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Previous research has supported the use of latent variables as the gold-standard in measuring executive function. However, for logistical reasons genome-wide association studies (GWAS) of executive function have largely eschewed latent variables in favour of singular task measures. As low correlations have traditionally been found between individual executive function (EF) tests, it is unclear whether these GWAS have truly been measuring the same construct. In this study, we addressed this question by performing a factor analysis on summary statistics from eleven GWAS of EF taken from five studies, using GenomicSEM. Models demonstrated a bifactor structure consistent with previous research, with factors capturing common EF and working memory- specific variance. Furthermore, the GWAS performed on this model identified 20 new genomic risk loci for common EF and 4 for working memory reaching genome-wide significance beyond what was found in the constituent GWAS, together resulting in 29 newly mapped EF genes. These results help to clarify the underlying genetic structure of EF and support the idea that EF GWAS are capable of measuring genetic variance related to latent EF constructs even when not using factor scores. Furthermore, they demonstrate that GenomicSEM can combine GWAS with divergent and non-ideal measures of the same phenotype to improve statistical power., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2025. The Author(s).)

Twin studies have suggested extremely high estimates of heritability for adolescent executive function, with no substantial contributions from shared environment. However, developmental psychology research has found significant correlations between executive function outcomes and elements of the environment that would be shared in twins. It is unclear whether these seemingly contradictory findings are best explained by genetic confounding in developmental studies or limitations in twin studies, which can potentially underestimate shared environment. In this study, we use genetic and phenotypic data from 5,939 participants, 4,827 participant mothers, and 2,903 participant fathers in the Millennium cohort to examine the role of genetics in explaining common environmental associations with executive function, assessed by the spatial working memory (SWM) task and Cambridge Gambling task. Bivariate genome-wide complex trait analysis (GCTA) revealed that single-nucleotide polymorphism effects were the sole significant predictor of the association between SWM and both maternal education and prenatal smoking. maternal GCTA and trioGCTA also found no significant evidence of indirect genetic effects on SWM, indicating that genetic nurture is unlikely to explain the bivariate GCTA results. The Cambridge Gambling task showed no significant single-nucleotide polymorphism heritability, suggesting that genetic influences on hot executive function may differ significantly from those on cool executive function. This study supports the twin study claim that the working memory component of executive function is primarily a genetic trait with minimal influence from shared environment, emphasizing the importance of using genetically sensitive designs to ensure that genetic confounding does not falsely inflate estimates of environmental influences on traits. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

To better understand the challenges of generally implementing and adapting computational phenotyping approaches, the performance of a Phenotype KnowledgeBase (PheKB) algorithm for rheumatoid arthritis (RA) was evaluated on a University of California, Los Angeles (UCLA) patient population, focusing on examining its performance on ambiguous cases. The algorithm was evaluated on a cohort of 4,766 patients, along with a chart review of 300 patients by rheumatologists against accepted diagnostic guidelines. The performance revealed low sensitivity towards specific subtypes of positive RA cases, which suggests revisions in features used for phenotyping. A close examination of select cases also indicated a significant portion of patients with missing data, drawing attention to the need to consider data integrity as an integral part of phenotyping pipelines, as well as issues around the usability of various codes for distinguishing cases. We use patterns in the PheKB algorithm's errors to further demonstrate important considerations when designing a phenotyping algorithm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Postpartum depression affects approximately 10% to 20% of mothers and impairs a mother's ability to engage with her child at an emotional and cognitive level, placing the child at greater risk for impaired development. Early diagnosis and management can reduce its negative impacts. Despite mothers being receptive to screening, screening rates are less than 50%., Methods: This article provides an appraisal of the current state of the evidence on implementing screening for postpartum depression in pediatric primary care. It describes how to use a clinical decision support algorithm for screening and follow-up and the process of developing an accompanying referral/resource list., Results: Evidence supports the use of clinical decision support algorithm and the need for having local resources and referrals available at the point of care., Discussion: Screening for postpartum depression in the pediatric primary care setting is feasible and can be adapted to the local setting., (Copyright © 2017 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Objectives: Over the past decade, the use of topical skin adhesives (TSA) for wound closure has increased. Among TSA characteristics, strength and flexibility are most important. Prior studies have compared the wound bursting strengths (WBSs) of the cyanoacrylates immediately after wound closure. In this study the authors compared the WBS and flexibility of multiple TSAs immediately and up to 2 days after closure., Methods: This was a controlled animal experiment. Two-centimeter incisions were created on both sides of 210 Sprague-Dawley rats and randomly closed with one of five commercially available TSAs (Dermabond [D], Indermil [I], Histoacryl [H], Liquiband [L], or GluStitch [G]). WBS and TSA flexibility were measured using the BTC-2000 device immediately after closure and at 1 and 2 days after closure. WBS and TSA flexibility were compared across groups with analysis of variance (ANOVA)., Results: Wound bursting strengths were higher (p < 0.05) at 0, 1, and 2 days for D (274, 388, 232 mm Hg) than for all other TSAs (I 182, 225, and 107; H 189, 214, and 69; L 146, 118, and 75; or G 161, 150, and 73). TSA flexibility was also greater (p < 0.05) at 0, 1, and 2 days for D (36, 27, and 29 mm Hg/mm) than for all other TSAs (I 18, 14, and 12; H 18, 13, and 15; L 19, 14, and 12; G 26, 23, and 18)., Conclusions: The octyl-cyanoacrylate-based adhesive is significantly stronger and more flexible than all the butyl-cyanoacrylate-based adhesives at 0, 1 and 2 days after closure.

