Performing Platform Governance: Facebook and the Stage Management of Data Relations.

Controversies surrounding social media platforms have provided opportunities for institutional reflexivity amongst users and regulators on how to understand and govern platforms. Amidst contestation, platform companies have continued to enact projects that draw upon existing modes of privatized governance. We investigate how social media companies have attempted to achieve closure by continuing to set the terms around platform governance. We investigate two projects implemented by Facebook (Meta)-authenticity regulation and privacy controls-in response to the Russian Interference and Cambridge Analytica controversies surrounding the 2016 U.S. Presidential Election. Drawing on Goffman's metaphor of stage management, we analyze the techniques deployed by Facebook to reinforce a division between what is visible and invisible to the user experience. These platform governance projects propose to act upon front-stage data relations: information that users can see from other users-whether that is content that users can see from "bad actors", or information that other users can see about oneself. At the same time, these projects relegate back-stage data relations-information flows between users constituted by recommendation and targeted advertising systems-to invisibility and inaction. As such, Facebook renders the user experience actionable for governance, while foreclosing governance of back-stage data relations central to the economic value of the platform. As social media companies continue to perform platform governance projects following controversies, our paper invites reflection on the politics of these projects. By destabilizing the boundaries drawn by platform companies, we open space for continuous reflexivity on how platforms should be understood and governed.

Rhabdoid tumor predisposition syndrome: A historical review of treatments and outcomes for associated pediatric malignancies.

Rhabdoid tumor predisposition syndrome (RTPS) is a rare disorder associated with malignant rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and/or other extracranial, extrarenal rhabdoid tumors (EERT), and these pediatric malignancies are difficult to treat. Presently, most of the information regarding clinical manifestations, treatment, and outcomes of rhabdoid tumors comes from large data registries and case series. Our current understanding of treatments for patients with rhabdoid tumors may inform how we approach patients with RTPS. In this manuscript, we review the genetic and clinical features of RTPS and, using known registry data and clinical reports, review associated tumor types ATRT, RTK, and EERT, closing with potential new approaches to treatment. We propose collaborative international efforts to study the use of SMARC (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin)-targeting agents, high-dose consolidative therapy, and age-based irradiation of disease sites in RTPS.

A suite of engineered mice for interrogating psychedelic drug actions.

Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases, including depression, anxiety, post-traumatic stress disorder, migraine, and cluster headaches. LSD and psilocybin exert their psychedelic effects via activation of the 5-hydroxytryptamine 2A receptor (HTR2A). Here we provide a suite of engineered mice useful for clarifying the role of HTR2A and HTR2A-expressing neurons in psychedelic drug actions. We first generated Htr2a-EGFP-CT-IRES-CreERT2 mice (CT:C-terminus) to independently identify both HTR2A-EGFP-CT receptors and HTR2A-containing cells thereby providing a detailed anatomical map of HTR2A and identifying cell types that express HTR2A. We also generated a humanized Htr2a mouse line and an additional constitutive Htr2A-Cre mouse line. Psychedelics induced a variety of known behavioral changes in our mice validating their utility for behavioral studies. Finally, electrophysiology studies revealed that extracellular 5-HT elicited a HTR2A-mediated robust increase in firing of genetically-identified pyramidal neurons--consistent with a plasma membrane localization and mode of action. These mouse lines represent invaluable tools for elucidating the molecular, cellular, pharmacological, physiological, behavioral, and other actions of psychedelic drugs in vivo.

The Rare Adverse Effect of Cefepime-Induced Neutropenia.

Cefepime is widely considered a safe and effective antibiotic, but it can have rare and serious side effects. We present a case of a 33-year-old female patient who developed severe and potentially life-threatening neutropenia after being on cefepime for 25 days. Despite extensive investigations, no other causes of neutropenia could be identified. Discontinuing the medication and administering a single dose of filgrastim produced a rapid and dramatic response. This case highlights the rare but serious risk of cefepime-induced neutropenia and underscores the need for clinicians to remain vigilant for this potential adverse effect. It is important to note that discontinuing the medication can rapidly reverse the effects, making timely recognition and intervention crucial for patient outcomes.

Meta-analysis assessing the sensitivity and specificity of 18F-FDG PET/CT for the diagnosis of prosthetic valve endocarditis (PVE) using individual patient data (IPD).

