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Stress and the associated correlates, such as depression, alcohol abuse, and suicidal ideation, are a global issue among college and university students. We assert that character is a personal resource that students have at their disposal to address personal, social, and environmental challenges they may encounter in their personal and academic lives. The results of a field study involving undergraduate business students show that character, operationalized as a higher order construct consisting of 11 interrelated dimensions, has a direct effect on the subjective well-being of students and an indirect effect through the perceived stressfulness of life events. Our results imply that it is essential for faculty and students at management education institutions to fully appreciate the importance of character for effective functioning and to develop the various character dimensions to address adverse personal, social, and environmental situations in a positive fashion.

A two-component reductive amination approach to the synthesis of peptide macrocycles is reported which leverages the inherent reactivity of proteinogenic amine nucleophiles. Unprotected peptides bearing α-amine and side chain amine motifs undergo two-fold reductive amination reactions with 2,6-pyridinedialdehyde linkers in aqueous media to afford macrocyclic peptide products with backbone embedded pyridine motifs. Dialdehyde staples bearing valuable azide and alkyne handles also enable the post-cyclisation modification of peptides using copper-catalysed azide-alkyne cycloaddition (CuAAC) chemistry.

To understand how policy is made, one must understand not only the individuals who make the decisions, but also the role of bureaucratic politics and the goals of the institutions themselves. Graham Allison’s classic Essence of Decision created the bureaucratic politics model and was the catalyst for a rich research agenda on decision-making. Using Allison as a starting point, researchers have expanded the understanding of the role of bureaucracies in deliberation and decision-making, particularly during times of crisis. Typically, institutions fill the day-to-day “politics as usual” role of decision-making, but their actions during crisis, by definition an abnormal event, allow bureaucracies to pursue their own objectives by way of a new opportunity to exert influence and to reshape the power structure of the political landscape. The research agenda on individuals and decision-making has also made great strides since the 1970s and helps to illuminate when the bureaucratic politics model has great explanatory power and when it is less useful. The level of influence bureaucracies have is dependent upon where they sit within the system and how they are utilized by the executive branch of government. Leaders, such as the President of the United States, hold a significant amount of power, and the ways in which they hold onto power, or allocate it to other actors, which is a function of their leadership style, can either empower or disempower bureaucracies. In other words, the importance of bureaucracies connected to the executive branch of government fluctuates with an individual’s personality characteristics and leadership style. Specifically, a leader’s personal need for power, their expertise, and their personal interest in policymaking, as well as their cognitive complexity, the amount of differing information they want and are capable of cognitively processing, influence the way in which the leader will delegate decision-making. Leaders like Lyndon B. Johnson relied heavily upon expert advisers and allocated decision-making to lower-level agencies. Alternatively, some leaders (e.g., Richard Nixon) have experience, particularly in foreign policy, and believe they are their own expert adviser; thus, they are involved in nuanced decision-making and rely upon only a very small number of advisers (in Nixon’s case, just Henry Kissinger). A common normative criticism of bureaucratic politics, and group decision-making in general, is the collective cognitive conformity, commonly known as groupthink. The general assumption is that individuals within a group will seek conformity and avoid the conflict caused by raising alternatives during policy deliberation. However, bureaucratic politics mitigates groupthink by bringing in a greater number of actors with differing goals and perspectives, making deliberation more open. Again, this is significantly influenced by how the leader utilizes advisers and their respective bureaucracies. Where Kennedy was very open-minded and actively sought various perspectives during the Cuban missile crisis, George W. Bush created an insulated decision-making environment after 9/11 and leading up to the invasion of Iraq. As society continues to change, particularly with regard to reliance upon technological adaptations, such as nuclear energy, new crises will occur. These crises will require the cooperation of more bureaucracies and occasionally new bureaucracies. Through these crises, bureaucracies will compete for political influence, and the power structure of the political landscape will inevitably change and affect policy decision-making.

