Search

Current investigations of exoplanet biosignatures have focused on static evidence of life, such as the presence of biogenic gases like O2 or CH4. However, the expected diversity of terrestrial planet atmospheres and the likelihood of both "false positives" and "false negatives" for conventional biosignatures motivate exploration of additional life detection strategies, including time-varying signals. Seasonal variation in atmospheric composition is a biologically modulated phenomenon on Earth that may occur elsewhere because it arises naturally from the interplay between the biosphere and time-variable insolation. The search for seasonality as a biosignature would avoid many assumptions about specific metabolisms and provide an opportunity to directly quantify biological fluxes - allowing us to characterize, rather than simply recognize, biospheres on exoplanets. Despite this potential, there have been no comprehensive studies of seasonality as an exoplanet biosignature. Here, we provide a foundation for further studies by reviewing both biological and abiological controls on the magnitude and detectability of seasonality of atmospheric CO2, CH4, O2, and O3 on Earth. We also consider an example of an inhabited world for which atmospheric seasonality may be the most notable expression of its biosphere. We show that life on a low O2 planet like the weakly oxygenated mid-Proterozoic Earth could be fingerprinted by seasonal variation in O3 as revealed in its UV Hartley-Huggins bands. This example highlights the need for UV capabilities in future direct-imaging telescope missions (e.g., LUVOIR/HabEx) and illustrates the diagnostic importance of studying temporal biosignatures for exoplanet life detection/characterization.

Ocean-atmosphere chemistry on Earth has undergone dramatic evolutionarychanges through its long history, with potentially significant ramificationsfor the emergence and long-term stability of atmospheric biosignatures. Thougha great deal of work has centered on refining our understanding of falsepositives for remote life detection, much less attention has been paid to thepossibility of false negatives, that is, cryptical biospheres that arewidespread and active on a planet's surface but are ultimately undetectable ordifficult to detect in the composition of a planet's atmosphere. Here, wesummarize recent developments from geochemical proxy records and Earth systemmodels that provide insight into the long-term evolution of the most readilydetectable potential biosignature gases on Earth - oxygen (O2), ozone (O3), andmethane (CH4). We suggest that the canonical O2-CH4 disequilibrium biosignaturewould perhaps have been challenging to detect remotely during Earth's ~4.5billion year history and that in general atmospheric O2/O3 levels have been apoor proxy for the presence of Earth's biosphere for all but the last ~500million years. We further suggest that detecting atmospheric CH4 would havebeen problematic for most of the last ~2.5 billion years of Earth's history.More broadly, we stress that internal oceanic recycling of biosignature gaseswill often render surface biospheres on ocean-bearing silicate worlds cryptic,with the implication that the planets most conducive to the development andmaintenance of a pervasive biosphere will often be challenging to characterizevia conventional atmospheric biosignatures.

To analyze the effect of intravenous (IV) iron administration on surgical outcomes for patients undergoing benign hysterectomy and myomectomy. Retrospective cohort study. Academic hospital/tertiary care center. All patients who underwent benign hysterectomy or myomectomy between 2013-2022 and had a pre-operative hemoglobin documented within 1 year of surgery (n=2858). Cohorts comparisons were based on whether patients did or did not receive IV iron prior to surgery. Pre-operative administration of IV iron. Of the 2858 patients included in the study, 420 patients received IV iron (15%). Ferric carboxymaltose was the most common iron formulation used (78%); patients received an average of 1.6 doses of IV iron. Patients who received IV iron had lower pre-operative hemoglobin (10.8 g/dL v 13.0 g/dL no iron, p<0.0001), were more likely to undergo laparotomy (v minimally invasive surgical routes) (43% v 21% no iron, p<0.0001) or myomectomy (v hysterectomy) (31% v 13% no iron, p<0.0001). Surgical outcomes for patients who received IV iron included longer duration (2.8 hours v 2.6 hours, p<0.0001), greater EBL (330 mL v 198 mL , p<0.0001), and longer hospital stay (2.2 days v 1.9 days, p=0.003) compared to patients who did not receive IV iron. Multivariable logistic regression investigating factors contributing to the need for post-operative blood transfusion identified IV iron as significantly associated with reduced odds of transfusion (adjusted odd's ratio (aOR) 0.43 (95% CI [0.23,0.77])), independent of other significantly associated factors (aOR, p): myomectomy (2.01, p=0.02), laparotomy (2.02, p=0.02), surgical duration (1.3, p=0.02), EBL (1.002, p<0.0001), and lower pre-operative hemoglobin (0.59, p<0.0001). Patients who received IV iron appeared to have more clinically complex surgeries with greater blood loss, surgical duration, myomectomy, and open approach. Though patients had lower starting hemoglobin values and these cases were more complex, IV iron showed a significant effect on reducing rates of blood transfusion. [ABSTRACT FROM AUTHOR]

AirSeal insufflation devices have been used to improve continuous pneumoperitoneum in minimally invasive surgery. This study compared adverse event reports (AEs) amongst AirSeal devices. A secondary analysis of the Manufacturer and User Facility Device Experience (MAUDE)-a voluntary reporting system by the Food and Drug Administration. N/A. Between 2014-present, 414 AEs involving AirSeal devices were identified. N/A. 414 AEs were identified, estimating a complication rate of 0.01% for AirSeal devices (approx. 4 million devices manufactured over 10 years). Most AEs did not result in harm to patients (N=269, 66.0%). Material fragmentation/separation of AirSeal components was the device problem in 54.3% of reports. Most AEs involved portions of the trocar (N=282, 68.1%): the shaft (16.7%), tip (39.0%), and cap (33.7%). Patient complications included: retained foreign body (24.8%), air embolism (22.1%), subcutaneous emphysema (18.6%), and pneumothorax (9.7%). Of those with retained foreign body (N=37), the majority (N=24) related to the AirSeal cap. When the surgical service was known (N=307), AEs were most reported during urologic surgery (N=82, 26.7%) followed by gynecologic surgery (N=55, 17.9%). Distribution of complication type was different between gynecologic and non-gynecologic procedures (p=0.003). Gynecologic surgeries had less reports of air embolism, pneumothorax, and retained foreign objects, but more events of subcutaneous emphysema and tissue injury compared to non-gynecologic surgeries. Over ten years, 414 AEs were reported involving AirSeal devices, representing an adverse event rate of 0.01%. Reassuringly, most reports had no direct patient impact. The most common device problem was material fragmentation/separation; the AirSeal cap was involved in most retained foreign bodies. Gynecologic surgeries had a distinct complication profile compared to other surgical services. While AirSeal offers improved maintenance of pneumoperitoneum in minimally invasive surgeries, surgeons must be aware of potential added surgical complications from this device. [ABSTRACT FROM AUTHOR]

