Forgiveness takes place on an attitudinal continuum from hostility to friendliness: Toward a closer union of forgiveness theory and measurement.

Researchers commonly conceptualize forgiveness as a rich complex of psychological changes involving attitudes, emotions, and behaviors. Psychometric work with the measures developed to capture this conceptual richness, however, often points to a simpler picture of the psychological dimensions in which forgiveness takes place. In an effort to better unite forgiveness theory and measurement, we evaluate several psychometric models for common measures of forgiveness. In doing so, we study people from the United States and Japan to understand forgiveness in both nonclose and close relationships. In addition, we assess the predictive utility of these models for several behavioral outcomes that traditionally have been linked to forgiveness motives. Finally, we use the methods of item response theory, which place person abilities and item responses on the same metric and, thus, help us draw psychological inferences from the ordering of item difficulties. Our results highlight models based on correlated factors models and bifactor (S-1) models. The bifactor (S-1) model evinced particular utility: Its general factor consistently predicts variation in relevant criterion measures, including 4 different experimental economic games (when played with a transgressor), and also suffuses a second self-report measure of forgiveness. Moreover, the general factor of the bifactor (S-1) model identifies a single psychological dimension that runs from hostility to friendliness while also pointing to other sources of variance that may be conceived of as method factors. Taken together, these results suggest that forgiveness can be usefully conceptualized as prosocial change along a single attitudinal continuum that ranges from hostility to friendliness. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

Diagnostic and Prognostic Significance of Complement in Patients with Alcohol-associated Hepatitis

BACKGROUND and AIMS: Given the lack of effective therapies and high mortality in acute alcohol-associated hepatitis (AH), it is important to develop rationally-designed biomarkers for effective disease management. Complement, a critical component of the innate immune system, contributes to uncontrolled inflammatory responses leading to liver injury, but is also involved in hepatic regeneration. Here we investigated if a panel of complement proteins and activation products would provide useful biomarkers for severity of AH and aid in predicting 90 days mortality. APPROACH and RESULTS: Plasma samples collected at time of diagnosis from 254 patients with moderate and severe AH recruited from four medical centers and 31 healthy individuals were used to quantify complement proteins by ELISA and Luminex arrays. Components of the classical and lectin pathways, including complement factors C2, C4b and C4d, as well as complement factor I (CFI) and C5, were reduced in AH patients compared to healthy individuals. In contrast, components of the alternative pathway, including complement factor Ba (CFBa) and factor D (CFD), were increased. Markers of complement activation were also differentially evident, with C5a increased and the soluble terminal complement complex (sC5b9) decreased in AH. Mannose binding lectin (MBL), C4b, CFI, C5 and sC5b9 were negatively correlated with model for end-stage liver disease (MELD) score, while CFBa and CFD were positively associated with disease severity. Lower CFI and sC5b9 were associated with increased 90-day mortality in AH. CONCLUSIONS: Taken together, these data indicate that AH is associated with a profound disruption of complement. Inclusion of complement, especially CFI and sC5b9, along with other laboratory indicators, could improve diagnostic and prognostic indications of disease severity and risk of mortality for AH patients

Precision radial velocities with CSHELL

Radial velocity identification of extrasolar planets has historically been dominated by optical surveys. Interest in expanding exoplanet searches to M dwarfs and young stars, however, has motivated a push to improve the precision of near infrared radial velocity techniques. We present our methodology for achieving 58 m/s precision in the K band on the M0 dwarf GJ 281 using the CSHELL spectrograph at the 3-meter NASA IRTF. We also demonstrate our ability to recover the known 4 Mjup exoplanet Gl 86 b and discuss the implications for success in detecting planets around 1-3 Myr old T Tauri stars.Comment: 31 pages, 3 figures, 2 tables, accepted for publication in Ap

SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration

High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. Here we show that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in male mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1β release, contributing to an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of male and female postmortem human brains demonstrate that SA is hyperactivated in Alzheimer's disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer's disease, providing mechanistic insight into the biology of neuroinflammation

Vitamin D Receptor Polymorphisms and Breast Cancer Risk: Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Background: Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene ( VDR ), rs1544410 ( Bsm I), and rs2228570 ( Fok I), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the Fok I ff genotype, which encodes a less transcriptionally active isoform of VDR , and reduced risk has been reported for the Bsm I BB genotype, a SNP in strong linkage disequilibrium with a 3′-untranslated region, which may influence VDR mRNA stability. Methods: We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression. Results: The odds ratio (OR) for the rs2228570 ( Fok I) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 ( Bsm I) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92). Conclusions: Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. (Cancer Epidemiol Biomarkers Prev 2009;18(1):297–305

2024 UK and Ireland modified Delphi consensus on myopia management in children and young people

Introduction: This work aimed to establish the largest UK and Ireland consensus on myopia management in children and young people (CYP). Methods: A modified Delphi consensus was conducted with a panel of 34 optometrists and ophthalmologists with expertise in myopia management. Results: Two rounds of voting took place and 131 statements were agreed, including that interventions should be discussed with parents/carers of all CYP who develop myopia before the age of 13 years, a recommendation for interventions to be publicly funded for those at risk of fast progression and high myopia, that intervention selection should take into account the CYP's hobbies and lifestyle and that additional training for eye care professionals should be available from non-commercial sources. Topics for which published evidence is limited or lacking were areas of weaker or no consensus. Modern myopia management contact and spectacles are suitable first-line treatments. The role and provision of low-concentration atropine needs to be reviewed once marketing authorisations and funding decisions are in place. There is some evidence that a combination of low-concentration atropine with an optical intervention can have an additive effect; further research is needed. Once an intervention is started, best practice is to monitor non-cycloplegic axial length 6 monthly. Conclusion: Research is needed to identify those at risk of progression, the long-term effectiveness of individual and combined interventions, and when to discontinue treatment when myopia has stabilised. As further evidence continues to emerge, this consensus work will be repeated to ensure it remains relevant.</p

A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression

Background Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. Methods We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients’ treatment assignments. Results Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and the psychotherapy group, as compared with 73 percent in the combined-treatment group (P Conclusions Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone