neighbors in the field and keep up with the changing number of surrounding active pits. Second, burying may be more important than PCI as an antipredator strategy. In our lab experiment, larvae had a more accurate idea of the conspecific density around their pit because they explored the area. We propose that knowing the absence of conspecifics triggered a shorter PCI duration. Under a high predation risk (i.e., no other prey to which the predator would redirect its attention), the larvae select the unequivocal antipredator behavior of burying. This work illustrates the relevance of accurate information in deciding how to avoid predation, especially when prey can prioritize between alternative behaviors, with success varying between the contexts.

Associations Between Sleep Health and Child Behavior at Age 6 Years in the INSIGHT Study.

Suboptimal sleep is associated with disruptive behaviors in childhood. We evaluate associations of mean and variability (SD) of sleep duration, quality, and timing with emotion regulation, impulsivity, and prosocial and antisocial behavior in children. Intervention Nurses Start Infants Growing on Healthy Trajectories, a randomized controlled trial designed for obesity prevention, compared a responsive parenting intervention delivered in the first 2.5 years after birth with a home safety control group. At age 6 years, children wore an actigraphy device for 7 days and participated in behavioral tasks evaluating behavioral control, emotion regulation, and prosocial and antisocial behaviors. Separate linear regression models examined associations between sleep and behavioral variables, adjusting for study group, child sex, and household income. Moderation analysis investigated whether the study group moderated relationships between sleep and positive age-appropriate behavior. Children (N = 143, age 6.7 ± 0.3 years) were predominantly non-Hispanic White (95%). Mean actigraphic sleep duration, quality, and timing were not associated with behavioral variables. By contrast, greater variability in sleep onset timing was associated with greater impulsivity (B = 0.85, p = 0.004) and poorer emotion regulation (B = -0.65, p = 0.01). Greater variability in sleep midpoint timing was associated with greater impulsivity (B = 0.80, p = 0.03). The study group moderated the effect of sleep onset variability on behavior; only the home safety control group exhibited a significant negative relationship between variability in sleep onset timing and emotion regulation (B = -1.28, p = 0.0002). Findings support the importance of consistency in sleep timing and how this may play a greater role in children's behavioral and emotional outcomes than mean actigraphic sleep duration and quality.

Duration of diabetes, glycemic control, and low heart rate variability: The Atherosclerosis Risk in Communities (ARIC) study

Persons with long-standing, poorly controlled diabetes or recent hyperglycemia had the highest burden of cardiac autonomic neuropathy. Cardiac autonomic neuropathy contributed to elevated long-term incidence of cardiovascular disease and mortality even in persons with well-controlled diabetes.

The effect of probiotic, prebiotic, and synbiotic supplements on anthropometric measures and respiratory infections in malnourished children: a systematic review and meta-analysis of randomized controlled trials

BackgroundMalnutrition remains a significant concern in many societies. This study systematically reviewed the effects of probiotics, prebiotics, and synbiotics on anthropometric measures in malnourished children, focusing on changes in weight, height, and respiratory infections (primary outcomes), and head circumference, hemoglobin, hematocrit, and body mass index (BMI) as secondary outcomes.MethodsThis systematic review and meta-analysis involved searching various databases in both Persian and English, including Scopus, Web of Science Core Collection, Cochrane Library, Science Direct, and PubMed up to October 5, 2024. Non-randomized controlled trials (RCTs) were excluded. The Cochrane Handbook Risk of Bias Version 2 tool was used to assess risk of bias, and RevMan 5.3 software was employed for analysis. Subgroup analyses were conducted based on the type of supplement received. Meta-regression was applied to identify factors influencing results, and the GRADE approach was used to evaluate evidence certainty.ResultsTwelve studies with a total of 3,086 children (aged up to 6 years, equally distributed between boys and girls) were included. All children were malnourished without underlying illnesses. Limitations of the study included variations in intervention type, dose, duration, and timing of outcome measurement. Meta-analysis revealed that probiotics, prebiotics, and synbiotics may increase weight (6 trials, mean difference: 0.33 kg, 95% CI: 0.15 to 0.50, low certainty of evidence), while probiotics and synbiotics may increase height compared to control groups (5 trials, mean difference: 0.44 cm, 95% CI: 0.02 to 0.85, low certainty of evidence). However, probiotics and synbiotics did not show a statistically significant effect on lower respiratory tract infections (5 trials, risk ratio: 0.84, 95% CI: 0.68 to 1.04, moderate certainty of evidence). Meta-regression indicated that intervention type, sample size, and follow-up duration were not significant moderators for outcomes related to weight, height, or respiratory infections.ConclusionThe current evidence suggests that probiotics, prebiotics, and synbiotics supplements may help manage malnutrition-related outcomes in malnourished children, but further research with stronger study designs is needed to confirm these findings due to the low certainty of evidence.

Evaluating the Effectiveness of Lifestyle Interventions in Preventing Chronic Diseases: A Systematic Review

This systematic review evaluates the effectiveness of lifestyle interventions, including dietary changes, physical activity, smoking cessation, and alcohol reduction, in preventing chronic diseases such as cardiovascular disease, diabetes, and obesity. Chronic diseases pose a significant burden globally, and lifestyle interventions are increasingly recommended to reduce risk factors. A comprehensive search was conducted in databases like PubMed, Cochrane Library, and Embase, focusing on studies published in the past decade. Included studies assessed adult populations at risk of chronic diseases, using interventions targeting lifestyle modifications with measurable health outcomes. Findings indicate that dietary changes and increased physical activity significantly reduce chronic disease risk, while smoking cessation and alcohol reduction further contribute to improved health outcomes. Combination interventions generally showed the most substantial impact on preventing chronic disease. Although the evidence strongly supports lifestyle changes for disease prevention, variations in intervention type, duration, and adherence remain a limitation. Future research should explore long-term effects and implementation strategies in diverse populations. This review underscores the need for integrating effective lifestyle interventions into healthcare policies to improve public health.

Learning and consolidating the contextualized contour representations of tones from F0 sequences and durational variations via transformers

Many speech characteristics, including conventional acoustic features such as mel frequency cepstrum coefficients and mel-spectrograms, as well as pre-trained contextualized acoustic representations such as wav2vec2.0, are used in a deep neural network or successfully fine-tuned with a connectionist temporal classification for Mandarin tone classification. In this study, the authors propose a transformer-based tone classification architecture, TNet-Full, which uses estimated fundamental frequency (F0) values and aligned boundary information on syllables and words. Key components of the model framework are the contour encoder and rhythm encoder, as well as the cross-attention between contours and rhythms established in the interaction encoder. Using contextual tonal contours as a reference, as well as rhythmic information derived from duration variations to consolidate more on contour representations for tone recognition, TNet-Full achieves absolute performance improvements of 24.4% for read speech (from 71.4% to 95.8%) and 6.3% for conversational speech (from 52.1% to 58.4%) when compared to a naive, simple baseline transformer, TNet-base. The relative improvements are 34.2% and 12.1%. As humans perceive tones, contour abstractions of tones can only be derived from F0 sequences, and tone recognition would be improved if syllable temporal organization was stable and predictable instead of fluctuating as seen in conversations.

Geospatial monitoring and analysis of agricultural drought to identify hotspots and risk assessment for Senegal

Agricultural drought, characterized by insufficient soil moisture crucial for crop growth, poses significant challenges to food security and economic sustainability, particularly in water-scarce regions like Senegal. This study addresses this issue by developing a comprehensive geospatial monitoring system for agricultural drought using the Regional Hydrologic Extremes Assessment System (RHEAS). This system, with a high-resolution of 0.05°, effectively simulates daily soil moisture and generates the Soil Moisture Deficit Index (SMDI)-based agricultural drought monitoring. The SMDI derived from the RHEAS has effectively captured historical droughts in Senegal over the recent 30 years period from 1993 to 2022. The SMDI, also provides a comprehensive understanding of regional variations in drought severity (S), duration (D), and frequency (F), through S-D-F analysis to identify key drought hotspots across Senegal. Findings reveal a distinct north-south gradient in drought conditions, with the northern and central Senegal experiencing more frequent and severe droughts. The study highlights that Senegal experiences frequent short-duration droughts with high severity, resulting in extensive spatial impact. Additionally, increasing trends in drought severity and duration suggest evolving climate change effects. These findings emphasize the urgent need for sustainable interventions to mitigate drought impacts on agricultural productivity. Specifically, the study identifies recurrent and intense drought hotspots affecting yields of staple crops like maize and rice, as well as cash crops like peanuts. The developed high-resolution drought monitoring system for Senegal not only identifies hotspots but can also enables prioritizing sustainable approaches and adaptive strategies, ultimately sustaining agricultural productivity and resilience in Senegal's drought-prone regions.

