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Ferroptosis—an iron-dependent, non-apoptotic cell death process—is involved in various degenerative diseases and represents a targetable susceptibility in certain cancers 1 . The ferroptosis-susceptible cell state can either pre-exist in cells that arise from certain lineages or be acquired during cell-state transitions 2 – 5 . However, precisely how susceptibility to ferroptosis is dynamically regulated remains poorly understood. Here we use genome-wide CRISPR–Cas9 suppressor screens to identify the oxidative organelles peroxisomes as critical contributors to ferroptosis sensitivity in human renal and ovarian carcinoma cells. Using lipidomic profiling we show that peroxisomes contribute to ferroptosis by synthesizing polyunsaturated ether phospholipids (PUFA-ePLs), which act as substrates for lipid peroxidation that, in turn, results in the induction of ferroptosis. Carcinoma cells that are initially sensitive to ferroptosis can switch to a ferroptosis-resistant state in vivo in mice, which is associated with extensive downregulation of PUFA-ePLs. We further find that the pro-ferroptotic role of PUFA-ePLs can be extended beyond neoplastic cells to other cell types, including neurons and cardiomyocytes. Together, our work reveals roles for the peroxisome–ether-phospholipid axis in driving susceptibility to and evasion from ferroptosis, highlights PUFA-ePL as a distinct functional lipid class that is dynamically regulated during cell-state transitions, and suggests multiple regulatory nodes for therapeutic interventions in diseases that involve ferroptosis. The cellular organelles peroxisomes contribute to the sensitivity of cells to ferroptosis by synthesizing polyunsaturated ether phospholipids, and changes in the abundances of these lipids are associated with altered sensitivity to ferroptosis during cell-state transitions.

Importance The extent of the disruption to surgical care during the COVID-19 pandemic has not been empirically characterized on a national level. Objective To characterize the use of surgical care across cohorts of surgical urgency during the COVID-19 pandemic, and to assess for racial and ethnic disparities. Design, Setting, and Participants This was a retrospective observational study using the geographically diverse, all payer data from 767 hospitals in the Premier Healthcare Database. Procedures were categorized into 4 cohorts of surgical urgency (elective, nonelective, emergency, and trauma). A generalized linear regression model with hospital-fixed effects assessed the relative monthly within-hospital reduction in surgical encounters in 2020 compared with 2019. Main Outcomes and Measures Outcomes were the monthly relative reduction in overall surgical encounters and across surgical urgency cohorts and race and ethnicity. Results The sample included 13 175 087 inpatient and outpatient surgical encounters. There was a 12.6% relative reduction in surgical use in 2020 compared to 2019. Across all surgical cohorts, the most prominent decreases in encounters occurred during Spring 2020 . For example, elective encounters began falling in March, reached a trough in April, and subsequently recovered but never to prepandemic levels (March: −26.8%; 95% CI, −29.6% to −23.9%; April: −74.6%; 95% CI, −75.5% to −73.5%; December: −13.3%; 95% CI, −16.6%, −9.8%). Across all operative surgical urgency cohorts, White patients had the largest relative reduction in encounters. Conclusions and Relevance As shown by this cohort study, the COVID-19 pandemic resulted in large disruptions to surgical care across all categories of operative urgency, especially elective procedures. Racial and ethnic minority groups experienced less of a disruption to surgical care than White patients. Further research is needed to explore whether the decreased surgical use among White patients was owing to patient discretion and to document whether demand for surgical care will rebound to baseline levels.

Superplastic forming and diffusion bonding is a well-established manufacturing process. It has been implemented with a variety of materials. This work specifically deals with titanium which, while being a very useful aerospace material, and is commonly used with both superplastic on diffusion bonding. It deals with the forming and bonding of double sheet structures and four sheet structures. There has been a significant amount of both experimental and theoretical work done on diffusion bonding and superplasticity with titanium. However, there has yet to be a definitive and accurate model for diffusion bonding and the effects of more complex sheet formation. Work progressed toward alleviating this knowledge gap. Several models were created with increasing complexity. Work started with more rigorous initial conditions applied to conventional bonding models. Then models were created that used conventional physics but in a freeform way to see how the voids changed without restriction on void shape. Finally, micrographs of voids were digitized and used as inputs into an energy-based phase field simulation that allowed each of the alloying elements to diffusion independently, grain growth, and for the voids to close due to strain energy. Superplasticity modelling was done using finite element methods in two and three dimensions to examine how the four-sheet forms. Research was also done to determine how one can better destructively and non-destructively test diffusion bonded specimens. The results of all this showed that while superplasticity and diffusion bonding are complex subjects there is a lot of information to gain through experiments and modelling of the process.

In response to the coronavirus disease 2019 (COVID-19) pandemic, the governor of Illinois, J. B. Pritzker, issued a Gubernatorial Disaster Proclamation on March 9, 2020, and a shelter-inplace order on March 21, 2020, instructing all individuals living within the state to remain in their place of residence, with few exceptions. By April 3, 2020, a total of 41 states, the District of Columbia, Puerto Rico, and the Navajo Nation had issued similar orders.1 Many governments, including here in Illinois, have called their shelter-in-place order \"safer at home.\" From a population perspective, these efforts are necessary and sound; however, they belie the reality that for some patients, home is the least safe place for their immediate health.Like many hospitals across the United States, we watched normal operations grind to a halt. However, the trauma team at the University of Chicago on the city's South Side has remained dishearteningly busy. Less than a week into the shelter-in-place order, a female patient presented to our trauma bay after having been brutally assaulted, suffering major penetrating injuries to her head and neck, with deep defensive wounds to her hands and forearms. She had a compromised airway, so we quickly intubated her and transported her emergently to the operating room to repair major vascular injuries. Her assailant was an intimate partner. Several days later, two middle-aged men presented, hours apart, with isolated stab wounds received from their respective female partners. These patients and many others we have cared for are survivors of intimate partner violence (IPV).

