Pure quartic modulational instability in weakly nonlocal birefringent fibers.

The modulational instability (MI) phenomenon is theoretically investigated in birefringent optical media with pure quartic dispersion and weak Kerr nonlocal nonlinearity. We find from the MI gain that instability regions are more expanded due to nonlocality, which is confirmed via direct numerical simulations showing the emergence of Akhmediev breathers (ABs) in the total energy context. In addition, the balanced competition between nonlocality and other nonlinear and dispersive effects exclusively gives the possibility of generating long-lived structures which deepens our understanding of soliton dynamics in pure-quartic dispersive optical systems and opens new investigation routes in fields related to nonlinear optics and lasers.

Detection of Acetylcholine at Nanoscale NPOE/Water Liquid/Liquid Interface Electrodes.

The interface between two immiscible electrolyte solutions (ITIES) has become a very powerful analytical platform for sensing a diverse range of chemicals (e.g., metal ions and neurotransmitters) with the advantage of being able to detect non-redox electroactive species. The ITIES is formed between organic and aqueous phases. Organic solvent identity is crucial to the detection characteristics of the ITIES [half-wave transfer potential (E1/2), potential window range, limit of detection, transfer coefficient (α), standard heterogeneous ion-transfer rate constant (k0), etc.]. Here, we demonstrated, for the first time at the nanoscale, the detection characteristics of the NPOE/water ITIES. Linear detection of the diffusion-limited current at different concentrations of acetylcholine (ACh) was demonstrated with cyclic voltammetry (CV) and i-t amperometry. The E1/2 of ACh transfer at the NPOE/water nanoITIES was -0.342 ± 0.009 V versus the E1/2 of tetrabutylammonium (TBA+). The limit of detection of ACh at the NPOE/water nanoITIES was 37.1 ± 1.5 µM for an electrode with a radius of ∼127 nm. We also determined the ion-transfer kinetics parameters, α and k0, of TBA+ at the NPOE/water nanoITIES by fitting theoretical cyclic voltammograms to experimental voltammograms. This work lays the basis for future cellular studies using ACh detection at the nanoscale and for studies to detect other analytes. The NPOE/water ITIES offers a potential window distinct from that of the 1,2-dichloroethane (DCE)/water ITIES. This unique potential window would offer the ability to detect analytes that are not easily detected at the DCE/water ITIES.

In Vivo Magnetic Resonance Spectroscopy of Hyperpolarized [1-13 C]Pyruvate and Proton Density Fat Fraction in a Guinea Pig Model of Non-Alcoholic Fatty Liver Disease Development After Life-Long Western Diet Consumption.

BACKGROUND: Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations. PURPOSE: To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life-long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. STUDY TYPE: Prospective. ANIMAL MODEL: Twenty-eight male guinea pigs weaned onto a control diet (N = 14) or WD (N = 14). FIELD STRENGTH/SEQUENCE: 3 T; T1-weighted gradient echo, T2-weighted spin-echo, three-dimensional gradient multi-echo fat-water separation (IDEAL-IQ), and broadband point-resolved spectroscopy (PRESS) chemical-shift sequences. ASSESSMENT: Median PDFF was calculated in the liver and hind limbs. [1-13 C]pyruvate dynamic MRS in the liver was quantified by the time-to-peak (TTP) for each metabolite. Animals were euthanized and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity. STATISTICAL TESTS: Unpaired Student's t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. RESULTS: Life-long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. DATA CONCLUSION: PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD-exposed livers. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Postoperative Outcomes Following Total Hip and Knee Arthroplasty in Patients with Pain Catastrophizing, Anxiety, or Depression.

