Accelerator physics relies on numerical algorithms to solve optimization problems in online accelerator control and tasks such as experimental design and model calibration in simulations. The effectiveness of optimization algorithms in discovering ideal solutions for complex challenges with limited resources often determines the problem complexity these methods can address. The accelerator physics community has recognized the advantages of Bayesian optimization algorithms, which leverage statistical surrogate models of objective functions to effectively address complex optimization challenges, especially in the presence of noise during accelerator operation and in resource-intensive physics simulations. In this review article, we offer a conceptual overview of applying Bayesian optimization techniques toward solving optimization problems in accelerator physics. We begin by providing a straightforward explanation of the essential components that make up Bayesian optimization techniques. We then give an overview of current and previous work applying and modifying these techniques to solve accelerator physics challenges. Finally, we explore practical implementation strategies for Bayesian optimization algorithms to maximize their performance, enabling users to effectively address complex optimization challenges in real-time beam control and accelerator design. Published by the American Physical Society 2024

The spindle assembly checkpoint (SAC) temporally regulates mitosis by preventing progression from metaphase to anaphase until all chromosomes are correctly attached to the mitotic spindle. Centrosomes refine the spatial organization of the mitotic spindle at the spindle poles. However, centrosome loss leads to elongated mitosis, suggesting that centrosomes also inform the temporal organization of mitosis in mammalian cells. Here, we find that the mitotic delay in acentrosomal cells is enforced by the SAC in a MPS1-dependent manner, and that a SAC-dependent mitotic delay is required for bipolar cell division to occur in acentrosomal cells. Although acentrosomal cells become polyploid, polyploidy is not sufficient to cause dependency on a SAC-mediated delay to complete cell division. Rather, the division failure in absence of MPS1 activity results from mitotic exit occurring before acentrosomal spindles can become bipolar. Furthermore, prevention of centrosome separation suffices to make cell division reliant on a SAC-dependent mitotic delay. Thus, centrosomes and their definition of two spindle poles early in mitosis provide a 'timely two-ness' that allows cell division to occur in absence of a SAC-dependent mitotic delay.

Typologies serve to organize knowledge and advance theory for many scientific disciplines, including more recently in the social and behavioral sciences. To date, however, no typology exists to categorize an individual's use of emotion regulation strategies. This is surprising given that emotion regulation skills are used daily and that deficits in this area are robustly linked with mental health symptoms. Here, we attempted to identify and validate a working typology of emotion regulation across six samples (collectively comprised of 1,492 participants from multiple populations) by using a combination of computational techniques, psychometric models, and growth curve modeling. We uncovered evidence for three types of regulators: a type that infrequently uses emotion regulation strategies (Lo), a type that uses them frequently but indiscriminately (Hi), and a third type that selectively uses some (cognitive reappraisal and situation selection), but not other (expressive suppression), emotion regulation strategies frequently (Mix). Results showed that membership in the Hi and Mix types is associated with better mental health, with the Mix type being the most adaptive of the three. These differences were stable over time and across different samples. These results carry important implications for both our basic understanding of emotion regulation behavior and for informing future interventions aimed at improving mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Understanding the prenatal origins of children's psychopathology is a fundamental goal in developmental and clinical science. Recent research suggests that inflammation during pregnancy can trigger a cascade of fetal programming changes that contribute to vulnerability for the emergence of psychopathology. Most studies, however, have focused on a handful of proinflammatory cytokines and have not explored a range of prenatal biological pathways that may be involved in increasing postnatal risk for emotional and behavioral difficulties. Using extreme gradient boosted machine learning models, we explored large-scale proteomics, considering over 1,000 proteins from first trimester blood samples, to predict behavior in early childhood. Mothers reported on their 3- to 5-year-old children's (N = 89, 51% female) temperament (Child Behavior Questionnaire) and psychopathology (Child Behavior Checklist). We found that machine learning models of prenatal proteomics predict 5%-10% of the variance in children's sadness, perceptual sensitivity, attention problems, and emotional reactivity. Enrichment analyses identified immune function, nervous system development, and cell signaling pathways as being particularly important in predicting children's outcomes. Our findings, though exploratory, suggest processes in early pregnancy that are related to functioning in early childhood. Predictive features included far more proteins than have been considered in prior work. Specifically, proteins implicated in inflammation, in the development of the central nervous system, and in key cell-signaling pathways were enriched in relation to child temperament and psychopathology measures.

