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Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.

Background: Gender clinic and single‐item questionnaire‐based data report increased co‐occurrence of gender diversity and neurodevelopmental conditions. The nuances of these associations are under‐studied. We used a transdiagnostic approach, combining categorical and dimensional characterization of neurodiversity, to further the understanding of its associations with gender diversity in identity and expression in children. Methods: Data from 291 children (Autism N = 104, ADHD N = 104, Autism + ADHD N = 17, neurotypical N = 66) aged 4–12 years enrolled in the Province of Ontario Neurodevelopmental Network were analyzed. Gender diversity was measured multi‐dimensionally using a well‐validated parent‐report instrument, the Gender Identity Questionnaire for Children (GIQC). We used gamma regression models to determine the significant correlates of gender diversity among age, puberty, sex‐assigned‐at‐birth, categorical neurodevelopmental diagnoses, and dimensional neurodivergent traits (using the Social Communication Questionnaire and the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scales). Internalizing and externalizing problems were included as covariates. Results: Neither a categorical diagnosis of autism nor ADHD significantly correlated with current GIQC‐derived scores. Instead, higher early‐childhood dimensional autistic social‐communication traits correlated with higher current overall gender incongruence (as defined by GIQC‐14 score). This correlation was potentially moderated by sex‐assigned‐at‐birth: greater early‐childhood autistic social‐communication traits were associated with higher current overall gender incongruence in assigned‐males‐at‐birth, but not assigned‐females‐at‐birth. For fine‐grained gender diversity domains, greater autistic restricted‐repetitive behavior traits were associated with greater diversity in gender identity across sexes‐assigned‐at‐birth; greater autistic social‐communication traits were associated with lower stereotypical male expression across sexes‐assigned‐at‐birth. Conclusions: Dimensional autistic traits, rather than ADHD traits or categorical neurodevelopmental diagnoses, were associated with gender diversity domains across neurodivergent and neurotypical children. The association between early‐childhood autistic social‐communication traits and overall current gender diversity was most evident in assigned‐males‐at‐birth. Nuanced interrelationships between neurodivergence and gender diversity should be better understood to clarify developmental links and to offer tailored support for neurodivergent and gender‐diverse populations. [ABSTRACT FROM AUTHOR]

Current accounts of the production effect suggest that production leads to the encoding of additional production-associated features and/or better feature encoding. Thus, if it is the act of production that leads to the storage and/or enhanced encoding of these features, then less of this act should reduce the resulting production effect. In two experiments, we provide a direct test of this idea by manipulating how much of a given item is produced within a single mode of production (typing). Results demonstrate that such partial production can yield a significant production effect that is smaller than the effect that emerges from producing the entire item. These results suggest that how much of an item is produced can moderate the size of the production effect and are considered in the context of recent modelling efforts., (© 2023. The Psychonomic Society, Inc.)

Objective: The Cox-Maze IV procedure (CMP-IV) is the most effective treatment for atrial fibrillation. Increased left atrial (LA) size has been identified as a risk factor for failure to restore sinus rhythm. This has biased many surgeons against ablation in patients with giant left atrium (GLA), defined as LA diameter >6.5 cm. In this study we aimed to define the efficacy of the CMP-IV in patients with GLA., Methods: From April 2004 through March 2020, 786 patients with a documented LA diameter underwent elective CMP-IV, 72 of whom had GLA. Median follow-up duration was 4 years (interquartile range, 1-7 years). Recurrence was defined as any documented atrial tachyarrhythmia (ATA) lasting 30 seconds. ATA recurrence and survival were analyzed across GLA versus non-GLA groups., Results: Median age at surgery was 65 (interquartile range, 56-73) years. Median LA diameter within the GLA group was 7.0 (range, 6.6-10.0) cm. There were no differences in rates of postoperative complications for the 2 groups, including rate of postoperative stroke and pacemaker placement (GLA 14%; non-GLA 12%; P = .682). A trend toward increased 30-day mortality in the GLA group did not reach statistical significance (GLA 6%; non-GLA 2%; P = .051). Freedom from ATAs at 5 years postoperatively was comparable for the 2 groups (GLA 82%; non-GLA 84%)., Conclusions: The CMP-IV had good efficacy in patients with GLA. Our results suggest that LA diameter >6.5 cm should not preclude a patient from undergoing surgical ablation for atrial fibrillation., (Copyright © 2022. Published by Elsevier Inc.)