Clinical studies show that immunogenicity observed against therapeutic proteins can limit efficacy and reduce the safety of the treatment. It is therefore beneficial to be able to predict the immunogenicity of therapeutic proteins before they enter the clinic. Studies using deimmunized proteins have highlighted the importance of T-cell epitopes in the generation of undesirable immunogenicity. In silico, in vitro, ex vivo and in vivo methods have therefore been developed that focus on identification of CD4+ T-cell epitopes in the sequence of therapeutic proteins. A case study of existing therapeutic proteins is presented to review these different approaches in order to assess their utility in predicting immunogenic potential.

CTLA-4 is an essential protein in the regulation of T cell responses that interacts with two ligands found on the surface of APCs (CD80 and CD86). CTLA-4 is itself poorly expressed on the T cell surface and is predominantly localized to intracellular compartments. We have studied the mechanisms involved in the delivery of CTLA-4 to the cell surface using a model Chinese hamster ovary cell system and compared this with activated and regulatory human T cells. We have shown that expression of CTLA-4 at the plasma membrane (PM) is controlled by exocytosis of CTLA-4-containing vesicles and followed by rapid endocytosis. Using selective inhibitors and dominant negative mutants, we have shown that exocytosis of CTLA-4 is dependent on the activity of the GTPase ADP ribosylation factor-1 and on phospholipase D activity. CTLA-4 was identified in a perinuclear compartment overlapping with the cis-Golgi marker GM-130 but did not colocalize strongly with lysosomal markers such as CD63 and lysosome-associated membrane protein. In regulatory T cells, activation of phospholipase D was sufficient to trigger release of CTLA-4 to the PM but did not inhibit endocytosis. Taken together, these data suggest that CTLA-4 may be stored in a specialized compartment in regulatory T cells that can be triggered rapidly for deployment to the PM in a phospholipase D- and ADP ribosylation factor-1-dependent manner.

CD28 and CTLA-4 are opposing regulators of T cell activation, triggered by the two ligands CD80 and CD86. How these ligands promote either T cell activation via CD28 or inhibition via CTLA-4 is not understood. Using CD80 and CD86 molecules expressed on transfected cells, we have identified a major difference between these ligands in that CD80 transfectants have the ability to inhibit activation of resting human peripheral blood T cells via interaction with CTLA-4, whereas CD86 transfectants do not. Rather, CTLA-4-CD86 interactions appear to contribute towards T cell proliferation. We also observed that CTLA-4 function is strongly influenced by TCR stimulation, effects being observed only at relatively low levels of TCR stimulation. The kinetics of CD80-CTLA-4 interactions revealed that CTLA-4 inhibition took place within the first 8 h of T cell stimulation, despite there being little measurable CTLA-4 expression on the majority T cells. However, significant amounts of CTLA-4 were observed in the CD25(+) CD4(+) subset of T cells which, when removed from the cultures, accounted for the CTLA-4 inhibition observed. Overall, these data provide evidence that CD80 and CD86 differ in their interactions with CTLA-4 and that CD80 appears to be the preferential inhibitory ligand for CTLA-4 working via a population of CD4(+) CD25(+) CTLA-4(+) regulatory T cells.

