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There is substantial evidence for timing (time perception) abnormalities related to developmental disabilities, particularly autism spectrum disorder. These findings have been reported in humans and nonhuman preclinical models. Our research objective was to extend that work to a genetic knockout (KO) model of fragile X/developmental disability, the FMR1 KO rat. We also sought to test delay discounting in the model and assess potential relations between timing and choice behavior. Consistent with previous human and nonhuman work, we found reduced timing precision in the FMR1 KO rats. We also discovered significantly increased smaller, sooner reward choice in the FMR1 KO rats. Performance on the timing task appeared to be unrelated to performance on the choice task for both model and control rats. These results add to what has become increasingly clear: timing is disrupted in humans diagnosed with developmental disabilities and in nonhuman models designed to model developmental disabilities. Our findings are consistent with those of previous work and the first to our knowledge to show such effects in the FMR1 KO rat. We discuss the potential clinical implications and future directions surrounding potential “timing interventions” for individuals diagnosed with developmental disabilities. [ABSTRACT FROM AUTHOR]

Saccadic eye movements, a critical aspect of real‐world visual behavior, are preceded by an initial accumulation of visual information followed by the selection of a single location to move one's eyes. However, it is currently unclear how each of these stages uniquely affects saccadic timing. In this study, participants searched for a contour integration target while EEG was used to measure posterior cortical activity between search display onset and first saccade initiation. The goal was to determine whether saccade timing could be attributed to differences in early ERP amplitudes, with the P1 reflecting the magnitude of early perceptual information accumulation and the N1 reflecting the strength of selection leading to the saccadic decision. EOG was used to measure saccade timing, and trials were divided into fast, middle, and slow bins. The N1 response was smallest in the slow saccade tertile, relative to both the fast and middle tertiles, suggesting weak selection. In contrast, the P1 response was largest for this same slow saccadic tertile relative to the middle saccadic tertile, suggesting vigorous information accumulation. Therefore, delays in saccadic behavior may occur when the visual system is overwhelmed with visual input, thus increasing the time to reach a saccadic decision. These findings reconcile models of eye movement behavior which often prioritize either the impact of information accrual or selection, rather than regarding both as an integrated whole. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion The optimal timing for implementing mechanical circulatory support (MCS) in cardiogenic shock (CS) remains indeterminate. This study aims to evaluate patient characteristics and outcome associated with the time interval between CS onset and veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) implementation.In this study, patients with CS treated with MCS at 15 tertiary care centres in three countries were enrolled. Patients treated with MCS were stratified into early (<2 h), intermediate (2–12 h) and delayed (≥12–24 h) MCS implantation by using the time interval between CS onset and MCS device implementation. Adjusted logistic and Cox regression models were fitted to assess the association between timing of MCS implementation, patient characteristics and 30‐day mortality. A total of 330 patients with CS treated with VA‐ECMO and/or microaxial flow pump were included in this study; 20.9% received early, 55.8% intermediate, and 23.3% delayed MCS. Although crude 30‐day mortality was slightly lower in patients with early MCS (58.1% vs. 64.7% vs. 64.3%), adjusted analyses showed no significant association between timing of MCS implantation and 30‐day all‐cause mortality (hazard ratio [HR] for early vs. intermediate MCS: 0.93, 95% confidence interval [CI] 0.59–1.46, p = 0.74; HR for early vs. delayed MCS: 1.29, 95% CI 0.78–2.13, p = 0.33). Moreover, the incidence of complications, related and unrelated to MCS, did not differ significantly among groups.In this exploratory study of patients with CS treated with MCS, the timing of device implantation within 24 h after CS onset was not associated with mortality. This supports a restrictive MCS approach, reserving its application for patients experiencing CS deterioration despite conventional therapy. [ABSTRACT FROM AUTHOR]

Augmented reality (AR) games offer significant potential to enhance learning experiences, yet the impact of when these games are introduced during the educational process remains underexplored. This study explored how the timing of providing the AR game influenced learners' achievement, satisfaction and acceptance. Using a quasi‐experimental design, 68 second‐graders engaged with the AR game AR Easy Sign Language: Grams and Kilograms, either before class or in class. Additionally, perspectives from eight students, one teacher and 24 parents (from the before‐class group) were collected. Results indicated that providing the AR game in class significantly improved learners' achievement and acceptance compared to providing it before class. While overall satisfaction was unaffected by timing, students' cognitive focus differed: in‐class participants emphasised the game's educational value, whereas those using it before class viewed it more as an entertaining tool with educational functionality. Both the teacher and parents acknowledged the educational value of AR games but expressed concerns regarding the cost and potential health issues. This study contributes to theoretical understanding and practical implementation strategies for AR games in education, particularly in optimising their timing for maximal impact. Practitioner notes What is already known about this topic AR games integrate the advantages of augmented reality and games, enabling learners to interact with virtual and physical objects in a fun way, bringing a new dynamic to education. Prior research has shown that AR games contribute to the improved learning process and learning outcomes. However, applying technologies such as AR games to authentic educational contexts is still challenging, as it involves many decision‐making issues to be investigated. One key issue that remains unresolved is determining the optimal timing of providing AR games. What this paper adds Providing AR games in class significantly enhanced students' learning achievement and acceptance, emphasising the need to carefully time such interventions. The timing of providing AR games influenced students' cognition, with in‐class use promoting a focus on learning, while before‐class use emphasised entertainment. Teachers and parents acknowledged the educational value of AR games for students, but they had concerns regarding potential visual health risks and the associated costs. Implications for practice and/or policy Educators should determine the timing of providing AR games depending on the desired goal. Providing AR games before class allows students to focus more on the game experience while providing AR games in class allows for a focus on learning through the game and enhancing learning achievement. Students' cognition of technology may influence their usage and outcomes. Developers should design AR games with mechanisms that guide learners' cognition of educational content, while researchers should explore the effectiveness of such designs to achieve better learning outcomes. Educational institutions should select devices with built‐in eye protection features and enforce screen time limits to mitigate visual health risks, addressing concerns raised by teachers and parents. AR games incorporating sign language have the potential to improve students' learning achievement, holding promise for applications in special education. What is already known about this topic AR games integrate the advantages of augmented reality and games, enabling learners to interact with virtual and physical objects in a fun way, bringing a new dynamic to education. Prior research has shown that AR games contribute to the improved learning process and learning outcomes. However, applying technologies such as AR games to authentic educational contexts is still challenging, as it involves many decision‐making issues to be investigated. One key issue that remains unresolved is determining the optimal timing of providing AR games. What this paper adds Providing AR games in class significantly enhanced students' learning achievement and acceptance, emphasising the need to carefully time such interventions. The timing of providing AR games influenced students' cognition, with in‐class use promoting a focus on learning, while before‐class use emphasised entertainment. Teachers and parents acknowledged the educational value of AR games for students, but they had concerns regarding potential visual health risks and the associated costs. Implications for practice and/or policy Educators should determine the timing of providing AR games depending on the desired goal. Providing AR games before class allows students to focus more on the game experience while providing AR games in class allows for a focus on learning through the game and enhancing learning achievement. Students' cognition of technology may influence their usage and outcomes. Developers should design AR games with mechanisms that guide learners' cognition of educational content, while researchers should explore the effectiveness of such designs to achieve better learning outcomes. Educational institutions should select devices with built‐in eye protection features and enforce screen time limits to mitigate visual health risks, addressing concerns raised by teachers and parents. AR games incorporating sign language have the potential to improve students' learning achievement, holding promise for applications in special education. [ABSTRACT FROM AUTHOR]

Background and purpose: The amplitude, timing, and determinants of improvement with available treatments are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). Our primary objective was to quantify categorized outcomes with routine care. Methods: We retrospectively studied treatment response within 36 months from initiation in 112 consecutive subjects with CIDP. Response was classified into a proposed new "CIDP treatment‐response category" (CT‐RC), based on achieved endpoints. Determinants of the CT‐RC, of timing of maximum improvement, and of treatment discontinuation were ascertained. Results: The CT‐RC demonstrated high concurrent validity with current outcome measures. Thirty‐six subjects (32.1%) achieved a "complete response," 37 (33%) a "good partial response," 10 (8.9%) a "moderate partial response," and 15 (13.4%) a "poor partial response." Fourteen subjects (12.5%) were "nonresponsive." The CT‐RC was independently predicted only by age. Mean time to maximum improvement was 12.1 months (range = 1–36) and was not associated with any pretreatment covariate. Treatment discontinuation occurred in 24 of 62 (38.2%) partial responders and was only associated with shorter pretreatment disease duration. Nonresponders were older and received a similar number of treatments compared to responders. Conclusions: CT‐RC classification indicates persistent disability in >60% of treatment responders in CIDP. Timing of maximum improvement is variable, frequently delayed, and unpredictable. Treatment withdrawal without deterioration is achievable in approximately 40% of subjects and may be more likely with prompt treatment. Treatment withdrawal in partial responders and limited escalation in nonresponders suggest implication of physician‐ and patient‐related factors in suboptimal response. More effective treatments/treatment methods and better understanding of other factors influencing response are needed in CIDP. [ABSTRACT FROM AUTHOR]

The timing and order of species arrival have been shown to be a significant factor in the assembly of biotic communities. Therefore, understanding priority effects, which refer to the impact of an early‐arriving species on a later‐arriving one, can help us better predict community assembly processes. However, little is known about the role of phylogenetic distance (PD) in priority effects and how they are mediated by the biogeographic history (BH) and the life stages (LSs) of interacting species.To shed light on the role of PD in priority effects, we conducted a multispecies greenhouse experiment. We created 10 allopatric and 10 sympatric species pairs, representing a PD gradient between early‐ and late‐arriving species from 5 to 270 Myr in evolutionary history and tested the priority effect of early‐arriving species on the late‐arriving species at multiple LSs.We found evidence of stronger competition between closely related species, as late‐arriving plants produced less above‐ground biomass when the PD was low. However, priority effects varied across the development of late‐arriving plants, as there were no effects on seedling emergence and survival, independent of PD. Regardless of PD, the pairs of allopatric and sympatric species did not differ in their responses.Synthesis. While many studies have produced contradictory results regarding the effect of PD on plant–plant interactions, our study provides experimental evidence that priority effects can be stronger when PD is small. This effect was independent of BH but varied across different LSs of late‐arriving plants. The dependence of the effect of PD on the LS of late‐arriving species highlights the importance of the timing of interactions for the assembly of plant communities, which could also have significant implications for the fields of invasion and restoration ecology. [ABSTRACT FROM AUTHOR]

Defining plant development timing through seasonal growth and dormancy phases is a valuable proxy for studying climate change and serves as an annual bioindicator. However, current methods for determining the growing season vary due to species‐specific interpretations and differing understandings of its main drivers. Körner et al. (2023) introduced four non‐interchangeable definitions of growing seasons to clarify this complex issue. While some studies have paired different methods, none have simultaneously applied a full set of methods at the individual tree or species level. Here, I aim to present a new perspective to understanding growing season timing by focusing on all facets of above‐ground tree growth and measurable biological and phenological markers. This approach calls for simultaneous, continuous monitoring during active and dormancy periods on the same trees and across different species at a large spatial scale. The goal is to comprehensively understand each method's errors, temporal lags, and the factors determining each growing season, as defined by Körner et al. (2023, Ecology Letters, 26, 1277). Accurate estimation of growing season timing can reshape our understanding of its environmental drivers, improve terrestrial ecosystem models, assess the impact of climate change on tree growth, determine the biological zero for various species, verify remote sensing indices and forecast species distribution. [ABSTRACT FROM AUTHOR]

Background: We investigated the proper timing, efficacy and safety of tacrolimus for juvenile myasthenia gravis (JMG). Methods: We conducted a retrospective cohort study for JMG patients treated with tacrolimus at Xiangya Hospital, Central South University, Changsha, China from 2010 to 2023. The clinical information of patients with a follow‐up of more than 1 year was collected. Comparisons of clinical features between groups of patients who achieved therapeutic goal and those who did not achieve therapeutic goal as well as between groups of patients treated with tacrolimus within or after 1 year from JMG onset was carried out. Results: Forty‐three patients were enrolled, of whom 28 achieved therapeutic goal. Tacrolimus reduced glucocorticoids (GC) dosages for the 28 cases and 15 cases discontinued GC completely. Generalized myasthenia gravis (GMG) subtype had an association with a group of patients who achieved therapeutic goal (p = 0.001). Median duration from JMG onset to tacrolimus use was 10.50 months for those who achieved therapeutic goal and 36.00 months for those who did not achieve therapeutic goal (p = 0.010). The median Myasthenia Gravis Activities of Daily Living (MG‐ADL) score improved significantly (p = 0.003). The initiation of tacrolimus within 1 year of JMG onset showed an association with achievement of therapeutic goal (p = 0.026). GMG subtype showed an association with a group of patients who received tacrolimus within 1 year (p = <0.001). Tacrolimus side effects were tolerable. Conclusion: The provision of tacrolimus within 1 year of JMG onset is effective and safe. [ABSTRACT FROM AUTHOR]

Invasions are commonly found to benefit from disturbance events. However, the importance of the relative timing of the invasion and disturbance for invader success and impact on community composition remains uncertain. Here, we experimentally test this by invading a five‐species bacterial community on eight separate occasions—four before a disturbance and four after. Invader success and impact on community composition was greatest when the invasion immediately followed the disturbance. However, the subsequent invasions had negligible success or impact. Pre‐disturbance, invader success and impact was greatest when the invader was added just before the disturbance. Importantly, however, the first three pre‐disturbance invasion events had significantly greater success than the last three post‐disturbance invasions. Moreover, these findings were consistent across a range of propagule pressures. Overall, we demonstrate that timing is highly important for both the success and impact on community composition of an invader, with both being lower as time since disturbance progresses. [ABSTRACT FROM AUTHOR]

Summary: Numerous studies have reported the negative impacts of poor sleep on work productivity in the general population. However, despite the known sleep issues that individuals living with neurological conditions experience, no study has explored its impact on their work productivity. Sleep health is a concept that includes multiple domains of sleep, measured with a combination of objective and subjective measures. Therefore, this study aimed to ascertain the associations between sleep health and its domains and work productivity in individuals with neurological conditions. Sleep health domains were determined through actigraphy data collected over 1 week and sleep questionnaires. Work productivity was assessed via the Work Productivity and Activity Impairment Questionnaire. A comparison of sleep health scores between demographic variables was performed using Mann–Whitney U and Kruskal–Wallis tests. Associations between the sleep health domains and work productivity were performed using linear regression models. There were no significant differences in sleep health scores between sex, smoking status, education level, employment status or any work productivity domain. Individuals with non‐optimal sleep timing had greater absenteeism (22.99%) than the optimal group. Individuals with non‐optimal sleep quality had an increase in presenteeism (30.85%), work productivity loss (26.44%) and activity impairment (25.81%) compared to those in the optimal group. The findings from this study highlight that self‐reported sleep quality has the largest impact on work productivity. Improving individuals' sleep quality through triage for potential sleep disorders or improving their sleep hygiene (sleep behaviour and environment) may positively impact work productivity. [ABSTRACT FROM AUTHOR]

The neural circuits of reward processing and interval timing (including the perception and production of temporal intervals) are functionally intertwined, suggesting that it might be possible for momentary reward processing to influence subsequent timing behavior. Previous animal and human studies have mainly focused on the effect of reward on interval perception, whereas its impact on interval production is less clear. In this study, we examined whether feedback, as an example of performance‐contingent reward, biases interval production. We recorded EEG from 20 participants while they engaged in a continuous drumming task with different realistic tempos (1728 trials per participant). Participants received color‐coded feedback after each beat about whether they were correct (on time) or incorrect (early or late). Regression‐based EEG analysis was used to unmix the rapid occurrence of a feedback response called the reward positivity (RewP), which is traditionally observed in more slow‐paced tasks. Using linear mixed modeling, we found that RewP amplitude predicted timing behavior for the upcoming beat. This performance‐biasing effect of the RewP was interpreted as reflecting the impact of fluctuations in reward‐related anterior cingulate cortex activity on timing, and the necessity of continuous paradigms to make such observations was highlighted. This study demonstrated that the reward positivity, an EEG signal associated with reward processing, could be observed in a continuous, naturalistic timing paradigm. By doing so, it provided neural evidence that reward influences subsequent behavioral adjustment, highlighting the interplay between reward processing and interval timing. [ABSTRACT FROM AUTHOR]

Phenological adjustment is the first line of adaptive response of vertebrates when seasonality is disrupted by climate change. The prevailing response is to reproduce earlier in warmer springs, but habitat changes, such as forest degradation, are expected to affect phenological plasticity, for example, due to loss of reliability of environmental cues used by organisms to time reproduction.Relying on a two‐decade, country‐level capture‐based monitoring of common songbirds' reproduction, we investigated how habitat anthropization, here characterized by the rural–urban and forest–farmland gradients, affected the average phenology and plasticity to local temperature in two common species, the great tit Parus major and the blue tit Cyanistes caeruleus.We built a hierarchical model that simultaneously estimated fledging phenology and its response to spring temperatures based on the changes in the proportion of juveniles captured over the breeding season.Both species fledge earlier in warmer sites (blue tit: 2.94 days/°C, great tit: 3.83 days/°C), in warmer springs (blue tit: 2.49 days/°C, great tit: 2.75 days/°C) and in most urbanized habitats (4 days for blue tit and 2 days for great tit). The slope of the reaction norm of fledging phenology to spring temperature varied across sites in both species, but this variation was explained by habitat anthropization only in the deciduous forest specialist, the blue tit. In this species, the responses to spring temperature were shallower in agricultural landscapes and slightly steeper in more urban areas. Habitat anthropization did not explain variation in the slope of the reaction norm in the habitat‐generalist species (great tit), for which mean fledgling phenology and plasticity were correlated (i.e., steeper response in later sites).The effects of habitat change on phenological reaction norms provide another way through which combined environmental degradations may threaten populations' persistence, to an extent depending on species and on the changes in their prey phenology and abundance. [ABSTRACT FROM AUTHOR]