BACKGROUND: The relationship among pain catastrophizing, emotional disorders, and total joint arthroplasty (TJA) outcomes is an emerging area of study. The purpose of this study is to examine the association of these factors with 1-year postoperative pain and functional outcomes. METHODS: A prospective cohort study of preoperative TJA patients using the Pain Catastrophizing Scale and Hospital Anxiety and Depression Scale (HADS-A/HADS-D) was conducted. Postoperative outcomes included Visual Analog Scale (VAS) pain, Oxford, Harris Hip (HHS) and Knee Society (KSS) scores. Median regression was used to assess the pattern of relationship among preoperative clinically relevant catastrophizing (CRC) pain, abnormal HADS, and 1-year postoperative outcomes. RESULTS: We recruited 463 TJA patients, all of which completed 1-year follow-up. At 1 year, CRC-rumination (adjusted median difference 1; 95% confidence interval [CI] 0.31-1.69, P = .005) and abnormal HADS-A (adjusted median difference 1; 95% CI 0.36-1.64, P = .002) were predictors of VAS pain, CRC magnification a predictor of HHS/KSS (adjusted median difference 1.3; 95% CI 5.23-0.11, P = .041), and abnormal HADS-A a predictor of Oxford (adjusted median difference 3.68; 95% CI 1.38-5.99, P = .002). CRC patients demonstrated inferior VAS pain (P = .001), Oxford (P < .0001), and HHS/KSS (P = .025). Abnormal HADS patients demonstrated inferior postoperative VAS (HADS-A, P = .025; HADS-D, P = .030) and Oxford (HADS-A, P = .001; HADS-D, P = .030). However, patients with CRC experienced significant improvement in VAS, Oxford, and HHS/KSS (P < .05) from preoperative to 1 year. Similarly, patients with abnormal HADS showed significant improvement in VAS pain and HHS/KSS (P < .05). CONCLUSION: TJA patients who are anxious, depressed, or pain catastrophizing have inferior preoperative and postoperative pain and function. However, as compared to their preoperative status, clinically significant improvement can be expected following hip/knee arthroplasty.

Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association.

Hypertriglyceridemia (triglycerides 200-499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and diabetes mellitus. In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2-4 g/d) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription agents containing EPA+DHA or EPA alone have been approved by the US Food and Drug Administration for treating very high triglycerides; these agents are also widely used for hypertriglyceridemia. The purpose of this advisory is to summarize the lipid and lipoprotein effects resulting from pharmacological doses of n-3 FAs (>3 g/d total EPA+DHA) on the basis of new scientific data and availability of n-3 FA agents. In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides. When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin. In the largest trials of 4 g/d prescription n-3 FA, non-high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin. The results of a trial of 4 g/d prescription EPA+DHA in hypertriglyceridemia are anticipated in 2020. We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.

German Adjuvant Intergroup Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients.

BACKGROUND: Dose-dense (dd) regimens are one of the preferred options for the adjuvant treatment of breast cancer patients with intermediate to high risk. The German Adjuvant Intergroup Node-positive trial aimed at optimizing intense dd (idd) strategies by evaluating drug combinations and the addition of capecitabine. PATIENTS AND METHODS: Women (aged 18 years and biologically <65 years) with histologically involved axillary lymph nodes were randomly assigned to receive three courses each of epirubicin (E) 150 mg/m2, paclitaxel (P) 225 mg/m2 and cyclophosphamide (C) 2500 mg/m2 (reduced to 2000 mg/m2 after recruitment of 1200 patients) q2w intravenously (i.v.) (iddEPC-regimen) or ddEC (E 112.5 mg/m2 + C 600 mg/m2, i.v. q2w for 4 cycles) followed by paclitaxel weekly (Pw 67.5 mg/m2 i.v. q8d for 10 weeks) plus capecitabine (X 2000 mg/m2 p.o. days 1-14, q22 for 4 cycles) (ddEC-PwX-regimen). Further randomization assigned patients to ibandronate for 2 years versus observation and to pegfilgrastim day 2 versus 4. RESULTS: From June 2004 to August 2008, 2994 patients were randomized to either iddEPC (N = 1498), or ddEC-PwX (N = 1496) and started treatment. Median age was 50 years; pN1 (37.8%), pN2 (35.3%); pN3 (26.9%); 46.4% were G3 tumors; 76.9% hormone receptor-positive and 22% HER2-positive. After a median follow-up of 74 months, 645 events and 383 deaths were recorded. Hematological adverse events grades 3-4 were more common with iddEPC (P < 0.001), nonhematological with ddEC-PwX (P = 0.04), even if the toxicity profile of the two regimens was different. At 5 years, estimated disease-free survival rates for ddEC-PwX and iddEPC were 81.7% [95% confidence interval (CI) 79.5-83.6] versus 80.2% (95% CI 78.0-82.2). Hazard ratio (HR)=0.95 (95% CI 0.81-1.11, log-rank P = 0.49). Five-year overall survival rates were 89.4% for ddEC-PwX (95% CI 87.7-91.0) and 89.0% for iddEPC (95% CI 87.2-90.6), HR = 0.85 (95% CI 0.69-1.04, log-rank P = 0.10). CONCLUSION: Adding capecitabine to ddEC-Pw did not improve outcome in comparison to iddEPC but increased toxicity and should not be recommended for further use.