The production effect is the finding that, relative to silent reading, producing information at study (e.g., reading aloud) leads to a benefit in memory. In most studies of this effect, individuals are presented with a set of unique items, and they produce a subset of these items (e.g., they are presented with the to-be-remembered target item TABLE and produce table ) such that the production is both unique and representative of the target. Across two preregistered experiments, we examined the influence of a production that is unique but that does not match the target (e.g., producing fence to the target TABLE, producing car to the target TREE, and so on). This kind of production also yielded a significant effect-the mismatching production effect-although it was smaller than the standard production effect (i.e., when productions are both unique and representative of their targets) and was detectable only when targets with standard productions were included in the same study phase (i.e., when the type of production was manipulated within participant). We suggest that target-production matching is an important precursor to the production effect and that the kind of production that brings about a benefit depends on the other productions that are present.

Objective: To develop a minimally invasive, reproducible model of chronic severe mitral regurgitation (MR) that replicates the clinical phenotype of left atrial (LA) and left ventricular dilation and susceptibility to atrial fibrillation., Methods: Under transesophageal echocardiographic guidance, chordae tendinae were avulsed using endovascular forceps until the ratio of regurgitant jet area to LA area was ≥70%. Animals survived for an average of 8.6 ± 1.6 months (standard deviation) and imaged with monthly transthoracic echocardiography (TTE). Animals underwent baseline and preterminal magnetic resonance imaging. Terminal studies included TTE, transesophageal echocardiography, and rapid atrial pacing to test inducibility of atrial tachyarrhythmias., Results: Eight dogs underwent creation of severe MR and interval monitoring. Two were excluded-one died from acute heart failure, and the other had resolution of MR. Six dogs underwent the full experimental protocol; only one required medical management of clinical heart failure. MR remained severe over time, with a mean terminal regurgitant jet area to LA area of 71 ± 14% (standard deviation) and regurgitant fraction of 52 ± 11%. Mean LA volume increased over 130% (TTE: 163 ± 147%, P  = .039; magnetic resonance imaging: 132 ± 54%, P  = .011). Mean left ventricular end-diastolic volume increased by 38 ± 21% ( P  = .008). Inducible atrial tachyarrhythmias were seen in 4 of 6 animals at terminal surgery, and none at baseline., Conclusions: Within the 6 dogs that successfully completed the full experimental protocol, this model replicated the clinical phenotype of severe MR, which led to marked structural and electrophysiologic cardiac remodeling. This model allowed for precise measurements at repeated time points and will facilitate future studies to elucidate the mechanisms of atrial and ventricular remodeling secondary to MR and the pathophysiology of valvular atrial fibrillation., (© 2023 The Author(s).)

