Space radiation measurements during the Artemis I lunar mission.

Space radiation is a notable hazard for long-duration human spaceflight1. Associated risks include cancer, cataracts, degenerative diseases2 and tissue reactions from large, acute exposures3. Space radiation originates from diverse sources, including galactic cosmic rays4, trapped-particle (Van Allen) belts5 and solar-particle events6. Previous radiation data are from the International Space Station and the Space Shuttle in low-Earth orbit protected by heavy shielding and Earth's magnetic field7,8 and lightly shielded interplanetary robotic probes such as Mars Science Laboratory and Lunar Reconnaissance Orbiter9,10. Limited data from the Apollo missions11-13 and ground measurements with substantial caveats are also available14. Here we report radiation measurements from the heavily shielded Orion spacecraft on the uncrewed Artemis I lunar mission. At differing shielding locations inside the vehicle, a fourfold difference in dose rates was observed during proton-belt passes that are similar to large, reference solar-particle events. Interplanetary cosmic-ray dose equivalent rates in Orion were as much as 60% lower than previous observations9. Furthermore, a change in orientation of the spacecraft during the proton-belt transit resulted in a reduction of radiation dose rates of around 50%. These measurements validate the Orion for future crewed exploration and inform future human spaceflight mission design.

Particle showers detected on ISS in Timepix pixel detectors.

We detect regular particle showers in several compact pixel detectors, distributed over the International Space Station. These showers are caused by high energy galactic cosmic rays, with energies often in the 10 s of TeV or higher. We survey the frequency of these events, their dependence on location on ISS, and their independence of the location of ISS, on its orbit. The Timepix detectors used allow individual particle tracks to be resolved, providing a possibility to perform physical analysis of shower events, which we demonstrate. In terms of radiation dosimetry, these showers indicate certain possible limitations of traditional dosimetric measures, in that (a) the dose measured in small sensor may be less than that received in a larger distribution of matter, such as a human and (b) the spatial and temporal extent of these events represents a regime of poorly documented biological response.

The importance of time-resolved personal Dosimetry in space: The ISS Crew Active Dosimeter.

Monitoring space radiation is of vital importance for risk reduction strategies in human space exploration. Radiation protection programs on Earth and in space rely on personal and area radiation monitoring instruments. Crew worn radiation detectors are crucial for successful crew radiation protection programs since they measure what each crewmember experiences in different shielding configurations within the space habitable volume. The Space Radiation Analysis Group at NASA Johnson Space Center investigated several compact, low power, real-time instruments for personal dosimetry. Following these feasibility studies, the Crew Active Dosimeter (CAD) has been chosen as a replacement for the legacy crew passive radiation detectors. The CAD device, based on direct ion storage technology, was developed by Mirion Dosimetry Services to meet the specified NASA design requirements for the International Space Station (ISS) and Artemis programs. After a successful Technology demonstration on ISS, the CAD has been implemented for ISS Crew operations since 2020. The current paper provides an overview of the CAD development, ISS results and comparison with the ISS Radiation Assessment Detector (RAD) and the Radiation Environment Monitor 2 (REM2) instruments.

Appendectomy by Pediatric Surgeons in North Carolina is Associated With Higher Charge Than General Surgeons.