An assessment of postcranial indices, ratios, and body mass versus eco-geographical variables of prehistoric Jomon, Yayoi agriculturalists, and Kumejima Islanders of Japan.

OBJECTIVES: We explore variations in body and limb proportions of the Jomon hunter-gatherers (14,000-2500 BP), the Yayoi agriculturalists (2500-1700 BP) of Japan, and the Kumejima Islanders of the Ryukyus (1600-1800 AD) with 11 geographically diverse skeletal postcranial samples from Africa, Europe, Asia, Australia, and North America using brachial-crural indices, femur head-breadth-to-femur length ratio, femur head-breadth-to-lower-limb-length ratio, and body mass as indicators of phenotypic climatic adaptation. Specifically, we test the hypothesis that variation in limb proportions seen in Jomon, Yayoi, and Kumejima is a complex interaction of genetic adaptation; development and allometric constraints; selection, gene flow and genetic drift with changing cultural factors (i.e., nutrition) and climate. METHODS: The skeletal data (1127 individuals) were subjected to principle components analysis, Manly's permutation multiple regression tests, and Relethford-Blangero analysis. RESULTS: The results of Manly's tests indicate that body proportions and body mass are significantly correlated with latitude, and minimum and maximum temperatures while limb proportions were not significantly correlated with these climatic variables. Principal components plots separated "climatic zones:" tropical, temperate, and arctic populations. The indigenous Jomon showed cold-adapted body proportions and warm-adapted limb proportions. Kumejima showed cold-adapted body proportions and limbs. The Yayoi adhered to the Allen-Bergmann expectation of cold-adapted body and limb proportions. Relethford-Blangero analysis showed that Kumejima experienced gene flow indicated by high observed variances while Jomon experienced genetic drift indicated by low observed variances. CONCLUSIONS: The complex interaction of evolutionary forces and development/nutritional constraints are implicated in the mismatch of limb and body proportions.

Safety of the lateral trauma position in cervical spine injuries: a cadaver model study.

BACKGROUND: Endotracheal intubation is not always an option for unconscious trauma patients. Prehospital personnel are then faced with the dilemma of maintaining an adequate airway without risking deleterious movement of a potentially unstable cervical spine. To address these two concerns various alternatives to the classical recovery position have been developed. This study aims to determine the amount of motion induced by the recovery position, two versions of the HAINES (High Arm IN Endangered Spine) position, and the novel lateral trauma position (LTP). METHOD: We surgically created global cervical instability between the C5 and C6 vertebrae in five fresh cadavers. We measured the rotational and translational (linear) range of motion during the different maneuvers using an electromagnetic tracking device and compared the results using a general linear mixed model (GLMM) for regression. RESULTS: In the recovery position, the range of motion for lateral bending was 11.9°. While both HAINES positions caused a similar range of motion, the motion caused by the LTP was 2.6° less (P = 0.037). The linear axial range of motion in the recovery position was 13.0 mm. In comparison, the HAINES 1 and 2 positions showed significantly less motion (-5.8 and -4.6 mm, respectively), while the LTP did not (-4.0 mm, P = 0.067). CONCLUSION: Our results indicate that in unconscious trauma patients, the LTP or one of the two HAINES techniques is preferable to the standard recovery position in cases of an unstable cervical spine injury.

Sports Concussion Management: part II.