Objectives: Multiple ligament knee injuries (MLKIs) are disruptive injuries, however, there are controversies in the results of acute and delayed reconstruction. Also, clinical outcomes between patients older or younger than 40 have not been compared in MLKIs. This study was designed to investigate the influence of age and timing of reconstruction on the outcomes of single‐stage reconstruction of MLKIs. Methods: The patients who underwent reconstruction of multiple injured ligaments because of MLKIs between May 2013 and July 2019 were added to the cohort. The postoperative complications, knee range of motion (ROM), Lysholm score, International Knee Documentation Committee (IKDC) 2000 score, Tegner activity level, patient satisfaction, and SF‐36 score were compared between young (≤ 40 years old, n = 41) and old patients (n = 61); acute (≤ 3 weeks after injury, n = 75) and delayed reconstruction (n = 27), using Mann–Whitney U test or χ2 test. Results: A total of 102 MLKI patients managed by single‐stage multi‐ligament reconstruction were retrospectively reviewed. Patients were followed up after surgery for a mean of 7.3 years (5.2‐10.7 years). At the last follow‐up, no significant difference was found in knee ROM, functional scores, and patient‐reported outcomes between patients older or younger than 40; acute and delayed reconstruction (p > 0.05). The rate of complications in the delayed reconstruction group was higher than that of the acute reconstruction group (22.2% vs 5.3%, p < 0.05). The IKDC objective scores reached grade A in 63.7%–80.4% of patients, and grade B in 11.8%–23.5% patients. Conclusion: The single‐stage reconstruction of MLKIs can obtain comparative long‐term functional and objective outcomes regardless of patients older or younger than 40; acute and delayed reconstruction, however, delayed reconstruction is related to a high rate of postoperative complications. [ABSTRACT FROM AUTHOR]

Musical instrument training has been linked to improved academic and cognitive abilities in children, but it remains unclear why this occurs. Moreover, access to instrument training is not always feasible, thereby leaving less fortunate children without opportunity to benefit from such training. Although music‐based video games may be more accessible to a broader population, research is lacking regarding their benefits on academic and cognitive performance. To address this gap, we assessed a custom‐designed, digital rhythm training game as a proxy for instrument training to evaluate its ability to engender benefits in math and reading abilities. Furthermore, we tested for changes in core cognitive functions related to math and reading to inform how rhythm training may facilitate improved academic abilities. Classrooms of 8–9 year old children were randomized to receive either 6 weeks of rhythm training (N = 32) or classroom instruction as usual (control; N = 21). Compared to the control group, results showed that rhythm training improved reading, but not math, fluency. Assessments of cognition showed that rhythm training also led to improved rhythmic timing and language‐based executive function (Stroop task), but not sustained attention, inhibitory control, or working memory. Interestingly, only the improvements in rhythmic timing correlated with improvements in reading ability. Together, these results provide novel evidence that a digital platform may serve as a proxy for musical instrument training to facilitate reading fluency in children, and that such reading improvements are related to enhanced rhythmic timing ability and not other cognitive functions associated with reading performance. Research Highlights: Digital rhythm training in the classroom can improve reading fluency in 8–9 year old childrenImprovements in reading fluency were positively correlated with enhanced rhythmic timing abilityAlterations in reading fluency were not predicted by changes in other executive functions that support readingA digital platform may be a convenient and cost‐effective means to provide musical rhythm training, which in turn, can facilitate academic skills [ABSTRACT FROM AUTHOR]

The potential for climate change to disrupt phenology‐mediated interactions in interaction networks has attracted considerable attention in recent decades. Frequently, studies emphasize the fragility of ephemeral seasonal interactions, and the risks posed by phenological asynchrony. Here, we argue that the fitness consequences of asynchrony in phenological interactions may often be more buffered than is typically acknowledged. We identify three main forms that buffering may take: (i) mechanisms that reduce asynchrony between consumer and resource; (ii) mechanisms that reduce the costs of being asynchronous; and (iii) mechanisms that dampen interannual variance in performance across higher organizational units. Using synchrony between the hatching of winter moth caterpillars and the leafing of their host‐plants as a case study, we identify a wide variety of buffers that reduce the detrimental consequences of phenological asynchrony on caterpillar individuals, populations, and meta‐populations. We follow this by drawing on examples across a breadth of taxa, and demonstrate that these buffering mechanisms may be quite general. We conclude by identifying key gaps in our knowledge of the fitness and demographic consequences of buffering, in the context of phenological mismatch. Buffering has the potential to substantially alter our understanding of the biotic impacts of future climate change—a greater recognition of the contribution of these mechanisms may reveal that many trophic interactions are surprisingly resilient, and also serve to shift research emphasis to those systems with fewer buffers and towards identifying the limits of those buffers. [ABSTRACT FROM AUTHOR]

Coalition policymaking concerns not only who decides what in which jurisdiction but also when, how speedy and in what rhythm. Due to the limited time budget and shadow of future elections, parties in charge of respective ministerial portfolios have to strategically organize their policy agendas to trade off between policy and electoral incentives in the face of coalition partners who monitor and control ministerial autonomy. However, despite the burgeoning literature on coalition governance, the temporal dimension of ministerial agenda control is less well understood. I advance this research by proposing a model to directly account for the influence of time budgets on timing decisions of ministers in policy initiation. In this model, I distinguish between different timing strategies of policy initiation a ministerial party may possibly adopt and identify in equilibrium a conditional postponing strategy by which ministers facing high scrutiny of coalition partners will postpone bill initiation till the end of the term. The empirical examination lends support to my argument and further demonstrates that the timing strategy of ministers can also be influenced by coalition conflict and policy saliency of bills. [ABSTRACT FROM AUTHOR]

Pexidartinib is a systemic treatment for patients with tenosynovial giant cell tumor not amenable to surgery. Oral absorption of pexidartinib is affected by food; administration with a high‐fat meal (HFM) or low‐fat meal (LFM) increases absorption by approximately 100% and approximately 60%, respectively, compared with the fasted state. Pexidartinib is currently dosed 250 mg orally twice daily with an LFM (approximately 11‐14 g of total fat). We developed a physiologically based pharmacokinetic model to determine the impact on drug exposure of dose timing with respect to meals, meal type, and caloric content. A 15%‐16% increase in plasma exposure was predicted when consuming an HFM 1 hour after dosing with an LFM, but almost no effect on pharmacokinetics was predicted when an HFM was consumed 3 hours or more before or after pexidartinib dosing with an LFM. Exposure was not significantly affected when pexidartinib was taken with a 500‐kcal LFM over the range of fat (approximately 11‐14 g of total fat; 20%‐25% calories from fat) for an LFM. These findings on timing of pexidartinib dose with respect to meals should be considered by patients and physicians to reduce the potential for side effects. [ABSTRACT FROM AUTHOR]

Background: The optimal timing of thoracic radiotherapy (TRT) in driver‐gene‐negative metastatic non‐small cell lung cancer (mNSCLC) patients was retrospectively investigated based on survival and safety profile. Methods: The efficacy and safety data of driver‐gene‐negative mNSCLC patients treated with TRT during maintenance after first‐line therapy was collected. Patients whose primary tumor and metastatic lesions remained no progression during maintenance and then received TRT were categorized as the NP (no progression) group, while patients who experienced slow progression during maintenance without reaching progressive disease and then received TRT were categorized as the SP (slow progression) group. The efficacy and adverse events of TRT were analyzed. Results: In total, 149 driver‐gene‐negative mNSCLC patients treated with TRT during maintenance were enrolled into the study, with 119 in the NP group and 30 in the SP group. After a median follow‐up of 30.83 (range: 26.62–35.04) months, the median progression‐free survival (PFS) in the NP group was 11.13 versus 9.53 months in the SP group (HR 0.599, p = 0.017). The median overall survival (OS) in the NP group was 32.27 versus 25.57 months in the SP group (HR 0.637, p = 0.088). The median PFS after radiotherapy (rPFS) was 6.33 versus 3.90 months (HR 0.288, p < 0.001). The adverse events were tolerable and manageable in both groups without significant difference (p > 0.05). Conclusion: The addition of TRT during the pre‐emptive no progression phase was associated with a significantly longer PFS than during the delayed slow progression phase and had an acceptable safety profile. Our results might support the earlier initiation of TRT after induction therapy for some patients with driver‐gene‐negative mNSCLC. [ABSTRACT FROM AUTHOR]

