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Science is among humanitys greatest achievements, yet scientific censorship is rarely studied empirically. We explore the social, psychological, and institutional causes and consequences of scientific censorship (defined as actions aimed at obstructing particular scientific ideas from reaching an audience for reasons other than low scientific quality). Popular narratives suggest that scientific censorship is driven by authoritarian officials with dark motives, such as dogmatism and intolerance. Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups. This perspective helps explain both recent findings on scientific censorship and recent changes to scientific institutions, such as the use of harm-based criteria to evaluate research. We discuss unknowns surrounding the consequences of censorship and provide recommendations for improving transparency and accountability in scientific decision-making to enable the exploration of these unknowns. The benefits of censorship may sometimes outweigh costs. However, until costs and benefits are examined empirically, scholars on opposing sides of ongoing debates are left to quarrel based on competing values, assumptions, and intuitions.

Over the past decade behavioral science, particularly psychology, has come under fire from critics for being fixated on progressive political ideology, most notably Diversity, Equity, and Inclusion (DEI). The critics' [...]

The pulmonary system represents a unique lipidomic environment as it contains cellular membrane-bound lipid species and a specialized reservoir of lipids in the airway epithelial lining fluid. As a major initial point of defense, airway lipids react to inhaled contaminants such as volatile organic compounds, oxides of nitrogen, or ozone (O3), creating lipokine signaling that is crucial for both the initiation and resolution of inflammation within the lung. Dietary modulation of eicosanoids has gained increased attention in recent years for improvements to cardiovascular health. The current study sought to examine how dietary supplementation with eicosanoid precursors (i.e, oils rich in saturated or polyunsaturated fatty acids) might alter the lung lipid composition and subsequently modify the inflammatory response to ozone inhalation. Our study demonstrated that mice fed a diet high in saturated fatty acids resulted in diet-specific changes to lung lipid profiles and increased cellular recruitment to the lung following ozone inhalation. Bioinformatic analysis revealed an ozone-dependent upregulation of several lipid species, including phosphoserine 37:5. Pathway analysis of lipid species revealed the process of lateral diffusion of lipids within membranes to be significantly altered due to ozone exposure. These results show promising data for influencing pulmonary lipidomic profiles via diet, which may provide a pragmatic therapeutic approach to protect against lung inflammation and damage following pulmonary insult.

Jerrica E Shuster,1,2 Barry E Bleske,1,2 Michael P Dorsch1,21University of Michigan Hospitals and Health Centers, Ann Arbor, MI, USA; 2College of Pharmacy, University of Michigan, Ann Arbor, MI, USAAbstract: Azilsartan–chlorthalidone fixed combination is a new drug in the management of hypertension. Azilsartan has been shown to have greater blood pressure-lowering effects than other angiotensin-receptor blockers (ARBs), and the debate regarding the superiority of chlorthalidone over hydrochlorothiazide has been ongoing for years. The combination is unique because it is the first to partner an ARB with this, possibly more effective, diuretic. This review will address trials involving both components of this drug, as well as phase III trials involving the fixed-combination product. The article will also discuss the benefit of combination therapy in the treatment of hypertension.Keywords: azilsartan, chlorthalidone, combination, hypertension

'It ain't what you don't know that gets you into trouble. It's what you know for sure that just ain't so.'--ATTRIBUTED TO MARK TWAIN When it comes to opinions concerning [...]