INTRODUCTION: The delivery of pediatric surgical care for acute appendicitis involves general surgeons (GS) and pediatric surgeons (PS), but the differences in clinical practice are primarily undescribed. We examined charge differences between GS and PS for the treatment of pediatric acute appendicitis. METHODS: We performed a retrospective review of the North Carolina hospital discharge database (2013-2017) in pediatric patients (≤18 y) who had surgery for appendiceal pathology (acute or chronic appendicitis and other appendiceal pathology). We performed a bivariate analysis of surgical charges over the type of surgical providers (GS, PS, other specialty, and unassigned surgeons). RESULTS: Over the study period, 21,049 patients had appendicitis or other diseases of the appendix, and 15,230 (72.4%) underwent appendectomy. Patients who were operated on by PS were younger (10 y, interquartile range (IQR): 6-13 versus 13 y, IQR: 9-16, P < 0.001). Acute appendicitis was diagnosed in 2860 (44.3%) and 3173 (49.2%) of the PS and GS cohorts, respectively, P = 0.008. PS compared to GS performed a higher percentage of laparoscopic (n = 2,697, 89.4% versus n = 2,178, 65.5%) than open appendectomies (n = 280, 9.3% versus n = 1,118, 33.6%), P < 0.001. The overall hospital charges were $28,081 (IQR: $21,706-$37,431) and $24,322 (IQR: $17,906-$32,226) for PS and GS, respectively, P < 0.001. Surgical charges where higher for PS than GS, $12,566 (IQR: $9802-$17,462) and $8051 (IQR: $5872-$2331), respectively. When controlling for diagnosis, surgical approach, emergent status, age, and surgical cost of appendiceal surgery, and hospital charges following appendiceal surgery were $4280 higher for PS than GS (95% CI: 3874-4687). CONCLUSIONS: The total charge for operations for appendiceal disease is significantly higher for PS compared to GS. Pediatric surgeons had increased surgical charges compared to GS but decreased radiology charges. The specific reasons for these differences are not clearly delineated in this data set and persist after controlling for relevant covariates. However, these data demonstrate that increasing value in pediatric appendicitis may require specialty-based targets.

Cholecystectomies performed in children by pediatric surgeons compared to general surgeons in North Carolina are associated with higher institutional charges.

INTRODUCTION: The delivery of pediatric surgical care for gallbladder (GB) and biliary disease involves both General Surgeons (GS) and Pediatric Surgeons (PS). There is a lack of data describing how surgeon specialty impacts practice patterns and healthcare charges. METHODS: We performed a retrospective review of the North Carolina Inpatient Hospital Discharge Database (2013-2017) on pediatric patients (≤18 years) undergoing surgery for biliary pathology. We performed multivariate linear regression comparing surgeons with surgical charge. RESULTS: 12,531 patients had GB or biliary pathology and 4023 (32.1%) had cholecystectomies. The most common procedure for PS and GS was cholecystectomy for cholecystitis (n = 509, 54.0% and n = 2275, 76.4%, p < 0.001), respectively. The hospital ($26,605, IQR $18,955-37,249, vs. $17,451, IQR $13,246-23,478, p < 0.001) and surgical charges ($15,465, IQR $12,233-22,203, vs. $10,338, IQR $6837-14,952, p < 0.001) were higher for PS than GS. Controlling for pertinent variables, surgical charges for PS were $4192 higher than for GS (95% CI: $2162-6122). CONCLUSION: The cholecystectomy charge differential between PS and GS is significant and persisted after controlling for pertinent covariates.

The Impact of General Surgeons on Pediatric Surgical Practice in North Carolina: The Reality of Pediatric Surgical Care Delivery.

OBJECTIVE: The aim of this study was to define the training background of the actual surgical workforce providing care to pediatric patients in North Carolina (NC). BACKGROUND: Due to database limitations, pediatric surgical workforce studies have not included general surgeons (GS) who operate on children. Defining the role of GS in care delivery affects policy for clinical care and general and pediatric surgical training. METHODS: We performed a retrospective review of the NC Hospital Discharge Database (2011-2017), including pediatric patients (<18 years) undergoing the most frequent general surgery procedures. Descriptive and correlational analysis over surgical provider [Pediatric Surgeon (PS), GS], and other specialties (OSS), was performed using logistic regression modeling to identify factors associated with surgery by a PS. RESULTS: Of the 57,265 discharges analyzed, pediatric, general, and other specialty surgeons operated on 25,514 (44.6%), 18,581 (32.5%), and 9049 (15.8%), respectively. In a logistic regression model, PS had lower odds of operating on older patients [odds ratio (OR) 0.9, 95% confidence interval (CI) 0.90-0.91]. However, PS were more likely to operate on female patients (OR 1.58, 95% CI 1.53-1.65), Black (OR 1.49, 95% CI 1.43-1.56), and other minority patients (OR 1.23, 95% CI 1.17-1.29) when compared to white patients. PS were also more likely to operate on patients with private insurance (OR 1.38, 95% CI 1.33-1.43) compared to government insurance, and patients undergoing emergency surgery (OR 1.44, 95% CI 1.38-1.50). CONCLUSION: In NC, general surgeons performed a third of the operations on children. After controlling for covariates, pediatric surgeons in NC are more likely to operate on minority and emergency surgery patients, and this is the first study to describe this important practice pattern.