Research progress on environmental stability of SARS-CoV-2 and influenza viruses.

We reviewed research on SARS-CoV-2 and influenza virus detection on surfaces, their persistence under various conditions, and response to disinfectants. Viral contamination in community and healthcare settings was analyzed, emphasizing survival on surfaces influenced by temperature, pH, and material. Findings showed higher concentrations enhance survivability at room temperature, whereas stability increases at 4°C. Both viruses decline in low pH and high heat, with influenza affected by salinity. On various material surfaces, SARS-CoV-2 and influenza viruses demonstrate considerable variations in survival durations, and SARS-CoV-2 is more stable than influenza virus. On the skin, both virus types can persist for ≥2 h. Next, we delineated the virucidal efficacy of disinfectants against SARS-CoV-2 and influenza viruses. In daily life, exposure to ethanol (70%), isopropanol (70%), bleach (10%), or hydrogen peroxide (1-3%) for 15-30 min can effectively inactive various SARS-CoV-2 variants. Povidone-iodine (1 mg/mL, 1 min) or cetylpyridinium chloride (0.1 mg/mL, 2 min) may be used to inactive different SARS-CoV-2 variants in the mouth. Chlorine disinfectants (500 mg/L) or ultraviolet light (222 nm) can effectively inhibit different SARS-CoV-2 variants in public spaces. In conclusion, our study provides a scientific basis and practical guidance for reduction of viral persistence (retention of infectivity) on surfaces and environmental cleanliness.

Duration of sinus rhythm after direct current cardioversion does not predict recurrence of atrial fibrillation after subsequent catheter ablation: a multicentre study

Abstract Background Catheter ablation (CA) for persistent atrial fibrillation (PsAF) is associated with high rates of AF recurrence. DC cardioversion (DCCV) is often performed before CA, with wide variation in duration of maintenance of sinus rhythm (SR) post-DCCV. Factors associated with short duration of SR after DCCV, such as raised body mass index, prior duration of AF, prolonged p wave duration on the 12-lead ECG, and indexed left atrial volume, are either associated with or indicative of atrial electrical and structural remodelling, suggesting that shorter duration of SR after DCCV reflects a more advanced substrate for AF, which could in turn also influence the likelihood of success after CA. Objective To determine if post-DCCV SR duration is associated with AF recurrence after subsequent CA. Methods We performed a multicentre retrospective study of patients undergoing first-time CA for PsAF between 2015-2018 with prior DCCV. SR duration after the last DCCV prior to CA was recorded. The primary outcome was the first recurrence of atrial arrhythmia post-CA (after a 90-day post-CA blanking period). We also performed a pre-specified sensitivity analysis for amiodarone use at DCCV, by performing repeat analysis after excluding all such patients across the three groups. Results A total of 331 patients were identified across five centres and categorised by post-DCCV SR duration: &amp;lt;7 days (group 1); 7-31 days (group 2); &amp;gt;31 days (group 3; Table 1). Over median post-CA follow-up of 591 days, 207 patients (62.5%) met the primary outcome. There was no significant between-group difference in the time to primary outcome (log rank p=0.82; Figure 1). There were significantly more blanking period arrhythmias in groups 1 and 2 than group 3 after post hoc Bonferroni correction (pairwise p=0.001, 0.002 respectively; Table 1). After exclusion of patients on amiodarone at time of DCCV, there remained no significant between-group difference in the time to primary outcome (log rank p=0.85). Conclusion Shorter duration of SR post-DCCV is associated with blanking period arrhythmia after CA, but crucially does not predict long-term AF recurrence. Early AF recurrence after DCCV should not influence decisions on CA suitability or be used to predict long-term CA success.

