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Dens invaginatus occurs in varied forms with potential impact on the restorability, potential for pulpal infection of the tooth and difficulty in undertaking endodontic treatment of the tooth. Diagnosis of dens invaginatus and the particular type of dens invaginatus can be challenging. This article describes abnormality of crown morphology, a classification of dens invaginatus, and its pathology and illustrates the diagnosis and management of an unusual case of dens invaginatus in a maxillary left second permanent molar diagnosed with the help of CBCT. CPD/Clinical Relevance: Dens invaginatus is a common occurrence and therefore all dentists need to have an appreciation of it.

The most prevalent insect sampling and surveillance problem is powering insect traps in the field. Most modern light traps use 6-V power supplies such as the Centers for Disease Control and Prevention (CDC) suction trap. Buck converter modules efficiently reduce 12-V direct current power to 6-V, which permits the use of higher voltage batteries with lower voltage traps, resulting in longer operational duration and reduced labor requirements associated with replacing and recharging batteries in the field. We evaluated several battery configurations of 6- and 12-V lead-acid batteries in various sizes (10–20 ampere-hours) and addressed, in the circuit design, common problems that occur when using the buck converter (such as crossing polarity and excessive battery depletion). The efficacy of each configuration was assessed by measuring the voltage and suction while powering a 6-V CDC light trap. The buck converter permitted the use of cheaper and more commonly available 12-V batteries to run the CDC light traps and resulted in longer effective operation time as measured by air speed.

Background Perineal reconstruction following salvage APR’s for squamous cell carcinoma of the anus (SCCA) are scant with conflicting results from large and single center studies. We analyzed these techniques taking into account sociodemographic and oncologic variables. Methods This is a retrospective cohort study from 2016-2019 using a targeted ACS/NSQIP database stratified into primary closure (PC), abdominal myocutaneous (AM), lower extremity (LE), and omental pedicled (OP) flaps. We analyzed major and wound complications through univariate and multivariate regression analysis. Results A total of 766 patients were analyzed, 512 (67%) had PC, 196 (25%) AM, 36 (5%) OP and 22 (3%) LE. Rates of chemotherapy and radiation within 90 days were similar between the groups. Having 2 or more additional organs resected was more common for the AM group (AM 4.1%, PC 1.6%, OP 3.3%, LE 0%). Overall, major complication rate was 41% (n = 324). Primary closure had 35.0%, OP 47.2%, AM 52.6%, and LE 45.5%. Wound complication rate was highest in AM with 11.7%, followed by OP 8.3%, PC 5.9%, and LE 0%. The multivariate regression analysis demonstrated none of the closure techniques to be associated with increasing or decreasing the probability of having a major or wound complication. Morbidity probability was the sole predictor of major complication (OR 1.07, 95% CI 1.04-1.1) Conclusions Myocutaneous and omental flaps are associated with comparable wound and major complications when taking into account the baseline, oncologic and perioperative variables that drive the clinical decision making when selecting a perineal reconstruction.

We assessed the effectiveness of food vouchers as a social protection strategy to enhance the adherence to tuberculosis treatment in health-care facilities in Brazil between 2014 and 2017. A cluster-randomized controlled trial was performed in four Brazilian capital cities. A total of 774 adults with newly diagnosed pulmonary tuberculosis were included in this study. Eligible participants initiated standard tuberculosis treatment per National Tuberculosis Program guidelines. Health clinics were assigned randomly to intervention groups (food voucher or standard treatment). The food voucher was provided by researchers, which could be used by subjects only for buying food. Most people with tuberculosis were poor, did receive benefits of the Bolsa Familia Program, and were unemployed. By Poisson regression analysis, with the total number of subjects included in the study, we found that individuals with tuberculosis who received food vouchers had a 1.13 greater risk of cure (95% CI, 1.03–1.21) compared with those who did not receive food vouchers. The provision of food vouchers improved outcomes of tuberculosis treatment and it should be enhanced even further as social protection for people with tuberculosis.

Due to the Covid-19 pandemic, practically all colleges and universities in the United States shifted their conventional instructional mode of the in-person face-to-face classroom teaching to the virtual online instruction in the middle of the spring 2020 semester. While online-only institutions, majority of which are for-profit, eagerly promoted their online education, all of the conventional colleges and universities struggled to provide the necessary training for the instructional faculty and to assure students and their parents that the quality of their college education would not be compromised. In this research, we explored the impact of such quickly adopted online instruction as an inevitable alternative during the pandemic on the student learning as the pandemic placed them in a natural quasi field experimental condition. We found a significant difference in the student learning outcome recorded in the semester grade between the two periods: the difference is particularly prominent in non-participation or withdrawal from the learning process as reported in the grades of fails and withdrawals. Implications of the study for college and university enrollment and the compelling need for further study are discussed.