Current developments in delivering customized care: a scoping review.

BACKGROUND: In recent years, there has been a growing interest in health care personalization and customization (i.e. personalized medicine and patient-centered care). While some positive impacts of these approaches have been reported, there has been a dearth of research on how these approaches are implemented and combined for health care delivery systems. The present study undertakes a scoping review of articles on customized care to describe which patient characteristics are used for segmenting care, and to identify the challenges face to implement customized intervention in routine care. METHODS: Article searches were initially conducted in November 2018, and updated in January 2019 and March 2019, according to Prisma guidelines. Two investigators independently searched MEDLINE, PubMed, PsycINFO, Web of Science, Science Direct and JSTOR, The search was focused on articles that included "care customization", "personalized service and health care", individualized care" and "targeting population" in the title or abstract. Inclusion and exclusion criteria were defined. Disagreements on study selection and data extraction were resolved by consensus and discussion between two reviewers. RESULTS: We identified 70 articles published between 2008 and 2019. Most of the articles (n = 43) were published from 2016 to 2019. Four categories of patient characteristics used for segmentation analysis emerged: clinical, psychosocial, service and costs. We observed these characteristics often coexisted with the most commonly described combinations, namely clinical, psychosocial and service. A small number of articles (n = 18) reported assessments on quality of care, experiences and costs. Finally, few articles (n = 6) formally defined a conceptual basis related to mass customization, whereas only half of articles used existing theories to guide their analysis or interpretation. CONCLUSIONS: There is no common theory based strategy for providing customized care. In response, we have highlighted three areas for researchers and managers to advance the customization in health care delivery systems: better define the content of the segmentation analysis and the intervention steps, demonstrate its added value, in particular its economic viability, and align the logics of action that underpin current efforts of customization. These steps would allow them to use customization to reduce costs and improve quality of care.

The Supply and Distribution of the Preventive Medicine Physician Workforce.

CONTEXT: Preventive medicine physicians work at the intersection of clinical medicine and public health. A previous report on the state of the preventive medicine workforce in 2000 revealed an ongoing decline in preventive medicine physicians and residents, but there have been few updates since. OBJECTIVE: The purpose of this study was to describe trends in both the number of board-certified preventive medicine physicians and those physicians who self-designate preventive medicine as a primary or secondary specialty and examine the age, gender distribution, and geographic distribution of this workforce. DESIGN: Analysis of the supply of preventive medicine physicians using data derived from board certification files of the American Board of Preventive Medicine and self-designation data from the American Medical Association Masterfile. SETTING: The 50 US states and District of Columbia. PARTICIPANTS: Board-certified and self-designated preventive medicine physicians in the United States. MAIN OUTCOME MEASURES: Number, demographics, and location of preventive medicine physicians in United States. RESULTS: From 1999 to 2018, the total number of physicians board certified in preventive medicine increased from 6091 to 9270; the number of self-identified preventive medicine physicians has generally decreased since 2000, with a leveling off in the past 4 years matching the trend of preventive medicine physicians per 100 000 population; there is a recent increase in women in the specialty; the practice locations of preventive medicine physicians do not match the US population in rural or micropolitan areas; and the average age of preventive medicine physicians is increasing. CONCLUSIONS: The number of preventive medicine physicians is not likely to match population needs in the United States in the near term and beyond. Assessing the preventive medicine physician workforce in the United States is complicated by difficulties in defining the specialty and because less than half of self-designated preventive medicine physicians hold a board certification in the specialty.