To compare rates of cardiometabolic outcomes in patients with fibroids who underwent no surgery (NS), hysterectomy (H), or myomectomy (M). A retrospective cohort study was developed from IBM MarketScan® Research Databases- a fully adjudicated, deidentified database from ICD9/10 and CPT claims collected by health plans- comparing cardiometabolic event prevalence and incidence in patients with fibroids. National database review. The cohort included: female sex, aged 18-55, fibroid diagnosis in 2010, and continuous enrollment through 2021 in MarketScan®; n= 20525. Patients self-selected for surgical management of fibroids in 2010 including no surgery (n=15551, 75.8%), hysterectomy (n=4045, 19.7%), or myomectomy (n=929, 4.5%). Chi-squared analyses were performed to compare patients with no surgery, hysterectomy, or myomectomy using SAS v9.4. Patients with prevalent disease were excluded in analyses of incident disease. Baseline prevalence of coronary artery disease (CAD) (1.4%NS, 1.7%H, 1.1%M), cerebrovascular disease (CVD) (1.2%NS, 1.2%H, 1.4%M), and diabetes mellitus (DM) (6.4%NS, 7.2%H, 5.4%M) was not different between the 3 intervention groups. At baseline, groups had significantly different rates of hypertension (HTN) (23.5%NS, 30.1%H, 20.6%M, p<0.0001) and hyperlipidemia (HLD) (20.3%NS, 20.9%H, 16.3%M, p=0.006). Incidence of CAD (8.8%NS, 9.8%H, 5.6%M, p=0.0003), HTN (43.2%NS, 46.7%H, 38.2%M, p<0.0001), CVD (8.0%NS, 9.0%H, 6.3%M, p=0.016), DM (18.0%NS, 20.5%H, 16.7%M, p=.001) and HLD (56.7%NS, 60.7%H, 46.1%M, p<0.0001) were significantly different with myomectomy having lowest rates of disease incidence and hysterectomy having the highest. Patients with fibroids who underwent myomectomy had significantly lower rates of developing HTN, CAD, CVD, DM, and HLD than patients who had a hysterectomy or no surgery. Patients who underwent hysterectomy had the highest incidence of all analyzed cardiometabolic outcomes. While additional study is needed to assess contribution of comorbid factors to cardiometabolic outcomes, myomectomy may have cardio-protective effects in management of fibroids. [ABSTRACT FROM AUTHOR]

To identify, quantify and evaluate quality of social media content about fibroids. The top 100 "liked" Facebook and TikTok posts with "#fibroids" were identified via the web-scraping application, Apify. Two reviewers separately evaluated creator demographics and content for English language fibroid-related posts. Discrepancies were re-reviewed. Information quality was assessed using the DISCERN instrument, while post understandability and actionability were measured with the Patient Education Materials Assessment Tool (PEMAT). IRB exemption was obtained. Online. Not applicable. None (observational study). Top "liked" 200 social media posts were analyzed (100 each from Facebook and TikTok) from October 19, 2019, to March 25, 2024. All TikTok posts and most Facebook posts (78%) were videos. TikTok content garnered higher engagement than Facebook with 23,150 median "likes" (IQR 14,425-47,350) and 510,800 median views (IQR 299,975-991,775). Most posts were by women (61.5%). TikTok creators were younger than Facebook (67% vs 36% age 20-40 years, p<0.001). Creators were predominantly patients on TikTok (48%) versus promoters of alternative medicine on Facebook (56%) (p<0.001); healthcare providers generated 17.5% of posts between both platforms. Content categories included promotional (56%), diet/supplements (55.5%), patient experience (32%), awareness (31%), education (29.5%), and surgery (24.5%). Myomectomy was discussed more than hysterectomy (14.0 vs 10.5%), and open surgery more than minimally invasive (11.5% vs 4.5%). Symptom discussion was limited (43% of posts), with bleeding (28%) and pain (22%) the most mentioned. Twenty-five percent of posts expressed delays in diagnosis of fibroids and/or distrust in healthcare providers or systems. DISCERN scores (mean 27.77, SD 9.8) indicated poor information quality, while PMAT scores (mean 94%, SD 10.8%) showed high understandability. Many patients turn to social media for guidance regarding fibroids and management options, yet evidence-based information is lacking. Improved efforts by healthcare providers and organizations are needed to ensure reliable content and promote awareness of sound treatment options. [ABSTRACT FROM AUTHOR]

This study was a prospective 2-year longitudinal investigation of associations between negative maternal parenting and disruptive child behavior across the preschool to school transition. Our main goals were to 1) determine the direction of association between early maternal negativity and child disruptive behaviors across this important developmental transition and 2) examine whether there would be different patterns of associations for boys and girls. Participants were 235 children (111 girls; T1; M = 37.7 months, T2; M = 63.4 months) and their mothers and teachers. Observational and multi-informant ratings of child disruptive behavior showed differential patterns of stability and associations with measures of parenting risk. Results indicated bidirectional and interactive contributions of externalizing behavior and negative parenting across time. Results also indicated that risk mechanisms operate similarly for both sexes. Findings support transactional models of disruptive child behavior that highlight the joint contributions of parents and children. [ABSTRACT FROM AUTHOR]

We examined the intergenerational transmission of physical punishment (PP) and whether marital satisfaction moderated this transmission. Participants were 241 mothers and 107 fathers with a three year-old child who completed a semi-structured interview assessing their endorsement of disciplinary methods and the methods their parents used to discipline them. Marital satisfaction was assessed using the Conflicts and Problem Solving Scales. Different predictive models were obtained for mothers and fathers. For mothers, socioeconomic status (SES) and their own mother's use of PP significantly predicted their current endorsement of PP. For fathers, SES and perceived harshness of childhood discipline predicted current endorsement of PP. Marital satisfaction moderated the intergenerational transmission of PP for fathers, but not mothers. Results indicated that PP by the same-sex parent and SES are important factors in its intergenerational transmission, and that the effects of childhood PP on current endorsement may be more direct for mothers and indirect for fathers. [ABSTRACT FROM AUTHOR]

Background: Existing measures of self-reported shoulder function fail to measure effectively the full range of shoulder functioning. The classic approach for improving the reliability of a scale is adding items, but a scale with a substantial number of items imposes a large response burden on participants. A more efficient approach is to use modern psychometric methods to construct an adaptive scale in which patients respond only to items that are targeted at their level of shoulder function.Methods: We developed a Flexilevel Scale of Shoulder Function (FLEX-SF). This scale includes three testlets that target low, medium, and high shoulder function. Scores on the testlets were equated to a common mathematical metric.Design and Subjects: We developed an initial pool of 68 items. This pool was administered to 400 patients, and responses were calibrated using a rating scale model. Subsets of items were identified for an easy, medium difficulty, and hard testlet. Properties of the scale were evaluated in a 3-month longitudinal study of 200 shoulder patients.Results: The FLEX-SF exhibited high reliability at both the scale level (intraclass correlation coefficient [3,1] = 0.90) and specific trait levels. The validity of the FLEX-SF was supported by its internal and external responsiveness (Guyatt responsiveness index = 1.12) and the pattern of its associations with other health status measures.Conclusions: The FLEX-SF can be used as a primary endpoint in clinical trials even when there are relatively few people in each treatment group. The scale also has excellent properties for use in clinical settings tracking individual changes over time. [ABSTRACT FROM AUTHOR]

