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The increased use of next-generation sequencing has led to the detection of pathogenic TP53 variants in the germline setting in patients without a personal or family history consistent with Li-Fraumeni syndrome (LFS). These variants can represent low-penetrance LFS, mosaic LFS, or clonal hematopoiesis of indeterminate potential. Additionally, TP53 variants of uncertain significance can be detected in patients with a history suspicious for LFS. The interpretation of the significance of these variants can be challenging but is crucial for an accurate diagnosis and appropriate medical management. This retrospective case review provides illustrative examples of the interpretation of challenging TP53 results through multidisciplinary expertise and use of a flowchart. The authors describe eight patients with TP53 variants associated with ambiguous diagnoses and, for each case, describe how the results were interpreted and the medical care that was implemented. This report presents illustrative cases to help guide clinicians to reach definitive diagnoses for patients when confronted with TP53 variants that are inconsistent with the clinical picture and to add to the body of literature regarding interpretation and medical management of TP53 variants discovered on germline testing., (© 2023 National Society of Genetic Counselors.)

NTHL1-associated tumor syndrome (NATS) is an autosomal recessive condition characterized by an increased risk for colorectal polyposis and colorectal cancer (CRC). Only 46 case reports have been previously published. In a retrospective review, we analyzed the clinical histories of six patients found to have NATS after genetic counseling and testing. NATS appears to be associated with an increased risk for colorectal polyposis, CRC, female breast cancer, meningiomas, and endometrial cancer. Although research is limited, prior publications have reported a multi-tumor predisposition for individuals with biallelic pathogenic or likely pathogenic variants in NTHL1. Additional data are necessary to further define the cancer risks so affected individuals can be appropriately managed., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Frameworks have been developed to help conceptualize clinical genetic counseling (GC), and observational studies have helped understand the process and content of GC sessions. However, additional research is needed to identify GC skills (behaviors or strategies) that practicing genetic counselors report consciously using to meet certain GC goals and determine what common terminology, if any, is being used to describe the various skills. Nineteen practicing genetic counselors in prenatal, pediatric, or cancer specialties were interviewed to elicit how they achieve session goals. Interview recordings were transcribed, coded thematically, and categorized using process categories from the communication strategy domain of the Framework for Outcomes in Clinical Communication Services (FOCUS). Reported skills largely fit within FOCUS, though findings prompted minor modifications of several FOCUS process categories and consolidation of the categories from 13 into 10. Although genetic counselor respondents reported a broad range of strategies and behaviors, they rarely had terms for skills they described. Results reveal concrete examples of GC skills, provide evidence for refinement of FOCUS, and highlight the need for establishing common terminology to describe these skills., (© 2022 National Society of Genetic Counselors.)

Purpose:  The COVID-19 pandemic disrupted the professional, social, and spiritual activities of resident physicians around the world, impacting wellness and personal relationships. Moreover, social distancing caused significant limitations or shutdown of places of worship, including churches, synagogues, mosques, etc. Our goal was to survey resident physicians in primary care and surgical subspecialties in the United States (U.S.) and Canada and to examine the effect of the COVID-19 pandemic on their well-being., Methods:  An international cross-sectional study was performed in November 2020, using an anonymous survey of programs in the U.S. and Canada, containing 20 questions to assess the impact of the pandemic on resident participation in social and spiritual activities and the effects on their wellness, and personal relationships. The emails with survey links attached were sent to individual program coordinators from accredited residency training programs in the United States and Canada. This consisted of programs accredited by the American Osteopathic Association (AOA), The Royal College of Physicians and Surgeons of Canada (RCPSC), and the Accreditation Council of Graduate Medical Education (ACGME). The survey was evenly divided among surgical programs (General Surgery, Neurological Surgery, Orthopedic Surgery, Urological Surgery, and Integrated Surgical Residency Programs such as Plastic Surgery, Cardiothoracic Surgery, Pediatric Surgery, and Vascular Surgery) as well as primary care programs (Internal Medicine and Family Medicine)., Results:  A total of 196 residents, 60 primary care residents, and 136 surgery residents participated in the study. Ninety-six participants (49%) were female, and 98 of the participants (50%) were male, with the remainder two residents identifying as "Other." Of the primary care residents, the majority (39, 65%) were female. Conversely, the majority (77, 57%) of surgery residents were male., Conclusion:  The COVID-19 pandemic has affected the social lives, relationships, and spiritual well-being of both surgical and primary care resident physicians. However, primary care residents reported significantly greater engagement in personal relationships and were more likely to express feelings of mental and physical exhaustion, prohibiting social attendance., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Farr et al.)