Background Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We collected saliva specimens from working-age adults undergoing SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. After bacterial culture enrichment, we tested for pneumococci by means of quantitative polymerase chain reaction targeting the lytA and piaB genes, and we measured associations with SARS-CoV-2 infection using conditional logistic regression. Results Analyses included 1278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. The prevalence of pneumococcal carriage was 9.2% (117 of 1278) among all participants (11.2% [63 of 564] in clinic-based testing and 7.6% [54 of 714] in outreach-based testing). The prevalence of SARS-CoV-2 infection was 27.4% (32 of 117) among pneumococcal carriers and 9.6% (112 of 1161) among noncarriers (adjusted odds ratio [aOR], 2.73 [95% confidence interval (CI): 1.58–4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR, 4.01 [95% CI: 2.08–7.75]) and among symptomatic participants (3.38 [1.35–8.40]), compared with findings within the outreach-based sample and among asymptomatic participants. The adjusted odds of SARS-CoV-2 coinfection increased 1.24-fold (95% CI: 1.00–1.55-fold) for each 1-unit decrease in piaB quantitative polymerase chain reaction cycle threshold value among pneumococcal carriers. Finally, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected coronavirus disease 2019 case (aOR, 7.64 [95% CI: 1.91–30.7] and 3.29 [1.94–5.59]) among pneumococcal carriers and noncarriers, respectively). Conclusions Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.

Rapid advancements of genome sequencing (GS) technologies have enhanced our understanding of the relationship between genes and human disease. To incorporate genomic information into the practice of medicine, new processes for the analysis, reporting, and communication of GS data are needed. Blood samples were collected from adults with a PCR-confirmed SARS-CoV-2 (COVID-19) diagnosis (target N = 1500). GS was performed. Data were filtered and analyzed using custom pipelines and gene panels. We developed unique patient-facing materials, including an online intake survey, group counseling presentation, and consultation letters in addition to a comprehensive GS report. The final report includes results generated from GS data: (1) monogenic disease risks; (2) carrier status; (3) pharmacogenomic variants; (4) polygenic risk scores for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group; and, (8) COVID-19 viral lineage. Participants complete pre-test genetic counseling and confirm preferences for secondary findings before receiving results. Counseling and referrals are initiated for clinically significant findings. We developed a genetic counseling, reporting, and return of results framework that integrates GS information across multiple areas of human health, presenting possibilities for the clinical application of comprehensive GS data in healthy individuals.

Compton Suppressed Spectrometry (CSS) provides a method to improve the peak-to-background ratio, and consequently counting statistics and the limit of detection. The NCSRD Fusion Technology Group CSS system consists of a NaI detector coupled to a 40% HPGe. The NaI detector consists of an annulus, surrounding the HPGe, and a plug, which can be removed for sample positioning, offering a 4π detection geometry. The signal processing chain of the configuration allows for the simultaneous collection of both the suppressed and the unsuppressed spectra. The simultaneous collection of suppressed and unsuppressed spectra allows the analyst to use the optimum spectrum, depending on the radionuclide to be determined. In this work, the performance of the CSS system in the analysis of dosimetry foils of different material samples irradiated at the Joint European Torus (JET) during the 2019 DD campaign is presented. The Compton continuum was significantly reduced providing better peak identification for peaks of non-cascade nuclides. The developed methodology will be applied to study the activation characteristics of materials to be used in ITER components manufacturing, after irradiation at the significant 14 MeV neutron yield during the JET DT campaign.

PURPOSE We aimed to characterize long-term quality of life (QOL) trajectories among patients with breast cancer treated with adjuvant chemotherapy and to identify related patterns of health behaviors. METHODS Female stage I-III breast cancer patients receiving chemotherapy in CANTO (CANcer TOxicity; ClinicalTrials.gov identifier: NCT01993498 ) were included. Trajectories of QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–C30 Summary Score) and associations with trajectory group membership were identified by iterative estimations of group-based trajectory models and multivariable multinomial logistic regression, respectively. RESULTS Four trajectory groups were identified (N = 4,131): excellent (51.7%), very good (31.7%), deteriorating (10.0%), and poor (6.6%) QOL. The deteriorating trajectory group reported fairly good baseline QOL (mean [95% CI], 78.3/100 [76.2 to 80.5]), which significantly worsened at year-1 (58.1/100 [56.4 to 59.9]) and never recovered to pretreatment values through year-4 (61.1/100 [59.0 to 63.3]) postdiagnosis. Healthy behaviors were associated with better performing trajectory groups. Obesity (adjusted odds ratio [aOR] v lean, 1.51 [95% CI, 1.28 to 1.79]; P < .0001) and current smoking (aOR v never, 1.52 [95% CI, 1.27 to 1.82]; P < .0001) at diagnosis were associated with membership to the deteriorating group, which was also characterized by a higher prevalence of patients with excess body weight and insufficient physical activity through year-4 and by frequent exposure to tobacco smoking during chemotherapy. Additional factors associated with membership to the deteriorating group included younger age (aOR, 1-year decrement 1.01 [95% CI, 1.01 to 1.02]; P = .043), comorbidities (aOR v no, 1.22 [95% CI, 1.06 to 1.40]; P = .005), lower income (aOR v wealthier households, 1.21 [95% CI, 1.07 to 1.37]; P = .002), and endocrine therapy (aOR v no, 1.14 [95% CI, 1.01 to 1.30]; P = .047). CONCLUSION This latent-class analysis identified some patients with upfront poor QOL and a high-risk cluster with severe, persistent postchemotherapy QOL deterioration. Screening relevant patient-level characteristics may inform tailored interventions to mitigate the detrimental impact of chemotherapy and preserve QOL, including early addressal of behavioral concerns and provision of healthy lifestyle support programs.

The fibula flap is the workhorse for mandibular reconstruction, but fibula bone width is not ideal to match mandibular height. In this study, in situ widening of the fibula with distraction osteogenesis before transfer is evaluated as a solution. The authors present a proof of concept of this technique with a patient series, including one patient who has undergone subsequent orthognathic surgery of the reconstructed mandible.A retrospective review of patients undergoing the authors' technique was performed. A longitudinal fibula osteotomy was made in situ and distraction was performed in the leg to widen the fibula. After distraction and consolidation periods, flaps were osteotomized and transferred to the mandible.This technique was applied to three patients (ages 9, 11, and 13 years) with Pruzansky III mandibular hypoplasia at the authors' institution over 15 years. In all cases, bony union was achieved. Mean surgical follow-up was 5 years. No significant morbidity occurred at the donor sites. Partial flap resorption was observed a number of years postoperatively in one patient. Temporomandibular joint ankylosis developed in one patient after closed treatment of an unrelated mandible fracture. A sinus tract developed in one patient, requiring débridement of a partial flap necrosis. One patient had orthognathic surgery, including osteotomy of the fibula.In situ fibula distraction osteogenesis is a novel technique to prelaminate a fibula flap before transfer to the mandible. This method allows for the reconstruction of challenging mandibular defects without compromising bone height, pedicle length, or the ability to perform orthognathic surgery.Therapeutic, IV.

Observational studies report that physical activity and metformin are associated with improved clinical outcome in patients with cancer. Inflammation is one biological mechanism hypothesized to mediate these associations. In this phase II, multicenter, 2 × 2 factorial trial, 139 patients with breast and colorectal cancer who completed standard therapy were randomized to one of four treatment groups for 12 weeks: exercise alone, metformin alone, exercise and metformin, or control. Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), soluble tumor necrosis factor alpha receptor two (sTNFαR2), and IL6. The primary modeling strategy evaluated the trial product estimand that was quantified using a generalized linear mixed model. Compared with control, exercise alone reduced hs-CRP [−30.2%; 95% confidence interval (CI), −50.3, −1.0] and IL6 (−30.9%; 95% CI, −47.3, −9.5) but did not change sTNFαR2 (1.0%; 95% CI, −10.4, 13.9). Compared with control, metformin alone did not change hs-CRP (−13.9%; 95% CI, −40.0, 23.4), sTNFαR2 (−10.4%; 95% CI, −21.3, 2.0), or IL6 (−22.9%; 95% CI, −42.3, 2.0). Compared with control, exercise and metformin reduced sTNFαR2 (−13.1%; 95% CI, −22.9, −1.0) and IL6 (−38.7%; 95% CI, −52.3, −18.9) but did not change hs-CRP (−20.5%; 95% CI, −44.0, 12.7). The combination of exercise and metformin was not synergistic for hs-CRP, sTNFαR2, or IL6. In survivors of breast and colorectal cancer with low baseline physical activity and without type 2 diabetes, exercise and metformin reduced measures of inflammation that are associated with cancer recurrence and mortality.

Nicotinamide, the amide form of vitamin B3, and budesonide, a synthetic glucocorticoid used in the treatment of asthma, were evaluated to determine their individual and combinational chemopreventive efficacy on benzo(a)pyrene-induced lung tumors in female A/J mice. Nicotinamide fed at a dietary concentration of 0.75% significantly inhibited tumor multiplicity. Nicotinamide by aerosol inhalation at doses up to 15 mg/kg/day did not result in a statistically significant reduction in tumor multiplicity. Finally, dietary nicotinamide was administered with aerosol budesonide and tumor multiplicity reduced by 90% at 1 week and 49% at 8 weeks post last carcinogen dose. We conclude nicotinamide is an effective and safe agent for lung cancer dietary prevention at both early- and late-stage carcinogenesis and that efficacy is increased with aerosol budesonide. Combination chemoprevention with these agents is a well-tolerated and effective strategy which could be clinically advanced to human studies.

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BACKGROUND: Regular physical activity is associated with improved symptom control in patients with breast cancer but its association with chemotherapy completion or response is unclear. METHODS: Using a prospective design, 1075 breast cancer patients receiving neoadjuvant chemotherapy between March 2012 and February 2017 were studied. Physical activity was assessed using the Global Physical Activity Questionnaire [GPAQ-16], quantified in standardised MET-h/wk. Chemotherapy completion was defined as the proportion of patients completing planned treatment course, requiring dose reduction, or requiring dose delay. Response was evaluated by pathologic complete response (pCR). Associations between physical activity and primary outcomes were assessed using multivariable logistic regression models. RESULTS: There was no differences between any chemotherapy completion outcome on the basis of physical activity classification. The percent of patients not completing planned treatment was 5.7% for ≦0.33 MET-h/wk, compared with 6.8% for 0.34–16.65 MET-h/wk, and 4.6% for ≥16.6 MET-h/wk (p = 0.52). No significant relationships were observed between physical activity dose classification and pCR for the overall cohort or upon stratification by clinical subtype. CONCLUSION: Future studies are required to further investigate the relationship between pre-treatment levels of physical activity and function on treatment completion and response in breast and other cancer populations. CLINICAL TRIAL REGISTRATION: NCT01993498.