IMPORTANCE: The use of 18F-FDG PET/CT in diagnostic algorithms for PVE has increased since publication of studies and guidelines advocating its use. The assessment of test accuracy has been limited by small study sizes. We undertook a systematic review using individual patient data (IPD) meta-analysis techniques. OBJECTIVE: To estimate the summary sensitivity and specificity of 18F-FDG PET/CT in diagnosing PVE. We also assessed the effect of patient factors on test accuracy as defined by changes in the odds ratios associated with each factor. The effect of the PET/CT study on the final diagnosis was also assessed when compared to the preliminary Duke classification to determine in which patient group 18F-FDG PET/CT had the greatest utility. STUDY SELECTION: Studies were included if PET/CT was performed for suspicion of PVE and IPD of both the PET/CT result and final diagnosis defined by a gold-standard assessment was available. There were 3 possible final diagnoses ("definite PVE," "possible PVE," and "rejected PVE"). RESULTS: Seventeen studies were included with IPD available for 537 patients (from 538 scans). The summary sensitivity and specificity were 85% (95% CI 74.2%-91.8%) and 86.5% (95% CI 75.8%-92.9%) respectively when patients with final diagnosis of "possible PVE" were classified as positive for PVE. When this group was classified as negative for PVE, sensitivity was 87.4% (95% CI 80.4%-92.1%) and specificity was 84.9% (95% CI 71.5%-92.6%). Patients with a known pathogen (especially coagulase negative staphylococcal species), elevated CRP, a biological or aortic valve infection appeared more likely to have an accurate PET/CT diagnosis. Those with a mechanical valve, prior antibiotic treatment or a transcatheter aortic valve replacement valve were less likely to have an accurate test. Time since valve implantation and the presence of surgical adhesive did not appear to affect test accuracy. Of the patients with a preliminary Duke classification of "possible PVE," 84% received a more conclusive final diagnosis of "definite" or "rejected" PVE after the PET/CT study. CONCLUSIONS AND RELEVANCE: 18F-FDG PET/CT has high sensitivity and specificity in diagnosing PVE and the diagnostic utility is greatest in patients with a preliminary Duke classification of "possible PVE." Some patient factors appear to affect test accuracy, though these results should be interpreted with caution given low patient numbers for subgroup analyses.

Association of neutrophil-lymphocyte ratio with survival in peripheral early-stage non-small cell lung cancer after stereotactic body radiation therapy.

BACKGROUND: The role of neutrophil-lymphocyte ratio (NLR) as a predictor for survival in single fraction SBRT-treated non-small cell lung cancer (NSCLC) patients remains unclear. We performed an observational cohort study to determine the role of pretreatment NLR in predicting survival of early-stage NSCLC patients after single fraction SBRT. METHODS: A single-institution database of peripheral early-stage NSCLC patients treated with SBRT from February 2007 to May 2022 was queried. Optimal threshold of neutrophil-lymphocyte ratio (NLR) was defined based on maximally selected rank statistics. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate outcomes. RESULTS: A total of 286 patients were included for analysis with median follow up of 19.7 months. On Cox multivariate analysis, as a continuous variable, NLR was shown to be an independent predictor of OS (adjusted hazards ratio [aHR] 1.06, 95% CI 1.02-1.10, p = 0.005) and PFS (aHR 1.05, 95% CI 1.01-1.09, p = 0.013). In addition, NLR was associated with DF (aHR 1.11, 95% CI 1.05-1.18, p < 0.001). Maximally selected rank statistics determined 3.28 as the cutoff point of high NLR versus low NLR. These findings were confirmed upon propensity matching. CONCLUSIONS: Pretreatment NLR is an independent predictor for survival outcomes of peripheral early-stage NSCLC patients after single fraction SBRT.

Comparison of Survival Outcomes of Single- and Five-Fraction Schedules of Stereotactic Body Radiation Therapy for Early-Stage Central or Peripheral NSCLC.