Introduction Surgical specialties consistently remain among the most competitive residency and fellowship programs with some of the highest rates of unmatched applicants. Attrition in surgical specialties is as high as 30% and particularly problematic given the extended duration of training and limited number of positions. Applicants are traditionally evaluated using a streamlined set of objective metrics, such as board scores, class rank, leadership, letters of recommendation, research productivity, and volunteerism. Consumer credit scores have been shown to be predictors of personality and work performance, however, the literature has yet to explore consumer credit histories in the context of surgical resident and fellow performance. This study aims to determine whether consumer credit scores of surgery residents and fellows are predictive of academic and professional performance. Methods This is a multi-institutional observational survey study across all American Council of Graduate Medical Education and Royal College of Physicians and Surgeons accredited surgical residency and fellowship programs in the United States and Canada. Ninety-nine surgical residents and fellows with educational status of post-graduate year two or higher participated in this study. Dichotomous (yes or no) survey items were formulated to assess performance indicators in the domains of notable achievements and awards, research output, written examination performance, professionalism, and surgical/technical skills. Three-digit Fair Isaac Corporation (FICO) credit scores, a widely accepted consumer reporting score, were collected to avoid calculation variability between algorithms.  Results Surgical residents and fellows reported credit scores between 611( fair) and 853 (exceptional) with a median (interquartile range) of 774 (715-833). The majority of participants 51.5%(51) reported very good credit scores. Those with higher credit scores (very good/exceptional) were 377% more likely to have one or more positive performance indicators OR (95% CI) = 3.77 (1.43-9.97). Similarly, residents with lower credit scores (fair/good) were only 40% more likely to have one or more negative performance indicators. The credit score has a moderate ability to distinguish between the presence and absence of positive performance indicators (area under the curve {AUC} = 0.70, p = 0.001). The use of 753 as a credit score cutoff is 78.9% sensitive and 52.4% specific for discerning surgery residents and fellows with one or more positive performance indicators. The credit score did not significantly discern those with negative performance indicators. Conclusions While credit score was significantly functional in discerning those with and without positive performance indicators, sensitivity and specificity rates leave much to be desired. This study suggests credit score may have a utility as a companion to traditional metrics used in identifying candidates for surgery residencies and fellowships who will have positive performance in the domains of research productivity, written examination performance, and professional awards and recognition. Additional studies are needed to assess this utility on a larger scale., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Berry et al.)

Context: Patients with severe traumatic brain injury (TBI) often have multiple autonomic disturbances that interfere with normal gastrointestinal motility. Many of the pharmacologic agents used in the intensive care unit (ICU) also adversely affect gastrointestinal motility. The body is further subjected to excessive levels of sympathetic discharge in states of traumatic injury and extreme stress, which can interfere with the proper absorption of fluids and nutrients., Objective: To determine whether mesenteric lift, an osteopathic manipulative treatment technique, is effective in relieving constipation in patients with TBI who are intubated in the ICU., Methods: This retrospective medical record review examined the effect of mesenteric lift on intubated patients with significant TBI who were unable to have a bowel movement within 72 hours of admission. The primary endpoint was the return of normal bowel function within 24 hours. A control group consisted of intubated patients with TBI during the same period who did not receive mesenteric lift., Results: Of patients who received mesenteric lift, 77% experienced bowel movements (n=27 of 35), compared with 36% (n=16 of 44) in the control group (P=.01)., Conclusion: The application of mesenteric lift to intubated patients with severe TBI in the intensive care unit significantly increased patients' ability to resume normal bowel function and expel waste.