The hippocampus has been implicated in temporal learning. Plasticity within the hippocampus requires NMDA receptor‐dependent glutamatergic neurotransmission. We tested the prediction that hippocampal NMDA receptors are required for learning about time by testing mice that lack postembryonal NMDARs in the CA1 and dentate gyrus (DG) hippocampal subfields on three different appetitive temporal learning procedures. The conditional knockout mice (Grin1ΔDCA1) showed normal sensitivity to cue duration, responding at a higher level to a short duration cue than compared to a long duration cue. Knockout mice also showed normal precision and accuracy of response timing in the peak procedure in which reinforcement occurred after 10 s delay within a 30 s cue presentation. Mice were tested on the matching of response rates to reinforcement rates on instrumental conditioning with two levers reinforced on a concurrent variable interval schedule. Pressing on one lever was reinforced at a higher rate than the other lever. Grin1ΔDGCA1 mice showed normal sensitivity to the relative reinforcement rates of the levers. In contrast to the lack of effect of hippocampal NMDAR deletion on measures of temporal sensitivity, Grin1ΔDGCA1 mice showed increased baseline measures of magazine activity and lever pressing. Furthermore, reversal learning was enhanced when the reward contingencies were switched in the lever pressing task, but this was true only for mice trained with a large difference between relative reinforcement rates between the levers. The results failed to demonstrate a role for NMDARs in excitatory CA1 and DG neurons in learning about temporal information. [ABSTRACT FROM AUTHOR]

Several authors have contributed extensively to the neurocognitive understanding of timing. In Autism Spectrum Disorder (ASD) on the contrary, internal timing and its functioning is not well understood. In this study, we have adapted a simple finger‐tapping motor task, with a timing component, as we aim at understanding whether the processing of time is preserved in this population. We have tested a group of people on the autism spectrum without intellectual disabilities and a control sample recruited from the general population, matched for age, sex, schooling and general cognitive abilities on this task with a learning and testing phase. In the testing phase, we have added two exploratory conditions where participants were exposed to intermittent light stimulation of 4 and 8 Hz. Results show that both in the learning and testing phase, besides troubles in the motor component encountered by the people on the spectrum, their timing component performance was also problematic. This reveals to be especially true for time intervals below the 1 s range, as hypothesized, whereas performance in longer intervals is clearly preserved. It was also observed that the exposure to intermittent light stimulation specifically overcomes the difficulties observed in the autistic group, at the timing components at this millisecond time range. The observed timing difficulties in this group seem to be restricted to the system responsible for the processing of time intervals in the milliseconds range, which helps accommodate disparate findings in the literature. [ABSTRACT FROM AUTHOR]

Objective: To assess whether earlier administration of antibiotic prophylaxis after prelabor rupture of membranes (PROM) at term would decrease the incidence of maternal and neonatal infections. Methods: This is a retrospective cohort study comparing women with term PROM who were initiated antibiotic prophylaxis within or after 6 h, and within or after 12 h from PROM to delivery during January 2019 to December 2021. Women with term PROM receiving cephalosporin and without contraindications to vaginal delivery or confirmed or suspected infection were included in the study. The primary outcome was puerperal infection, which refers to the reproductive tract infection occurring within 42 days of delivery. The type of pharmacoeconomic evaluation was selected based on the results of compared effectiveness between the early group and the late group. Propensity‐score matching (PSM) was used to adjust confounding. Subgroup and sensitivity analyses were used to verify the robustness of results. Results: We enrolled 5353 women with term PROM, including 4331 initiated with antibiotic within 6 h, 1022 after 6 h, 5077 within 12 h, and 276 after 12 h. After PSM, no significant difference was observed in the baseline characteristics of the groups. There was no statistical difference between antibiotic use within 6 h and after 6 h, or within 12 h and after 12 h, in puerperal infection (4.6% vs. 4.3%, P = 0.826; 2.9% vs. 4.6%, P = 0.471, respectively), total maternal infection, neonatal sepsis, and total neonatal infection. Cost‐minimization analysis showed there was no significant difference between antibiotic use within 6 h and after 6 h, or within 12 h and after 12 h, in direct medical costs. Conclusion: This study showed that there was no statistical difference in the efficacy and economy of antibiotic prophylaxis used within 6–12 h after rupture of membranes versus after 6–12 h in women with term PROM. Synopsis: Early use of antibiotics after term PROM did not reduce the incidence of maternal and neonatal infections. [ABSTRACT FROM AUTHOR]

Reacting in an unpredictable context increases error monitoring as evidenced by greater error‐related negativity (ERN), an electrophysiological marker linked to an evaluation of response outcomes. We investigated whether ERN also increased when participants evaluated their responses to events that appeared in unpredictable versus predictable moments in time. We complemented electroencephalographic (EEG) analysis of cortical activity by measuring performance monitoring processes at the peripheral level using electromyography (EMG). Specifically, we used EMG data to quantify how temporal unpredictability would affect motor time (MT), the interval between the onset of muscle activity, and the mechanical response. MT increases following errors, indexing online error detection, and an attempt to stop incorrect actions. In our temporally cued version of the stop‐signal task, symbolic cues predicted (temporally predictable condition) or not (temporally unpredictable condition) the onset of a target. In 25% of trials, an auditory signal occurred shortly after the target presentation, informing participants that they should inhibit their response completely. Response times were slower, and fewer inhibitory errors were made during temporally unpredictable than predictable trials, indicating enhanced control of unwanted actions when target onset time was unknown. Importantly, the ERN to inhibitory errors was greater in temporally unpredictable relative to temporally predictable conditions. Similarly, EMG data revealed prolonged MT when reactions to temporally unpredictable targets had not been stopped. Taken together, our results show that a temporally unpredictable environment increases the control of unwanted actions, both at cortical and peripheral levels, suggesting a higher subjective cost of maladaptive responses to temporally uncertain events. Previous research has shown increased error monitoring when behaving in an unpredictable context. In the current study, we demonstrate for the first time that reacting to temporally unpredictable events leads to greater error monitoring as evidenced by EEG (increased error‐related negativity, ERN) and EMG (prolonged motor time, MT). [ABSTRACT FROM AUTHOR]

Trans‐Saharan migrants often spend a large proportion of their annual cycle wintering in the Sahel. Advances in fieldwork and tracking technology have greatly enhanced our ability to study their ecology in these areas. Using GPS‐tracking we aimed to investigate the little known non‐breeding movements of the lesser kestrel Falco naumanni in sub‐Saharan Africa. We segment non‐breeding tracks (n = 79 tracks by 54 individuals) into staging events (131 ± 25 days per non‐breeding cycle), itinerant movements between staging sites (11 ± 10 days), and non‐directed exploratory movements (6 ± 5 days). We then describe timing and directionality of itinerant movements by male and female kestrels throughout the non‐breeding season. Regardless of sex, lesser kestrels spent on average 89% of the non‐breeding season staging at two (range = 1–4) sites in West Africa. At the end of September, kestrels arrived along a broad front throughout the northern Sahel. By December, however, they congregated into two distinct clusters in Senegal and along the Malian–Mauritanian border. The birds stayed for longer periods and showed greater daily activity in the latter areas, compared to their first and intermediate ones. Among 24 individuals tracked along multiple annual cycles, 20 individuals consistently used the Senegalese or Malian–Mauritanian cluster. The remaining four birds either used these clusters in the 2nd or 3rd year of tracking or alternated between them across different years. The eastward and westward itinerant movements of lesser kestrels during the non‐breeding season, coupled with their tendency to cluster geographically towards the end, differ from the southward movements of other insectivorous raptors in West Africa. While 31% of Spanish lesser kestrels converged in Senegal, where roosts of > 20 000 birds are known, 68% moved into the Malian‐Mauritanian border region where more groundwork is needed. [ABSTRACT FROM AUTHOR]

Background: The optimal timing for therapeutic drug monitoring (TDM) of voriconazole in Asians, who have higher rates of poor metabolisers than non‐Asians, is unclear. This can cause unexpectedly high concentrations and delays in reaching steady‐state levels. Objectives: To determine the appropriate timing of TDM in Japanese patients receiving voriconazole. Patients/Methods: Trough levels (Cmin) were measured on days 3–5 (recommended timing, RT) and days 6–14 (delayed timing, DT) after starting voriconazole in patients receiving an appropriate dosage. Considering bioavailability, Cmin was only compared in patients receiving oral voriconazole. Results: A total of 289 and 186 patients were included in the safety and pharmacokinetic analyses, respectively. There was a significant difference in Cmin measured no later than and after day 5 (3.59 ± 2.12 [RT] vs. 4.77 ± 3.88 μg/mL [DT], p =.023), whereas no significant difference was observed on cutoff day 6 (3.91 ± 2.60 vs. 4.40 ± 3.94 μg/mL, p =.465), suggesting that Cmin close to the steady‐state was achieved after day 5. DT causes a delay in achieving the therapeutic range. The hepatotoxicity rates were 21.5% and 36.8% in the RT and DT groups, respectively (p =.004); DT was an independent risk factor for hepatotoxicity. Conclusion: Although steady‐state concentrations may not be achieved by day 5, early dose optimisation using RT can prevent hepatotoxicity in Japanese patients. TDM should be performed on days 3–5 to ensure safety. However, subsequent TDM may be necessary due to a possible further increase in Cmin. [ABSTRACT FROM AUTHOR]