To analyze patients, injury patterns, and treatment of femoral neck fractures (FNFs) in young patients with FNFs associated with shaft fractures (assocFNFs) to improve clinical outcomes. The secondary goal was to compare this injury pattern to that of young patients with isolated FNFs (isolFNFs). Retrospective multicenter cohort series. Twenty-six North American level-1 trauma centers. Skeletally mature patients, <50 years old, treated with operative fixation of an FNF with or without an associated femoral shaft fracture. The main outcome measurement was treatment failure defined as nonunion, malunion, avascular necrosis, or subsequent major revision surgery. Odds ratios for these modes of treatment were also calculated. Eighty assocFNFs and 412 isolFNFs evaluated in this study were different in terms of patients, injury patterns, and treatment strategy. Patients with assocFNFs were younger (33.3 ± 8.6 vs. 37.5 ± 8.7 years old, P < 0.001), greater in mean body mass index [BMI] (29.7 vs. 26.6, P < 0.001), and more frequently displaced (95% vs. 73%, P < 0.001), "vertically oriented" Pauwels type 3, P < 0.001 (84% vs. 43%) than for isolFNFs, with all P values < 0.001. AssocFNFs were more commonly repaired with an open reduction (74% vs. 46%, P < 0.001) and fixed-angle implants (59% vs. 39%) (P < 0.001). Importantly, treatment failures were less common for assocFNFs compared with isolFNFs (20% vs. 49%, P < 0.001) with lower rates of failed fixation/nonunion and malunion (P < 0.001 and P = 0.002, respectively). Odds of treatment failure [odds ratio (OR) = 0.270, 95% confidence interval (CI), 0.15-0.48, P < 0.001], nonunion (OR = 0.240, 95% CI, 0.10-0.57, P < 0.001), and malunion (OR = 0.920, 95% CI, 0.01-0.68, P = 0.002) were also lower for assocFNFs. Excellent or good reduction was achieved in 84.2% of assocFNFs reductions and 77.1% in isolFNFs (P = 0.052). AssocFNFs treated with fixed-angle devices performed very well, with only 13.0% failing treatment compared with 51.9% in isolFNFs treated with fixed-angle constructs (P = <0.001) and 33.3% in assocFNFs treated with multiple cannulated screws (P = 0.034). This study also identified the so-called "shelf sign," a transverse ≥6-mm medial-caudal segment of the neck fracture (forming an acute angle with the vertical fracture line) in 54% of assocFNFs and only 9% of isolFNFs (P < 0.001). AssocFNFs with a shelf sign failed in only 5 of 41 (12%) cases. AssocFNFs in young patients are characterized by different patient factors, injury patterns, and treatments, than for isolFNFs, and have a relatively better prognosis despite the need for confounding treatment for the associated femoral shaft injury. Treatment failures among assocFNFs repaired with a fixed-angle device occurred at a lower rate compared with isolFNFs treated with any construct type and assocFNFs treated with multiple cannulated screws. The radiographic "shelf sign" was found as a positive prognostic sign in more than half of assocFNFs and predicted a high rate of successful treatment. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

When considering sparse motion capture marker data, one typically struggles to balance its overfitting via a high dimensional blendshape system versus underfitting caused by smoothness constraints. With the current trend towards using more and more data, our aim is not to fit the motion capture markers with a parameterized (blendshape) model or to smoothly interpolate a surface through the marker positions, but rather to find an instance in the high resolution dataset that contains local geometry to fit each marker. Just as is true for typical machine learning applications, this approach benefits from a plethora of data, and thus we also consider augmenting the dataset via specially designed physical simulations that target the high resolution dataset such that the simulation output lies on the same so-called manifold as the data targeted.