Nuclear pasta, with nonspherical shapes, is expected near the base of the crust in neutron stars. Large-scale molecular dynamics simulations of pasta show long lived topological defects that could increase electron scattering and reduce both the thermal and electrical conductivities. We model a possible low-conductivity pasta layer by increasing an impurity parameter Q_{imp}. Predictions of light curves for the low-mass x-ray binary MXB 1659-29, assuming a large Q_{imp}, find continued late time cooling that is consistent with Chandra observations. The electrical and thermal conductivities are likely related. Therefore, observations of late time crust cooling can provide insight on the electrical conductivity and the possible decay of neutron star magnetic fields (assuming these are supported by currents in the crust).

The neutron-rich isotope ²²Ne may be a significant impurity in carbon and oxygen white dwarfs and could impact how the stars freeze. We perform molecular dynamics simulations to determine the influence of ²²Ne in carbon-oxygen-neon systems on liquid-solid phase equilibria. Both liquid and solid phases are present simultaneously in our simulation volumes. We identify liquid, solid, and interface regions in our simulations using a bond angle metric. In general we find good agreement for the composition of liquid and solid phases between our MD simulations and the semianalytic model of Medin and Cumming. The trace presence of a third component, neon, does not appear to strongly impact the chemical separation found previously for two-component carbon and oxygen systems. This suggests that small amounts of ²²Ne may not qualitatively change how the material in white dwarf stars freezes. However, we do find systematically lower melting temperatures (higher Γ) in our MD simulations compared to the semianalytic model. This difference seems to grow with impurity parameter Q_{imp} and suggests a problem with simple corrections to the linear mixing rule for the free energy of multicomponent solid mixtures that is used in the semianalytic model.

We determine the liquid-solid phase diagram for carbon-oxygen and oxygen-selenium plasma mixtures using two-phase molecular dynamics simulations. We identify liquid, solid, and interface regions using a bond angle metric. To study finite-size effects, we perform 27,648- and 55,296-ion simulations. To help monitor nonequilibrium effects, we calculate diffusion constants D(i). For the carbon-oxygen system we find that D(O) for oxygen ions in the solid is much smaller than D(C) for carbon ions and that both diffusion constants are 80 or more times smaller than diffusion constants in the liquid phase. There is excellent agreement between our carbon-oxygen phase diagram and that predicted by Medin and Cumming. This suggests that errors from finite-size and nonequilibrium effects are small and that the carbon-oxygen phase diagram is now accurately known. The oxygen-selenium system is a simple two-component model for more complex rapid proton capture nucleosynthesis ash compositions for an accreting neutron star. Diffusion of oxygen, in a predominantly selenium crystal, is remarkably fast, comparable to diffusion in the liquid phase. We find a somewhat lower melting temperature for the oxygen-selenium system than that predicted by Medin and Cumming. This is probably because of electron screening effects.

Diffusion in Coulomb crystals can be important for the structure of neutron star crusts. We determine diffusion constants D from molecular dynamics simulations. We find that D for Coulomb crystals with relatively soft-core 1/r interactions may be larger than D for Lennard-Jones or other solids with harder-core interactions. Diffusion, for simulations of nearly perfect body-centered-cubic lattices, involves the exchange of ions in ringlike configurations. Here ions "hop" in unison without the formation of long lived vacancies. Diffusion, for imperfect crystals, involves the motion of defects. Finally, we find that diffusion, for an amorphous system rapidly quenched from Coulomb parameter Γ=175 to Coulomb parameters up to Γ=1750, is fast enough that the system starts to crystalize during long simulation runs. These results strongly suggest that Coulomb solids in cold white dwarf stars, and the crust of neutron stars, will be crystalline and not amorphous.