BackgroundModified radical mastectomy (MRM) still is largely performed in inpatient settings. This study sought to determine the value (expenditures and complications) of ambulatory MRM.MethodsHealth Care Utilization Project (HCUP) state databases from 2016 were queried for patients who underwent MRM. The study examined rates of 30-day readmission for surgical-site infection (SSI) or hematoma, charges by index care setting, and predictors of 30-day readmission. ResultsOverall, 8090 patients underwent MRM: 5113 (63 %) inpatient and 2977 (37 %) ambulatory patients. Compared with the patients who underwent inpatient MRM, those who underwent ambulatory MRM were older (61 vs. 59 years), more often white (66 % vs. 57 %), in the lowest income quartile (28 % vs. 21 %), insured by Medicare (43 % vs. 33 %) and residents in a small metro area (6 % vs. 4 %) (all p < 0.01). Of the 5113 patients treated as inpatients, 126 (2.5 %) were readmitted, whereas 50 (1.7 %) of the ambulatory patients were readmitted (p = 0.02). The adjusted charge for inpatient MRM without readmission was $113,878 (range, $107,355–120,402) compared with $94,463 (range, $86,021–102,907) for ambulatory MRM, and the charge for inpatient MRM requiring readmission was $159,355 (range, $147,142–171,568) compared with $139,940 (range, $125,808–154,073) for ambulatory MRM (all p < 0.01). This difference remained significant after adjustment for hospital length of stay. Adjusted logistic regression showed that the ambulatory setting was protective for readmission (odds ratio, 0.49; 95 % confidence interval, 0.35–0.70; p < 0.01). ConclusionsThe analyses suggest that ambulatory MRM is both safe and less expensive. The findings advocate that MRM, a last holdout of inpatient care within breast surgical oncology, can be transitioned to the ambulatory setting for appropriate patients.

In Canada, coverage for ambulatory prescription drug expenditures is provided to some groups by provincial drug plans through a provincial formulary. Little is known about the drugs provincial formularies give access to. We report the variation in availability of new drug molecules (NDM) across provincial formularies. We identified 108 NDM approved in Canada between 1991 and 1998. From each drug plan bulletin or formulary, we abstracted names of NDM listed as per 15 January 1999. We compared the level of listing across provinces using kappa coefficients. In the Quebec, BC, Manitoba and Saskatchewan formularies, more than 70% of the NDM were listed. In four provinces, this proportion was lower than 50%. In general, the agreement between formularies was poor. There is a wide variation across provinces in terms of NDM listed in the formularies. This variation reflects inter-provincial differences in the way drugs are selected for coverage. Au Canada, les programmes provinciaux d'assurance-médicaments permettent aux citoyens admissibles d'obtenir sur ordonnance les médicaments dont le nom figure sur la liste provinciale. On en sait très peu sur le contenu de ces listes. Notre étude visait à répertorier les écarts entre les listes provinciales quant aux nouvelles molécules (NM). Entre 1991 et 1998, 108 NM ont été approuvées au Canada. Nous avons extrait le nom des NM figurant sur les listes provinciales le 15 janvier 1999, puis évalué la concordance entre les listes à l'aide de coefficients Kappa. Au Québec, en Colombie-Britannique, au Manitoba et en Saskatchewan, plus de 70 % des NM figuraient sur les listes. Dans quatre autres provinces, cette proportion n'atteignait pas 50 %. En général, la concordance entre les listes était faible. Les listes varient beaucoup d'une province à l'autre, ce qui traduit les différences interprovinciales dans la façon de sélectionner les médicaments remboursables.

The traditional paradigm of career psychology is becoming redundant in a changing world and particularly in a South African context. The traditional paradigm is based on the Orthodox Positivist epistemology, which perceives the social and physical worlds to consist of objective, unambiguous facts that are open to investigation, explanation and prediction by objective scientific methods (Collin & Young, 1986). The aim is to discover a singular objective reality using rational and accurate methods of observation. Career interventions have objectified interests, values and abilities and used predefined standardized inventories to obtain a person-environment fit as an objective attainable reality (Savickas, 1993). This perspective fails to recognize that career decisions are made in context and does not make provision for the social, economic and political factors that may constrain, challenge or encourage the individual in his career decision-making process (Collin & Young, 1986; Hansen, 1997; Steenbarger, 1991). The subjective experience of the career life role, that is the personal experiences and struggles of the individual in attempting to come to terms with available options, is also typically ignored (Naicker, 1994). The relationship of career to other life roles is disregarded (Hansen, 1997). The client is also not helped to make more effective life planning decisions with due consideration for individual interests and community needs (Hansen, 1997; Naicker, 1994). Career counselling needs to move away from an exclusively autonomous and fragmented perspective, as described above, if it is to avoid redundancy. Emerging trends that are taking place internationally and that may need to be accommodated within career interventions include the following. The composition of the labour force has become increasingly diverse, resulting in a wider range of values, needs and motivations (Osipow, 1991). The structure of corporations is changing, leading to shifts in the organisation of the work force (Hansen, 1997; Nel, 1999). Advances in communication, information and computer technology have complicated career patterns (Spokane, 1991)...