The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this response, including the transforming growth factor (TGF)-β1 target gene Mss51, an inhibitor of skeletal muscle mitochondrial respiration. Although Mss51 is implicated in the pathophysiology of obesity and musculoskeletal disease, how Mss51 is regulated is not entirely understood. Site-1 protease (S1P) is a key activator of several transcription factors required for cellular adaptation. However, the role of S1P in muscle is unknown. Here, we identify S1P as a negative regulator of muscle mass and mitochondrial respiration. S1P disruption in mouse skeletal muscle reduces Mss51 expression and increases muscle mass and mitochondrial respiration. The effects of S1P deficiency on mitochondrial activity are counteracted by overexpressing Mss51, suggesting that one way S1P inhibits respiration is by regulating Mss51. These discoveries expand our understanding of TGF-β signaling and S1P function., Competing Interests: Declaration of interests R.T.B. and B.N.F. are inventors on a U.S. patent (patent number: US11534423B2). R.T.B. is an inventor on a U.S. patent application (application number: 63/370,712). B.N.F. is a member of the Cell Reports advisory board., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This study evaluated the impact of anatomic aortic root parameters during valve-sparing root replacement on the probability of postoperative aortic insufficiency and freedom from aortic valve reoperation., Methods: From 1995 to 2020, 177 patients underwent valve-sparing root replacement (163 reimplantations, 14 remodeling). Preoperative and postoperative echocardiograms were analyzed to measure annulus and sinus diameters, effective height of leaflet coaptation, and degree of aortic insufficiency. Logistic regression was used to evaluate predictors of 2+ or greater late postoperative aortic insufficiency. Fine-Gray regression determined predictors for aortic valve reintervention., Results: The study population included 122 (69%) men with a mean age of 43 ± 15 years. A total of 119 patients (67%) had an identified connective tissue disorder. The cumulative incidence of aortic valve reoperation was estimated as 7% at 5 years and 12% at 10 years. The probability of 2+ or greater late postoperative aortic insufficiency was inversely related to effective height during valve-sparing root replacement (P = .018). As postoperative effective height fell below 11 mm, the probability of 2+ or greater aortic insufficiency exceeded 10%. On multivariable logistic regression, effective height (odds ratio, 0.53; 0.33-0.86; P = .010), preoperative annulus diameter (odds ratio, 1.44; 1.13-1.82; P = .003), and degree of preoperative aortic insufficiency (odds ratio, 2.57; 1.45-4.52; P = .001) were associated with increased incidence of 2+ or greater late postoperative aortic insufficiency. On multivariable Fine-Gray regression, risk factors for aortic valve reintervention included preoperative annulus diameter (subdistribution hazard ratio, 1.28 [1.03-1.59], P = .027), history of 3+ or greater aortic insufficiency (subdistribution hazard ratio, 4.28; 1.60-11.44; P = .004), and 2+ or greater early postoperative aortic insufficiency (subdistribution hazard ratio, 5.22; 2.29-11.90; P < .001)., Conclusions: Measures to increase effective height during valve-sparing root replacement may decrease the risk of more than mild postoperative aortic insufficiency after repair and the need for aortic valve reoperation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) after cardiac surgery remains a common complication that has been associated with increased morbidity and mortality. This study implemented Kidney Disease Improving Global Outcomes criteria to evaluate renal outcomes after concomitant surgical ablation for atrial fibrillation., Methods: Patients with a history of atrial fibrillation who underwent elective cardiac surgery at our institution from 2008 to 2018 were retrospectively reviewed. Those with preoperative renal dysfunction were excluded. Patients were classified as those who underwent concomitant Cox-Maze IV (CMP-IV) (n = 376) or no surgical ablation (n = 498). Nearest neighbor 1:1 propensity matching was conducted on fourteen covariates. AKI was evaluated by mixed effects logistic regression analysis. Long-term survival was evaluated by proportional hazards regression., Results: Propensity matching yielded 308 patients in each group (n = 616). All preoperative variables were similar between groups. The concomitant CMP-IV group had a greater incidence of AKI: 32% (n = 99) versus 16% (n = 49), P < .001. After accounting for bypass time and nonablation operations on mixed effects analysis, concomitant CMP-IV was associated with increased risk of AKI (odds ratio, 1.89; confidence interval, 1.12-3.18; P = .017). While AKI was associated with decreased late survival (P < .001), patients who received a concomitant CMP-IV maintained superior 7-year survival to patients who received no ablation (P < .001). No patients required permanent dialysis., Conclusions: Concomitant CMP-IV was independently associated with increased risk of AKI in the acute postoperative period. However, the long-term risks of AKI were offset by the significant survival benefit of CMP-IV. Concerns regarding new-onset renal dysfunction should not prohibit recommendation of this procedure in appropriate patients., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Previous work demonstrates that individuals often recall less information if, at study, there is expectation that an external memory store will be available at test. One explanation for this effect is that when individuals can expect access to an external memory store, they forgo intentional, controlled efforts at encoding. The present work offers a novel test of this account by examining study effort, indexed by study time and self-reported strategy use, as a function of instructed external store availability. In two preregistered experiments, participants studied lists of to-be-remembered items for a free recall test and were either instructed that they could use their study list to support them at test or that they could not. Critically, participants controlled their own study time, and no participant had their study list at test, regardless of instruction. Consistent with the effort at encoding account, external store availability influenced both study time and strategy use, and there was evidence that these effects mediated the influence of external store availability on recall performance. Interestingly, much of the memory cost remained when controlling for study effort, thus, suggesting that the cost is potentially multiply determined., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We often rely on external devices to store to-be-remembered information in our everyday lives (e.g., writing grocery lists, setting reminders), yet there is limited research about how certain information (i.e., valuable information) may be differentially encoded when we rely on our internal memory versus an external store. Across three preregistered experiments, we examined the effect of relying on an external store on the recall of high-value and low-value information. In Experiments 1a and 1b, we presented participants with words associated with point values and examined mean recall performance during two critical trials in which the external store was not available: (1) a trial in which participants were told that they would have access to an external memory store at test (told-external-store) and (2) a trial in which participants were told that they would not have access to their external store at test (told-no-external-store). In Experiment 2, we explored participants' metacognitive predictions of performance on the recall test. Critically, across all of the experiments, we found that the value effect (i.e., better recall for valuable information) was significantly reduced when individuals were told that they could rely on an external store. The same pattern was present in participant's metacognitive judgements. Together, these results suggest that when relying on external stores, individuals forgo (to some extent, at least) selective encoding by value and that individuals might be aware of this change in strategy., (© 2022. The Psychonomic Society, Inc.)