Sedimentation of the neutron rich isotope 22Ne may be an important source of gravitational energy during the cooling of white dwarf stars. This depends on the diffusion constant for 22Ne in strongly coupled plasma mixtures. We calculate self-diffusion constants D(i) from molecular dynamics simulations of carbon, oxygen, and neon mixtures. We find that D(i) in a mixture does not differ greatly from earlier one component plasma results. For strong coupling (coulomb parameter Γ> few), D(i) has a modest dependence on the charge Z(i) of the ion species, D(i)∝Z(i)(-2/3). However, D(i) depends more strongly on Z(i) for weak coupling (smaller Γ). We conclude that the self-diffusion constant D(Ne) for 22Ne in carbon, oxygen, and neon plasma mixtures is accurately known so that uncertainties in D(Ne) should be unimportant for simulations of white dwarf cooling.

We determine the phase diagram for dense carbon-oxygen mixtures in white dwarf (WD) star interiors using molecular dynamics simulations involving liquid and solid phases. Our phase diagram agrees well with predictions from Ogata et al. and from Medin and Cumming and gives lower melting temperatures than Segretain et al. Observations of WD crystallization in the globular cluster NGC 6397 by Winget et al. suggest that the melting temperature of WD cores is close to that for pure carbon. If this is true, our phase diagram implies that the central oxygen abundance in these stars is less than about 60%. This constraint, along with assumptions about convection in stellar evolution models, limits the effective S factor for the 12C(α,γ)16O reaction to S(300)≤170  keV b.

Recently, crust cooling times have been measured for neutron stars after extended outbursts. These observations are very sensitive to the thermal conductivity kappa of the crust and strongly suggest that kappa is large. We perform molecular dynamics simulations of the structure of the crust of an accreting neutron star using a complex composition that includes many impurities. The composition comes from simulations of rapid proton capture nucleosynthesis followed by electron captures. We find that the thermal conductivity is reduced by impurity scattering. In addition, we find phase separation. Some impurities with low atomic number Z are concentrated in a subregion of the simulation volume. For our composition, the solid crust must separate into regions of different compositions. This could lead to an asymmetric star with a quadrupole deformation. Observations of crust cooling can constrain impurity concentrations.

Nucleosynthesis, on the surface of accreting neutron stars, produces a range of chemical elements. We perform molecular dynamics simulations of crystallization to see how this complex composition forms new neutron star crust. We find chemical separation, with the liquid ocean phase greatly enriched in low atomic number elements compared to the solid crust. This phase separation should change many crust properties such as the thermal conductivity and shear modulus.

Over the past several years, substantial concern has been expressed by some in Congress, environmental groups, and members of the public concerning the lack of progress in regulating toxic air pollutants by the U.S. Environmental Protection Agency (EPA). As a result, a number of amendments to the Federal Clean Air Act have been introduced to require EPA to regulate in a relatively rapid timeframe, a large number of potentially toxic pollutants that are released to the ambient air. This paper discusses EPA's current understanding of the magnitude and nature of the air toxics problem in the U.S., and the pollutants and source categories that pose the most significant risk to the public. The focus of the discussion is on routine releases, as opposed to catastrophic, accidental releases such as the one in Bhopal, India. The paper then discusses the strategy that EPA has put in place to deal with the problem and presents the status of a number of regulatory and non-regulatory activities under way to better understand the problem and to mitigate it. The strategy involves important roles for: (1) EPA to regulate national problems using a variety of Federal authorities in addition to the Clean Air Act, and (2) States to develop their own air toxic control programs to deal with unique local problems involving high risk point sources and multipollutant, multisource problems in large urban or industrialized areas.