Maternal concepts of desirable and undesirable child characteristics were compared across two contrastive cultures: Japan and the United States. Sixty mothers of preschool-age children, half from Japan and half from the United States, were asked to describe the behavioral characteristics they found most desirable and undesirable in young children and to choose one characteristic in each list that they considered most highly positive or negative. In describing positive characteristics, mothers in both cultures tended to emphasize social cooperativeness and interpersonal sensitivity. However, concerns about positive emotional adjustment were more salient among U.S. than Japanese mothers. Comparisons of negative behaviors revealed striking cultural contrasts. U.S. mothers were far more likely than Japanese mothers to designate aggressive and disruptive behaviors as negative, whereas Japanese mothers tended to highlight social insensitivity and uncooperativeness. Moreover, qualities of emotional maladjustment were described by U.S. mothers, but did not appear in the Japanese protocols. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Myofascial trigger points (TPs) are found among patients who have neck and upper back pain. The purpose of this study was to determine the effectiveness of a home program of ischemic pressure followed by sustained stretching for the treatment of myofascial TPs. SUBJECTS: Forty adults (17 male, 23 female), aged 23 to 58 years (mean=30.6, SD=9.3), with one or more TPs in the neck or upper back participated in this study. METHODS: Subjects were randomly divided into 2 groups receiving a 5-day home program of either ischemic pressure followed by general sustained stretching of the neck and upper back musculature or a control treatment of active range of motion. Measurements were obtained before the subjects received the home program instruction and on the third day after they discontinued treatment. Trigger point sensitivity was measured with a pressure algometer as pressure pain threshold (PPT). Average pain intensity for a 24-hour period was scored on a visual analog scale (VAS). Subjects also reported the percentage of time in pain over a 24-hour period. A multivariate analysis of covariance, with the pretests as the covariates, was performed and followed by 3 analyses of covariance, 1 for each variable. RESULTS Differences were found between the treatment and control groups for VAS scores and PPT. No difference was found between the groups for percentage of time in pain. CONCLUSION AND DISCUSSION: A home program, consisting of ischemic pressure and sustained stretching, was shown to be effective in reducing TP sensitivity and pain intensity in individuals with neck and upper back pain. The results of this study indicate that clinicians can treat myofascial TPs through monitoring of a home program of ischemic pressure and stretching. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Shoulder scales are often used to evaluate treatment efficacy, yet little is known about the psychometric properties of these scales. Only one scale has undergone psychometric scrutiny: the Shoulder Pain and Disability Index (SPADI). This study compared 2 shoulder measures-the University of California-Los Angeles (UCLA) Shoulder Scale and the Simple Shoulder Test (SST)-with the SPADI. SUBJECTS: One hundred ninety-two patients with shoulder disorders were recruited from one physician's office to complete the self-report sections of the 3 scales. METHODS: Cronbach alpha values and standard errors of measurement (SEM) were calculated for each of the multi-item subscales. Validity was examined through calculation of correlation coefficients among the 3 scales. Factor analysis was completed to assess the underlying constructs of the SPADI and the SST. RESULTS: Cronbach alpha values ranged from.85 to.95. The SEM values for the multi-item scales ranged from 4.75 to 11.65. Evidence for validity to reflect function was indicated by the correlation between the SST and the SPADI disability subscale. The factor analysis of the SPADI revealed loading on 1 factor, whereas the SST loaded on 2 factors. CONCLUSION AND DISCUSSION: All scales demonstrated good internal consistency, suggesting that all items for each scale measure the same construct. However, the SEMs for all scales were high. Factor loading was inconsistent, suggesting that patients may not distinguish between pain and function. [ABSTRACT FROM AUTHOR]

The high prevalence of shoulder-related dysfunction has focused increased attention on functional activity assessment. This study (1) tested the reliability of three-dimensional shoulder complex movements during four functional tasks representing different levels of task difficulty, (2) characterized the four functional tasks, and (3) examined the relationships between age and shoulder movements. Twenty-five asymptomatic subjects, all veterans aged 30-82, performed the four functional tasks. Good within-session reliability was found (movement pattern: similarity index = 0.81 to 0.97, peak values: intraclass correlation coefficients = 0.88 to 0.99). The raising arm to overhead height task (hard task) placed the greatest demand on scapular motions and humeral elevation (p < 0.005). During the functional tasks, significant correlations existed between age and scapular tipping, humeral elevation, and scapular upward rotation (r = -0.62 to 0.50, p < 0.05). Correlation results indicated that elderly subjects have a greater potential for serratus anterior muscle weakness and shoulder capsule tightness. [ABSTRACT FROM AUTHOR]

Background: The Global Iliac Branch Study (NCT05607277) is an international, multicenter, retrospective cohort study of anatomic predictors of adverse iliac events (AIEs) in aortoiliac aneurysms treated with iliac branch devices (IBDs)., Methods: Patients with pre-IBD and post-IBD computed tomography imaging were included. We measured arterial diameters, stenosis, calcification, bifurcation angles, and tortuosity indices using a standardized, validated protocol. A composite of ipsilateral AIE was defined, a priori, as occlusion, type I or III endoleak, device constriction, or clinical event requiring reintervention. Paired t-test compared tortuosity indices and splay angles pretreatment and post-treatment for all IBDs and by device material (stainless steel and nitinol). Two-sample t-test compared anatomical changes from pretreatment to post-treatment by device material. Logistic regression assessed associations between AIE and anatomic measurements. Analysis was performed by IBD., Results: We analyzed 297 patients (286 males, 11 females) with 331 IBDs (227 stainless steel, 104 nitinol). Median clinical follow-up was 3.8 years. Iliac anatomy was significantly straightened with all IBD treatment, though stainless steel IBDs had a greater reduction in total iliac artery tortuosity index and aortic splay angle compared to nitinol IBDs (absolute reduction -0.20 [-0.22 to -0.18] vs. -0.09 [-0.12 to -0.06], P < 0.0001 and -19.6° [-22.4° to -16.9°] vs. -11.2° [-15.3° to -7.0°], P = 0.001, respectively). There were 54 AIEs in 44 IBDs in 42 patients (AIE in 13.3% of IBD systems), requiring 35 reinterventions (median time to event 41 days; median time to reintervention 153 days). There were 18 endoleaks, 29 occlusions, and 5 device constrictions. There were no strong associations between anatomic measurements and AIE overall, though internal iliac diameter was inversely associated with AIE in nitinol devices (n AIE, nitinol  = 8)., Conclusions: Purpose-built IBDs effectively treat aortoiliac disease, including that with tortuous anatomy, with a high patency rate (91.5%) and low reintervention rate (9.1%) at 4 years. Anatomic predictors of AIE are limited., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: As surgical residents continue in their training, they are expected to not only take part in more complicated procedures, but to also serve as leaders in their respective care teams. While surgical skills are intensively taught in surgical residency programs, leadership is often learned informally, to the detriment of residents. Our curriculum was developed and implemented to provide foundational knowledge for surgical residents as they take on senior roles so that they may successfully act as leaders. This educational workshop was effective and efficient and can be applied at other residency programs that seek to improve the leadership skills of their residents., Design: Implementation of a 3-day program focused on leadership, surgical skills, and career development to provide rising PGY-4 surgical residents with the abilities necessary for successful training., Setting: This program was implemented at the University of Minnesota General Surgery residency program., Participants: Rising PGY-4 general surgery residents., Results: The program consisted of a 3-day workshop which all rising PGY-4 residents participating in before transitioning into their respective roles. The program was led by the general surgery faculty., Conclusions: Curricula focused on developing leadership skills in residents can be effectively applied in a time-efficient manner that can benefit the residents as they move into official leadership roles on the care team., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