In malaria, rosetting is a phenomenon involving the cytoadherence of uninfected erythrocytes to infected erythrocytes (IRBC) harboring the late erythrocytic stage of Plasmodium spp. Recently, artesunate-stimulated rosetting has been demonstrated to confer a survival advantage to P. falciparum late-stage IRBC. This study investigated the rosetting response of P. falciparum and P. vivax clinical isolates to ex vivo antimalarial treatments. Brief exposure of IRBC to chloroquine, mefloquine, amodiaquine, quinine, and lumefantrine increased the rosetting rates of P. falciparum and P. vivax. Furthermore, the ex vivo combination of artesunate with mefloquine and piperaquine also resulted in increased the rosetting rates. Drug-mediated rosette-stimulation has important implications for the therapeutic failure of rapidly cleared drugs such as artesunate. However, further work is needed to establish the ramifications of increased rosetting rates by drugs with longer half-lifves, such as chloroquine, mefloquine, and piperaquine. Agency for Science, Technology and Research (A*STAR) Published version W-C. L. and L. R. were supported by core funding from A*STAR. W-C. L. was also funded by the Open Fund-Young Individual Research grant OF-YIRG NMRC/OFYIRG/0070/2018. L. R. was also funded by A*STAR grant JCO-DP BMSI/15-800006-SIGN. B. R. was supported by a HRC e-ASIA grant (17/678) and a University of Otago Deans Bequest Grant. Shoklo Malaria Research Unit is part of the Mahidol-Oxford University Research Unit, supported by the Wellcome Trust Thailand/Laos Major Overseas Program Renewal (grant no. 106698).

PurposeThis study examines how managers' human capital, time spent with employees and employees' human capital can influence employees' career advancement. While research tends to find a positive relationship between human capital and career advancement, less attention is paid the effect of managers' human capital on employee careers. A combination of human capital and social capital theories is used to develop hypotheses.Design/methodology/approachA five-year sample of American football players selected in the National Football League (NFL) draft is used to test the hypotheses. Archival data for human capital, social capital and career success measures are used, and OLS regression analyses test the hypotheses.FindingsThe authors find employees with higher levels of human capital experience greater career advancement. Managers' human capital moderates this relationship and the length of time worked together by the employee–manager dyad. The relationship between employees' human capital and career advancement is strengthened when managers have high levels of human capital.Practical implicationsThe results of this study indicate that individuals with higher levels of human capital and social capital have greater career success. When individuals have higher levels of human capital it is important for them to determine how long they should work for a particular manager before advancing in their careers. Individuals with higher levels of human capital may need lees time working for a manager than those with lower levels of human capital before advancing in their careers.Originality/valueThis study contributes to careers and human resource management research by examining the moderating impact that manager human capital and time employees spend with a manager have on the relationship between employee human capital and employee career advancement.

Background Estimated peak oxygen consumption (Vo2peak) is widely used in oncology; however, estimated Vo2peak equations were developed in noncancer settings. Objectives The aim of this study was to evaluate the validity of estimated Vo2peak in women with primary breast cancer and to develop oncology-specific estimated Vo2peak equations. Methods Vo2peak was directly measured (TrueOne 2400, Parvo Medics) during 380 cardiopulmonary exercise tests in women previously treated for breast cancer (mean age: 59 ± 10 years; 3.1 ± 1.2 years post-therapy). The American College of Sports Medicine (ACSM), the Fitness Registry and the Importance of Exercise National Database (FRIEND), and heart failure (HF)-FRIEND equations were used to estimate Vo2peak. New equations were developed using patient and peak (Oncpeak) or submaximal (Oncsub) exercise test characteristics. Results The median differences between measured and estimated Vo2peak were 7.0 mL O2·kg−1·min−1, 3.9 mL O2·kg−1·min−1, and −0.2 mL O2·kg−1·min−1 for ACSM, FRIEND, and HF-FRIEND, respectively. The number of estimated Vo2peak values within ±3.5 mL O2·kg−1·min−1 of the measured values was 70 (18%), 164 (43%), and 306 (81%) for ACSM, FRIEND, and HF-FRIEND, respectively. The Oncpeak and OncSub models included body mass index, age, a history of chemotherapy or radiation, the peak measured heart rate, and the treadmill grade and/or speed. The median differences between measured and estimated Vo2peak were 0.02 mL O2·kg−1·min−1 (Oncpeak) and −0.2 mL O2·kg−1·min−1 (Oncsub). Eighty-six percent (n = 325) and 76% (n = 283) estimated Vo2peak values were within ±3.5 mL O2·kg−1·min−1 of the measured Vo2peak values for Oncpeak and Oncsub, respectively. Conclusions HF-FRIEND or oncology-specific equations could be applied to estimate Vo2peak in patients previously treated for breast cancer in settings where cardiopulmonary exercise tests are not available. (Trial Comparing the Effects of Linear Versus Nonlinear Aerobic Training in Women With Operable Breast Cancer