Major obstacles in brain cancer treatment include the blood-tumor barrier (BTB), which limits the access of most therapeutic agents, and quiescent tumor cells, which resist conventional chemotherapy. Here, we show that Sox2

This is the first study to document the training and tapering practices of elite CrossFit athletes. Seventy-two CrossFit athletes (39 females, 33 males) (mean ±SD; 26.5 ± 3.6 y, 167.1 ± 9.5 cm, 74.5 ± 12.7 kg, 12.8 ± 6.5 y general training, 5.4 ± 1.7 y CrossFit training) who competed at the “Regionals” level or higher in the 2018 CrossFit Games season completed a self-reported 5-page online survey. Almost all athletes (98.6%) tapered before important competitions. Taper length was 5.4 ± 2.7 days, with the step and linear tapering styles being most commonly utilised. Strength training volume peaked 5.1 ± 4.6 weeks before competition, whereas conditioning training volume peaked 4.0 ± 4.4 weeks before competition. Strength training intensity peaked 3.1 ± 2.4 weeks before competition, whereas conditioning training intensity peaked 2.8 ± 2.2 weeks before competition. Almost all athletes (90.0%) reduced training duration during tapering, but changes to frequency and intensity were mixed. Training volume decreased by 41.2 ± 15.5% during the taper, all training ceased 2.0 ± 1.1 days before competition. Tapering was performed to achieve peak performance, recover (physically and psychologically), and reduce feelings of fatigue. Poor results from tapering were experienced when athletes tapered for too long or insufficiently. This observational data may be valuable for coaches and athletes engaged in CrossFit as well as other sports with concurrent training and competition demands.

Glioblastoma multiforme (GBM) contains a subpopulation of cells, GBM stem cells (GSCs), that maintain the bulk tumor and represent a key therapeutic target. Norrin is a Wnt ligand that binds Frizzled class receptor 4 (FZD4) to activate canonical Wnt signaling. Although Norrin, encoded by NDP, has a well-described role in vascular development, its function in human tumorigenesis is largely unexplored. Here, we show that NDP expression is enriched in neurological cancers, including GBM, and its levels positively correlated with survival in a GBM subtype defined by low expression of ASCL1, a proneural factor. We investigated the function of Norrin and FZD4 in GSCs and found that it mediated opposing tumor-suppressive and -promoting effects on ASCL1lo and ASCL1hi GSCs. Consistent with a potential tumor-suppressive effect of Norrin suggested by the tumor outcome data, we found that Norrin signaling through FZD4 inhibited growth in ASCL1lo GSCs. In contrast, in ASCL1hi GSCs Norrin promoted Notch signaling, independently of WNT, to promote tumor progression. Forced ASCL1 expression reversed the tumor-suppressive effects of Norrin in ASCL1lo GSCs. Our results identify Norrin as a modulator of human brain cancer progression and reveal an unanticipated Notch-mediated function of Norrin in regulating cancer stem cell biology. This study identifies an unanticipated role of Norrin in human brain cancer progression. In addition, we provide preclinical evidence suggesting Norrin and canonical Wnt signaling as potential therapeutic targets for GBM subtype-restricted cancer stem cells.