This study aimed to examine independent and interactive contributions of parenting behaviors (e.g., physical punishment, inductive discipline, warm responsiveness) and child effortful control on child externalizing problems during early and middle childhood. Participants were 241 children (123girls) of middle-income families in the U.S. who were primarily European Americans (91%) and at risk for school-age problem behaviors. Data were collected at ages 3, 6, and 10 using multiple methods, informants, and contexts. Results of hierarchical regression analyses indicated both independent and interactive influences of parenting behaviors and child effortful control on children's externalizing behaviors. Importantly, effortful control buffered the negative influence of physical punishment, but not other parenting behaviors, such that physical punishment was associated with external behaviors at 6 years only for children with poorer effortful control abilities. The results highlight both parental discipline strategies and child effortful control as promising targets for early identification and prevention of future problem behaviors. Summary: Parenting and child effortful control have long been topics of research on child development. However, relatively little is known about the long-term effects of early parenting in the context of effortful control and the possibility that those processes may differ across different dimensions of parenting (i.e., warm responsiveness, inductive discipline, and physical punishment) Therefore, this study aimed to examine independent and interactive contributions of parenting behaviors and child effortful control on child externalizing problems during early and middle childhood. Participants were 241 children (123girls) of middle-income families who were at risk for school-age problem behaviors. Data were collected using multiple methods, informants, and contexts. Specifically, child effortful control at 3 years was measured using multiple tasks, and parenting at 3 years was assessed via maternal report during home interview. Teachers contributed ratings of child externalizing behaviors at 3, 6, and 10 years. Results indicated both independent and interactive influences of parenting behaviors and child effortful control on children's externalizing behaviors. Importantly, effortful control buffered the negative influence of physical punishment, but not other parenting behaviors, such that physical punishment was associated with external behaviors at 6 years only for children with poorer effortful control abilities. Moreover, parents' use of physical punishment at age 3 showed a long-lasting association with children's problem behaviors at ages 6 and 10 years. The findings suggest that children with more advanced effortful control may be less susceptible to long-term detrimental contribution of physical punishment, although by no means they are protected from harmful effects of punitive discipline. This study provides more sophisticated explanations on the influence of early parenting and child effortful control on externalizing behaviors spanning early to middle childhood. The results also highlight different parental discipline strategies and child effortful controls as promising targets for early identification and prevention of children's future problem behaviors in childhood., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Interoceptive signals dynamically interact with the environment to shape appropriate defensive behaviors. Hypothalamic hormones arginine-vasopressin (AVP) and oxytocin (OT) regulate physiological states, including water and electrolyte balance, circadian rhythmicity, and defensive behaviors. Both AVP and OT neurons project to dorsolateral bed nucleus of stria terminalis (BNST DL ), which expresses oxytocin receptors (OTR) and vasopressin receptors and mediates fear responses. However, understanding the integrated role of neurohypophysial hormones is complicated by the cross-reactivity of AVP and OT and their mutual receptor promiscuity. Here, we provide evidence that the effects of neurohypophysial hormones on BNST excitability are driven by input specificity and cell type-specific receptor selectivity. We show that OTR-expressing BNST DL neurons, excited by hypothalamic OT and AVP inputs via OTR, play a major role in regulating BNST DL excitability, overcoming threat avoidance, and reducing threat-elicited anxious arousal. Therefore, OTR-BNST DL neurons are perfectly suited to drive the dynamic interactions balancing external threat risk and physiological needs., Competing Interests: 6.Declaration of interest The authors declare no competing interest. JD reports US patent 11,559,231 issued on 1.24.2023 entitled: System and method for determining a discrimination index for fear-potentiated startle, which has no competing interest with the current study.