The cognitive preparation of an operation without overt motor execution is referred to as imagery (of any kind). Over the last two decades of progress in brain timing studies, the timing of imagery has received little focus. This study compared the time perception of ten professional violinists' actual and imagery performances to see if such an analysis could offer a different model of timing in musicians' imagery skills. When comparing the timing profiles of the musicians between the two situations (actual and imagery), we found a significant correlation in overestimation of time in the imagery. In our fMRI analysis, we found high activation in the left cerebellum. This finding seems consistent with dedicated models of timing such as the cerebellar timing hypothesis, which assigns a "specialized clock" for tasks. In addition, the present findings might provide empirical data concerning imagery, creativity, and time. Maintaining imagery over time is one of the foundations of creativity, and understanding the underlying temporal neuronal mechanism might help us to apprehend the machinery of creativity per se. [ABSTRACT FROM AUTHOR]

National estimates suggest that more than 35% of American children, ages 2–19 years, are overweight or obese, which increases their risk for weight‐related comorbidities including diabetes, cancer, cardiovascular disease risk factors, depression, and anxiety. While obesity prevention is most cost‐effective, for youth with existing obesity, the United States Preventive Services Task Force recommends ≥26 h of comprehensive lifestyle intervention over 6–12 months. This include standard behavioral therapy, dietary counseling, and an emphasis on physical activity. Although such programs are effective in reducing weight status, there are many barriers to completing these programs. A novel consideration for both the prevention and treatment of childhood obesity is the recognition that the timing of intervention, both duration and time of the year, can impact family engagement and intervention effectiveness. This paper discusses the potential of targeting high‐risk periods for weight gain and offering brief behavioral intervention, in hopes of inspiring research on novel approaches to the prevention and treatment of childhood obesity. [ABSTRACT FROM AUTHOR]

Precise energy management in distribution power system requires high‐precision time synchronization among large‐scale deployed devices. Multiple clock sources‐based time synchronization possesses advantages of reliability, high precision, and robustness, but still faces several challenges such as coupling between time synchronization error and delay, as well as different timescales between clock source and clock weight optimization. In this paper, a multi‐clock source time synchronization model is constructed and a problem is formulated to minimize the synchronization error and delay through jointly optimizing large‐timescale clock source selection and small‐timescale weight selection. A reinforcement learning‐based multi‐timescale multi‐clock source time synchronization algorithm named RL‐M2 is proposed to solve the formulated problem from a learning perspective. Besides, a lossless switching method is proposed to address the switching problem for multiple clock sources. Simulation results demonstrate the superior performance of RL‐M2 and the lossless switching method in time synchronization delay and error. [ABSTRACT FROM AUTHOR]

Summary: Guidance for the timing of surgery following SARS‐CoV‐2 infection needed reassessment given widespread vaccination, less virulent variants, contemporary evidence and a need to increase access to safe surgery. We, therefore, updated previous recommendations to assist policymakers, administrative staff, clinicians and, most importantly, patients. Patients who develop symptoms of SARS‐CoV‐2 infection within 7 weeks of planned surgery, including on the day of surgery, should be screened for SARS‐CoV‐2. Elective surgery should not usually be undertaken within 2 weeks of diagnosis of SARS‐CoV‐2 infection. For patients who have recovered from SARS‐CoV‐2 infection and who are low risk or having low‐risk surgery, most elective surgery can proceed 2 weeks following a SARS‐CoV‐2 positive test. For patients who are not low risk or having anything other than low‐risk surgery between 2 and 7 weeks following infection, an individual risk assessment must be performed. This should consider: patient factors (age; comorbid and functional status); infection factors (severity; ongoing symptoms; vaccination); and surgical factors (clinical priority; risk of disease progression; grade of surgery). This assessment should include the use of an objective and validated risk prediction tool and shared decision‐making, taking into account the patient's own attitude to risk. In most circumstances, surgery should proceed unless risk assessment indicates that the risk of proceeding exceeds the risk of delay. There is currently no evidence to support delaying surgery beyond 7 weeks for patients who have fully recovered from or have had mild SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Small‐cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is prone to spread extensively. Compared to non‐small‐cell lung cancer (NSCLC), SCLC treatment progresses slowly. Although SCLC is highly sensitive to chemotherapy during the initial treatment, most patients still experience resistance and recurrence after receiving chemotherapy. A meta‐analysis demonstrated that thoracic radiotherapy (TRT) improves overall survival in SCLC. The results of the CALGB and CONVERT trials provide evidence for the efficacy of once‐daily high‐dose TRT. TRT at 60 Gy administered twice daily significantly improved survival without increasing toxicity. The long‐standing debate over the optimal timing of radiotherapy has not been fully resolved. SBRT has excellent local control rates and is a safe and effective treatment option for patients with stage I or II SCLC. Prophylactic cranial irradiation (PCI) is used to reduce treatment‐related neurotoxicity to the extent that there has been a recent discussion on whether magnetic resonance imaging (MRI) monitoring can replace PCI. Radiotherapy combined with immunotherapy significantly improves the survival rate of patients with NSCLC; however, its clinical effectiveness has not been systematically explored in patients with SCLC. Therefore, we summarize the evolving therapeutic strategies, (TRT for limited stage‐SCLC and consolidative TRT for extensive stage‐SCLC) and improved radiotherapy techniques (role of SBRT in stage I or II node‐negative SCLC, progress of PCI, and stereotactic radiosurgery), and discuss the possibilities and prospects of radiotherapy combined with immunotherapy for SCLC. [ABSTRACT FROM AUTHOR]

Attention‐deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that often presents with abnormal time perception and increased impulsive choice behavior. The spontaneously hypertensive rat (SHR) is the most widely used preclinical model of the ADHD‐Combined and ADHD‐Hyperactive/Impulsive subtypes of the disorder. However, when testing the spontaneously hypertensive rat from Charles River (SHR/NCrl) on timing and impulsive choice tasks, the appropriate control strain is not clear, and it is possible that one of the possible control strains, the Wistar Kyoto from Charles River (WKY/NCrl), is an appropriate model for ADHD‐Predominately Inattentive. Our goals were to test the SHR/NCrl, WKY/NCrl, and Wistar (WI; the progenitor strain for the SHR/NCrl and WKY/NCrl) strains on time perception and impulsive choice tasks to assess the validity of SHR/NCrl and WKY/NCrl as models of ADHD, and the validity of the WI strain as a control. We also sought to assess impulsive choice behavior in humans diagnosed with the three subtypes of ADHD and compare them with our findings from the preclinical models. We found SHR/NCrl rats timed faster and were more impulsive than WKY/NCrl and WI rats, and human participants diagnosed with ADHD were more impulsive compared to controls, but there were no differences between the three ADHD subtypes. [ABSTRACT FROM AUTHOR]

Aim: Diverting loop ileostomy reversal (DLI‐R) is routinely performed from 2–6 months following ileal pouch‐anal anastomosis (IPAA). The safety of delayed reversal after IPAA is not well‐defined. The aim of this study was to determine if prolonged diversion is associated with adverse outcomes compared to routine closure. Methods: Adult patients undergoing primary IPAA with DLI from 2000 to 2021 were included in this retrospective cohort study from our institutional database. Patients were stratified into tertiles based on timing of reversal: Routine (56–116 days), Delayed (117–180 days), or Prolonged (>6 months). Univariate analysis compared categorical variables between groups. Patients reversed at <8 weeks were excluded. Results: In total, 2615 patients underwent DLI‐R following IPAA (3‐stage 61%, 2‐stage 39%; mean age 39.9 years). DLI‐R was performed as Routine, Delayed and Prolonged in 1908 (72.9%), 426 (16.4%) and 281 (10.8%), respectively. Overall, DLI‐R related complications occurred in 12.4% (n = 324). The complication rate in the Routine group was 11% (n = 210), in the Delayed group was 12.2% (n = 52) and in the Prolonged group was 22.1% (n = 62). Reasons for prolonged diversion in the Prolonged group were complications at the time of IPAA in 207 (73.9%) or patient preference/scheduling in 73 (26.1%). DLI‐R >6 months after IPAA due to complications had higher rates of overall complications following ileostomy reversal (OR 2.6, 95% CI 1.85–3.72, p < 0.001) whereas when DLI‐R was delayed due to preference/scheduling outcomes were not different than the Routine group (p = 0.28). Conclusion: Prolonged time to ileostomy reversal after IPAA is probably safe without increased risk of complications when due to patient preference. [ABSTRACT FROM AUTHOR]