IMPORTANCE The use of perioperative, prophylactic, intravenous antibiotics is standard practice to reduce the risk of surgical site infection after oncologic resection and complex endoprosthetic reconstruction for lower extremity bone tumors. However, evidence guiding the duration of prophylactic treatment remains limited.OBJECTIVE To assess the effect of a 5-day regimen of postoperative, prophylactic, intravenous antibiotics compared with a 1-day regimen on the rate of surgical site infections within 1 year after surgery.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical superiority trial was performed at 48 clinical sites in 12 countries from January 1, 2013, to October 29, 2019. The trial included patients with a primary bone tumor or a soft tissue sarcoma that had invaded the femur or tibia or oligometastatic bone disease of the femur or tibia with expected survival of at least 1 year who required surgical management by excision and endoprosthetic reconstruction. A total of 611 patients were enrolled, and 7 were exduded for ineligibility.INTERVENTIONS A 1- or 5-day regimen of postoperative prophylactic intravenous cephalosporin (cefazolin or cefuroxime) that began within 8 hours after skin closure and was administered every 8 hours thereafter. Those randomized to the 1-day regimen received identical saline doses every 8 hours for the remaining 4 days; patients, care providers, and outcomes assessors were blinded to treatment regimen.MAIN OUTCOMES AND MEASURES The primary outcome in this superiority trial was a surgical site infection (superficial incisional, deep incisional, or organ space) classified according to the criteria established by the Centers for Disease Control and Prevention within 1year after surgery. Secondary outcomes included antibiotic-related complications, unplanned additional operations, oncologic and functional outcomes, and mortality.RESULTS Of the 604 patients included in the final analysis (mean [SD] age, 41.2 [21.9] years; 361 [59.8%] male; 114 [18.9%] Asian, 43 [7.1%) Black, 34 [5.6%] Hispanic, 15 [2.5%] Indigenous, 384 [63.8%] White. and 12 [2.0%] other), 293 were randomized to a 5-day regimen and 311 to a 1-day regimen. A surgical site infection occurred in 44 patients (15.0%) allocated to the 5-day regimen and in 52 patients (16.7%) allocated to the 1-day regimen (hazard ratio, 0.93; 95% CI, 0.62-1.40; P = .73). Antibiotic-related complications occurred in 15 patients (5.1%) in the 5-day regimen and in 5 patients (1.6%) allocated to the 1-day regimen (hazard ratio, 3.24; 95% CI, 1.17-8.98; P = .02). Other secondary outcomes did not differ significantly between treatment groups.CONCLUSIONS AND RELEVANCE This randomized clinical trial did not confirm the superiority of a 5-day regimen of postoperative intravenous antibiotics over a 1-day regimen in preventing surgical site infections after surgery for lower extremity bone tumors that required an endoprosthesis. The 5-day regimen group had significantly more antibiotic-related complications.

Background Textbook outcome has been proposed as a tool for the assessment of oncological surgical care. However, an international assessment in patients undergoing oesophagectomy for oesophageal cancer has not been reported. This study aimed to assess textbook outcome in an international setting. Methods Patients undergoing curative resection for oesophageal cancer were identified from the international Oesophagogastric Anastomosis Audit (OGAA) from April 2018 to December 2018. Textbook outcome was defined as the percentage of patients who underwent a complete tumour resection with at least 15 lymph nodes in the resected specimen and an uneventful postoperative course, without hospital readmission. A multivariable binary logistic regression model was used to identify factors independently associated with textbook outcome, and results are presented as odds ratio (OR) and 95 per cent confidence intervals (95 per cent c.i.). Results Of 2159 patients with oesophageal cancer, 39.7 per cent achieved a textbook outcome. The outcome parameter ‘no major postoperative complication’ had the greatest negative impact on a textbook outcome for patients with oesophageal cancer, compared to other textbook outcome parameters. Multivariable analysis identified male gender and increasing Charlson comorbidity index with a significantly lower likelihood of textbook outcome. Presence of 24-hour on-call rota for oesophageal surgeons (OR 2.05, 95 per cent c.i. 1.30 to 3.22; P = 0.002) and radiology (OR 1.54, 95 per cent c.i. 1.05 to 2.24; P = 0.027), total minimally invasive oesophagectomies (OR 1.63, 95 per cent c.i. 1.27 to 2.08; P < 0.001), and chest anastomosis above azygous (OR 2.17, 95 per cent c.i. 1.58 to 2.98; P < 0.001) were independently associated with a significantly increased likelihood of textbook outcome. Conclusion Textbook outcome is achieved in less than 40 per cent of patients having oesophagectomy for cancer. Improvements in centralization, hospital resources, access to minimal access surgery, and adoption of newer techniques for improving lymph node yield could improve textbook outcome.