Are children from "Eastern" cultures less emotionally expressive and reactive than children from "Western" cultures? To answer this, we used a multi-level and multi-contextual approach to understand variations in emotion displays and cortisol reactivity among preschoolers living in China and the United States. One hundred two preschoolers from China (N = 58; 55% males) and the United States (N = 44, 48% males) completed three (i.e., control, interpersonal-related, and achievement-related) emotion-challenging paradigms over 3 days. Behavioral emotion expressions were coded, and salivary cortisol was sampled 30 minutes before and across 90 minutes post-task. Without considering context, Chinese preschoolers displayed fewer levels of positive and negative emotion expressions relative to their United States counterparts. However, Chinese preschoolers displayed similar levels of expressions as their United States counterparts during an achievement-related challenge that is more salient to their sociocultural emphases and showed higher negative emotion expressions in this challenge, relative to other contexts. Moreover, only the achievement-related challenge elicited increased cortisol levels among Chinese preschoolers, and this was correlated with higher levels of negative expressions. For US preschoolers, no cortisol increase was observed in any challenging paradigms, nor was cortisol associated with emotional expressions. Findings counter prior notions that East Asian children are generally less emotionally expressive. Instead, an achievement-related challenge elicited higher emotion expression and cortisol reactivity among Chinese preschoolers, suggesting that children's emotion expression and biological reactivity may be most responsive to contexts salient to their socio-cultural environments. We discuss the importance of considering cultural contexts when studying emotion regulation. RESEARCH HIGHLIGHTS: Chinese preschoolers displayed lower overall positive and negative expressions relative to their US counterparts without considering situational contexts. Chinese preschoolers displayed similar levels of emotion expressions as their US counterparts during an achievement-related challenge salient to their social-cultural environment. Chinese preschoolers are particularly responsive to achievement-related challenges, relative to other emotion-challenging situations that are less culturally salient. No cortisol increase was observed in any of the emotion-challenging paradigms among US preschoolers. Children's emotion expression and biological reactivity may be most responsive to challenges relevant to their socio-cultural environments., (© 2023 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Introduction: Frailty and sarcopenia are associated with an increased risk of hospitalization and mortality in patients with end-stage liver disease. The ability to identify frail patients at risk of adverse outcomes could help optimize liver transplant (LT) evaluations and pre-transplant care. This study compared sarcopenia, via L3-psoas muscle index (L3-PMI), to frailty, via liver frailty index (LFI) and analyzed associated outcomes after liver transplantation (LT)., Methods: A retrospective review of consecutive LT-recipients with cross-sectional abdominal/pelvic imaging were reviewed over 5 years at a single transplant center., Results: Four hundred and twenty-six patients underwent transplant during this study interval; 31% of patients were sarcopenic. Two hundred eight patients underwent LFI evaluation: 25% were frail, 59% were prefrail, and 16% were robust. Sarcopenic patients had higher LFI scores indicating greater frailty (p = 0.02). Both sarcopenia and LFI-frailty were associated with significantly higher MELD-Na scores. Length of post-LT hospital stay was increased in sarcopenic (mean 14 vs. nonsarcopenic 11 days, p = 0.02) and LFI-frail patients (mean 13 vs. 10 prefrail, 8 robust, p = 0.04). As a categorical variable, neither LFI-frailty nor sarcopenia were significantly associated with reduced survival at 1-year (robust 100%, prefrail 93.5%, frail 91.1%, p = 0.31) (nonsarcopenic 94.4%, sarcopenic 91.4%, p = 0.30). However, LFI score was significantly associated with mortality at 1-year (OR 2.133, p = 0.047)., Conclusions: Radiographic sarcopenia is a suitable proxy for in-person frailty assessment as both L3-PMI and LFI capture frail patients' pre-LT. However, physical assessment with frailty better predicts 1-year mortality post-LT than the measurement of muscle mass., (© 2024 The Author(s). Clinical Transplantation published by Wiley Periodicals LLC.)

Background: Doxycycline has been shown to prevent arterial calcification via attenuation of matrix metalloproteinases (MMP) in preclinical models. We assessed the effects of doxycycline on progression of arterial calcification in patients enrolled in the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA 3 CT)., Methods: Two hundred and sixty-one patients were randomized to 100 mg doxycycline twice daily or placebo. Arterial calcification was measured in abdominal vessels on noncontrast computed tomography scans. Patients with baseline computed tomography scan and 1 or more follow-up scans within the 2-year study were included for analysis. For individual arteries, mean change in iliofemoral artery calcification over time was calculated via linear regression. Serum MMP-3 and MMP-9 levels were measured at baseline and 6 months., Results: Sixty-five patients in the doxycycline and 66 in the placebo arm were included in this analysis. Baseline characteristics between the groups were similar. The unadjusted mean change in iliofemoral calcium score per year trended toward higher values in patients treated with doxycycline compared with placebo (322 ± 399 units/year vs. 217 ± 307 units/year, P = 0.09). After 6 months, changes in serum MMP-3 and MMP-9 levels were not significantly different between study arms., Conclusions: In patients with small aortic aneurysm, treatment with doxycycline 100 mg twice daily did not decrease circulating levels of the matrix degrading enzymes MMP-3 and 9 or alter the progression of arterial calcification., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Uterine fibroids are the most common tumors in females affecting up to 70% of women world-wide, yet targeted therapeutic options are limited. Oxidative stress has recently surfaced as a key driver of fibroid pathogenesis and provides insights into hypoxia-induced cell transformation, extracellular matrix pathophysiology, hypoxic cell signaling cascades, and uterine biology. Hypoxia drives fibroid tumorigenesis through (1) promoting myometrial stem cell proliferation, (2) causing DNA damage propelling transformation of stem cells to tumor initiating cells, and (3) driving excess extracellular matrix (ECM) production. Common fibroid-associated DNA mutations include MED12 mutations, HMGA2 overexpression, and Fumarate hydratase loss of function. Evidence suggests an interaction between hypoxia signaling and these mutations. Fibroid development and growth are promoted by hypoxia-triggered cell signaling via various pathways including HIF-1, TGFβ, and Wnt/β-catenin. Fibroid-associated hypoxia persists due to antioxidant imbalance, ECM accumulation, and growth beyond adequate vascular supply. Current clinically available fibroid treatments do not take advantage of hypoxia-targeting therapies. Growing pre-clinical and clinical studies identify ROS inhibitors, anti-HIF-1 agents, Wnt/β-catenin inhibition, and TGFβ cascade inhibitors as agents that may reduce fibroid development and growth through targeting hypoxia.

The purpose of this article is to review the effects of four commonly consumed beverage types-sugar-sweetened beverages (SSBs), caffeinated beverages, green tea, and alcohol-on five common benign gynecological conditions: uterine fibroids, endometriosis, polycystic ovary syndrome (PCOS), anovulatory infertility, and primary dysmenorrhea (PD). Here we outline a plethora of research, highlighting studies that demonstrate possible associations between beverage intake and increased risk of certain gynecological conditions-such as SSBs and dysmenorrhea-as well as studies that demonstrate a possible protective effect of beverage against risk of gynecological condition-such as green tea and uterine fibroids. This review aims to help inform the diet choices of those with the aforementioned conditions and give those with uteruses autonomy over their lifestyle decisions., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest.

Objective: Endovascular repair is the preferred treatment for aortoiliac aneurysm, with preservation of at least one internal iliac artery recommended. This study aimed to assess pre-endovascular repair anatomical characteristics of aortoiliac aneurysm in patients from the Global Iliac Branch Study (GIBS, NCT05607277) to enhance selection criteria for iliac branch devices (IBD) and improve long-term outcomes., Methods: Pre-treatment CT scans of 297 GIBS patients undergoing endovascular aneurysm repair were analyzed. Measurements included total iliac artery length, common iliac artery length, tortuosity index, common iliac artery splay angle, internal iliac artery stenosis, calcification score, and diameters in the device's landing zone. Statistical tests assessed differences in anatomical measurements and IBD-mediated internal iliac artery preservation., Results: Left total iliac artery length was shorter than right (6.7 mm, P = .0019); right common iliac artery less tortuous (P = .0145). Males exhibited greater tortuosity in the left total iliac artery (P = .0475) and larger diameter in left internal iliac artery's landing zone (P = .0453). Preservation was more common on right (158 unilateral, 34 bilateral) than left (105 unilateral, 34 bilateral). There were 192 right-sided and 139 left-sided IBDs, with 318 IBDs in males and 13 in females., Conclusion: This study provides comprehensive pre-treatment iliac anatomy analysis in patients undergoing endovascular repair with IBDs, highlighting differences between sides and sexes. These findings could refine patient selection for IBD placement, potentially enhancing outcomes in aortoiliac aneurysm treatment. However, the limited number of females in the study underscores the need for further research to generalize findings across genders., (© 2024. The Author(s).)