Millions of concussions occur every year in the United States. The public interest in concussion has increased after a number of high-profile deaths in high school athletes from sports-related head trauma and in some professional athletes from chronic traumatic encephalopathy. One of the most active areas of research in sports medicine during the last decade has been the evaluation and management of concussion. In this second article of a two-part series, we provide an overview of the latest scientific advances in concussion research. This overview includes an update on the pathobiological changes that occur during concussion and the results of biomechanical studies. In addition, to aid the practicing clinician, we review the literature on proven and currently studied concussion risk factors, including a history of concussion, fatigue, and age. Genetic polymorphisms and biomarkers may provide risk-prediction capability, but at present the research remains inconclusive. Diffusion tensor imaging and functional magnetic resonance imaging are promising technologies that reveal more sophisticated data about the impact of concussion on the brain. We review the existing literature on the application of these neuroimaging modalities to sports concussion. An update from the Fourth International Conference on Concussion in Sport, with highlights of new recommendations, and the presentation of the third edition of the Sports Concussion Assessment Tool to evaluate acute concussion, concludes our review.

Improved radiographic outcomes with patient-specific total knee arthroplasty.

Patient-specific guides can improve limb alignment and implant positioning in total knee arthroplasty, although not all studies have supported this benefit. We compared the radiographs of 100 consecutively-performed patient-specific total knees to a similar group that was implanted with conventional instruments instead. The patient-specific group showed more accurate reproduction of the theoretically ideal mechanical axis, with fewer outliers, but implant positioning was comparable between groups. Our odds ratio comparison showed that the patient-specific group was 1.8 times more likely to be within the desired +3° from the neutral mechanical axis when compared to the standard control group. Our data suggest that reliable reproduction of the limb mechanical axis may accrue from patient-specific guides in total knee arthroplasty when compared to standard, intramedullary instrumentation.

Metabolic responses of running shod and barefoot in mid-forefoot runners.

BACKGROUND: The purposes of this study were to compare the oxygen cost, metabolic parameters and temporalspatial variables between barefoot and shod running in trained mid-forefoot runners. METHODS: Experienced runners (N.=21; 30±10.9 years; 16 men) performed two separate 20 minute treadmill running bouts at ~77% of estimated maximal heart rate. Rate of oxygen consumption (VO2), energy cost, fuel use and heart rate (HR) were collected continuously using a portable gas analyzer. Three-dimensional motion capture was used to measure temporalspatial parameters. RESULTS: Participants ran at a mean self-selected speed of 3.1±0.3 m/s for both conditions, at intensities corresponding to mean HR values of 146 bpm (shod) and 144 bpm (barefoot). Steady State VO2 was not different between the shod and barefoot conditions (39.4± 4.7 mL/kg*min vs. 40±5.2 mL/kg*min, respectively). The total energy expended in the shod and barefoot conditions was 974±134 kJ and 979±142 kJ. The average non-protein respiratory exchange ratios, proportions and amount of fat and carbohydrate used were not different between conditions. Cadence was 2.5% higher and center of gravity vertical displacement was 0.5 cm less for the barefoot condition (P<0.05). CONCLUSION: In trained mid-forefoot runners experienced with barefoot running, there are not significant metabolic differences between shod and barefoot running conditions. Barefoot running increases cadence and decreases foot contact time and vertical displacement. Experienced participants were likely able to titrate kinematics to standardize energy output and fuel use for a given running distance and speed irrespective of shoe wear.

A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients.

Major histocompatibility class II (MHC-II) molecules are transmembrane proteins that have a central role in development and control of the immune system. They are encoded by a multigene family and their expression is tightly regulated. MHC-II deficiency (OMIM 209920) is an autosomal recessive immunodeficiency syndrome resulting from defects in trans-acting factors essential for transcription of MHC-II genes. There are four genetic complementation groups (A, B, C and D), reflecting the existence of four MHC-II regulators. The factors defective in groups A (CIITA), C (RFX5) and D (RFXAP) have been identified. CIITA is a non-DNA-binding co-activator that controls the cell-type specificity and inducibility of MHC-II expression. RFX5 and RFXAP are two subunits of RFX, a multi-protein complex that binds the X box motif of MHC-II promoters. Mutations in the genes encoding RFX5 (RFX5) or RFXAP (RFXAP) abolish binding of RFX (refs 7,8,12). Similar to groups C and D, group B is characterized by a defect in RFX binding, and although it accounts for the majority of patients, the factor defective in group B has remained unknown. We report here the isolation of RFX by a novel single-step DNA-affinity purification approach and the identification of RFXANK, the gene encoding a third subunit of RFX. RFXANK restores MHC-II expression in cell lines from patients in group B and is mutated in these patients. RFXANK contains a protein-protein interaction region consisting of three ankyrin repeats. Its interaction with RFX5 and RFXAP is essential for binding of the RFX complex to MHC-II promoters.