Relying on external memory aids is a common memory strategy that has long allowed us to "remember" vast amounts of information more reliably than with our internal memory alone. However, recent work has provided evidence consistent with the idea that offloading memory demands encourages a reduced engagement in intentional or top-down memory strategies/efforts, leading to lower memory performance in general. Evidence for this view comes from results demonstrating a reduced primacy effect but intact recency and isolation effects when individuals could offload memory demands (but had to unexpectedly rely on their internal memory at test). In the present investigation, we attempt a replication of these critical results, given some inconsistencies in the findings between studies. In addition, we extend the examination of offloading's impact on memory via examining individual differences in reliance on the external store (when available) and different strategies for the use of that store. Results of the replication are generally consistent with previous research. An individual differences analysis yielded results consistent with the notion that increased reliance on an external store can compromise internal/biological memory in the absence of that store. Finally, a verbal model of offloading memory demands within a framework of effort and study time allocation is presented. Together, the results both reinforce extant research and extend it in new directions., (© 2021. The Psychonomic Society, Inc.)

Offloading memory to external stores (e.g., a saved file) allows us to evade the limitations of our internal memory. One cost of this strategy is that the external memory store used may be accessible to others and, thus, may be manipulated. Here we examine how reducing the perceived reliability of an external memory store and manipulating one's expectation for future access to such a store can influence participants' susceptibility to its manipulation (i.e., endorsing manipulated information as authentic). Across three pre-registered experiments, participants were able to store to-be-remembered information in an external store. On a critical trial, we surreptitiously manipulated the information in that store. Results demonstrated that an explicit notification of a previous manipulation of that store and the warning that the store will be inaccessible in the future can decrease susceptibility to manipulation of that store. Results are discussed in the context of the metacognitive monitoring and control of memory reports in situations that involve the distribution of memory demands across both internal and external spaces.