Post-operative or adjuvant endocrine therapy (AET) is the mainstay of treatment for hormone receptor-positive (HR+) breast cancer. When taken daily for 5-to-10 years, AET improves the time to disease recurrence and overall survival rates. However, past work has shown that Black women are less likely to begin prescribed AET treatments and less likely to take these medications as directed, often discontinuing treatment early. For hormone receptor-positive (HR+) breast cancer, rates of death from breast cancer are higher than those of similar White women. This study investigates the patient-, provider-, and practice-level barriers to AET initiation and adherence faced by Black women with the ultimate goal of developing an intervention to address these barriers. This study consists of qualitative semi-structured interviews with two populations, Black breast cancer survivors with HR+ breast cancer who were prescribed AET and cancer care providers (including medical doctors and advance-practice providers). All participants were recruited from the same comprehensive cancer center with a dedicated breast cancer clinic. Data collection is ongoing; thus far, the sample includes fifteen interviews with breast cancer survivors and nine with providers. Participants were asked about the barriers to care they (or their patients) face, their (or their patients’) perception of AET, and their views of possible interventions to improve clinical practices related to AET initiation and adherence. Preliminary findings include differences in perceived barriers to care between Black women and their providers. Providers understood barriers to AET initiation and adherence as minimal compared to other treatments, in terms of cost, toxicity, and burden of care. Meanwhile, patients understood the cost of the treatment as very high, largely due to side-effect. While the price of the medications were not a common barrier, the side effects (including brain fog, bone aches, fatigue, and depression) impact patients’ interpersonal relationships, employment, and/or ability to perform care work for family members, were seen as a heavy burden. In addition, patient interviews showed a need for higher quality education regarding how AET therapy works and its importance in preventing recurrence. While providers described the myriad ways in which they educate their patients about AET and its importance in breast cancer care, patients interviewed described gaps in their knowledge related to how AET works and why it is an essential aspect of their care. These findings point to a need for reframing barriers to breast cancer care for providers and the implementation of new clinical procedures to address and rectify racial disparities in AET use. Citation Format: Hayden J. Fulton, Dannelle R. Charles, Kimberley T. Lee. Barriers to use of adjuvant endocrine therapy among Black women with breast cancer: A qualitative investigation [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B086.

Travis, SK, Pritchard, HJ, Mujika, I, Gentles, JA, Stone, MH, and Bazyler, CD. Characterizing the tapering practices of United States and Canadian raw powerlifters. J Strength Cond Res 35(12S): S26-S35, 2021-The purpose of this study was to characterize the tapering practices used by North American powerlifters. A total of 364 powerlifters completed a 41-item survey encompassing demographics, general training, general tapering, and specific tapering practices. Nonparametric statistics were used to assess sex (male and female), competition level (regional/provincial, national, and international), and competition lift (squat, bench press, and deadlift). The highest training volume most frequently took place 5-8 weeks before competition, whereas the highest training intensity was completed 2 weeks before competition. A step taper was primarily used over 7-10 days while decreasing the training volume by 41-50% with varied intensity. The final heavy (>85% 1 repetition maximum [1RM]) back squat and deadlift sessions were completed 7-10 days before competition, whereas the final heavy bench press session was completed

We report anatomically correct 3D-printed mouse phantoms that can be used to plan experiments and evaluate analysis protocols for magnetic particle imaging (MPI) studies. The 3D-printed phantoms were based on the Digimouse 3D whole body mouse atlas and incorporate cavities representative of a liver, brain tumor, and orthotopic breast cancer tumor placed in anatomically correct locations, allowing evaluation of the effect of precise doses of MPI tracer. To illustrate their use, a constant tracer iron mass was present in the liver for the breast (200 μg

Objectives: In the SPRINT trial, 18% of patients with a tibial shaft fracture (TSF) treated with intramedullary nailing (IMN) had one or more unplanned subsequent surgical procedures. It is clinically relevant for surgeon and patient to anticipate unplanned secondary procedures, other than operations that can be readily expected such as reconstructive procedures for soft tissue defects. Therefore, the objective of this study was to develop a machine learning (ML) prediction model using the SPRINT data that can give individual patients and their care team an estimate of their particular probability of an unplanned second surgery. Methods: Patients from the SPRINT trial with unilateral TSFs were randomly divided into a training set (80%) and test set (20%). Five ML algorithms were trained in recognizing patterns associated with subsequent surgery in the training set based on a subset of variables identified by random forest algorithms. Performance of each ML algorithm was evaluated and compared based on (1) area under the ROC curve, (2) calibration slope and intercept, and (3) the Brier score. Results: Total data set comprised 1198 patients, of whom 214 patients (18%) underwent subsequent surgery. Seven variables were used to train ML algorithms: (1) Gustilo-Anderson classification, (2) Tscherne classification, (3) fracture location, (4) fracture gap, (5) polytrauma, (6) injury mechanism, and (7) OTA/AO classification. The best-performing ML algorithm had an area under the ROC curve, calibration slope, calibration intercept, and the Brier score of 0.766, 0.954, -0.002, and 0.120 in the training set and 0.773, 0.922, 0, and 0.119 in the test set, respectively. Conclusions: An ML algorithm was developed to predict the probability of subsequent surgery after IMN for TSFs. This ML algorithm may assist surgeons to inform patients about the probability of subsequent surgery and might help to identify patients who need a different perioperative plan or a more intensive approach.