Background: This study evaluated the effect of coated polyglactin 910 suture with triclosan on tissue response and wound healing over a 28-day period on full-thickness linear wounds in the hairless guinea pig model., Methods: In situ wound strength was assessed, and histopathologic effects on tissue response and wound healing were evaluated. Four (1.9 cm) full-thickness incisional wounds were created on the dorsolateral region (two left and two right, approximately 3 cm apart) in 40 Hartley male hairless guinea pigs (400-500 g). A 1.9-cm segment of suture material was implanted "length-wise" into the incision and the sites closed with simple interrupted closure with 3-0 nylon sutures. The test material was 2-0 coated polyglactin 910 suture with triclosan and the control material was 2-0 Coated VICRYL* Suture (coated polyglactin 910 suture). On days 3, 7, 14, and 28 postimplantation (n = 10/time interval), body weights were recorded, tissue specimens harvested, and bursting strength testing performed., Results: There was no significant difference (P > 0.05) in bursting strength between the study groups for any of the time intervals studied. The bursting strengths (mm Hg) for the sutures with triclosan were 95.8 (day 3), 268.8 (day 7), 542.6 (day 14), and 633.8 (day 28). Both materials demonstrated comparable tissue response to implantation, and there were no significant differences (P > 0.05) observed in wound healing based on cellular response and collagen formation and orientation., Conclusion: Based on the in vivo biomechanical testing and histological results, no evidence of impedance to wound healing was detected.

Removing excess subcutaneous fat with the assistance of ultrasonic energy has recently become a technique of interest in the United States after nearly a decade of use in Europe. There are a number of reported advantages of ultrasound-assisted lipoplasty over traditional liposuction, and there are also some theoretical concerns. Ultrasound-assisted lipoplasty involves the conversion of electrical energy to mechanical energy and transfer to the tissues through acoustic pressure waves, with the formation of heat as a by-product. Heat generated in this process dissipates through the body's own cooling mechanisms and conduction to the surrounding tissues, and it does not contribute to the clinical treatment of the adipose tissue. Reports of "burns" and ischemic skin injuries in the literature, and concerns for potential heat-related problems, prompted us to investigate whether significant temperature elevations occur in the clinical setting. Subcutaneous tissue temperature determinations during ultrasound-assisted lipoplasty were begun in February of 1996, and data were collected from 55 patients who had the procedure performed during a 6-month period. Intraoperatively, temperature measurements were made with a data-logging instrument and a needle microprobe inserted into the subcutaneous tissues. Temperatures were taken in the area of liposuction before the infusion of tumescent fluid, after tumescent fluid infusion, and at 5-minute intervals until the end of the procedure. The patient's core body temperature remained stable during the procedure within a narrow range (35.7 degrees C to 36.3 degrees C). There was a gradual increase in the temperature of the subcutaneous tissues over time during the application of ultrasonic energy; however, average subcutaneous temperatures remained below the core temperature (p < 0.05) at all time intervals. Room-temperature tumescent fluid further enhanced the thermal safety zone without lowering core body temperature. There were no temperature related complications in our study population and no untoward effects of performing temperature measurements. We conclude that there is no clinically significant elevation of subcutaneous temperatures during ultrasound-assisted lipoplasty. Reported ischemic skin complications are more likely the result of injury to the subdermal plexus rather than a temperature-induced thermal injury. Although heat is a natural by-product of the energy transfer involved in ultrasound-assisted lipoplasty, the risk of thermal injury is negligible when the procedure is performed by experienced operators. Complete understanding of the technique along with strict adherence to basic principles of flap vascularity will ensure safe and effective performance of ultrasound-assisted lipoplasty.