Surgical, Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Systematic Review.

INTRODUCTION: Thymic epithelial tumors are rare and are classified as thymoma, thymic carcinoma, and thymic neuroendocrine tumors. The objective of this systematic review was to evaluate the treatment options for patients with thymic epithelial tumors. METHODS: This systematic review was developed by Ontario Health (Cancer Care Ontario)'s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group. MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing surgical, radiotherapy, or systemic treatments against any combination of these treatments in patients with thymic epithelial tumors. Meta-analyses were conducted with clinically homogenous studies. RESULTS: A total of 106 studies were included, mainly from observational studies. There was an overall survival benefit with postoperative radiotherapy for patients with thymic carcinoma (hazard ratio = 0.65, 95% confidence interval: 0.47-0.89) and for patients with thymoma (hazard ratio = 0.70, 95% confidence interval: 0.59-0.82), especially for those with a high risk for mortality. Patients with thymic carcinoma or thymoma had a response to chemotherapy. Selection bias affected the results for studies that evaluated neoadjuvant chemotherapy or minimally invasive surgical techniques. Furthermore, the overall survival benefit found for adjuvant chemotherapy may have been confounded by the administration of postoperative radiotherapy. CONCLUSIONS: For patients with thymoma or thymic carcinoma, the literature is of low quality and subject to bias. There were overall survival benefits with postoperative radiotherapy. The results of this systematic review were used to inform treatment recommendations in a clinical practice guideline. Future large-scale prospective studies that control for confounders are needed.

Host kinase regulation of Plasmodium vivax dormant and replicating liver stages.

Upon transmission to the liver, Plasmodium vivax parasites form replicating schizonts, which continue to initiate blood-stage infection, or dormant hypnozoites that reactivate weeks to months after initial infection. P. vivax phenotypes in the field vary significantly, including the ratio of schizonts to hypnozoites formed and the frequency and timing of relapse. Evidence suggests that both parasite genetics and environmental factors underly this heterogeneity. We previously demonstrated that data on the effect of a panel of kinase inhibitors with overlapping targets on Plasmodium liver stage infection, in combination with a computational approach called kinase regression (KiR), can be used to uncover novel host regulators of infection. Here, we applied KiR to evaluate the extent to which P. vivax liver-stage parasites are susceptible to changes in host kinase activity. We identified a role for a subset of host kinases in regulating schizont and hypnozoite infection and schizont size and characterized overlap as well as variability in host phosphosignaling dependencies between parasite forms and across multiple patient isolates. Striking, our data point to variability in host dependencies across P. vivax isolates, suggesting one possible origin of the heterogeneity observed across P. vivax in the field.

Surgical, Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Clinical Practice Guideline.

INTRODUCTION: The aim of this guideline was to provide recommendations for the most effective therapy for patients with thymic epithelial tumors, including thymoma, thymic carcinoma, and thymic neuroendocrine tumors (NETs). This guideline is intended to be used by all health care professionals managing patients with thymic epithelial tumors. METHODS: The guideline was developed by Ontario Health (Cancer Care Ontario)'s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of the evidence, expert consensus, and formal internal and external reviews. RESULTS: Evidence-based recommendations were developed to improve the management of patients with thymic epithelial tumors. The guideline includes recommendations for surgical, radiation, and systemic treatments for patients with thymoma, thymic carcinoma, and thymic NETs separated by stage of disease using the TNM staging system. Recommendations for patients with thymic NETs were endorsed from the 2021 National Comprehensive Cancer Network Neuroendocrine and Adrenal Tumors Guideline. CONCLUSIONS: This guideline reflects the new staging system for patients with thymoma and thymic carcinoma and includes supporting evidence from the best available studies.

Prevalence and Workplace Drivers of Burnout in Cancer Care Physicians in Ontario, Canada.