α-Catenin levels determine direction of YAP/TAZ response to autophagy perturbation.

The factors regulating cellular identity are critical for understanding the transition from health to disease and responses to therapies. Recent literature suggests that autophagy compromise may cause opposite effects in different contexts by either activating or inhibiting YAP/TAZ co-transcriptional regulators of the Hippo pathway via unrelated mechanisms. Here, we confirm that autophagy perturbation in different cell types can cause opposite responses in growth-promoting oncogenic YAP/TAZ transcriptional signalling. These apparently contradictory responses can be resolved by a feedback loop where autophagy negatively regulates the levels of α-catenins, LC3-interacting proteins that inhibit YAP/TAZ, which, in turn, positively regulate autophagy. High basal levels of α-catenins enable autophagy induction to positively regulate YAP/TAZ, while low α-catenins cause YAP/TAZ activation upon autophagy inhibition. These data reveal how feedback loops enable post-transcriptional determination of cell identity and how levels of a single intermediary protein can dictate the direction of response to external or internal perturbations.

Using State Licensure Data to Assess North Carolina's Health Workforce COVID-19 Response Capacity.

BACKGROUND In the early months of the COVID-19 pandemic, health care decision-makers in North Carolina needed information about the available health workforce in order to conduct workforce surge planning and to anticipate concerns about professional or geographic workforce shortages.METHOD Descriptive and cartographic analyses were conducted using licensure data held by the North Carolina Health Professions Data System to assess the supply of respiratory therapists, nurses, and critical care physicians in North Carolina. Licensure data were merged with population data and numbers of intensive care unit (ICU) beds drawn from the Centers for Medicare and Medicaid Services (CMS) Healthcare Cost Report Information System (HCRIS).RESULTS The pandemic highlighted how critical data infrastructure is to public health infrastructure. Respiratory therapists and acute care, emergency, and critical care nurses were diffused broadly throughout the state, with higher concentrations in urban areas. Critical care physicians were primarily based in areas with academic health centers.LIMITATIONS Data were unavailable to capture the rapid changes in supply due to clinicians reentering or exiting the workforce. County-level analyses did not reflect individual, facility-level supply, which was needed to plan organizational responses.CONCLUSIONS Health care decision-makers in North Carolina were able to access information about the supply of clinicians critical to caring for COVID-19 patients due to the state's long-standing investments in health workforce data infrastructure. Ability to respond was made easier due to strong working relationships between the University of North Carolina at Chapel Hill Cecil G. Sheps Center for Health Services Research, the North Carolina Area Health Education Centers Program, the health professional licensure boards, and state government health care agencies.

Measuring the migration of surgical specialists.

BACKGROUND: The lack of access to essential surgical care in low-income countries is aggravated by emigration of locally-trained surgical specialists to more affluent regions. Yet, the global diaspora of surgeons, obstetricians, and anesthesiologists from low-income and middle-income countries has never been fully described and compared with those who have remained in their country of origin. It is also unclear whether the surgical workforce is more affected by international migration than other medical specialists. In this study, we aimed to quantify the proportion of surgical specialists originating from low-income and middle-income countries that currently work in high-income countries. METHODS: We retrieved surgical workforce data from 48 high-income countries and 102 low-income and middle-income countries using the database of the World Health Organization Global Surgical Workforce. We then compared this domestic workforce with more granular data on the country of initial medical qualification of all surgeons, anesthesiologists, and obstetricians made available for 14 selected high-income countries to calculate the proportion of surgical specialists working abroad. RESULTS: We identified 1,118,804 specialist surgeons, anesthesiologists, or obstetricians from 102 low-income and middle-income countries, of whom 33,021 (3.0%) worked in the 14 included high-income countries. The proportion of surgical specialists abroad was greatest for the African and South East Asian regions (12.8% and 12.1%). The proportion of specialists abroad was not greater for surgeons, anesthesiologists, or obstetricians than for physicians and other medical specialists (P = .465). Overall, the countries with the lowest remaining density of surgical specialists were also the countries from which the largest proportion of graduates were now working in high-income countries (P = .011). CONCLUSION: A substantial proportion of all surgeons, anesthesiologists, and obstetricians from low-income and middle-income countries currently work in high-income countries. In addition to decreasing migration from areas of surgical need, innovative strategies to retain and strengthen the surgical workforce could involve engaging this large international pool of surgical specialists and instructors.