New introductions to invasive mosquitoes, Aedes aegypti and Aedes albopictus, increase the risk for vector-borne diseases such as dengue, chikungunya, and Zika in the United States. Tracking these new introductions is more important than ever. This lesson plan focuses on the collection of mosquito larvae and pupae before the onset of summer with a focus on insect development. Students will observe the immature mosquitoes grow and metamorphose into adults. Novel aspects include collecting larvae and pupae around the home/school, observing the mosquito life cycle by safely rearing them from immature stages (larvae and pupae) to adults, and learning important background information on mosquito biology and pathogens that mosquitoes can transmit. The lesson describes new tools to use with the Invasive Mosquito Project, an international citizen science–based mosquito surveillance program exploring mosquitoes and the pathogens they may transmit to interested community members (including students and teachers) and their companion animals. This project is a stand-alone or follow-up lesson plan to the mosquito egg collection lesson used prior to the onset of winter (see Cohnstaedt et al., 2016). Students are able to participate in a hands-on tutorial to build a sealed emergence chamber to safely raise mosquitoes. Long-term data sets can also be used by teachers and students for further classroom discussions on the risks of mosquito-borne illnesses nationwide. This lesson further focuses on how individuals must play an active role in protecting their communities and pets from illness and increasing awareness of the dangerous pathogens mosquitoes can transmit and the importance of mosquito management. Materials from this lesson plan (available at http://www.citizenscience.us) can be adapted for each classroom but are best-suited for middle school to high school classes, as well as Advanced Placement classes.

The Society of Orthodontic Specialty Certifying Boards aims to encourage the formation of new certifying orthodontic boards worldwide and stimulate existing orthodontic certifying boards to review and revise their certification process. The main goal of Society of Orthodontic Specialty Certifying Boards is to motivate more orthodontists to become board certified by demonstrating their skills through time to protect the public and the specialty from unqualified practitioners. This article identifies the existing barriers in board certification and suggests a scenario-based clinical examination.

Log hazard smoothing spline plot.

To investigate whether the impact of postdiagnosis exercise on breast cancer outcomes in women diagnosed with early-stage breast cancer differs on the basis of tumor clinicopathologic and molecular features. Using a prospective design, 6,211 patients with early-stage breast cancer from two large population-based cohort studies were studied. Age-adjusted and multivariable Cox regression models were performed to determine the relationship between exercise exposure (total MET-hours/week) and recurrence and breast cancer–related death for: (i) all patients (“unselected” cohort), and on the basis of (ii) classic clinicopathologic features, (iii) clinical subtypes, (iv) PAM50-based molecular intrinsic subtypes, and (v) individual PAM50 target genes. After a median follow-up of 7.2 years, in the unselected cohort (n = 6,211) increasing exercise exposure was not associated with a reduction in the risk of recurrence (adjusted Ptrend = 0.60) or breast cancer–related death (adjusted Ptrend = 0.39). On the basis of clinicopathologic features, an exercise-associated reduction in breast cancer–related death was apparent for tumors +/PR+/HER2−/low-grade clinical subtype was preferentially responsive to exercise (recurrence: adjusted HR, 0.63; 95% CI, 0.45–0.88; breast cancer–related death: adjusted HR, 0.57; 95% CI, 0.37–0.86). The impact of exercise on cancer outcomes appears to differ as a function of pathologic and molecular features in early-stage breast cancer. Cancer Res; 76(18); 5415–22. ©2016 AACR.

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Supplementary Figure S1. White adipose tissue inflammation. A. CLS-B positive breast WAT. H&E (upper panel) and anti-CD68 immunostaining (lower panel); 40x (left panel) and 400x (right panel). Arrow indicates CLS-B. B. CLS-B negative breast WAT. H&E (upper panel) and anti-CD68 immunostaining (lower panel); 40x (left panel) and 400x (right panel). WAT, white adipose tissue; CLS-B, crown-like structures of the breast.

A major objective of the emerging field of exercise–oncology research is to determine the efficacy of, and biological mechanisms by which, aerobic exercise affects cancer incidence, progression, and/or metastasis. There is a strong inverse association between self-reported exercise and the primary incidence of several forms of cancer; similarly, emerging data suggest that exercise exposure after a cancer diagnosis may improve outcomes for early-stage breast, colorectal, or prostate cancer. Arguably, critical next steps in the development of exercise as a candidate treatment in cancer control require preclinical studies to validate the biological efficacy of exercise, identify the optimal “dose”, and pinpoint mechanisms of action. To evaluate the current evidence base, we conducted a critical systematic review of in vivo studies investigating the effects of exercise in cancer prevention and progression. Studies were evaluated on the basis of tumor outcomes (e.g., incidence, growth, latency, metastasis), dose–response, and mechanisms of action, when available. A total of 53 studies were identified and evaluated on tumor incidence (n = 24), tumor growth (n = 33), or metastasis (n = 10). We report that the current evidence base is plagued by considerable methodologic heterogeneity in all aspects of study design, endpoints, and efficacy. Such heterogeneity precludes meaningful comparisons and conclusions at present. To this end, we provide a framework of methodologic and data reporting standards to strengthen the field to guide the conduct of high-quality studies required to inform translational, mechanism-driven clinical trials. Cancer Res; 76(14); 4032–50. ©2016 AACR.