Abstract Smoke from wildland fires has been shown to produce neuroinflammation in preclinical models, characterized by neural infiltrations of neutrophils and monocytes, as well as altered neurovascular endothelial phenotypes. To address the longevity of such outcomes, the present study examined the temporal dynamics of neuroinflammation and metabolomics after inhalation exposures from biomass-derived smoke. 2-month-old female C57BL/6 J mice were exposed to wood smoke every other day for 2 weeks at an average exposure concentration of 0.5 mg/m3. Subsequent serial euthanasia occurred at 1-, 3-, 7-, 14-, and 28-day post-exposure. Flow cytometry of right hemispheres revealed two endothelial populations of CD31Hi and CD31Med expressors, with wood smoke inhalation causing an increased proportion of CD31Hi. These populations of CD31Hi and CD31Med were associated with an anti-inflammatory and pro-inflammatory response, respectively, and their inflammatory profiles were largely resolved by the 28-day mark. However, activated microglial populations (CD11b+/CD45low) remained higher in wood smoke-exposed mice than controls at day 28. Infiltrating neutrophil populations decreased to levels below controls by day 28. However, the MHC-II expression of the peripheral immune infiltrate remained high, and the population of neutrophils retained an increased expression of CD45, Ly6C, and MHC-II. Utilizing an unbiased approach examining the metabolomic alterations, we observed notable hippocampal perturbations in neurotransmitter and signaling molecules, such as glutamate, quinolinic acid, and 5-α-dihydroprogesterone. Utilizing a targeted panel designed to explore the aging-associated NAD+ metabolic pathway, wood smoke exposure drove fluctuations and compensations across the 28-day time course, ending with decreased hippocampal NAD+ abundance on day 28. Summarily, these results indicate a highly dynamic neuroinflammatory environment, with potential resolution extending past 28 days, the implications of which may include long-term behavioral changes, systemic and neurological sequalae directly associated with wildfire smoke exposure.

When a romantic relationship ends, individuals often look back and wish they had done things differently. What may seem clear in hindsight, however, is often unclear in foresight. We investigated the effects of outcome knowledge on individuals’ judgments of a dating couple. In Study 1 (181 U.S. college students, 334 U.S. community adults), participants read about a couple with an uncertain relationship trajectory; then, experimental group participants received knowledge about the couple’s status six months down the road as broken up or still together, while control group participants received no outcome knowledge. Individuals who were told the dating couple broke up perceived that outcome as more likely and obvious compared to those who were not given outcome knowledge or who were told the couple stayed together. In Study 2 (262 U.S. college students, 333 U.S. community adults), participants in the experimental conditions received knowledge about the couple’s status six months later as broken up or engaged, while control group participants received no outcome knowledge. In both samples, outcome knowledge of a breakup had a negative effect on individuals’ judgments about the couple. Among community adults, but not among college students, outcome knowledge of an engagement positively affected judgments of the couple. We offer directions for future research and discuss the mechanisms by which hindsight bias might affect evaluations of our own and others’ relationships.

Despite recent interest in online learning, systematic comparisons of online learning environments with traditional classroom environments are limited, particularly in the sciences. Here, we report on a systematic comparison of an online and face-to-face classroom for a sophomore-level, lecture-only introductory inorganic chemistry course that is designed for students pursuing a chemistry major or minor. The online group consisted of three sections of students enrolled in Introduction to Inorganic Chemistry during two 8 week summer terms and one 4 week winter term. The face-to-face group consisted of two sections of students enrolled in Introduction to Inorganic Chemistry during two 15 week semesters. Both groups of students completed ten common exam questions, and a validated and reliable measure of their attitudes toward chemistry (Attitude toward the Subject of Chemistry Inventory Version 2: ASCIv2). Students in the online course and face-to-face course did not differ in their performance on the common exam questions, course grade distribution, or attitudes toward chemistry. Although few studies have compared online and face-to-face learning environments in the physical sciences, our results are consistent with the idea that students who complete an online course fare just as well as those who attend face-to-face classes.