Comparison of Number and Geographic Distribution of Pediatric Subspecialists and Patient Proximity to Specialized Care in the US Between 2003 and 2019.

Importance: Geographic proximity to a pediatric subspecialist is a key factor in obtaining specialized care. However, comparative data regarding the number of pediatric subspecialists, distribution of subspecialists, and patient proximity to subspecialists in the United States between 2003 and 2019 have not been explored; the last known national analysis was published in 2006 and used data from 2003. Objective: To compare the number and distribution of pediatric subspecialists and patient proximity to pediatric subspecialists in the United States between 2003 and 2019 and to assess whether the increase in the number of pediatric subspecialists is associated with improvements in patient proximity to specialized care and the geographic distribution of pediatric subspecialists. Design, Setting, and Participants: This national repeated cross-sectional study used data from the American Board of Pediatrics to examine the overall change in the number of subspecialists for 20 pediatric subspecialties between 2003 and 2019. The study included 24 375 pediatric subspecialists who were 70 years or younger, had active certification from the American Board of Pediatrics as of June 2019, and had addresses in the United States. Subspecialists' addresses were linked by zip code to child population data to evaluate the geographic distribution of subspecialists, the population-weighted averages for service areas, and the straight-line distances to subspecialists. Descriptive statistics and maps were used to examine patient proximity to subspecialists and regional subspecialist distribution and dispersion by hospital referral region. Subspecialist-to-child population ratios per 100 000 children, changes over time, and coefficients of variation were calculated to further elucidate subspecialist distribution. Data were collected in June 2019 and analyzed from July 8, 2019, to December 17, 2019. Main Outcomes and Measures: Values from 2019 were compared with data from 2003 for mean straight-line distance in miles from patients to subspecialists, by subspecialty; percentage of children younger than 18 years living at specific distance ranges; subspecialist-to-child population ratios across hospital referral regions; and coefficients of variation for population ratios. Results: Among 24 375 pediatric subspecialists 70 years and younger, 23 436 subspecialists were certified in 1 subspecialty, and 939 subspecialists were certified in more than 1 subspecialty. The number of certified pediatric subspecialists in the United States increased by 76.8% between 2003 and 2019, with increases varying across subspecialties. The estimated means for travel distances decreased among all subspecialties; however, depending on the subspecialty, an estimated 1 million to 39 million children (2%-53%) resided 80 miles or more from a subspecialist. An analysis across hospital referral regions indicated increased subspecialist-to-child ratios and an increased number of regions with a subspecialist but continued wide variation across regions for most subspecialties. Eleven subspecialties had 1 or fewer subspecialists per 100 000 children across hospital referral regions. Conclusions and Relevance: Although patient proximity to pediatric subspecialty care has improved nationally, substantial distribution gaps among specific subspecialties remain. Long-term solutions that encourage movement of subspecialists to underserved locations or that extend the practice of current subspecialties may warrant consideration, particularly among subspecialties with a limited number of practitioners.

Author Correction: Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing.

Neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Huntington's disease manifest with the neuronal accumulation of toxic proteins. Since autophagy upregulation enhances the clearance of such proteins and ameliorates their toxicities in animal models, we and others have sought to re-position/re-profile existing compounds used in humans to identify those that may induce autophagy in the brain. A key challenge with this approach is to assess if any hits identified can induce neuronal autophagy at concentrations that would be seen in humans taking the drug for its conventional indication. Here we report that felodipine, an L-type calcium channel blocker and anti-hypertensive drug, induces autophagy and clears diverse aggregate-prone, neurodegenerative disease-associated proteins. Felodipine can clear mutant α-synuclein in mouse brains at plasma concentrations similar to those that would be seen in humans taking the drug. This is associated with neuroprotection in mice, suggesting the promise of this compound for use in neurodegeneration.