Stakeholder perspectives on supplemental milk for infants under six months with growth faltering

Abstract Background Growth faltering is a significant public health issue among infants aged &amp;lt;6 months (m). Supplemental milk is commonly used for infants with growth faltering, with variations in type and duration. We synthesized qualitative evidence on stakeholder perspectives about equity, feasibility, and acceptability of the type and duration of supplemental milk for infants aged &amp;lt;6m with growth faltering. Methods We conducted a comprehensive search of six electronic databases in addition to manual searches to identify all qualitative studies published during January 2000-June 2022. Identified articles were screened in two stages against an inclusion criteria with titles and abstract screened first followed by full-text screening. Included studies were quality appraised using the Critical Appraisal Skills Programme checklist. The primary outcome was equity, feasibility, and acceptability of various supplemental milk for infants &amp;lt;6mwith growth faltering. Results Eighteen studies, reporting perspectives of mothers, fathers, grandmothers and healthcare providers were included. Studies were conducted in North America (9), Africa (5) and Asia (3) and South Australia (1). Donor human milk (DHM) (13) and infant formula(9) were the main supplementary milk reported followed by cow/goat milk (2). Key sub-themes derived were: education/awareness, socio-economic status (SES), race and religion, practicality, availability of resources, sustainability, cost, affective attitude, perceived effectiveness and ethicality. Maternal/caregiver SES was a key sub-theme across all three supplemental milk feeds, acting either as a barrier or facilitator for uptake. Conclusions DHM and infant formula were the most commonly reported supplemental feed for infants aged &amp;lt;6m with growth faltering. Maternal/care giver factors were perceived as key to ensure equity, feasibility, and acceptability with respect to type and duration of supplemental milk for infants aged &amp;lt;6m with growth faltering. Key messages • Stakeholders perceived donor human milk and infant formula as main supplemental milk for infants aged &amp;lt;6 months with growth faltering. • Maternal/care giver factors are key to ensure equity, feasibility, and acceptability of supplemental milk for infants aged &amp;lt;6 months with growth faltering.

Procollagen-lysine 2-oxoglutarate 5-dioxygenases are responsible for 5R-hydroxylysine modification of therapeutic T-cell bispecific monoclonal antibodies produced by Chinese hamster ovary cells.

We present a detailed mass spectrometric analysis of three 2 + 1 T-cell bispecific monoclonal antibodies (TCB mAbs), where an unexpected +15.9950Da mass shift in tryptic peptides was observed. This modification was attributed to the occurrence of 5R-hydroxylysine (Hyl) using a hybrid LC-MS/MS molecular characterization and CRISPR/Cas9 gene deletion approach. The modification was found at various sites within TCB mAbs, with a conspicuous hot spot motif mirroring a prior observation where Hyl was mapped to the CH1-VH Fab domain interface of IgGs. In contrast to the preceding report, our structural modeling analysis on TCB mAbs unveiled substantial differences in the orientation and flexibility of motifs in immediate proximity and across the artificial CH1-VL cross Fab interface and upstream elbow segment. Utilizing a hybrid database search, RNAseq, and a CRISPR/Cas9 knockout methodology in Chinese hamster ovary (CHO) production cell lines, procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) were conclusively identified as the catalyzing enzymes accountable for the 5R-Hyl modification in TCB mAbs. To quantitatively inhibit Hyl formation in TCB mAbs, the activity of all three Chinese hamster PLOD isoenzymes needs to be depleted via CRISPR/Cas9 gene knockout. Moreover, our investigation identified cell culture iron availability, process duration, and clonal variability in CHO cells as elements influencing the levels of Hyl formation in TCB mAbs. This research offers a solution for circumventing Hyl formation in therapeutic complex mAb formats, such as TCB mAbs, produced in CHO cell culture processes, thereby addressing potential technical and biological challenges associated with unintended Hyl modification.