Chronic pain begins with acute pain. Physicians tend to classify pain by duration (acute vs chronic) and mechanism (nociceptive, neuropathic and nociplastic). Although this taxonomy may facilitate diagnosis and documentation, such categories are to some degree arbitrary constructs, with significant overlap in terms of mechanisms and treatments. In clinical practice, there are myriad different definitions for chronic pain and a substantial portion of chronic pain involves mixed phenotypes. Classification of pain based on acuity and mechanisms informs management at all levels and constitutes a critical part of guidelines and treatment for chronic pain care. Yet specialty care is often siloed, with advances in understanding lagging years behind in some areas in which these developments should be at the forefront of clinical practice. For example, in perioperative pain management, enhanced recovery protocols are not standardized and tend to drive treatment without consideration of mechanisms, which in many cases may be incongruent with personalized medicine and mechanism-based treatment. In this educational document, we discuss mechanisms and classification of pain as it pertains to commonly performed surgical procedures. Our goal is to provide a clinical reference for the acute pain physician to facilitate pain management decision-making (both diagnosis and therapy) in the perioperative period.

Background: The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear. Setting: A cohort study of 36,322 PWH enrolled (1996–2014) in the North American AIDS Cohort Collaboration on Research and Design. Methods: We followed individuals from ART initiation (protease inhibitor [PI]-based, nonnucleoside reverse transcriptase inhibitor [NNRTI]-based, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, December 31, 2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses). Cancers were grouped (nonmutually exclusive) as follows: any cancer, AIDS-defining cancers (ADC), non-AIDS-defining cancers (NADC), any infection-related cancer, and common individual cancer types. We estimated adjusted hazard ratios (aHR) comparing cancer risk by ART class using marginal structural models emulating ITT and PP trials. Results: We observed 17,004 PWH (954 cancers) with PI-based (median 6 years follow-up), 17,536 (770 cancers) with NNRTI-based (median 5 years follow-up), and 1782 (29 cancers) with INSTI-based ART (median 2 years follow-up). Analyses with 85-month follow-up indicated no cancer risk differences. In truncated analyses, the risk of ADCs (aHR 1.33; 95% CI: 1.00, 1.77 [PP analysis]) and NADCs (aHR 1.23; 95% CI: 1.00 to 1.51 [ITT analysis]) was higher comparing PIs vs. NNRTIs. Conclusions: Results with longer-term follow-up suggest being on a PI-based versus NNRTI-based ART regimen does not affect cancer risk. We observed shorter-term associations that should be interpreted cautiously and warrant further study. Further research with a longer duration of follow-up that can evaluate INSTIs, the current first-line recommended therapy, is needed to comprehensively characterize the association between ART class and cancer risk.

To study the results of displaced femoral neck fractures (FNFs) in adults less than 60 years of age by comparing patients, injury, treatment, and the characteristics of treatment failure specifically according to patients' age at injury, that is, by their "decade of life" [ie, "under 30" (29 years and younger), "the 30s" (30-39 years), "the 40s" (40-49 years), and "the 50s" (50-59 years)]. Multicenter retrospective comparative cohort series. Twenty-six North American Level 1 Trauma Centers. Skeletally mature patients aged 18-59 years with operative repair of displaced FNFs. Main outcome measures were treatment failures (fixation failure and/or nonunion, osteonecrosis, malunion, and the need for subsequent major reconstructive surgery (arthroplasty or proximal femoral osteotomy). These were compared across decades of adult life through middle age (<30 years, 30-39 years, 40-49 years, and 50-59 years). Overall, treatment failure was observed in 264 of 565 (47%) of all hips. The mean age was 42.2 years, 35.8% of patients were women, and the mean Pauwels angle was 53.8 degrees. Complications and the need for major secondary surgeries increased with each increasing decade of life assessed: 36% of failure occurred in patients <30 years of age, 40% in their 30s, 48% in their 40s, and 57% in their 50s (P < 0.001). Rates of osteonecrosis increased with decades of life (under 30s and 30s vs. 40s vs. 50s developed osteonecrosis in 10%, 10%, 20%, and 27% of hips, P < 0.001), while fixation failure and/or nonunion only increased by decade of life to a level of trend (P = 0.06). Reparative methods varied widely between decade-long age groups, including reduction type (open vs. closed, P < 0.001), reduction quality (P = 0.030), and construct type (cannulated screws vs. fixed angle devices, P = 0.024), while some variables evaluated did not change with age group. Displaced FNFs in young and middle-aged adults are a challenging clinical problem with a high rate of treatment failure. Major complications and the need for complex reconstructive surgery increased greatly by decade of life with the patients in their sixth decade experiencing osteonecrosis at the highest rate seen among patients in the decades studied. Interestingly, treatments provided to patients in their 50s were notably different than those provided to younger patient groups. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.