PURPOSE: Provider well-being has become the fourth pillar of the quadruple aim for providing quality care. Exacerbated by the global COVID-19 pandemic, provider well-being has become a critical issue for health care systems worldwide. We describe the prevalence and key system-level drivers of burnout in oncologists in Ontario, Canada. METHODS: This is a cross-sectional survey study conducted in November-December 2019 of practicing cancer care physicians (surgical, medical, radiation, gynecologic oncology, and hematology) in Ontario, Canada. Ontario is Canada's largest province (with a population of 14.5 million), and has a single-payer publicly funded cancer system. The primary outcome was burnout experience assessed through the Maslach Burnout Inventory. RESULTS: A total of 418 physicians completed the questionnaire (response rate was 44% among confirmed oncologists). Seventy-three percent (n = 264 of 362) of oncologists had symptoms of burnout (high emotional exhaustion and/or depersonalization scores). Significant drivers of burnout identified in multivariable regression modeling included working in a hectic or chaotic atmosphere (odds ratio [OR] = 15.5; 95% CI, 3.4 to 71.5; P < .001), feeling unappreciated on the job (OR = 7.9; 95% CI, 2.9 to 21.3; P < .001), reporting poor or marginal control over workload (OR = 7.9; 95% CI, 2.9 to 21.3; P < .001), and not being comfortable talking to peers about workplace stress (OR = 3.0; 95% CI, 1.1 to 7.9; P < .001). Older age (≥ 56 years) was associated with lower odds of burnout (OR = 0.16; 95% CI, 0.1 to 0.4; P < .001). CONCLUSION: Nearly three quarters of participants met predefined standardized criteria for burnout. This number is striking, given the known impact of burnout on provider mental health, patient safety, and quality of care, and suggests Oncologists in Ontario may be a vulnerable group that warrants attention. Health care changes being driven by the COVID-19 pandemic provide an opportunity to rebuild new systems that address drivers of burnout. Creating richer peer-to-peer and leadership engagement opportunities among early- to mid-career individuals may be a worthwhile organizational strategy.

Contiguous ∼16 Mb 1p36 deletion: Dominant features of classical distal 1p36 monosomy with haplo-lethality.

Monosomy 1p36 results from heterozygous deletions of the terminal short chromosome 1 arm, the most common terminal deletion in humans. The microdeletion is split in two usually non-overlapping and clinically distinct classical distal and proximal 1p36 monosomy syndromes. Using comparative genome hybridization, MLPA and qPCR we identified the largest contiguous ∼16 Mb terminal 1p36 deletion reported to date. It covers both distal and proximal regions, causes a neonatally lethal variant with virtually exclusive features of distal 1p36 monosomy, highlighting the key importance of the gene-rich distal region for the "compound" 1p36 phenotype and a threshold deletion-size effect for haplo-lethality.

How do I deal with the axilla in patients with a positive sentinel lymph node?

OPINION STATEMENT: Optimal management of the axilla in a patient with a positive sentinel node biopsy is not yet defined.These patients usually have Breast Conserving Surgery and receive adjuvant systemic therapy and whole breast radiation.Treatment options for the axilla include: no further surgery with or without radiation completion axillary nodal dissection with or without radiation Radiation options in addition to whole breast radiation include axillary and supraclavicular nodal irradiation regional nodal irradiationincludes supraclavicular and internal mammary nodes Completion axillary dissection has been standard practice in patients with positive sentinel nodes. the number of involved nodes provides prognostic information. theoretically improves local control, but may be obviated by systemic chemotherapy. but avoidance of dissection may not adversely affect locoregional control or survival. dissection has significant morbidity so safe avoidance is desirable. There is little worldwide concordance on the use of radiation: whole breast radiation (commonly used after breast conserving surgery) may radiate the lower axilla supraclavicular radiation is most commonly recommended for patients with four or more nodes but may confer a survival benefit on patients with lower risk disease. adding nodal irradiation reduces local recurrence with only modest toxicity. Adjuvant systemic therapy provides a survival benefit for patients with nodal disease. Most will receive cytostatic chemotherapy containing an anthracycline and a taxane. Hormone therapy is appropriate for estrogen receptor positive disease. The extent to which systemic therapy controls microscopic nodal disease is unknown. Node positive patients should generally receive adjuvant chemotherapy.A small group of patients benefit from specific nodal therapy. Further studies are needed to better identify these patients.