When we can offload to-be-remembered information to an external store, our ability to recall that information from internal memory can be diminished. However, previous research has suggested that associative memory processes may remain intact in the face of offloading behaviour. In the present investigation, we examine how the opportunity to offload memory demands affects the learning of categorised word lists. Across six experiments, participants studied and wrote down word lists that were either strongly associated with a semantic theme (categorised) or word lists that consisted of the same set of words but shuffled across the categorised lists (shuffled). When participants expected to have access to their written lists during the recall test (i.e., a condition that would encourage offloading) but were not given access to it, we found the typical recall advantage for categorised lists. This effect was found to be the same size or larger compared to a condition where participants did not expect to have access to their written lists during the recall test (i.e., a condition that would not allow offloading). We propose that gist memory supported by semantic associations is not substantially reduced in offloading.

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and results in significant morbidity and mortality. The Cox-Maze IV procedure (CMP-IV) has been shown to have excellent efficacy in returning patients to sinus rhythm, but there have been few reports of late follow-up in sizable cohorts of patients with longstanding persistent AF, the most difficult type of AF to treat., Methods and Results: Between May 2003 and March 2020, 174 consecutive patients underwent a stand-alone CMP-IV for longstanding persistent AF. Rhythm outcome was assessed postoperatively for up to 10 years, primarily via prolonged monitoring (Holter monitor, pacemaker interrogation, or implantable loop recorder). Fine-Gray regression was used to investigate factors associated with atrial tachyarrhythmia (ATA) recurrence, with death as a competing risk. Median duration of preoperative AF was 7.8 years (interquartile range: 4.0-12.0 years), with 71% (124/174) having failed at least one prior catheter-based ablation. There were no 30-day mortalities. Freedom from ATAs was 94% (120/128), 83% (53/64), and 88% (35/40) at 1, 5, and 7 years, respectively. On regression analysis, preoperative AF duration and early postoperative ATAs were associated with late ATAs recurrence., Conclusion: Despite the majority of patients having a long-duration of preoperative AF and having failed at least one catheter-based ablation, the stand-alone CMP-IV had excellent late efficacy in patients with longstanding persistent AF, with low morbidity and no mortality. We recommend consideration of stand-alone CMP-IV for patients with longstanding persistent AF who have failed or are poor candidates for catheter ablation., (© 2021 Wiley Periodicals LLC.)

Objective: Obesity is a strong and independent factor for the development of atrial fibrillation (AF), and adversely impacts the success of catheter ablation procedures for AF. This study evaluated the impact of body mass index (BMI) on the outcomes following surgical ablation of AF., Methods: Between 2003 and 2019, 236 patients underwent a stand-alone biatrial Cox maze IV procedure (CMP-IV) for refractory AF. Obesity was defined as BMI ≥30 kg/m 2 . Patients were divided into two groups: BMI <30 kg/m 2 ( n = 100) and BMI ≥30 kg/m 2 ( n = 136). Freedom from atrial tachyarrhythmia (ATA) was determined using electrocardiography, Holter, or pacemaker interrogation at 1 year and annually thereafter. Recurrence was defined as any documented ATA lasting ≥30 s. Predictors of recurrence were determined using multivariable logistic regression. Preoperative and procedural outcomes were compared between groups., Results: Obese patients had a higher rate of diabetes (16% vs 7%, P = 0.044) and larger left atrial diameter (4.9 ± 1.1 cm vs 4.6 ± 1.0 cm, P = 0.021) when compared to non-obese patients. There was no difference in major complication rate between the groups (4% vs 7%, P = 0.389). There was no operative mortality in either group. During 4.1 ± 2.4 years of follow-up, there was no significant difference in freedom from ATA with or without antiarrhythmic drugs in obese patients when compared to the non-obese group ( P > 0.05). Absence of sinus rhythm at discharge predicted AF recurrence up to 7 years postoperatively., Conclusions: As opposed to catheter ablation, obesity did not adversely impact the short and long-term outcomes of stand-alone surgical ablation with CMP-IV, and BMI was not a predictor of AF recurrence. Additionally, there was no significant increase in major complications in obese patients.