Purpose: Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance.Experimental Design: WAT inflammation was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS) of the breast. Two independent groups were examined in cross-sectional (cohort 1) and retrospective (cohort 2) studies. Cohort 1 included 100 women undergoing mastectomy for breast cancer risk reduction (n = 10) or treatment (n = 90). Metabolic syndrome–associated circulating factors were compared by CLS-B status. The association between CLS of the breast and the metabolic syndrome was validated in cohort 2, which included 127 women who developed metastatic breast cancer. Distant recurrence-free survival (dRFS) was compared by CLS-B status.Results: In cohorts 1 and 2, breast WAT inflammation was detected in 52 of 100 (52%) and 52 of 127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and IL6 and lower high-density lipoprotein cholesterol and adiponectin (P < 0.05) in cohort 1. In cohort 2, breast WAT inflammation was associated with hyperlipidemia, hypertension, and diabetes (P < 0.05). Compared with patients without breast WAT inflammation, the adjusted HR for dRFS was 1.83 (95% CI, 1.07–3.13) for patients with inflammation.Conclusions: WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis. Clin Cancer Res; 22(9); 2283–9. ©2015 AACR.

Overview of study characteristics

Concept Vocabulary

Supplementary Figure 2 from Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression after Whole-Brain Irradiation

Supplementary Methods and Materials from Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression after Whole-Brain Irradiation

Supplementary Figure 1 from Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression after Whole-Brain Irradiation

Hansen’s disease (HD) is an infectious, treatable, and chronic disease. It is the main cause of infectious peripheral neuropathy. Due to the current limitations of laboratory tests for the diagnosis of HD, early identification of infected contacts is an important factor that would allow us to control the magnitude of this disease in terms of world public health. Thus, a cross-sectional study was conducted in the Brazilian southeast with the objective of evaluating humoral immunity and describing the accuracy of the immunoassay based on IgA, IgM, and IgG antibodies against surface protein Mce1A of Mycobacterium, the predictive potential of these molecules, the clinical significance of positivity, and the ability to segregate new HD cases (NC; n = 200), contacts (HHC; n = 105), and healthy endemic controls (HEC; n = 100) as compared to α-PGL-I serology. α-Mce1A levels for all tested antibodies were significantly higher in NC and HHC than in HEC (p 0.85) for screening HD patients. Among HD patients (NC), positivity was 77.5% for IgA α-Mce1A ELISA, 76.5% for IgM, and 61.5% for IgG, while α-PGL-I serology showed only 28.0% positivity. Multivariate PLS-DA showed two defined clusters for the HEC and NC groups [accuracy = 0.95 (SD = 0.008)] and the HEC and HHC groups [accuracy = 0.93 (SD = 0.011)]. IgA was the antibody most responsible for clustering HHC as compared to NC and HEC, evidencing its usefulness for host mucosal immunity and as an immunological marker in laboratory tests. IgM is the key antibody for the clustering of NC patients. Positive results with high antibody levels indicate priority for screening, new clinical and laboratory evaluations, and monitoring of contacts, mainly with antibody indexes ≥2.0. In light of recent developments, the incorporation of new diagnostic technologies permits to eliminate the main gaps in the laboratory diagnosis of HD, with the implementation of tools of greater sensitivity and accuracy while maintaining satisfactory specificity.

AimsThe most appropriate timing of exercise therapy to improve cardiorespiratory fitness (CRF) among patients initiating chemotherapy is not known. The effects of exercise therapy administered during, following, or during and following chemotherapy were examined in patients with breast cancer.Methods and resultsUsing a parallel-group randomized trial design, 158 inactive women with breast cancer initiating (neo)adjuvant chemotherapy were allocated to receive (1:1 ratio): usual care or one of three exercise regimens—concurrent (during chemotherapy only), sequential (after chemotherapy only), or concurrent and sequential (continuous) (n = 39/40 per group). Exercise consisted of treadmill walking three sessions/week, 20–50 min at 55%–100% of peak oxygen consumption (VO2peak) for ≈16 (concurrent, sequential) or ≈32 (continuous) consecutive weeks. VO2peak was evaluated at baseline (pre-treatment), immediately post-chemotherapy, and ≈16 weeks after chemotherapy. In intention-to-treat analysis, there was no difference in the primary endpoint of VO2peak change between concurrent exercise and usual care during chemotherapy vs. VO2peak change between sequential exercise and usual care after chemotherapy [overall difference, −0.88 mL O2·kg−1·min−1; 95% confidence interval (CI): −3.36, 1.59, P = 0.48]. In secondary analysis, continuous exercise, approximately equal to twice the length of the other regimens, was well-tolerated and the only strategy associated with significant improvements in VO2peak from baseline to post-intervention (1.74 mL O2·kg−1·min−1, P < 0.001).ConclusionThere was no statistical difference in CRF improvement between concurrent vs. sequential exercise therapy relative to usual care in women with primary breast cancer. The promising tolerability and CRF benefit of ≈32 weeks of continuous exercise therapy warrant further evaluation in larger trials.

