Political differences in free will belief are associated with differences in moralization

In fourteen studies, we tested whether political conservatives’ stronger free will beliefs were linked to stronger and broader tendencies to moralize, and thus a greater motivation to assign blame. In Study 1 (meta-analysis of five studies, n=308,499) we show that conservatives have stronger tendencies to moralize than liberals, even for moralization measures containing zero political content (e.g., moral badness ratings of faces and personality traits). In Study 2, we show that conservatives report higher free will belief, and this is statistically mediated by the belief that people should be held morally responsible for their bad behavior (n=14,707). In Study 3, we show that political conservatism is associated with higher attributions of free will for specific events. Turning to experimental manipulations to test our hypotheses, we show that: when conservatives and liberals see an action as equally wrong there is no difference in free will attributions (Study 4); when conservatives see an action as less wrong than liberals, they attribute less free will (Study 5); and specific perceptions of wrongness account for the relation between political ideology and free will attributions (Study 6a and 6b). Finally, we show that political conservatives and liberals even differentially attribute free will for the same action depending on who performed it (Studies 7a-d). These results are consistent with our theory that political differences in free will belief are at least partly explicable by conservatives’ tendency to moralize, which strengthens motivation to justify blame with stronger belief in free will and personal accountability

Lapatinib-related rash and breast cancer outcome in the ALTTO phase III randomized trial

Background: Previously we have shown that early development of rash is associated with a higher chance of achieving pathological complete response to neoadjuvant lapatinib. In the current analysis, we investigate its impact on survival in the ALTTO phase III adjuvant trial. Methods: In ALTTO, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomly assigned to adjuvant trastuzumab, lapatinib, their sequence, or their combination for a total duration of one year. We evaluated whether the development of early lapatinib-related rash (ie, within 6 weeks) is associated with disease-free (DFS) and overall survival (OS). Landmark analysis at eight weeks and time-dependent analysis were tested in a multivariable model stratifying on trial's stratification factors. All statistical tests were two-sided. Results: Out of 6098 lapatinib-treated patients, 3973(65.2%) were included in the landmark analysis, of whom 1389 (35.0%) had developed early rash. After median follow-up of 4.5 years, the development of early rash was associated with a trend of improved DFS (multivariable: hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.73 to 1.03, P =.10) and statistically significantly improved OS (multivariable: HR=0.63, 95% CI=0.48 to 0.82, P <.001) compared with subjects without early rash. Compared with patients randomly assigned to trastuzumab (n=2051), patients who were randomly assigned to trastuzumab/lapatinib combination and developed early rash (n=692) had superior DFS (multivariable: HR=0.72, 95% CI=0.55 to 0.92, P =.01) and OS (multivariable: HR=0.59, 95% CI=0.39 to 0.90, P =.01). Time-dependent analysis suggests that the occurrence of rash is predictive of lapatinib benefit, both when given in combination or sequential to trastuzumab. Conclusions: Our results indicate that early development of rash identifies patients who derive superior benefit from lapatinib-based therapy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas.

SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes have been shown to cause severe developmental and adult syndromes, referred to as SOXopathies. We here provide evidence that SOX6 variants also cause a SOXopathy. Using clinical and genetic data, we identify 19 individuals harboring various types of SOX6 alterations and exhibiting developmental delay and/or intellectual disability; the individuals are from 17 unrelated families. Additional, inconstant features include attention-deficit/hyperactivity disorder (ADHD), autism, mild facial dysmorphism, craniosynostosis, and multiple osteochondromas. All variants are heterozygous. Fourteen are de novo, one is inherited from a mosaic father, and four offspring from two families have a paternally inherited variant. Intragenic microdeletions, balanced structural rearrangements, frameshifts, and nonsense variants are predicted to inactivate the SOX6 variant allele. Four missense variants occur in residues and protein regions highly conserved evolutionarily. These variants are not detected in the gnomAD control cohort, and the amino acid substitutions are predicted to be damaging. Two of these variants are located in the HMG domain and abolish SOX6 transcriptional activity in vitro. No clear genotype-phenotype correlations are found. Taken together, these findings concur that SOX6 haploinsufficiency leads to a neurodevelopmental SOXopathy that often includes ADHD and abnormal skeletal and other features