Background: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, and is associated with increased morbidity and mortality. Inflammation has been implicated as an etiology of POAF. Mitochondrial DNA (mtDNA) has been shown to initiate inflammation. This study analyzed inflammatory mechanisms of POAF by evaluating mtDNA, neutrophils, and cytokines/chemokines in the pericardial fluid and blood after cardiac surgery., Methods: Blood and pericardial fluid from patients who underwent coronary artery bypass or heart valve surgery, or both, were collected intraoperatively and at 4, 12, 24, and 48 hours postoperatively. Real-time polymerase chain reaction was used to quantify mtDNA in the pericardial fluid and blood. A Luminex (Luminex Corp, Austin, TX) assay was used to study cytokine and chemokine levels. Flow cytometry was used to analyze neutrophil infiltration and activation in the pericardial fluid., Results: Samples from 100 patients were available for analysis. Postoperatively, mtDNA and multiple cytokine levels were higher in the pericardial fluid versus blood. Patients who had POAF had significantly higher levels of mtDNA in the pericardial fluid compared with patients who did not (P < .001, area under the curve 0.74). There was no difference in the mtDNA concentration in the blood between the POAF group and non-POAF group (P = .897). Neutrophil concentration increased in the pericardial fluid over time from a baseline of 0.8% to 56% at 48 hours (P < .01)., Conclusions: The pericardial space has a high concentration of inflammatory mediators postoperatively. Mitochondrial DNA in the pericardial fluid was strongly associated with the development of POAF. This finding provides insight into a possible mechanism of inflammation that may contribute to POAF, and may offer novel therapeutic targets., (Copyright © 2021. Published by Elsevier Inc.)

Offloading to-be-remembered information is a ubiquitous memory strategy, yet in relying on external memory stores, our ability to recall from internal memory is often diminished. In the present investigation, we examine how offloading impacts true and false recall. Across three experiments, participants studied and wrote down word lists that were each strongly associated with an unstudied critical word. Recall in the Offloading condition (i.e., when they were told that they would have access to their written lists during recall) was contrasted with a No-Offloading condition (i.e., when they were told that they would not have access to their written lists during recall). We found that offloading decreased true recall of presented words while increasing false recall for unpresented critical words. Results are discussed in terms of offloading's differential effects on the formation of gist and verbatim traces during encoding., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We often offload memory demands onto external artefacts (e.g., smartphones). While this practice allows us to subvert the limitations of our biological memory, storing memories externally exposes them to manipulation. To examine the impact of such manipulation, we report three experiments, two of which were pre-registered. Individuals performed a memory task where they could offload to-be-recalled information to an external store and on a critical trial, we surreptitiously manipulated the information in that store. Results demonstrated that individuals rarely noticed this manipulation. In addition, when individuals had information inserted into their external memory stores, they often encoded it into their biological memory, thereby leading to the creation of a false memory. The reported results highlight one of the cognitive consequences of offloading our memory to external artefacts., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Despite the long history and pervasiveness of cognitive offloading as a memory strategy, the memorial fate of offloaded information is not well understood. Recent work has suggested that offloading information may engage similar mechanisms as instructions to forget (e.g., directed forgetting). In the present investigation, we test this prediction by examining the serial position effect for offloaded information. Previous research has demonstrated that "forget" instructions can eliminate the primacy effect while leaving an intact recency effect. Across two experiments, participants completed a number of free recall trials using an external aid and then a final recall trial without the external aid. We compared a group that was expecting to use the aid for the final trial (offloading) with a group that was not (no-offloading). We found a memory impairment for offloaded items that was characterized by a reduced primacy effect but a typical recency effect, similar to what has been reported in research on intentional/directed forgetting.