Although internalizing problems are the most common forms of psychological distress among adolescents and young adults, they have precursors in multiple risk domains established during childhood. This study examined cascading risk pathways leading to depression and anxiety symptoms in emerging adulthood by integrating broad contextual (i.e., multiple contextual risks), parental (i.e., negative parenting), and child (i.e., internalizing behaviors) characteristics in early and middle childhood. We also compared common and differential pathways to depression and anxiety symptoms depending on the conceptualization of symptom outcomes (traditional symptom dimension vs. bifactor dimensional model). Participants were 235 children (109 girls) and their families. Data were collected at 3, 6, 10, and 19 years of child age, using multiple informants and contexts. Results from a symptom dimension approach indicated mediation pathways from early childhood risk factors to depression and anxiety symptoms in emerging adulthood, suggesting common and distinct risk processes between the two disorders. Results from a bifactor modeling approach indicated several indirect pathways leading to a general internalizing latent factor, but not to symptom-specific (i.e., depression, anxiety) latent factors. Our findings highlighted comparative analytic approaches to examining transactional processes associated with later internalizing symptoms and shed light on issues of early identification and prevention.

Objective: Endovascular aneurysm repair (EVAR) is a widely used option for patients with suitable vascular anatomy who have a large infrarenal abdominal aortic aneurysm (AAA). Neck diameter is the primary anatomical determinant of EVAR eligibility and device durability. Doxycycline has been proposed to stabilise the proximal neck after EVAR. This study explored doxycycline mediated aortic neck stabilisation in patients with small AAA, monitored by computed tomography over two years., Methods: This was a multicentre prospective randomised clinical trial. Subjects from the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA 3 CT, NCT01756833) were included in this secondary a priori analysis. Female baseline AAA maximum transverse diameter was between 3.5 and 4.5 cm, and male was between 3.5 and 5.0 cm. Subjects were included if they completed pre-enrolment and two year follow up computed tomography (CT) imaging. Proximal aortic neck diameter was measured at the lowest renal artery, and 5, 10, and 15 mm caudal to this point; mean neck diameter was calculated from these values. Unpaired, two tailed parametric t test analysis with post hoc Bonferroni correction was used to detect differences between neck diameters in subjects treated with placebo vs. doxycycline at baseline and two years., Results: One hundred and ninety-seven subjects (171 male, 26 female) were included in the analysis. All patients, regardless of treatment arm, demonstrated larger neck diameter caudally, a slight increase in diameter at all anatomical levels over time, and greater growth caudally. There was no statistically significant difference in infrarenal neck diameter between treatment arms at any anatomical level at any time point, nor mean change in neck diameter over two years., Conclusion: Doxycycline does not demonstrate infrarenal aortic neck growth stabilisation in small AAA followed for two years by thin cut CT imaging using a standardised acquisition protocol and cannot be recommended for mitigation of growth of the aortic neck in patients with untreated small abdominal aortic aneurysms., Competing Interests: L.K. is a consultant for Alucent Biomedical. J.N.M. is a cofounder and stockholder of Vessel Wave Technologies and Aquablade. B.K. serves on the WL Gore Scientific Advisory Board. A.P., S.O., B.R., W.B., B.T.B., and S.B. have no conflicts of interest to disclose., (© 2023 The Author(s).)

Background: Evidence of health disparities for Indigenous children requiring surgical care is lacking. We present a systematic review of the literature examining possible disparities in surgical care and outcomes for pediatric patients of Indigenous ethnicity., Data Sources: PubMed, Cochrane, MEDLINE, gray literature., Methods: Literature review, using PubMed, Cochrane, MEDLINE, and gray literature was conducted to identify articles published more than 2010-2020 examining children's surgical health service delivery (epidemiology, access, operations provided) and outcomes for pediatric patients of Indigenous ethnicity compared with others. Extracted data included study design, setting, participant race/ethnicity, operations examined, and surgical outcomes. Article quality was assessed using the Newcastle-Ottawa Scales., Results: From 411 abstracts, 125 articles were reviewed and 33 included for data abstraction. These were cohort and cross-sectional studies investigating a wide range of patient populations and procedures across the United States, Canada, Australia, and New Zealand. Articles were organized naturally by theme into birth malformations (15 articles), trauma (6 articles), pediatric general surgery/appendicitis (5 articles), pediatric otolaryngology (6 articles), and renal transplant (1 article) surgery. Four articles also described access and resource utilization related to inpatient care. Notable disparities observed included apparent increased prevalence of gastroschisis, rates of traumatic fatality, non accidental injury, and self harm among North American Indigenous children., Conclusions: Indigenous children appear to be vulnerable to a number of health and treatment outcome disparities related to conditions treated by surgeons. Surgeons are thus uniquely poised to act in identifying and eliminating Indigenous ethnicity-based pediatric health disparities., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose, (Copyright © 2022. Published by Elsevier Inc.)

Mesenteric artery dissection (D) and wall-thickening (WT) are rare vasculopathies that can lead to serious complications. This is a single center analysis of all patients evaluated for mesenteric arterial (celiac, superior (SMA) and/or inferior mesenteric (IMA)) D and/or WT from January 1, 2000, to January 31, 2020 at our hospital. Among the 101 included patients, the average age was 55.6 ± 13.6 years, mostly affecting men (62%). There were 20 celiac artery D, 8 WT, 15 D with WT, 15 SMA D, 7 WT, 8 D with WT, one IMA D, two WT, and 25 with multiple arterial involvement. Primary etiologies included segmental arterial mediolysis (SAM) (n = 17), isolated D (n = 17), localized vasculitis of the gastrointestinal tract (LVGT) (n = 16), fibromuscular dysplasia (FMD) (n = 13), extension of thoracoabdominal aortic D (n = 12), and trauma (n = 12). Most (71%) patients presented with abdominal pain. Hypertension (55%), hyperlipidemia (33%) and tobacco use (31%) were prevalent. Management included conservative (22%), medical (47%), endovascular (19%), and/or open repair (12%) with high in-hospital survival (98%) and symptom relief (73%). Our paper complements the scarce literature addressing the diagnosis and management of rare mesenteric vasculopathies. Most patients improved with conservative management, reserving endovascular or surgical interventions for symptomatic patients with more complicated presentations.