Abstract Trandolapril, an angiotensin‐converting enzyme inhibitor prodrug, needs to be activated by carboxylesterase 1 (CES1) in the liver to exert its intended therapeutic effect. A previous in vitro study demonstrated that the CES1 genetic variant G143E (rs71647871) abolished CES1‐mediated trandolapril activation in cells transfected with the variant. This study aimed to determine the effect of the G143E variant on trandolapril activation in human livers and the pharmacokinetics (PKs) and pharmacodynamics (PDs) in human subjects. We performed an in vitro incubation study to assess trandolapril activation in human livers (5 G143E heterozygotes and 97 noncarriers) and conducted a single‐dose (1 mg) PK and PD study of trandolapril in healthy volunteers (8 G143E heterozygotes and 11 noncarriers). The incubation study revealed that the mean trandolapril activation rate in G143E heterozygous livers was 42% of those not carrying the variant (p = 0.0015). The clinical study showed that, relative to noncarriers, G143E carriers exhibited 20% and 15% decreases, respectively, in the peak concentration (Cmax) and area under the curve from 0 to 72 h (AUC0–72 h) of the active metabolite trandolaprilat, although the differences were not statistically significant. Additionally, the average maximum reductions of systolic blood pressure and diastolic blood pressure in carriers were ~ 22% and 23% less than in noncarriers, respectively, but the differences did not reach a statistically significant level. In summary, the CES1 G143E variant markedly impaired trandolapril activation in the human liver under the in vitro incubation conditions; however, this variant had only a modest impact on the PK and PD of trandolapril in healthy human subjects.

Sex differences in the use of competitive tactics have been well established. Although many factors may contribute to these sex differences, according to social role theory (SRT), stereotypes and expectations about men's and women's typical social roles are crucial. We addressed the potential impact of social roles by studying massively multiplayer online role-playing games (MMORPGs), a setting where individuals represent themselves with avatars and thus enjoy the opportunity to compete without regard to the typical expectations and behaviors associated with men's and women's roles. We surveyed players via MTurk (63 women, 191 men) and Reddit (166 women, 1,326 men) regarding their frequency of engaging in five competitive behaviors and the sex and role of their primary avatar. As expected, there were reliable sex differences in competitiveness: men were more likely than women to engage in player-versus-player duels (MTurk d = 0.19; Reddit d = 0.51), do solo runs of difficult content (0.30, 0.35), and work to acquire expensive items (0.32, 0.19); women were more likely than men to seek in-game awards (−0.38, −0.36) and spend real-world money on expensive microtransactions (−0.16, −0.27). Contrary to SRT, these sex differences in forms of competitive behavior were generally unrelated to players’ chosen avatar sex or avatar role. These results instead indicate that sex differences in competitiveness largely reflect evolved predispositions.

Purpose: Ranolazine is a novel anti-angina treatment approved in the United States for chronic stable angina. Ranolazine pharmacokinetics have not been studied previously in patients who receive maintenance hemodialysis. This study describes the pharmacokinetics of ranolazine and three major metabolites (CVT-2738, CVT-2512, CVT-2514) in patients receiving thrice weekly hemodialysis. Methods: Eight participants receiving maintenance hemodialysis completed this prospective, open-label study (study identifier NCT01435174 at Clinicaltrials.gov). Three participants received a single tablet of ranolazine 500 mg (followed by an interim analysis), and five received 2 tablets of ranolazine 500 mg. Blood samples were collected over 65 h to determine the pharmacokinetic characteristics during and between hemodialysis sessions. Non-compartmental analysis was used to determine the individual pharmacokinetic parameters. Results: Ranolazine off-hemodialysis elimination phase half-lives were 3.6 and 3.9 h for 500 mg and 1000 mg doses, respectively. The time to maximum concentration ranged from 2 to 18 hours and the average maximum concentration was 0.65 ± 0.27 mcg/mL and 1.18 ± 0.48 mcg/mL for ranolazine 500 mg and 1000 mg dose, respectively. The mean hemodialysis percent reduction ratio for the ranolazine 500 mg dose was 52.3 ± 8.1% and for the ranolazine 1000 mg dose was 69.2 ± 37.6%. Conclusions: Data on ranolazine dosing in patients receiving maintenance hemodialysis is almost non-existent. Given the extent of pharmacokinetic variability observed with the 500 mg and 1000 mg oral doses of ranolazine, neither can be recommended as a starting dose in patients receiving maintenance hemodialysis. Guided by the information gained form this study about the extent of hemodialytic drug clearance, further multi-dose clinical trials of ranolazine are needed to optimize therapeutic outcomes in this patient population.

IN 1998, 11-YEAR OLD EMILY ROSA CAUSED A NATIONAL sensation when she published the results of her 4th grade science experiment in the Journal of the American Medical Association. (1) [...]