By the end of the 20 th century, health care organizations worldwide were recognizing the benefits of a quick response when patients were experiencing a clinical decline and the difficulty in achieving that goal. The University of Missouri STAT Nurse program, developed in 1989, was an early innovation to deliver the "right care" at the "right time" every time. Over the years, the STAT Nurse program evolved and became the core component of a Rapid Response System. Today Rapid Response at University of Missouri Health Care is called the Targeted Interventional Group Emergency Response Team, also known as the TIGER Team after the much beloved University mascot.

Collisions with and attachment to natural colloids (heteroaggregation) is likely to influence significantly the fate, transport, and toxicity of engineered nanoparticles (ENPs). This study investigated heteroaggregation between hematite (α-Fe2O3) colloids and citrate-capped gold nanoparticles (Cit-AuNPs) using a novel approach involving time-resolved dynamic light scattering and parallel experiments designed to quantify nanoparticle attachment and heteroaggregate surface charge. Experiments were performed in low ionic strength synthetic water at environmentally relevant pH in the presence and absence of Suwannee River Natural Organic Matter (SRNOM). In the absence of SRNOM at pH values where Cit-AuNPs and hematite are oppositely charged, attachment efficiencies are high and Cit-AuNPs are capable of destabilizing hematite following an "electrostatic patch" mechanism. Furthermore, maximum observed surface coverages were far below those predicted by geometry alone, a fact predicted by the random sequential adsorption (RSA) model that has significant implications for the estimation of heteroaggregate attachment efficiencies. At pH values where both particles are negative or in the presence of small amounts of SRNOM, attachment was minimal. Calculated attachment efficiencies using the measured surface coverages corroborate these findings. The calculation of attachment efficiencies and the identification of mechanisms governing heteroaggregation represents an important step toward predicting the transport, fate, and toxicity of ENPs in the environment.

Assimilate partitioning has been identified as a key process in the control of yield. Although the role of reproductive structures in this process has received intensive study, our understanding of the role of the maternal plant is limited. We suggest that the Sn gene of pea (Pisum sativum L.) is a potentially valuable genetic tool for studying maternal regulation of partitioning. In this study, nearly isogenic lines differing at the Sn locus were compared with respect to seed-filling characteristics and carbon assimilation. Lines with the Sn gene had a slower rate and shorter duration of seed growth than the line recessive for this gene, and these traits could not be ascribed to reduced carbon assimilation. Flowers of the two nearly isogenic lines were manually pollinated to control the genotype of the developing embryo independently of the maternal genotype. The final dry weight of the seed was determined by the genotype of the maternal plant and not by the genotype of the embryo, supporting the hypothesis that the Sn gene acts in the vegetative plant to regulate the partitioning of assimilates between vegetative and reproductive growth. Although the Sn gene has been noted for delaying apical senescence, it also delayed leaf senescence in this study; leaves of the Sn line continued to photosynthesize long past the time that leaves of the recessive line had senesced and after the seeds and pods were dry.

Dark-treated Merit corn (Zea mays L.) roots are diagravitropic and lose curvature upon withdrawal of the gravity stimulus (springback). Springback was not detected in a variety of corn that is orthogravitropic in the dark, nor in Merit roots in which tropistic response was enhanced either with red light or with abscisic acid. A possible interpretation is that springback may be associated with a weak growth response of diagravitropic roots.