A study was designed to attempt to develop an experimental animal model for the transverse rectus abdominis musculocutaneous (TRAM) flap. The rat has a well-formed superior epigastric artery with musculocutaneous perforators that have been shown to support a musculocutaneous flap on a single superior pedicle. Despite the anatomical differences between the dominance of the axial longitudinal cutaneous circulation in loose-skinned animals compared with humans, as well as a dominant superior intramuscular pedicle, the rat TRAM model appears to be reproducible and has predictable zones of viability as well as areas that typically do not survive when based on a single superior pedicle. These areas of nonviability correspond to those zones at high risk of nonviability in the human clinical situation: zone 3 and 4 on the contralateral side and zone 3 on the ipsilateral side (tissue lateral to the superficial inferior epigastric supply). Once the reliability and reproducibility of this model was demonstrated (coefficient of variation 18.9%), a study was undertaken to determine whether pharmacological manipulation of this flap altered survival in those areas that are inadequately perfused. The two agents tested were allopurinol (xanthine oxidase inhibitor, antioxidant) and pentoxifylline (microcirculatory rheological agents that is a xanthine analogue and is also believed to have antioxidant potential). The study involved creating right unipedicled TRAM flaps in 30 male specific pathogen-free Sprague-Dawley rats weighing 375 to 450 gm. The transverse skin paddle was centered over the umbilical dimple and measured 5.5 x 2 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Topical silicone-gel sheeting has been shown to be beneficial in the treatment of established hypertrophic and keloid scars. Certain individuals and incisions in specific body sites appear to be at increased risk for the development of such scars. A simple, inexpensive, and preventive treatment in these individuals at increased risk could potentially minimize the extended period of pressure therapy and repeated steroid injections that are often required to optimize outcome. However, the effects of applying silicone-gel sheeting in the immediate postoperative period as a preventive measure have not been investigated to date. Because silicone-gel sheeting influences the remodeling and maturation phase of collagen formation, we believed it prudent to determine whether silicone-gel sheeting had any deleterious effect on early wound healing, as demonstrated by in vivo biomechanical testing of wound strength and histological assessment. To investigate the potential effects of silicone-gel sheeting on acute wound healing and its possible application for prevention of hypertrophic scars, a study was designed in the hairless guinea pig. In phase 1 of the study, bilateral dorsolateral incisions were made, allowing each guinea pig to serve as its own control. One wound was dressed with silicone-gel sheeting, and the control site was dressed with Nu-gauze dressing. Wounds were then assessed visually and with in vivo biomechanical analysis of wound strength at days 3, 5, and 7 postoperatively (n = 7 per group). Phase 2 of the study compared identical dressings in a similar animal model using a single dorsal midline incision, in which alternate halves of each wound served as the control.(ABSTRACT TRUNCATED AT 250 WORDS)

There has been ongoing clinical and laboratory research to determine the role of surface morphology on capsular contracture. The purpose of this study was to develop a rat model in which capsular contracture occurred frequently and to determine whether surface texturing had any effect on the incidence or degree of capsular contracture as determined by in vivo biomechanical analysis of tissue modulus and histological examination of the tissue at the capsule-implant interface. A new sublatissimus implantation site in the rat was developed in an attempt to avoid subpannicular placement, which has been associated with inconsistent results because of contracture despite texturing, and a high rate of implant exposure secondary to trauma. Each rat (N = 43) was implanted with two devices--one smooth-surface 6-ml implant and one textured Biocell 6-ml implant--both with remote ports to allow for biomechanical analysis. Evaluation was carried out at 1, 2, and 3 months (n = 10) and 6 months (n = 5). Biomechanical evaluation of the implants was carried out in vivo and anonymously. The animals were then killed, and sectioning of the overlying capsule-implant interface from the dome of the implant was performed. Histological evaluation was carried out anonymously with regards to the implant type. Capsular contracture developed in smooth-surface devices in 95% of sites; this became evident on biomechanical analysis at 2 months and progressed to 3 months, after which it remained relatively stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Using a biomechanical model designed to reproduce the forces exerted by the soft tissues of the chest wall, the contours created by several currently available round as well as anatomically shaped tissue expanders were evaluated. Parameters that describe expander shape were defined, the most useful of which proved to be the point of maximal projection and the percentage of upper pole deformity. Direct comparison of seven different expanders with respect to these variables revealed the anatomically shaped expanders to offer improved contours over traditional round designs. Continuing modifications in expander design should focus on lowering the point of maximal projection and minimizing the upper pole deformity.

The purpose of this study was to assess and evaluate the role of transforming growth factor-beta(1), epidermal growth factor, and their respective carriers (collagen and liposomes) in the early phases of the wound-healing process in linear incision wounds; we used an in vivo biomechanical testing system. One hundred twenty specific pathogen-free male Sprague-Dawley rats were divided into five experimental groups (n = 24), including one group receiving no treatment at all. Each animal received one abdominal midline incision. At 3 and 5 days after wounding, 12 animals per group were randomly selected for in vivo biomechanical evaluation. Specimens were also randomly obtained from nondisrupted tissues for histologic analysis. Statistical analysis comparing groups revealed that transforming growth factor-beta(1) significantly increased wound strength at day 5, and liposomes decreased wound strength at day 3. There were no other significant differences among groups for each of the time intervals studied. Our results suggest that in vivo biomechanical evaluation of tissue response to injury and treatments will add new dimension to future studies of skin and wound healing.