Like other biological processes, aging is not random but subject to molecular control. Natural products that modify core metabolic parameters, including fat content, may provide entry points to extend animal life span and promote healthy aging. Here, we show that a botanical extract from Artemisia scoparia (SCO), which promotes fat storage and metabolic resiliency in mice, extends the life span of the nematode Caenorhabditis elegans by up to 40%. Notably, this life-span extension depends significantly on SCO’s effects on fat; SCO-treated worms exhibit heightened levels of unsaturated fat, and inhibition of Δ9 desaturases, which oversee biosynthesis of monounsaturated fatty acids, prevents SCO-dependent fat accumulation and life-span extension. At an upstream signaling level, SCO prompts changes to C. elegans fat regulation by stimulating nuclear translocation of transcription factor DAF-16/FOXO, an event that requires AMP-activated protein kinase under this condition. Importantly, animals treated with SCO are not only long-lived but also show improved stress resistance in late adulthood, suggesting that this fat-promoting intervention may enhance some aspects of physiological health in older age. These findings identify SCO as a natural product that can modify fat regulation for longevity benefit and add to growing evidence indicating that elevated fat can be prolongevity in some circumstances.

High efficiency lunate-tail swimming with high-aspect-ratio lifting surfaces has evolved in many vertebrate lineages, from fish to cetaceans. Baleen whales (Mysticeti) are the largest swimming animals that exhibit this locomotor strategy, and present an ideal study system to examine how morphology and the kinematics of swimming scale to the largest body sizes. We used data from whale-borne inertial sensors coupled with morphometric measurements from aerial drones to calculate the hydrodynamic performance of oscillatory swimming in six baleen whale species ranging in body length from 5 to 25 m (fin whale, Balaenoptera physalus; Bryde's whale, Balaenoptera edeni; sei whale, Balaenoptera borealis; Antarctic minke whale, Balaenoptera bonaerensis; humpback whale, Megaptera novaeangliae; and blue whale, Balaenoptera musculus). We found that mass-specific thrust increased with both swimming speed and body size. Froude efficiency, defined as the ratio of useful power output to the rate of energy input ( Sloop, 1978), generally increased with swimming speed but decreased on average with increasing body size. This finding is contrary to previous results in smaller animals, where Froude efficiency increased with body size. Although our empirically parameterized estimates for swimming baleen whale drag were higher than those of a simple gliding model, oscillatory locomotion at this scale exhibits generally high Froude efficiency as in other adept swimmers. Our results quantify the fine-scale kinematics and estimate the hydrodynamics of routine and energetically expensive swimming modes at the largest scale., Summary: Tags attached to baleen whales demonstrate how thrust power output, drag coefficient and Froude efficiency scale with swimming speed and body length.

Winwood, PW, Pritchard, HJ, Wilson, D, Dudson, M, and Keogh, JWL. The competition-day preparation strategies of strongman athletes. J Strength Cond Res 33(9): 2308-2320, 2019-This study provides the first empirical evidence of the competition-day preparation strategies used by strongman athletes. Strongman athletes (n = 132) (mean ± SD: 33.7 ± 8.1 years, 178.2 ± 11.1 cm, 107.0 ± 28.6 kg, 12.8 ± 8.0 years general resistance training, 5.9 ± 4.8 years strongman implement training) completed a self-reported 4-page internet survey on their usual competition-day preparation strategies. Analysis of the overall group and by sex, age, body mass, and competitive standard was conducted. Ninety-four percent of strongman athletes used warm-ups in competition, which were generally self-directed. The typical warm-up length was 16.0 ± 8.9 minutes, and 8.5 ± 4.3 minutes was the perceived optimal rest time before the start of an event. The main reasons for warming up were injury prevention, to increase activation, and increase blood flow/circulation, temperature, and heart rate. Athletes generally stated that competition warm-ups were practiced in training. Dynamic stretching, foam rolling, and myofascial release work were performed during warm-ups. Warm-up intensity was monitored using the rate of perceived exertion, perceived speed of movement, and training load (as a percentage of 1 repetition maximum). Cognitive strategies were used to improve competition performance, and psychological arousal levels needed to increase or be maintained in competition. Electrolyte drinks, caffeine, and preworkout supplements were the commonly used supplements. These data will provide strongman athletes and coaches some insight into common competition-day preparation strategies, which may enhance competition performances. Future research could compare different competition-day preparation strategies in an attempt to further improve strongman competition performance and injury prevention.