Roots of Merit variety corn (Zea mays L.) require red light for orthogravitropic curvature. Experiments were undertaken to identify the step in the pathway from gravity perception to asymmetric growth on which light may act. Red light was effective in inducing gravitropism whether it was supplied concomitant with or as long as 30 minutes after the gravity stimulus (GS). The presentation time was the same whether the GS was supplied in red light or in darkness. Red light given before the GS slightly enhanced the rate of curvature but had little effect on the lag time or on the final curvature. This enhancement was expanded by a delay between the red light pulse and the GS. These results indicate that gravity perception and at least the initial transduction steps proceed in the dark. Light may regulate the final growth (motor) phase of gravitropism. The time required for full expression of the light enhancement of curvature is consistent with its involvement in some light-stimulated biosynthetic event.

The sensitivity of excised hypocotyl segments to indoleacetic acid (IAA) in two assays, ethylene production and elongation, was determined in the ethylene-requiring tomato (Lycopersicon esculentum Mill.) mutant, diageotropica (dgt), and its isogenic parent, cv VFN8. Endogenous (uninduced) ethylene synthesis rates were slightly lower in dgt hypocotyls than in VFN8 hypocotyls. Ethylene production was essentially unaffected by IAA in dgt, but was stimulated up to 10-fold by 10 micromolar IAA in VFN8. Elongation of dgt hypocotyls was also insensitive to concentrations of IAA as high as 100 micromolar, as compared to significant elongation of VFN8 hypocotyls in response to 0.1 micromolar IAA. A range of IAA analogs active in VFN8 was also ineffective in stimulating elongation of dgt hypocotyls, suggesting that the differences were not due to rapid metabolism of IAA by dgt tissues. Auxin-induced elongation of VFN8 hypocotyls was unaffected by 2,3,5-triiodobenzoic acid and naphthylphthalamic acid, indicating that polar auxin transport was not a factor in these experiments. Exogenous and auxin-induced ethylene had no effect on the elongation respone of either genotype, nor did exogenous ethylene restore the sensitivity of dgt hypocotyls to IAA. Despite their apparent insensitivity to auxin, dgt hypocotyls elongated dramatically and synthesized ethylene rapidly in response to 1.2 micromolar fusicoccin. These results suggest that the primary effect of the dgt mutation is to reduce the sensitivity of the tissue to auxin. As altered regulation of ethylene synthesis is only one symptom of this fundamental deficiency, dgt should more properly be considered to be the auxin-insensitive tomato mutant.

Apical senescence but not flower initiation is delayed by short days (SD) compared to long days (LD) in pea plants (Pisum sativum L.) of genotype E Sn Hr. We recently reported that delay of senescence correlated with slower reproductive development, suggesting that fruits are weaker sinks for assimilates under delayed senescence conditions. Thus, we have examined assimilate partitioning in peas to determine if genotype and photoperiod regulate relative sink strength. Assimilate diversion by developing fruit has been implicated in senescence induction. A greater percentage of leaf-exported (14)C was transported to fruits and a smaller percentage to the apical bud of G2 peas (genotype E Sn Hr) in LD than in SD. Relatively more of the (14)C delivered to the apical bud of G2 peas was transported to flower buds than to young leaves in LD as compared to SD. There was no striking photoperiodic difference in carbon partitioning in genetic lines without the Sn Hr allele combination. The Sn Hr allele combination and photoperiod may regulate the relative strength of reproductive and vegetative sinks. Photoperiodic differences in sink strength early in reproduction suggest that these genes regulate sink strength by affecting the physiology of the whole plant. High vegetative sink strength in SD may maintain assimilate supply to the apical bud, delaying senescence.

Tomato (Lycopersicon esculentum Mill. var Castlemart) fruit ripening was inhibited by tissue concentrations of ethanol that were produced by either exposure to exogenous ethanol vapors or synthesis under anaerobic atmospheres. Ethanol was not detected in aerobically ripened tomato fruit. Ripening was not inhibited by exposure to methanol at an equivalent molar concentration to inhibitory concentrations of ethanol, while ripening was slightly more inhibited by n-propanol than by equivalent molar concentrations of ethanol. The mottled appearance of a few ripened ethanol-treated fruit was not observed in n-propanol-treated fruit.