The World Health Organization released a statement warning of increased risk for the incidence of multidrug resistant microorganisms and the absence of new drugs to control such infections soon. Since the beginning of the COVID-19 pandemic, the prescription of antimicrobial agents has increased and may have accelerated the emergence of multidrug resistant (MDR) bacteria. This study aimed to evaluate maternal and pediatric infections within a hospital from January 2019 to December 2021. An observational retrospective cohort study was performed at a quaternary referral hospital in a metropolitan area of Niteroi city, Rio de Janeiro state, Brazil. A total of 196 patients’ medical records were analyzed. The data from 90 (45.9%) patients were collected before the SARS-CoV-2 pandemic, 29 (14.8%) from the 2020 pandemic period, and 77 (39.3%) from the 2021 pandemic period. A total of 256 microorganisms were identified during this period. Out of those, 101 (39.5%) were isolated in 2019, 51 (19.9%) in 2020, and 104 (40.6%) in 2021. Antimicrobial susceptibility tests were performed on 196 (76.6%) clinical isolates. The exact binomial test showed that the distribution of Gram-negative bacteria was predominant. The most common microorganism was Escherichia coli (23%; n = 45), followed by Staphylococcus aureus (17.9%, n = 35), Klebsiella pneumoniae (12.8%, n = 25), Enterococcus faecalis (7.7%, n = 15), Staphylococcus epidermidis (6.6%, n = 13) and Pseudomonas aeruginosa (5.6%, n = 11). Staphylococcus aureus was the predominant species among resistant bacteria. Among the antimicrobial agents tested, the following were resistant, presented on a descending scale: penicillin (72.7%, p = 0.001, Binomial test), oxacillin (68.3%, p = 0.006, Binomial test), ampicillin (64.3%, p = 0.003, Binomial test), and ampicillin/sulbactam (54.9%, p = 0.57, Binomial test). Infections with S. aureus were 3.1 times greater in pediatrics and maternal units than in other hospital wards. Despite the global reduction in the incidence of MRSA, we observed an increase in MDR S. aureus in this study. No changes were observed in the frequency of resistance profiles of the clinical isolates after the establishment of the global SARS-CoV-2 pandemic. More comprehensive studies are needed to understand the impact of the global SARS-CoV-2 pandemic on the resistance levels of bacteria associated with neonate and pediatric patients.

Most population genetic studies concern spatial genetic differentiation, but far fewer aim at analyzing the temporal genetic changes that occur within populations. Vector species, including mosquitoes and biting midges, are often characterized by oscillating adult population densities, which may affect their dispersal, selection, and genetic diversity over time. Here, we used a population ofCulicoides sonorensisfrom a single site in California to investigate short-term (intra-annual) and long-term (inter-annual) temporal variation in genetic diversity over a three year period. This biting midge species is the primary vector of several viruses affecting both wildlife and livestock, thus a better understanding of the population dynamics of this species can help inform epidemiological studies. We found no significant genetic differentiation between months or years, and no correlation between adult populations and the inbreeding coefficient (FIS). However, we show that repeated periods of low adult abundance during cooler winter months resulted in recurring bottleneck events. Interestingly, we also found a high number of private and rare alleles, which suggests both a large, stable population, as well as a constant influx of migrants from nearby populations. Overall, we showed that the high number of migrants maintains a high level of genetic diversity by introducing new alleles, while this increased diversity is counterbalanced by recurrent bottleneck events potentially purging unfit alleles each year. These results highlight the temporal influences on population structure and genetic diversity inC. sonorensisand provide insight into factors effecting genetic variation that may occur in other vector species with fluctuating populations.

Background West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental USA. WNV occurrence has high spatiotemporal variation, and current approaches to targeted control of the virus are limited, making forecasting a public health priority. However, little research has been done to compare strengths and weaknesses of WNV disease forecasting approaches on the national scale. We used forecasts submitted to the 2020 WNV Forecasting Challenge, an open challenge organized by the Centers for Disease Control and Prevention, to assess the status of WNV neuroinvasive disease (WNND) prediction and identify avenues for improvement. Methods We performed a multi-model comparative assessment of probabilistic forecasts submitted by 15 teams for annual WNND cases in US counties for 2020 and assessed forecast accuracy, calibration, and discriminatory power. In the evaluation, we included forecasts produced by comparison models of varying complexity as benchmarks of forecast performance. We also used regression analysis to identify modeling approaches and contextual factors that were associated with forecast skill. Results Simple models based on historical WNND cases generally scored better than more complex models and combined higher discriminatory power with better calibration of uncertainty. Forecast skill improved across updated forecast submissions submitted during the 2020 season. Among models using additional data, inclusion of climate or human demographic data was associated with higher skill, while inclusion of mosquito or land use data was associated with lower skill. We also identified population size, extreme minimum winter temperature, and interannual variation in WNND cases as county-level characteristics associated with variation in forecast skill. Conclusions Historical WNND cases were strong predictors of future cases with minimal increase in skill achieved by models that included other factors. Although opportunities might exist to specifically improve predictions for areas with large populations and low or high winter temperatures, areas with high case-count variability are intrinsically more difficult to predict. Also, the prediction of outbreaks, which are outliers relative to typical case numbers, remains difficult. Further improvements to prediction could be obtained with improved calibration of forecast uncertainty and access to real-time data streams (e.g. current weather and preliminary human cases). Graphical Abstract

Antarctic glaciers are losing ice rapidly to the ocean through basal melting of ice shelves/tongues. To better predicate future sea level rise, it is urgent to detect the rapid basal melting of ice shelves/tongues as well as ocean’s role in this process. In this study, basal melting of Drygalski Ice Tongue (DIT), the seaward extension of David Glacier in Northern Victoria Land, East Antarctica has been detected using a surface deployed Autonomous Phase-sensitive Radio-Echo-Sounder (ApRES). The ocean water changes adjacent to DIT front has been revealed using an ocean mooring. ApRES observation suggests a rapid basal melting > 10 m/a close to DIT front in February and mooring data shows a synchronous ocean warming in austral summer, indicating Antarctica Surface Water intrusion to the base of DIT. The mooring data has been used to simulate the basal melting of DIT front, which coincides with ApRES measurements. We conclude that rapid basal melting close to the tongue front was likely triggered by intrusion of Antarctica Surface Water in austral summer. Glacier-ocean interactions, such as glacier basal melting, can be detected from spaceborne, terrestrial and oceanic observations and are important processes to predict future sea level changes. To better understand the driving forces of glacier changes, multi-disciplinary observation and numerical modeling are required., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