BACKGROUND: The treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) frequently involves different fractionation schemes for peripheral and central tumors due to concerns with toxicity. We performed an observational cohort study to determine survival outcomes for patients with peripheral and central NSCLC treated with SBRT. METHODS: A single-institutional database of patients with early-stage NSCLC treated with SBRT from September 2008 to December 2018 was evaluated. Outcomes were progression-free survival (PFS), overall survival (OS), local failure (LF), nodal failure (NF), and distant failure (DF). Cox multivariable analysis (MVA), Kaplan-Meier plotting, Fine-Gray competing risk MVA, and propensity score matching were performed. RESULTS: A total of 265 patients were included with a median follow-up of 44.2 months. There were 191 (72%) and 74 (28%) patients with peripheral and central tumors treated with single-fraction SBRT to a dose of 27 Gy and five-fraction SBRT to a dose of 50 Gy, respectively. On Cox MVA, there was no difference in OS (adjusted hazards ratio (aHR) of 1.04, 95% CI of 0.74-1.46) or PFS (aHR of 1.05, 95% CI of 0.76-1.45). On Fine-Gray competing risk MVA, there were no differences in LF, NF, or DF. Propensity matching confirmed these findings. CONCLUSION: The survival outcomes of patients treated with SBRT for early-stage NSCLC were equivalent for central and peripheral tumors.

Generating Options and Choosing Between Them Depend on Distinct Forms of Value Representation.

Humans have a remarkable capacity for flexible decision-making, deliberating among actions by modeling their likely outcomes. This capacity allows us to adapt to the specific features of diverse circumstances. In real-world decision-making, however, people face an important challenge: There are often an enormous number of possibilities to choose among, far too many for exhaustive consideration. There is a crucial, understudied prechoice step in which, among myriad possibilities, a few good candidates come quickly to mind. How do people accomplish this? We show across nine experiments (N = 3,972 U.S. residents) that people use computationally frugal cached value estimates to propose a few candidate actions on the basis of their success in past contexts (even when irrelevant for the current context). Deliberative planning is then deployed just within this set, allowing people to compute more accurate values on the basis of context-specific criteria. This hybrid architecture illuminates how typically valuable thoughts come quickly to mind during decision-making.

Metformin for pediatric obesity and insulin resistance: a retrospective study within an integrated health care system.

OBJECTIVE: Few treatments exist for pediatric obesity. Metformin holds potential for pediatric weight loss. This large retrospective study examined the effect of metformin on weight, BMI, BMI z score, and cardiometabolic outcomes. METHODS: The study included 7,068 patients aged 10 to 17 years with BMI at or above the 95th percentile and evidence of insulin resistance. The final cohort of 955 patients with BMI data at 0 to 24 months was categorized into three groups: metformin plus intensive lifestyle changes, intensive counseling alone, and routine counseling. In order to adjust for pubertal BMI changes, a subgroup analysis was conducted for adolescents aged 15 to 17 years. RESULTS: At 6 and 12 months, metformin treatment produced significant reductions in weight (-3.5 kg and -5.3 kg, p < 0.0001), BMI (-1.06 kg/m² and -1.23 kg/m², p < 0.0001), and BMI z score (-0.05 and -0.07, p ≤ 0.002), which continued to decrease at 24 months (-0.05 and -0.08, p = 0.11 and 0.01), compared with control groups. Adolescents aged 15 to 17 years showed similar improvements. Systolic blood pressure and high-density lipoprotein cholesterol also improved in the metformin group. CONCLUSIONS: Metformin with lifestyle interventions significantly reduced weight, BMI, and BMI z score in pediatric patients with obesity and insulin resistance up to 24 months, compared with intensive and routine counseling alone.

Many Faces of the Hidden Souls: Medical and Neurological Complications and Comorbidities in Disorders of Consciousness.

Early and goal-directed management of complications and comorbidities is imperative to facilitate neurorecovery and to optimize outcomes of disorders of consciousness (DoC). This is the first large retrospective cohort study on the primary medical and neurological complications and comorbidities in persons with DoC. A total of 146 patients admitted to a specialized inpatient DoC rehabilitation program from 1 January 2014 to 31 October 2018 were included. The incidences of those conditions since their initial brain injuries were reviewed per documentation. They were categorized into reversible causes of DoC, confounders and mimics, and other medical/neurological conditions. The common complications and comorbidities included pneumonia (73.3%), pain (75.3%), pressure ulcers (70.5%), oral and limb apraxia (67.1%), urinary tract infection (69.2%), and 4-limb spasticity (52.7%). Reversible causes of DoC occurred very commonly. Conditions that may confound the diagnosis of DoC occurred at surprisingly high rates. Conditions that may be a source of pain occurred not infrequently. Among those that may diminish or confound the level of consciousness, 4.8 ± 2.0 conditions were identified per patient. In conclusion, high rates of various complications and comorbidities occurred in persons with DoC. Correcting reversible causes, identifying confounders and mimics, and managing general consequences need to be seriously considered in clinical practice.

IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies.

Neutralizing antibodies to adeno-associated virus (AAV) vectors are highly prevalent in humans1,2, and block liver transduction3-5 and vector readministration6; thus, they represent a major limitation to in vivo gene therapy. Strategies aimed at overcoming anti-AAV antibodies are being studied7, which often involve immunosuppression and are not efficient in removing pre-existing antibodies. Imlifidase (IdeS) is an endopeptidase able to degrade circulating IgG that is currently being tested in transplant patients8. Here, we studied if IdeS could eliminate anti-AAV antibodies in the context of gene therapy. We showed efficient cleavage of pooled human IgG (intravenous Ig) in vitro upon endopeptidase treatment. In mice passively immunized with intravenous Ig, IdeS administration decreased anti-AAV antibodies and enabled efficient liver gene transfer. The approach was scaled up to nonhuman primates, a natural host for wild-type AAV. IdeS treatment before AAV vector infusion was safe and resulted in enhanced liver transduction, even in the setting of vector readministration. Finally, IdeS reduced anti-AAV antibody levels from human plasma samples in vitro, including plasma from prospective gene therapy trial participants. These results provide a potential solution to overcome pre-existing antibodies to AAV-based gene therapy.

Veil-of-ignorance reasoning favors the greater good.

The "veil of ignorance" is a moral reasoning device designed to promote impartial decision making by denying decision makers access to potentially biasing information about who will benefit most or least from the available options. Veil-of-ignorance reasoning was originally applied by philosophers and economists to foundational questions concerning the overall organization of society. Here, we apply veil-of-ignorance reasoning in a more focused way to specific moral dilemmas, all of which involve a tension between the greater good and competing moral concerns. Across 7 experiments (n = 6,261), 4 preregistered, we find that veil-of-ignorance reasoning favors the greater good. Participants first engaged in veil-of-ignorance reasoning about a specific dilemma, asking themselves what they would want if they did not know who among those affected they would be. Participants then responded to a more conventional version of the same dilemma with a moral judgment, a policy preference, or an economic choice. Participants who first engaged in veil-of-ignorance reasoning subsequently made more utilitarian choices in response to a classic philosophical dilemma, a medical dilemma, a real donation decision between a more vs. less effective charity, and a policy decision concerning the social dilemma of autonomous vehicles. These effects depend on the impartial thinking induced by veil-of-ignorance reasoning and cannot be explained by anchoring, probabilistic reasoning, or generic perspective taking. These studies indicate that veil-of-ignorance reasoning may be a useful tool for decision makers who wish to make more impartial and/or socially beneficial choices.

WormBot, an open-source robotics platform for survival and behavior analysis in C. elegans.

Caenorhabditis elegans is a popular organism for aging research owing to its highly conserved molecular pathways, short lifespan, small size, and extensive genetic and reverse genetic resources. Here we describe the WormBot, an open-source robotic image capture platform capable of conducting 144 parallel C. elegans survival and behavioral phenotyping experiments. The WormBot uses standard 12-well tissue culture plates suitable for solid agar media and is built from commercially available robotics hardware. The WormBot is controlled by a web-based interface allowing control and monitoring of experiments from any internet connected device. The standard WormBot hardware features the ability to take both time-lapse bright field images and real-time video micrographs, allowing investigators to measure lifespan, as well as heathspan metrics as worms age. The open-source nature of the hardware and software will allow for users to extend the platform and implement new software and hardware features. This extensibility, coupled with the low cost and simplicity of the system, allows the automation of C. elegans survival analysis even in small laboratory settings with modest budgets.

It helps to ask: The cumulative benefits of asking follow-up questions.

