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Illicit opioid use is a growing public health emergency and is associated with adverse medical and social outcomes. Opioid use in the pregnant population is increasing globally, and optimal management incorporates opioid substitution programs with improved concurrent engagement in medical care. The two main drugs used in opioid substitution programs are methadone and buprenorphine. Methadone has been used since the 1970s and provides treatment stability leading to improved engagement with obstetric services. Buprenorphine is a newer treatment, has greater dosing flexibility, and may be associated with fewer neonatal adverse effects. Direct comparisons of methadone and buprenorphine treatments are limited but suggest that buprenorphine is associated with less severe neonatal withdrawal; however, it is not universally well-tolerated and tends to be prescribed to less severely affected mothers. Given the lack of clear evidence to support one opioid substitution therapy over another, the principal aim of therapy should be to stabilize treatment and promote more comprehensive engagement with multidisciplinary services.

Introduction: A non-interventional, multicenter, European, prospective evaluation of the effectiveness, tolerability, and safety of a topical preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) demonstrating insufficient response to topical beta-receptor blockers or prostaglandin analogue (PGA) monotherapy. Methods: Mean intraocular pressure (IOP) change from baseline was measured at study visits following a switch to PF tafluprost/timolol FC. Primary endpoint was absolute mean IOP change at month 6. Change from baseline concerning ocular signs and symptoms was also explored. Results: Analyses included 577 patients (59.6% female). Mean age (SD) was 67.8 (11.67) years. Mean (SD) IOP reduction from baseline was significant at all study visits; 5.4 (3.76) mmHg (23.7%) at week 4, 5.9 (3.90) mmHg (25.6%) at week 12, and 5.7 (4.11) mmHg (24.9%) at month 6 (p < 0.0001 for all visits). At month 6, 69.2%, 53.6%, 40.0%, and 25.8% were responders based on ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% cutoff values for mean IOP, respectively. Significant reductions were observed concerning corneal fluorescein staining (p < 0.0001), dry eye symptoms, irritation, itching, and foreign body sensation (p < 0.001 for each parameter). Conjunctival hyperemia was significantly reduced at all study visits (p < 0.0001 at each visit). Overall, 69 treatment-related adverse events (AEs) were reported, one of which was serious (status asthmaticus). Most AEs were mild to moderate in severity, and the majority had resolved or were resolving at the end of the study period. Conclusion: In clinical practice, PF tafluprost/timolol FC provided statistically and clinically significant IOP reductions in patients with OAG and OHT insufficiently controlled on or intolerant to PGA or beta-receptor blocker monotherapy. The full IOP reduction appeared at week 4 and was maintained over the 6-month study period. Key symptoms of ocular surface health improved. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.

The authors would like to acknowledge missing data for all prior latanoprost users as a whole. The following sentence has been added to the manuscript (page 8, first paragraph): Mean (SD) reduction from baseline at Month 6 for users of all latanoprost formulations (preserved and PF) was 6.1 (4.25) mmHg (25.9%; p\0.0001). The authors have also prepared a table to summarise the change in intraocular pressure following a switch to the preservative-free tafluprost/timolol fixed-dose combination from all latanoprost formulations (preserved and preservative-free formulations). See Table 1 below.(Table Preseneted.) .The original article has been corrected.

Introduction: The VISIONARY study demonstrated statistically significant intraocular pressure (IOP) reductions with the preservative-free fixed-dose combination of tafluprost 0.0015% and timolol 0.5% (PF tafluprost/timolol FC) in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients, sub-optimally controlled with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Current subanalyses have examined these data according to the baseline monotherapy. Methods: A European, prospective, observational study included adults (aged ≥ 18 years) with OAG or OHT, who were switched to the PF tafluprost/timolol FC from PGA or beta-blocker monotherapy. Treatment outcomes were reported according to prior monotherapy subgroup: beta-blocker, preserved latanoprost, PF-latanoprost, bimatoprost, tafluprost, and travoprost. Endpoints included the mean change from baseline regarding IOP, conjunctival hyperemia, and corneal fluorescein staining (CFS) at Week 4 and Week 12, and at Month 6. Results: The subanalysis included 577 patients. All prior monotherapy subgroups demonstrated statistically significant IOP reductions from baseline at Week 4, that were maintained through Month 6 (p

At the turn of the 20th century, researchers and clinicians compared case studies of patients diagnosed with hysteria and mediums who claimed to channel spirits based on alterations they observed in their sense of self. Yet, notwithstanding its early promise, this comparative approach to such “nonordinary experiences” (NOEs) was never fully realize due to disciplinary siloing and the challenges involved in comparing culture-laden accounts. Today, psychologists tend to reify constructs, such as religious or spiritual, extraordinary (psychical, paranormal, anomalous, or exceptional), and psychopathological. In doing so, they face an unresolved challenge: experiences with phenomenologically distinct features may be appraised similarly within a culture (that is, viewed as evidence for the same culturally-specific construct) and experiences that share phenomenological features may be appraised differently across cultures. Here, we call for a renewed approach to comparing NOEs across cultures that prioritizes subjectively recognizable features instead of constructs. First, we review the history of the comparative approach in psychology and where it is today. Second, we introduce a feature- based approach, building on the event cognition literature, where “lived experiences” are broken down into their phenomenological features and the claims made about them. Third, we propose ways in which cultural learning shapes experiences, and possibly the ordinary-nonordinary distinction itself. We conclude by highlighting that by building on and shifting the focus of previous efforts, the feature-based approach provides a way to compare experiences at the population level.

Quickly and flexibly exploring high-dimensional datasets, such as scRNAseq data, is underserved but critical for hypothesis generation, dataset annotation, publication, sharing, and community reuse. cellxgene is a highly generalizable, web-based interface for exploring high dimensional datasets along categorical, continuous and spatial dimensions, as well as feature annotation. cellxgene is differentiated by its ability to performantly handle millions of observations, and bridges a critical gap by enabling computational and experimental biologists to iteratively ask questions of private and public datasets. In doing so, cellxgene increases the utility and reusability of datasets across the single-cell ecosystem.The codebase can be accessed at https://github.com/chanzuckerberg/cellxgene. For questions and inquiries, please contact cellxgene@chanzuckerberg.com.

When operationalizing ‘religiosity’ or ‘spirituality’ or ‘religious experience’ as measurable constructs, researchers tacitly treat them as if they were cross-culturally stable ‘things’ rather than investigating the way culturally-laden concepts, such as ‘religious’ or ‘spiritual,’ are used to interpret or appraise contested aspects of human life within and across cultures. To illustrate the distinction, we contrast the traditional research design that the Religious Experience Research Centre used to survey and compare “religious experience” in the UK and China with the appraisal-based design used by the Inventory of Nonordinary Experiences (INOE). Instead of operationalizing “religious experience,” the INOE distinguishes between generically-worded experiences and the way the experiences are appraised. When coupled with item level validation to ensure that queries are understood as intended, the generically-worded experiences function as common features that allow us to compare similarities and differences between culturally-embedded “lived” experiences. Separating generic experiences from appraisals allows us to (1) treat culture-bound concepts, such as ‘religious’ and ‘spiritual,’ as appraisals, and (2) view these and other concepts (e.g., dharmic, paranormal, psychotic) as advancing claims about how and why an experience occurred. In so far as we can establish the cross-cultural validity of common features, we can set up culturally-balanced (rather than Western-centric) comparisons and avoid operationalizing culture-specific concepts.