Biomechanical studies of wound strength are important because of new investigations in growth factors, cytokines, and fetal wounds. We compared two traditional methods of wound disruption measurement with a novel computerized model designed for in vivo experiments. An Instron tensiometer (INSTS) and an air insufflated positive pressure device (AIPPD) were compared with a vacuum-controlled wound chamber device (VCWCD). The VCWCD produced vacuum at the wound site and wound disruption was monitored with two video camera/recorders. Rats were marked with a template guide for a 2.5 cm, full-thickness, abdominal incisional wound. Rats were divided into three groups and studied at 2, 7, or 14 days after wounding. The recorded images were computer digitalized to generate wound strength curves from a three-dimensional model. A comparison of the wound disruption curves demonstrated that the VCWCD was comparable to the INST or AIPPD in normal wound healing (P greater than .40). The VCWCD provided data with less standard error at 2 days after wounding (P less than 05). In separate series of experiments, VCWCD was tested in the early phases of healing and was found to be sensitive to change at intervals of 48 hr after wounding (P less than .005). The INST or AIPPD methods could not perform this task because of an unacceptable level of random error after tissue manipulation. The VCWCD system was considered superior for evaluating early wound healing because it was an in vivo method which required minimal wound manipulation.

Fourth- through seventh-grade children (mean age 11.5 years) estimated the likelihood that various consequences would occur following hypothetical acts of aggression toward victimized and nonvictimized classmates. Children also indicated how much they would care if the consequences were to occur. When contemplating aggression toward victimized classmates, children were more likely to expect tangible rewards, more likely to expect signs of victim suffering, and less likely to expect retaliation than when considering aggression against nonvictimized classmates. Also, when considering aggression toward victimized classmates, children cared more about securing tangible rewards but were less disturbed by the thought of hurting their victims or by the thought of their victims retaliating than when imagining aggression toward nonvictimized classmates. The foregoing pattern was stronger for boys than for girls. Implications for theories of aggression and for intervention with aggressive and victimized children are discussed.

Two differential eyelid conditioning studies employed grammatically correct and incorrect adjective-noun phrases as conditioned stimuli. For different groups of subjects, the nouns were either high or low in imagery. The hypothesis that congruency between grammatical correctness and reinforcement consequences (i.e., the aversive stimulus contingent upon presence of incorrect rather than correct grammar) would facilitate conditioned discrimination was not supported, but the hypothesis that high noun imagery would facilitate differential response to syntax received strong support. Cognitive awareness of the syntactic discriminandum was also related to effective differential responding, as well as being implicated as a mediating mechanism in the imagery effects. Finally, performance was also significantly related to conditioned-response topography, with better conditioned discrimination by voluntary-form (V) than by conditioned-form (C) responders, and also evidence of more effective utilization of contingency awareness by Vs than by Cs.

This research explored links between aggression in elementary school children and 2 classes of social cognitions that might influence children's decisions about whether to behave aggressively. Aggressive and nonaggressive children (mean age 11.3 years) responded to 2 questionnaires. One questionnaire measured children's perceptions of their abilities to perform aggression and related behaviors (perceptions of self-efficacy), and the other measured children's beliefs about the reinforcing and punishing consequences of aggression (response-outcome expectancies). Compared to nonaggressive children, aggressive subjects reported that it is easier to perform aggression and more difficult to inhibit aggressive impulses. Aggressive children also were more confident that aggression would produce tangible rewards and would reduce aversive treatment by others. There were negligible sex differences in perceived self-efficacy for aggression but large sex differences in anticipated social and personal consequences for aggression, with girls expecting aggression to cause more suffering in the victim and to be punished more severely by the peer group and by the self. It was concluded that children's knowledge of their capabilities and children's knowledge of the consequences of their actions are factors that need to be taken into account by cognitive models of aggression.

This experiment investigated speed of processing the grammaticality of phrases consisting of the adjective "one" or "two" followed by a singular or plural noun. The subject's task was to press one of two keys, depending upon whether the phrase was grammatically correct or incorrect. There were eight types of phrases, formed by the factorial combinations of singular or plural adjectives, singular or plural nouns, and high or low noun imageD'. These served as within-subjects variables. Between-subjects variables were the factorial combinations of sex of subject, duration of stimulus phrase (.2 or 2.5 sec), and hand assigned to the correct-grammar key. A fourth between-subjects variable was whether or not the subject reported using an artificial phrase-scanning strategy to determine grammaticality. Correct grammar, singular noun form, high noun imagery, and reported use of the strategy all produced highly significant reductions in reaction times. Only 1% of the interactions were significant. A multistage serial processing model that could be based upon Sternberg's additive factor paradigm or even Donders' subtraction method was found to be highly successful in describing the results.