In a recent article published in Journal of Personality and Social Psychology (JPSP; Huang, Yeomans, Brooks, Minson, & Gino, 2017), we reported the results of 2 experiments involving "getting acquainted" conversations among strangers and an observational field study of heterosexual speed daters. In all 3 studies, we found that asking more questions in conversation, especially follow-up questions (that indicate responsiveness to a partner), increases interpersonal liking of the question asker. Kluger and Malloy (2019) offer a critique of the analyses in Study 3 of our article. Though their response is a positive signal of engaged interest in our research, they made 3 core mistakes in their analyses that render their critique invalid. First, they tested the wrong variables, leading to conclusions that were erroneous. Second, even if they had analyzed the correct variables, some of their analytical choices were not valid for our speed-dating dataset, casting doubt on their conclusions. Third, they misrepresented our original findings, ignoring results in all 3 of our studies that disprove some of their central criticisms. In summary, the conclusions that Kluger and Malloy (2019) drew about Huang et al. (2017)'s findings are incorrect. The original results are reliable and robust: Asking more questions, especially follow-up questions, increases interpersonal liking. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Mitigating malicious envy: Why successful individuals should reveal their failures.

People often feel malicious envy, a destructive interpersonal emotion, when they compare themselves to successful peers. Across 3 online experiments and a field experiment of entrepreneurs, we identify an interpersonal strategy that can mitigate feelings of malicious envy in observers: revealing one's failures. Despite a general reluctance to reveal one's failures-as they are happening and after they have occurred-across four experiments, we find that revealing both successes and failures encountered on the path to success (compared to revealing only successes) decreases observers' malicious envy. This effect holds regardless of the discloser's status and cannot be explained by a decrease in perceived status of the individual. Then, in a field experiment at an entrepreneurial pitch competition, where pride displays are common and stakes are high, we find suggestive evidence that learning about the failures of a successful entrepreneur decreases observers' malicious envy while increasing their benign envy and decreasing their perceptions of the entrepreneur's hubristic pride (i.e., arrogance) while increasing their perceptions of the entrepreneur's authentic pride (i.e., confidence). These findings align with previous work on the social-functional relation of envy and pride. Taken together, our results highlight how revealing failures encountered on the way to success can be a counterintuitive yet effective interpersonal emotion regulation strategy. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Screening for depression in rosacea patients.

Rosacea patients often are burdened with embarrassment, social anxiety, and psychiatric comorbidities. The Patient Health Questionnaire 9 (PHQ-9) is a validated and reliable self-administered tool for diagnosis of depression and designation of depression severity. This study aimed to examine the relationship between rosacea severity scores and level of depression using a validated rosacea self-assessment tool and the PHQ-9, respectively. Our results indicated that there is a direct relationship between rosacea severity and level of depression, and the PHQ-9 could prove useful in screening for depression in rosacea patients given the high incidence of psychiatric comorbidities in this patient population.

Rosacea Triggers: Alcohol and Smoking.

A variety of triggers are thought to exacerbate rosacea. A validated self-assessment tool and survey was used to study the relationship between rosacea severity and triggers. Subjects were adult patients with a clinical diagnosis of rosacea. Increased severity of disease was significantly associated with consumption of many alcoholic beverages in 1 day and employment at a job requiring extensive sun exposure. The authors' findings may inform physician counseling practices; patients may be provided with practical measures for managing their rosacea, such as limiting alcohol consumption over short periods of time and increasing sun protection, especially in the summer.

Patient Costs Associated with Rosacea.

The recalcitrance of rosacea to many treatment options may prompt patients to spend exorbitant amounts of money on unsubstantiated treatment regimens in an effort to achieve relief. The authors examine the relationship between disease severity and treatment cost across several demographic and socioeconomic strata. Familiarization of evidence-based clinical recommendations and consensus guidelines may equip physicians to educate patients about the most efficacious and cost-effective treatment options to assist patients in making cost-conscious decisions in the management of their rosacea.

Validity and Reliability of a Rosacea Self-Assessment Tool.

The lack of validated rosacea assessment tools is a hurdle in assessing rosacea severity. This article discusses a valid and reliable rosacea severity self-assessment tool (RSAT) to measure rosacea severity. To determine test-retest validity, participants completed the self-assessment twice. A blinded physician graded the participant's disease severity with the Investigator Global Severity (IGS) score. Pearson correlations were used to assess the relationship between the self-assessment measure and the IGS. Test-retest RSAT measurements were correlated. The RSAT represents a valid and reliable tool. This tool may facilitate determination of rosacea severity in survey research studies.