Rhythmicity in the millisecond to second range is a fundamental building block of communication and coordinated movement. But how widespread are rhythmic capacities across species, and how did they evolve under different environmental pressures? Comparative research is necessary to answer these questions but has been hindered by limited crosstalk and comparability among results from different study species.Most acoustics studies do not explicitly focus on characterising or quantifying rhythm, but many are just a few scrapes away from contributing to and advancing the field of comparative rhythm research. Here, we present an eight‐level rhythm reporting framework which details actionable steps researchers can take to report rhythm‐relevant metrics. Levels fall into two categories: metric reporting and data sharing. Metric reporting levels include defining rhythm‐relevant metrics, providing point estimates of temporal interval variability, reporting interval distributions, and conducting rhythm analyses. Data sharing levels are: sharing audio recordings, sharing interval durations, sharing sound element start and end times, and sharing audio recordings with sound element start/end times.Using sounds recorded from a sperm whale as a case study, we demonstrate how each reporting framework level can be implemented on real data. We also highlight existing best practice examples from recent research spanning multiple species. We clearly detail how engagement with our framework can be tailored case‐by‐case based on how much time and effort researchers are willing to contribute. Finally, we illustrate how reporting at any of the suggested levels will help advance comparative rhythm research.This framework will actively facilitate a comparative approach to acoustic rhythms while also promoting cooperation and data sustainability. By quantifying and reporting rhythm metrics more consistently and broadly, new avenues of inquiry and several long‐standing, big picture research questions become more tractable. These lines of research can inform not only about the behavioural ecology of animals but also about the evolution of rhythm‐relevant phenomena and the behavioural neuroscience of rhythm production and perception. Rhythm is clearly an emergent feature of life; adopting our framework, researchers from different fields and with different study species can help understand why. [ABSTRACT FROM AUTHOR]

Objectives: Cranial ultrasound (cUS) screening is recommended for preterm neonates born before 32 weeks' gestational age (GA). The primary aim of this study was to determine if both a day 3 and day 8 cUS screening examination is necessary for all neonates. Methods: A retrospective observational study was performed at a tertiary‐level Australian hospital. Frequencies of cranial ultrasound abnormality (CUA) were compared between routine screening performed at postnatal days 3, 8, and 42. Univariate and multivariate analyses of risk factors for intraventricular hemorrhage (IVH) was performed using logistic regression. Results: cUS examinations on 712 neonates born before 32 weeks' GA were included. Neonates were divided into 2 groups: 99 neonates in the 23–25 weeks 6 days GA (group A) and 613 neonates in the 26–31 weeks 6 days GA (group B). All CUA occurred more frequently in group A neonates and in the subset of group B neonates who had defined risk factors. Low‐risk group B neonates had lower incidence of CUAs demonstrated on day 8 cUS than high‐risk group B neonates, with no significant differences between day 3 and day 8. Logistic regression analysis identified a number of risk factors (vaginal delivery, small for GA, Apgar score <7 at 5 minutes, intubation, patent ductus arteriosus and infection) that were associated with increased frequency of IVH on day 8. In neonates born between 30 and 31 weeks 6 days GA, 35% had a CUA identified. Conclusions: Low‐risk preterm neonates born between 26 and 31 weeks 6 days GA, without complications, could be screened with a single early cUS examination around day 8 without missing substantial abnormality. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes is reaching epidemic proportions. First line therapy approaches are lifestyle interventions including exercise. Although a vast amount of studies reports on beneficial effects of exercise on metabolism in humans per se, overall data are contradictory which makes it difficult to optimize interventions. Innovative exercise strategies and its underlying mechanism are needed to elucidate in order to close this therapeutic gap. The skeletal muscle produces and secretes myokines and microRNAs in response to exercise and both are discussed as mechanisms linking exercise and metabolic adaptation. Aspects of chronophysiology such as diurnal variation in insulin sensitivity or exercise as a signal to reset dysregulated peripheral clocks are of growing interest in the context of impaired metabolism. Deep insight of how exercise timing determines metabolic adaptations is required to optimize exercise interventions. This review aims to summarize the current state of research on the interaction between timing of exercise and metabolism in humans, providing insights into proposed mechanistic concepts focusing on myokines and microRNAs. First evidence points to an impact of timing of exercise on health outcome, although data are inconclusive. Underlying mechanisms remain elusive. It is currently unknown if the timed release of mykokines depends on time of day when exercise is performed. microRNAs have been found as an important mediator of processes associated with exercise adaptation. Further research is needed to evaluate their full relevance. In conclusion, it seems to be too early to provide concrete recommendations on timing of exercise to maximize beneficial effects. [ABSTRACT FROM AUTHOR]

This article develops an explanatory framework of institutional change in intergovernmental relations. Using new institutionalism, we focus on a main explanatory factor—the players' perceptions of their own accountability and that of others. Integrating the concepts of multiple accountability and felt accountability, we develop the concept of an accountability gap, meaning differences between the perceptions of players in the central government about their responsibility to provide local services and the perceptions of players at the local level about their responsibilities. Our claim is that perceptual gaps concerning accountability in a two‐tiered or multi‐tiered system may influence their interests, strategies, and behavior and hence determine the timing and pace of specific institutional changes. We illustrate the theoretical framework by examining how Spain managed the COVID‐19 pandemic. Related Articles: Aguado, N. Alexander. 2018. "Mayor‐Council Form of Government and Policy Responses in Times of Economic Travail." Politics & Policy 46(5): 714–30. https://doi.org/10.1111/polp.12273. French, Edward P., and Doug Goodman. 2011. "Local Government Human Resource Management Past, Present, and Future: Revisiting Hays and Kearney's Anticipated Changes a Decade Later." Politics & Policy 39(5): 761–85. https://doi.org/10.1111/j.1747‐1346.2011.00312.x. Kwon, Sung‐Wook, and Sylvia Gonzalez‐Gorman. 2019. "Influence of Local Political Institutions on Policy Punctuation in Three Policy Areas." Politics & Policy 47(2): 300–25. https://doi.org/10.1111/polp.12295. [ABSTRACT FROM AUTHOR]

With its focus on wetlands, the Ramsar Convention provides the clearest global agreement helping the conservation of migratory waterbirds. Two specific criteria (5 and 6) support the scientific basis for sites to achieve Ramsar recognition based on waterbird counts, while criterion 4, on species and ecological communities, also plays a role. Other international conventions and agreements follow these criteria. We identify several reasons why the listing thus established can only "catch" the absolute minimum wetland network for the conservation of migratory waterbirds. We argue that individual tracking and modern observational tools allow to better delineate the areas needed to effectively give migratory waterbird populations full life cycle protection. The sophisticated techniques to measure population characteristics now available should be used to modernize the guidance for the application of Criteria 4 and 6 of the Ramsar Convention for waterbirds, based on (i) time spent in a site throughout migration; (ii) critical ("untouchable") sites; (iii) robustness of designated site network including buffer areas; (iv) full life cycle information—including early life phases; and (v) refuges used on‐and‐off during migration in emergency situations. In these enhanced ways, migratory waterbirds can enact their roles as effective sentinels of the ecological state of the world. [ABSTRACT FROM AUTHOR]

At present, whole‐brain radiation therapy/stereotactic radiosurgery is one of the main local treatments for brain metastasis of non‐small‐cell lung cancer (NSCLC). Currently, it has been proved that radiotherapy (RT) can regulate the immune response, and small‐sample studies have shown that patients with NSCLC brain metastases (BMs) can benefit from RT combined with immunotherapy (IO). However, the efficacy and safety of the combination treatment have not been deeply elaborated. Notably, as a challenge that is still being explored, the timing of RT combined with IO is likely to be an important factor affecting efficacy and prognosis. This article reviews the current application and challenges of RT combined with IO from the perspectives of molecular mechanism, combination timing, safety, and efficacy. The purpose is to provide information on clinical evidence‐based medicine of combination between RT with IO. For further investigation, we also discuss the major challenges and prospects of RT combined with IO in NSCLC BMs. [ABSTRACT FROM AUTHOR]

Climate change is increasing the intensity, duration, and frequency of extreme climate events (ECEs). These ECEs can have major ecological consequences, e.g., changing nutrient flows, causing extirpation, and altering organismal development. Many ECEs are discrete events that occur at distinctive times during the biological processes they impact. Because of this, ECEs are likely to have differing ecological impacts depending on when they happen, yet we lack on studies that explore how the ecological consequences of ECEs vary with when they occur. Drawing upon evidence from physiological, population, and community ecology, and previous work on ecological disturbances, we suggest that the consequences of ECEs will be sensitive to when they occur. We illustrate the importance of timing by showing how the effects of an ECE could vary depending on when it occurs through the course of (1) organismal ontogeny, (2) population dynamics, and (3) community assembly. An enhanced focus on the timing of extreme weather in climate change research will reveal how and when ECEs are altering ecosystems, possible mechanisms behind these impacts, and what ecosystems or species are most vulnerable to ECEs, helping us to make more informed predictions about the ecological consequences of climate change. [ABSTRACT FROM AUTHOR]