We present a short overview of the TeV-Halos objects as a discovery and a relevant contribution of the High Altitude Water \v{C}erenkov (HAWC) observatory to TeV astrophysics. We discuss history, discovery, knowledge, and the next step through a new and more detailed analysis than the original study in 2017. TeV-Halos will contribute to resolving the problem of the local positron excess observed on the Earth. To clarify the latter, understanding the diffusion process is mandatory., Comment: Work presented in the 21st International Symposium on Very High Energy Cosmic Ray Interactions(ISVHECRI 2022) as part of the Ph. D. Thesis of Ramiro Torres-Escobedo (SJTU, Shanghai, China). Accepted for publication in SciPost Physics Proceedings (ISSN 2666-4003). 11 pages, 3 Figures. Short overview of HAWC and TeV Halos objects until 2022

Background: Modifiable lifestyle-related factors heighten the risk and severity of coronavirus disease 2019 (COVID-19) in patients with cancer. Whether exercise lowers susceptibility or severity is not known. Methods: We identified 944 cancer patients from Memorial Sloan Kettering Cancer Center (mean age: 64; 85% female; 78% White) completing an exercise survey before receiving a confirmed positive or negative SARS-CoV-2 test. Exercise was defined as reporting moderate-intensity ≥5 days per week, ≥30 minutes/session or strenuous-intensity ≥3 days per week, ≥20 minutes/session. Multivariable logistic regression was used to determine the relationship between exercise and COVID-19 susceptibility and severity (i.e., composite of hospital admission or death events) with adjustment for clinical–epidemiologic covariates. Results: Twenty-four percent (230/944) of the overall cohort were diagnosed with COVID-19 and 35% (333/944) were exercisers. During a median follow-up of 10 months, 26% (156/611) of nonexercising patients were diagnosed with COVID-19 compared with 22% (74/333) of exercising patients. The adjusted OR for risk of COVID-19 was 0.65 [95% confidence interval (CI), 0.44–0.96, P = 0.03] for exercisers compared with nonexercisers. A total of 20% (47/230) of COVID-19 positive patients were hospitalized or died. No difference in the risk of severe COVID-19 as a function of exercise status was observed (P > 0.9). Conclusions: Exercise may reduce the risk of COVID-19 infection in patients with a history of cancer, but not its severity. Impact: This study provides the first data showing that exercise might lower the risk of COVID-19 in cancer patients, but further research is required.

Using numerical simulations of the formation and evolution of stellar clusters within molecular clouds, we show that the stars in clusters formed within collapsing molecular cloud clumps exhibit a constant velocity dispersion regardless of their mass, as expected in a violent relaxation processes. In contrast, clusters formed in turbulence-dominated environments exhibit an {\it inverse} mass segregated velocity dispersion, where massive stars exhibit larger velocity dispersions than low-mass cores, consistent with massive stars formed in massive clumps, which in turn, are formed through strong shocks. We furthermore use Gaia EDR3 to show that the stars in the Orion Nebula Cluster exhibit a constant velocity dispersion as a function of mass, suggesting that it has been formed by collapse within one free-fall time of its parental cloud, rather than in a turbulence-dominated environment during many free-fall times of a supported cloud. Additionally, we have addressed several of the criticisms of models of collapsing star forming regions: namely, the age spread of the ONC, the comparison of the ages of the stars to the free-fall time of the gas that formed it, the star formation efficiency, and the mass densities of clouds vs the mass densities of stellar clusters, showing that observational and numerical data are consistent with clusters forming in clouds undergoing a process of global, hierarchical and chaotic collapse, rather than been supported by turbulence., Comment: Accepted for publication in MNRAS

PurposeAs ethical leadership has advanced as a construct, the degree to which healthy relational systems explain its effect on employee outcomes has been understudied. With this manuscript we conceptualize and test a model based on a Relational Systems approach to ethical leadership and its relationship with conflict and turnover intentions.Design/methodology/approachTwo studies were conducted to test our hypothesized first- and second-stage moderated mediation model. In Study 1, online surveys were completed by 168 working adults across two different time points. Study 2 extended Study 1 by surveying 115 working adults across three time points using the Mechanical Turk platform.FindingsThe indirect relationship between ethical leadership and turnover intentions via relationship conflict was conditional based on follower moral identity. The negative influence of ethical leadership on relationship conflict and, in turn, turnover intentions was stronger for followers who had higher moral identities. In addition, our findings suggest that leader holding behaviors strengthen the negative indirect effects of ethical leadership on turnover intentions.Originality/valueThis paper demonstrates the usefulness of a Relational Systems theoretical approach to understanding ethical leadership. Specifically, ethical leaders, through their desire and ability to help employees feel known and not alone at work, are better able to reduce relationship conflict and, in turn, reduce employees' desire to leave the organization.