Objectives: This study reports the learning phase of the minimally invasive anterior lumbar interbody fusion (mini-ALIF) approach with a vascular and orthopaedic spine surgeon team., Methods: Adult patients who underwent primary mini-ALIF at the lowest two segments of the lumbar spine (i.e., L4/5, L5/S1) between January 2010 and December 2018 were analyzed., Results: One hundred twenty-seven patients were included. There was no notable change in total surgical time over the study period. Estimated blood loss markedly decreased until stabilizing at case 30 and slowly declined thereafter. The mean estimated blood loss was 184 mL for L5/S1, 232 mL for L4/L5, and 458 mL for two-level mini-ALIF. There were 20 vascular issues requiring primary repair or packing. Vascular issues declined over time, with a rate of 32% in the first 25 cases and 0% in the last 25. The postoperative complication rate was highest in the first 25 cases (7 of 21 total complications). The odds ratio of vascular injury with body mass index (BMI) > 35 was 4.09 (1.4 to 11.7 confidence interval, P ≤ 0.008). Total surgical time and postoperative complications increased with increasing BMI., Conclusion: Performance of the mini-ALIF approach is associated with a learning curve of 25 to 30 cases before complications begin to decline. BMI > 35 is associated with increased surgical time and complications., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Introduction: The topics of sub-specialization and regionalization of care have garnered increased attention among pediatric surgeons. Thyroid surgeries are one such sub-specialty and are commonly concentrated within practices. A national survey was conducted examining current surgeon practices and beliefs surrounding pediatric thyroid surgery., Methods: Non-resident members of the American Pediatric Surgical Association (APSA) were surveyed in October 2020. Respondents were stratified based on self-reported thyroid surgical experience. Those who performed thyroid surgery were asked about surgical technique and operative practices; those who did not were asked about referral patterns. All respondents were asked about perceptions surrounding the volume-outcome relationship for pediatric thyroid surgery., Results: Among 1015 APSA members, 405 (40%) responded, with 79% (317/400) practicing at academic hospitals, 58% (232/401) practicing in major metropolitan area, and 41% (161/392) with over 10 years of attending pediatric surgery experience. Most respondents (88%, n = 356) agreed that thyroid surgery volume affects outcome, though wide variation was reported in the annual case threshold for "high volume" surgery. Eighty-four respondents (21%) reported performing ≥ 1 pediatric thyroid surgery in the past year. Of these, 82% routinely use recurrent laryngeal nerve monitoring, 32% routinely send hemithyroidectomy patients home the same day, and there was little consensus surrounding postoperative hypocalcemia management. The majority of respondents endorse performing thyroid procedures with a colleague., Conclusions: Pediatric thyroid surgery appears to be performed by a subset of active pediatric surgeons, most of whom endorse the use of a dual operating team. More evidence is needed to build consensus around additional perioperative practices., (Copyright © 2022. Published by Elsevier Inc.)

Background: Pediatric thyroidectomy has been identified as a surgical procedure that may benefit from concentrating cases to high-volume surgeons. This systematic review aimed to address the definition of "high-volume surgeon" for pediatric thyroidectomy and to examine the relationship between surgeon volume and outcomes., Methods: PubMed, Embase, Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, and OpenGrey databases were searched for through February 2020 for studies which reported on pediatric thyroidectomy and specified surgeon volume and surgical outcomes., Results: Ten studies, encompassing 6430 patients, were included in the review. Five single-center retrospective studies reported only on high-volume surgeons, one single center retrospective study reported on only low-volume surgeons, and four national database studies (2 cross sectional, 2 retrospective reviews) reported outcomes for both high-volume and low-volume surgeons. Majority of patients underwent total thyroidectomy (54.9%); common indications for surgery were malignancy (41.7%) and hyperthyroidism/thyroiditis (40.5%). Rates of transient hypocalcemia (11.4% - 74.2%), transient recurrent laryngeal nerve injury (0% - 9.7%), and bleeding (0.5% - 4.3%) varied across studies. Definitions for high-volume pediatric thyroid surgeons ranged from ≥9 annual pediatric thyroid operations to >200 annual thyroid operations (with >30 pediatric cases). Four studies reported significantly better outcomes, including lower post-operative complications and shorter length of hospital stay, for patients treated by high-volume surgeons., Conclusions: Despite significant variation in caseloads to define volume, pediatric thyroid patients have generally better outcomes when operated on by higher volume surgeons. Concentration thyroidectomy cases to a smaller cohort of surgeons within pediatric practices may confer improved outcomes., Level of Evidence: Systematic Reviews and Meta-Analyses; Level IV., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Current management of small abdominal aortic aneurysms (AAAs) primarily involves serial imaging surveillance of maximum transverse diameter (MTD) to estimate rupture risk. Other measurements, such as volume and tortuosity, are less well-studied and may help characterize and predict AAA progression. This study evaluated predictors of AAA volume growth and discusses the role of volume in clinical practice., Methods: Subjects from the Non-invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (baseline AAA MTD, 3.5-5.0 cm) with ≥2 computed tomography scans were included in this study (n = 250). Computed tomography scans were conducted approximately every 6 months over 2 years. MTD, volume, and tortuosity were used to model growth. Univariable and multivariable backwards elimination least squares regressions assessed associations with volume growth., Results: Baseline MTD accounted for 43% of baseline volume variance (P < .0001). Mean volume growth rate was 10.4 cm 3 /year (standard deviation, 8.8 cm 3 /year) (mean volume change +10.4%). Baseline volume accounted for 30% of volume growth variance; MTD accounted for 13% of volume growth variance. More tortuous aneurysms at baseline had significantly larger volume growth rates (difference, 32.8 cm 3 /year; P < .0001). Univariable analysis identified angiotensin II receptor blocker use (difference, -3.4 cm 3 /year; P = .02) and history of diabetes mellitus (difference, -2.8 cm 3 /year; P = .04) to be associated with lower rates of volume growth. Baseline volume, tortuosity index, current tobacco use, and absence of diabetes mellitus remained significantly associated with volume growth in multivariable analysis. AAAs that reached the MTD threshold for repair had a wide range of volumes: 102 cm 3 to 142 cm 3 in female patients (n = 5) and 105 cm 3 to 229 cm 3 in male patients (n = 20)., Conclusions: Baseline AAA volume and MTD were found to be moderately correlated. On average, AAA volume grows about 10% annually. Baseline volume, tortuosity, MTD, current tobacco use, angiotensin II receptor blocker use, and history of diabetes mellitus were predictive of volume growth over time., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Endovascular aneurysm repair (EVAR) is a widely used option for patients with suitable vascular anatomy who have a large infrarenal abdominal aortic aneurysm (AAA). Patients with small AAAs are managed with careful surveillance and it is a common concern that their anatomy may change with AAA growth, and their option for EVAR may become limited. Device innovation has resulted in expanded ranges of anatomy that may be eligible for EVAR. This study sought to identify changes in anatomic eligibility for repair with contemporary endovascular devices in AAA patients, monitored by computed tomography scan over the course of 2 years., Methods: Patients from the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA 3 CT, NCT01756833) were included in this analysis. Females had baseline AAA maximum transverse diameter between 3.5 and 4.5 cm, and males had baseline maximum transverse diameter between 3.5 and 5.0 cm. Patients were included in this analysis if they completed pre-enrollment and 2-year follow-up computed tomography imaging. Pertinent anatomic measurements were performed on a postprocessing workstation in a centralized imaging core laboratory. EVAR candidacy was determined by measuring proximal aortic neck diameter, AAA length, and infrarenal neck angulation. Patients were considered to be eligible for EVAR if they qualified for at least one of the seven studied devices' instructions for use at baseline and at 2 years. A paired t test analysis was used to detect differences in aortic measurements over 2 years, and the McNemar test was used to compare eligibility over 2 years., Results: We included 192 patients in this analysis-168 male and 24 female. Of these patients, 85% were eligible for EVAR at baseline and 85% after 2 years of follow-up (P = 1.00; 95% confidence interval -0.034 to 0.034). Of the 164 EVAR candidates at baseline, 160 (98%) remained eligible over 2 years of surveillance. Insufficient neck length was the most common reason for both ineligibility at baseline (18 of 28 patients) as well as loss of candidacy over 2 years (3 of 4 patients)., Conclusions: The majority of patients eligible for EVAR when entering a surveillance program for small AAA remain eligible after 2 years. Substantial changes in AAA neck anatomy resulting in loss of EVAR treatment options are infrequent. Patients with anatomic AAA progression beyond EVAR eligibility remain candidates for complex EVAR and open repair., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Targeting the JAK/STAT and BCL2 pathways in patients with relapsed/refractory T cell acute lymphoblastic leukemia (T-ALL) may provide an alternative approach to achieve clinical remissions. Ruxolitinib and venetoclax show a dose-dependent effect on T-ALL individually, but combination treatment reduces survival and proliferation of T-ALL in vitro . Using a xenograft model, the combination treatment fails to improve survival, with death from hind limb paralysis. Despite on-target inhibition by the drugs, histopathology demonstrates increased leukemic infiltration into the central nervous system (CNS) as compared to liver or bone marrow. Liquid chromatography-tandem mass spectroscopy shows that ruxolitinib and venetoclax insufficiently cross into the CNS. The addition of the CXCR4 inhibitor plerixafor with ruxolitinib and venetoclax reduces clinical scores and enhances survival. While combination therapy with ruxolitinib and venetoclax shows promise for treating T-ALL, additional inhibition of the CXCR4-CXCL12 axis may be needed to maximize the possibility of complete remission.