Public involvement in health outcomes research: lessons learnt from the development of the recovering quality of life (ReQoL) measures.

BACKGROUND: To provide a model for Public involvement (PI) in instrument development and other research based on lessons learnt in the co-production of a recently developed mental health patient reported outcome measure called Recovering Quality of Life (ReQoL). While service users contributed to the project as research participants, this paper focuses on the role of expert service users as research partners, hence referred to as expert service users or PI. METHODS: At every stage of the development, service users influenced the design, content and face validity of the measure, collaborating with other researchers, clinicians and stakeholders who were central to this research. Expert service users were integral to the Scientific Group which was the main decision-making body, and also provided advice through the Expert Service User Group. RESULTS: During the theme and item generation phase (stage 1) expert service users affirmed the appropriateness of the seven domains of the Patient Reported Outcome Measure (activity, hope, belonging and relationships, self-perception, wellbeing, autonomy, and physical health). Expert service users added an extra 58 items to the pool of 180 items and commented on the results from the face and content validity testing (stage 2) of a refined pool of 88. In the item reduction and scale generation phase (stage 3), expert service users contributed to discussions concerning the ordering and clustering of the themes and items and finalised the measures. Expert service users were also involved in the implementation and dissemination of ReQoL (stage 4). Expert service users contributed to the interpretation of findings, provided inputs at every stage of the project and were key decision-makers. The challenges include additional work to make the technical materials accessible, extra time to the project timescales, including time to achieve consensus from different opinions, sometimes strongly held, and extra costs. CONCLUSION: This study demonstrates a successful example of how PI can be embedded in research, namely in instrument development. The rewards of doing so cannot be emphasised enough but there are challenges, albeit surmountable ones. Researchers should anticipate and address those challenges during the planning stage of the project.

A novel Atg5-shRNA mouse model enables temporal control of Autophagy in vivo.

Macroautophagy/autophagy is an evolutionarily conserved catabolic pathway whose modulation has been linked to diverse disease states, including age-associated disorders. Conventional and conditional whole-body knockout mouse models of key autophagy genes display perinatal death and lethal neurotoxicity, respectively, limiting their applications for in vivo studies. Here, we have developed an inducible shRNA mouse model targeting Atg5, allowing us to dynamically inhibit autophagy in vivo, termed ATG5i mice. The lack of brain-associated shRNA expression in this model circumvents the lethal phenotypes associated with complete autophagy knockouts. We show that ATG5i mice recapitulate many of the previously described phenotypes of tissue-specific knockouts. While restoration of autophagy in the liver rescues hepatomegaly and other pathologies associated with autophagy deficiency, this coincides with the development of hepatic fibrosis. These results highlight the need to consider the potential side effects of systemic anti-autophagy therapies.

Contact inhibition controls cell survival and proliferation via YAP/TAZ-autophagy axis.

Contact inhibition enables noncancerous cells to cease proliferation and growth when they contact each other. This characteristic is lost when cells undergo malignant transformation, leading to uncontrolled proliferation and solid tumor formation. Here we report that autophagy is compromised in contact-inhibited cells in 2D or 3D-soft extracellular matrix cultures. In such cells, YAP/TAZ fail to co-transcriptionally regulate the expression of myosin-II genes, resulting in the loss of F-actin stress fibers, which impairs autophagosome formation. The decreased proliferation resulting from contact inhibition is partly autophagy-dependent, as is their increased sensitivity to hypoxia and glucose starvation. These findings define how mechanically repressed YAP/TAZ activity impacts autophagy to contribute to core phenotypes resulting from high cell confluence that are lost in various cancers.