Introduction: In the Netherlands, the sentinel lymph node procedure protocol consists of preoperative lymphoscintigraphy combined with intraoperative blue dye for identifying sentinel lymph nodes in early vulvar squamous cell carcinoma. This study aimed at investigating the role of early and late lymphoscintigraphy. Material and methods: From January 2015 to January 2019, early and late lymphoscintigraphies of 52 women were retrospectively analyzed. Lymphoscintigraphy was performed 30 minutes (early) and 2.5–4 hours (late) after vulvar injection of 99mTc‐labeled nanocolloid. We calculated the concordance correlation coefficient (CCC) between number of sentinel lymph nodes detected on both images using the Lins concordance coefficient and correlated with clinicopathological data. Results: Thirty‐four women had a midline tumor and 18 had a lateral tumor. Detection rates with early and late scintigraphy were 88.5% and 98.1%, respectively. Median number of detected nodes was 1.0 (0–7) and 2.0 (0–7). Good statistical correlation between number of sentinel lymph nodes detected on early and late imaging was found (CCC = 0.76) in most patients. In 18 women (35%) a mismatch occurred: a higher number of nodes was detected on late imaging. In 11 of 18 women re‐injection was performed because no sentinel lymph nodes were visualized on early images. Late imaging and intraoperative detection showed a good statistical correlation (CCC = 0.61). One woman showed an isolated groin recurrence despite negative sentinel lymph nodes. Conclusions: This study showed good statistical correlations between early and late scintigraphy in most patients. However, in 35% of women late scintigraphy detected more nodes. In case of poor visualization after the first scintigraphy, re‐injection should be considered. Late scintigraphy is probably helpful in confirming successful re‐injection and in showing deviating lymph flow in women with failed mapping after the first injection and successful re‐injection. Because missing metastatic sentinel lymph nodes often leads to a poor prognosis, we prefer optimal correlations between imaging and intraoperative identification. Hence, late scintigraphy cannot be safely omitted. [ABSTRACT FROM AUTHOR]

Background: Appropriate implantable cardioverter‐defibrillator (ICD) shocks are associated with an increased risk of mortality and heart failure (HF) events. The first appropriate shock may occur late after implantation. However, whether the timing of the first appropriate shock influences prognosis is unknown. This study aimed to evaluate the clinical significance of the timing of the first appropriate shock in patients with ICD. Methods: This retrospective and observational study enrolled 565 consecutive ICD patients. Patients who received an appropriate shock were divided into the early group (first appropriate shock <1 year after ICD implantation) and late group (first appropriate shock ≥1 year after ICD implantation). All‐cause mortality was compared between the two groups. Results: Over a median follow‐up of 5.6 years, 112 (19.8%) patients received an appropriate shock, including 32 patients (28.6%) in the early group and 80 patients (71.4%) in the late group. Comparisons of baseline characteristics at ICD implantation revealed that the late group was more likely to receive cardiac resynchronization therapy (66.3% vs. 31.3%, p < 0.001), ICD for primary prevention (60.0% vs. 31.3%, p = 0.001), and angiotensin‐converting enzyme inhibitor or angiotensin‐receptor blocker treatment (88.8% vs. 71.9%, p = 0.028). Survival after shock was significantly worse in the late group than in the early group (p = 0.027). In multivariable Cox proportional hazards analysis, the late group had an increased risk of all‐cause mortality compared with the early group (HR: 2.22; 95% CI 1.01–4.53; p = 0.029). In both groups, the most common cause of death was HF. Conclusions: Late occurrence of the first appropriate ICD shock was associated with a worse prognosis compared with early occurrence of the first appropriate shock. Cardiac death was the most common cause of death in patients who experienced late occurrence of the first appropriate ICD shock, resulting from HF in most cases. [ABSTRACT FROM AUTHOR]

Firms tend to seek optimal distinctiveness when choosing CSR engagement timing. Building on the perspectives of optimal distinctiveness and competitive dynamics, this paper explains why firms' CSR engagement timing toward a certain event is affected by dynamic competitive effects. That is, to achieve optimal distinctiveness, focal firms pay more attention to their main competitors that are similar in market, size and resources. We apply a discrete‐time survival analysis of 869 Chinese listed firms' CSR engagement action toward the COVID‐19 pandemic during the first half of 2020. The results support the mechanism that when a highly similar competitor engages in CSR activities, it raises the probability that the focal firm engages itself beyond levels based solely on its own characteristics and common time‐dependent factors. [ABSTRACT FROM AUTHOR]

Spatial and temporal shifts in the migratory patterns of birds have become more frequent as climate change and habitat alteration continue to impact ecosystems and the species dependent on them. In this study, we used eBird community science data collected over ten years to examine potential changes in the migratory patterns of three North American bluebird species: eastern (Sialia sialis), western (Sialia mexicana), and mountain (Sialia currucoides) bluebirds. Community science datasets such as those provided through eBird are a valuable tool for examining population‐level processes, as such data are often costly and time‐consuming to collect through other approaches (e.g., directly tracking individuals). Using generalized additive models, we produced smoothed migration paths for all three species over each season from 2009 to 2018. We asked whether there were changes over this 10‐year period in the timing of spring and fall migration and migration speed, and the population centroids during breeding and migration. In contrast to many species that are experiencing poleward shifts in their distributions, the population centroids during the breeding period of all three bluebird species appear to have shifted southward over the past decade. Perhaps most surprisingly, we also detected strong longitudinal shifts in the population centroids during migration in eastern and western bluebirds, with both species shifting toward the center of the continent. Despite these changes in migratory routes and breeding distributions, we detected no change in the migratory timing or speed of any of the species. Our analysis indicates that bluebirds are rapidly altering the pattern of their migration, likely in response to changing environmental conditions, but not always in the direction predicted. [ABSTRACT FROM AUTHOR]

Background: Mechanical circulatory support (MCS) has been widely utilized in critically ill cardiac transplant candidates. Few studies have investigated the impact of duration of MCS before heart transplantation (HTx) on long‐term patient survival. Methods: A retrospective HTx database was reviewed between 2009 and 2019. Patients who did not or did undergo MCS before HTx were categorized into two groups: (1) A (did not) and (2) B (did), respectively. A receiver operating characteristic (ROC) curve was plotted to assess the cutoff level of MCS duration before HTx in evaluating 5‐year survival. Result: A total of 270 HTx patients (group A: 120, group B: 150) were analyzed. Group B patients had a higher percentage of blood type O, a higher incidence of resuscitation, a shorter listing duration, and a higher likelihood of having United Network for Organ Sharing (UNOS) 1A status than group A. The ROC curve revealed 24 days as a good cut‐off level for determining the best MCS before HTx timing. Group B was categorized into two subgroups: (1) B1 (MCS < 24 days, n = 65) and (2) B2 (MCS > 24 days, n = 85). B2 had a higher incidence of cardiopulmonary resuscitation (CPR), hemodialysis, longer waiting time after MCS, and better ventricular assist device implantation than B1. However, the survival curves showed that B1 outcomes were significantly worse than in groups A and B2. Groups A and B2 had similar survival curves without an increased incidence of infection. Conclusion: The preliminary data demonstrated that a longer duration of MCS may be associated with better outcomes than urgent HTx. [ABSTRACT FROM AUTHOR]

Introduction: The impact of timing of hemodialysis (HD) for end‐stage renal disease (ESRD) patients treated with twice‐weekly HD remains unclear. We aimed to determine the effects of late initiation of HD on short‐term mortality and hospitalization. Methods: A multicenter cohort study was conducted in 11 HD centers in Northeastern Thailand (HEmodialysis Network of the NorthEastern Thailand study group). We recruited adult ESRD patients who were treated with twice‐weekly HD for more than 3 months and had data on eGFR at HD initiation. Clinical and laboratory values at the time of recruitment were recorded. Late and early (eGFR at start <5 and >5 ml/min/1.73 m2) initiations were defined. Outcomes were disease‐related death (excluding any accidental deaths) and first hospitalization. Data analysis was performed by multivariable cox‐regression analysis. Findings: A total of 407 patients who had data on eGFR at HD initiation (303 in late group and 104 in early group) were included for analysis. There were 56.8% male with a mean age of 55 years. During the 15.1 months of follow‐up, there were 27 (6.6%) disease‐related deaths. The 1‐year survival rate was similar among late and early initiation groups. The incidence density of first hospitalization in the late group was significantly lower than those in the early group (HR adjusted, 0.63; 95% CI, 0.40–0.99, p = 0.047). Among 303 patients who were in the late start group, patients with diabetes had a higher mortality rate (HR, 3.49; 95% CI, 1.40–8.70, p = 0.007) when compared to non‐diabetic patients. Discussion: Early initiation of HD at eGFR >5 ml/min/1.73 m2 had no short‐term survival benefit compared to the late group in ESRD patients treated with twice‐weekly HD for at least 3 months in a resource‐limited setting. A survival benefit from an early start of HD was found among diabetic patients. [ABSTRACT FROM AUTHOR]