Supportive maternal and paternal caregiving have been found to be associated with children's effortful control abilities. However, many studies did not assess both maternal and paternal parenting in the same analytic model, making it difficult to parse out the unique contributions of mothers versus fathers. Thus, we aimed to simultaneously assess the role of parent gender in associations between observations of supportive caregiving in the preschool years and observations of children's effortful control abilities in the early school-age years. At approximately age 3, children ( N = 113) participated in videotaped father-child and mother-child interactions, as well as a battery of effortful control tasks. At approximately age 6, children participated in another battery of effortful control tasks. Covariates included parental education, child age, child preschool-age effortful control, and child gender. Structural equation modeling revealed that maternal and paternal supportive caregiving behaviors in the preschool years were independently associated with children's school-age effortful control abilities. In sum, we found that supportive caregiving in the preschool years was associated with children's early school-age effortful control abilities, regardless of parent gender. Findings have implications for the development of interventions aimed at improving children's effortful control abilities through improvements in both paternal and maternal parenting., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest.

Importance: Small abdominal aortic aneurysms (AAAs) are common in the elderly population. Their growth rates and patterns, which drive clinical surveillance, are widely disputed., Objective: To assess the growth patterns and rates of AAAs as documented on serial computed tomography (CT) scans., Design, Setting, and Participants: Cohort study and secondary analysis of the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT), a randomized, double-blind placebo-controlled clinical trial conducted from 2013 to 2018, with CT imaging every 6 months for 2 years. The trial was a multicenter, observational secondary analysis, not related to treatment hypotheses of data collected in the N-TA3CT. Participants included 254 patients with baseline AAA diameter between 3.5 and 5.0 cm., Exposures: Patients received serial CT scan measurements, analyzed for maximum transverse diameter, at 6-month intervals., Main Outcomes and Measures: The primary study outcome was AAA annual growth rate. Secondary analyses included characterizing AAA growth patterns, assessing likelihood of AAA diameter to exceed sex-specific intervention thresholds over 2 years., Results: A total of 254 patients, 35 women with baseline AAA diameter 3.5 to 4.5 cm and 219 men with baseline diameter 3.5 to 5.0 cm, were included. Yearly growth rates of AAA diameters were a median of 0.17 cm/y (interquartile range [IQR], 0.16) and a mean (SD), 0.19 (0.14) cm/y. Ten percent of AAAs displayed minimal to no growth (<0.05 cm/y), 62% displayed low growth (0.05-0.25 cm/y), and 28% displayed high growth (>0.25 cm/y). Baseline AAA diameter accounted for 5.4% of variance of growth rate (P < .001; R2, 0.054). Most AAAs displayed linear growth (70%); large variations in interval growth rates occurred infrequently (3% staccato growth and 4% exponential growth); and some patients' growth patterns were not clearly classifiable (23% indeterminate). No patients with a maximum transverse diameter less than 4.25 cm exceeded sex-specific repair thresholds at 2 years (men, 0 of 92; 95% CI, 0.00-0.055; women, 0 of 25 ; 95% CI, 0.00-0.247). Twenty-six percent of patients with a maximum transverse diameter of at least 4.25 cm exceeded sex-specific repair thresholds at 2 years (n = 12 of 83 men with diameter ranging from 4.25 to <4.75 cm; 95% CI, 0.091-0.264; n = 21 of 44 men with diameter ranging from 4.75-5.0 cm; 95% CI, 0.362-0.669; n = 3 of 10 women with diameter ≥4.25 cm; 95% CI, 0.093-0.726)., Conclusions and Relevance: Most small AAAs showed linear growth; large intrapatient variations in interval growth rates were infrequently observed over 2 years. Linear growth modeling of AAAs in individual patients suggests smaller AAAs (<4.25 cm) can be followed up with a CT scan in at least 2 years with little chance of exceeding interventional thresholds., Trial Registration: ClinicalTrials.gov Identifier: NCT01756833.