The Statecraft IR simulation has received a significant amount of attention in the pedagogical literature. Some instructors have asserted that Statecraft is biased toward the behavior and learning ...

Background DriveSafe DriveAware (DSDA) has been validated as an off-road screening tool for predicting on-road driving performance in clinical populations, but its utility in people with Huntington's disease (HD) is unknown. Objective Our aim was to evaluate the utility of DSDA in people with HD by demonstrating sensitivity of DSDA scores to HD progression and exploring associations between DSDA performance and cognitive functions that are essential to driving and impaired in people with HD. Methods We administered the iPad application version of DSDA to 26 pre-symptomatic and symptomatic participants with HD. Disease progression was assessed via measures of motor impairment, disease burden and functional capacity. Standardised neuropsychological tests were used to assess cognitive function across several domains including attention, processing speed, planning, and visuoperception. Results Results underscore the sensitivity of DSDA to HD progression and cognitive impairment; that is, poorer DSDA performance was associated with greater HD severity and poorer cognitive ability across the domains of attention, processing speed, and planning. Nevertheless, we identified a proportion of participants with HD who were predicted to pass on-road testing based on DSDA, but scored in the impaired range on multiple cognitive tests. These participants tended to score closer to the cut-off score used by DSDA to categorise pass/fail outcomes. Conclusions Our findings demonstrate potential for use of DSDA in the HD population, however, significant variability in cognitive performance among those predicted to 'pass' on-road driving assessment suggests the screening tool requires further development for use with HD drivers.

Background: Breast cancer, is increasing in prevalence amongst South East (SE) Asian women, highlighting the need for high quality, early diagnoses. This study investigated radiologists’ detection efficacy in a developing (DC) and developed (DDC) SE Asian country, as compared to Australian radiologists. Methods: Using a test-set of 60 mammographic cases, 20 containing cancer, JAFROC figures of merit (FOM) and ROC area under the curves (AUC) were calculated as well as location sensitivity, sensitivity and specificity. The test set was examined by 35, 15, and 53 radiologists from DC, a DDC and Australia, respectively. Results: DC radiologists, compared to both groups of counterparts, demonstrated significantly lower JAFROC FOM, ROC AUC and specificity scores. DC radiologists had a significantly lower location sensitivity than Australian radiologists. DC radiologists also demonstrated significantly lower values for age, hours of reading per week, and years of mammography experience when compared with other radiologists. Conclusion: Significant differences in breast cancer detection parameters can be attributed to the experience of DC radiologists. The development of inexpensive, innovative, interactive training programs are discussed. This nonuniform level of breast cancer detection between countries must be addressed to achieve the World Health Organisation goal of health equity.

We applied continuous flash suppression (CFS) during an interocular transfer paradigm to evaluate the importance of awareness and the contribution of early versus late visual structures in size recognition. Specifically, we tested if size judgements of a visible target could be influenced by a congruent or incongruent prime presented to the same or different eye. Without CFS, participants categorised a target as “small” or “large” more quickly when it was preceded by a congruent prime – regardless of whether the prime and target were presented to the same or different eye. Interocular transfer enabled us to infer that the observed priming was mediated by late visual areas. In contrast, there was no priming under CFS, which underscores the importance of awareness. We conclude that awareness and late visual structures are important for size perception and that any subconscious processing of the stimulus has minimal effect on size recognition.