Animal migration is one of the most spectacular and visible behavioural phenomena in nature with profound implications for a range of ecological and evolutionary processes. Successful migration hinges on the ability to exploit temporary resources (e.g. food) and evade threats (e.g. predators) as they arise, and thus the timing of migration is often regarded as a dominant predictor of individual migratory success.However, with the exception of intensively studied taxa (mainly birds), relatively few studies have investigated inter‐individual annual and seasonal variation in migratory timing and performance, or tested predictions on how migration across high and low predation‐risk habitats may exert selection on migratory timing. In particular, studies that assess the survival consequences of variation in migratory timing remain rare, which is most likely due to the logistical challenges associated with monitoring survival success and population‐level characteristics simultaneously.Here, we address the above‐mentioned questions using roach Rutilus rutilus, a fish that migrates from lakes characterised by high predation risk into low‐risk streams during winter. Specifically, we used individual‐based tracking of roach in two European lake systems over multiple migration periods (9 and 7 years respectively), to obtain highly detailed (year‐round scheduling, repeat journeys and the fate of individuals) data on the variability/synchrony of migratory timing in spring and autumn respectively.We report seasonal differences in the variability of migratory timing, with lower variance and higher migration synchrony in spring lake arrival timing as compared to autumn lake departure timing. Furthermore, the timing of autumn migration is more variable across years than the timing of spring migration. Second, we find that later arrival to the lake habitat is positively associated with apparent survival from 1 year to the next, whereas we found no effect of lake departure timing on survival probability.These findings represent rare evidence showing how intraspecific variation in timing in migratory fish differs across years and seasons, and how variation in timing can translate into survival consequences for prey in systems characterised by high predation risk. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to identify at what time patients with cancer and their relatives want to be informed about and receive psychosocial counselling. Methods: In a multi‐centre prospective study, both users and non‐users of psychosocial cancer counselling were asked to participate in a qualitative interview about their preferences for psychosocial counselling. A second interview was scheduled 3–6 months thereafter. Interviews were transcribed verbatim and coded according to content analysis. Results: Altogether, 61 patients and 42 relatives participated, resulting in 183 interviews (103 at t1, 80 at t2). Most often, the optimal time‐point for cancer counselling was defined by the participants according to the treatment trajectory, and the most frequently mentioned preferred time‐point was 'as early as possible': at the time of cancer diagnosis (mentioned in 22% of interviews with men and 10% of interviews with women). In particular, men also said that they wanted psychosocial counselling while waiting for test results (5%), at the point of returning to work and/or when under the threat of unemployment (3%). Women especially preferred this support during therapy (4%) and 'when one has the capacity for it' (4%), in terms of time and emotional capacity. Conclusions: Healthcare providers should inform their cancer patients and the relatives about the possibilities of professional psychosocial support early on in the disease trajectory (i.e. at the time of diagnosis) and repeatedly thereafter, especially in times of uncertainty, while ensuring the patients' capacity to process information at each time‐point is taken into consideration. [ABSTRACT FROM AUTHOR]

Lack of adequate effector T cells infiltrated in tumor is one of the main problems in the failure of immune checkpoint blockade therapy (ICBT). Photodynamic therapy (PDT) induced acute inflammation can sensitize tumors and activate T cells, thus assisting immune checkpoint inhibitors (ICI) against tumor growth and metastasis. T cells maturation and activation lag 3 to 7 days behind PDT. However, such timing in the combination therapy of ICI and PDT is commonly ignored in designing numerous multi‐functional integrated nanomedicines. Herein, the authors illustrate that intervention timing of ICI after PDT affects the anti‐tumor efficacy. A tumor‐targeting nanomedicine is prepared by encapsulating indocyanine green into CD44 specifically binding material, a hyaluronic acid conjugated lipid poly(ethylene glycol). The PDT nanomedicine is designed to induce a robust immune response in tumor. The optimal group (Combo‐STAR), ICI gave 5 days after PDT, significantly suppresses local tumor growth and eliminates metastasis. What should be highlighted is the time point of administration because if ICI is given too early, T cells are immature, otherwise, T cells are exhausted if ICI is given too late. This work presents theoretical guidance for raising awareness of intervention timing when augmenting ICBT with immune response inducers in clinic. [ABSTRACT FROM AUTHOR]

Although there is mounting evidence indicating that the relative timing of predator and prey phenologies determines the outcome of trophic interactions, we still lack a comprehensive understanding of how the environmental context (e.g., abiotic conditions) influences this relationship. Environmental conditions not only frequently drive shifts in phenologies, but they can also affect the very same processes that mediate the effects of phenological shifts on species interactions. Therefore, identifying how environmental conditions shape the effects of phenological shifts is key to predicting community dynamics across a heterogeneous landscape and how they will change with ongoing climate change in the future. Here I tested how environmental conditions shape the effects of phenological shifts by experimentally manipulating temperature, nutrient availability, and relative phenologies in two predator–prey freshwater systems (mole salamander–bronze frog vs. dragonfly larvae–leopard frog). This allowed me to (1) isolate the effects of phenological shifts and different environmental conditions; (2) determine how they interact; and (3) evaluate how consistent these patterns are across different species and environments. I found that delaying prey arrival dramatically increased predation rates, but these effects were contingent on environmental conditions and the predator system. Although nutrient addition and warming both significantly enhanced the effect of arrival time, their effect was qualitatively different across systems: Nutrient addition enhanced the positive effect of early arrival in the dragonfly–leopard frog system, whereas warming enhanced the negative effect of arriving late in the salamander–bronze frog system. Predator responses varied qualitatively across predator–prey systems. Only in the system with a strong gape limitation were predators (salamanders) significantly affected by prey arrival time and this effect varied with environmental context. Correlations between predator and prey demographic rates suggest that this was driven by shifts in initial predator–prey size ratios and a positive feedback between size‐specific predation rates and predator growth rates. These results highlight the importance of accounting for temporal and spatial correlations of local environmental conditions and gape limitation when predicting the effects of phenological shifts and climate change on predator–prey systems. [ABSTRACT FROM AUTHOR]

Changes in phenology and distribution are being widely reported for many migratory species in response to shifting environmental conditions. Understanding these changes and the situations in which they occur can be aided by understanding consistent individual differences in phenology and distribution and the situations in which consistency varies in strength or detectability.Studies tracking the same individuals over consecutive years are increasingly reporting migratory timings to be a repeatable trait, suggesting that flexible individual responses to environmental conditions may contribute little to population‐level changes in phenology and distribution. However, how this varies across species and sexes, across the annual cycle and in relation to study (tracking method, study design) and/or ecosystem characteristics is not yet clear.Here, we take advantage of the growing number of publications in movement ecology to perform a phylogenetic multilevel meta‐analysis of repeatability estimates for avian migratory timings to investigate these questions. Of 2,433 reviewed studies, 54 contained suitable information for meta‐analysis, resulting in 177 effect sizes from 47 species.Individual repeatability of avian migratory timings averaged 0.414 (95% confidence interval: 0.3–0.5) across landbirds, waterbirds and seabirds, suggesting consistent individual differences in migratory timings is a common feature of migratory systems. Timing of departure from the non‐breeding grounds was more repeatable than timings of arrival at or departure from breeding grounds, suggesting that conditions encountered on migratory journeys and outcome of breeding attempts can influence individual variation.Population‐level shifts in phenology could arise through individual timings changing with environmental conditions and/or through shifts in the numbers of individuals with different timings. Our findings suggest that, in addition to identifying the conditions associated with individual variation in phenology, exploring the causes of between‐individual variation will be key in predicting future rates and directions of changes in migratory timings. We therefore encourage researchers to report the within‐ and between‐ individual variance components underpinning the reported repeatability estimates to aid interpretation of migration behaviour. In addition, the lack of studies in the tropics means that levels of repeatability in less strongly seasonal environments are not yet clear. [ABSTRACT FROM AUTHOR]

Neural oscillations in the alpha band (8–12 Hz) have been proposed as a key mechanism for the temporal resolution of visual perception. Higher alpha frequencies have been related to improved segregation of visual events over time, whereas lower alpha frequencies have been related to improved temporal integration. Similarly, also the phase of ongoing alpha has been shown to correlate with temporal integration/segregation. To test a causal relationship between alpha oscillations and perception, we here employed multi‐channel transcranial alternating current stimulation (mc‐tACS) over the right parietal cortex, whereas participants performed a visual temporal integration/segregation task that used identical stimuli with different instructions. Before and after mc‐tACS we recorded the resting‐state electroencephalogram (EEG) to extract the individual alpha frequency (IAF) and delivered electrical stimulation at slightly slower and faster frequencies (IAF±2 Hz). We hypothesized that this would not only drive endogenous alpha rhythms, but also affect temporal integration and segregation in an opposite way. However, the mc‐tACS protocol used here did not consistently increase or decrease the IAF after the stimulation and did not affect temporal integration/segregation accuracy as expected. Although we found some preliminary evidence for an influence of tACS phase on temporal integration accuracy, the ongoing phase of mc‐tACS oscillations did not reliably modulate temporal integration/segregation accuracy in a sinusoidal way as would have been predicted by an effective entrainment of brain oscillations. These findings may guide future studies using different stimulation montages for investigating the role of cortical alpha oscillations for human vision. [ABSTRACT FROM AUTHOR]