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Empathy, or the ability to imagine what someone else may be feeling or thinking, is a crucial component of meaningful care provision, including person-centered care (PCC), and has been shown to enhance care provider and patient well-being. The purpose of the current review was to examine the impact of interventions focused on improving the ability of health care providers or students to experience and/or communicate with empathy. Of 1,427 publications reviewed, 18 articles met inclusion criteria. All studies incorporated empathy or empathic communication competencies in their training or intended variables of change. PCC concepts were used in guiding the development of most interventions. Some interventions significantly improved participant empathy, attitudes toward patients with dementia, and certain verbal and nonverbal communication skills. Current study reports on improved positive interpersonal communication skills by nursing assistants are promising. Future study to improve therapeutic communication and delivery of dementia care with empathy using enhanced study design and measurement are needed. [ Research in Gerontological Nursing, 13 (3), 158–168.]

This volume presents a selection from the papers given at the 13th International Conference on Historical Linguistics. It offers a window on the current state of the art in historical linguistics: the papers cover a wide range of different languages, different language families, and different approaches to the study of linguistic change, ranging from optimality theory, theories of grammaticalization and the invisible hand, treatments of language contact and creolization to the linguistic consequences of political correctness. Among the languages under discussion are Akkadian, Catalan, Dutch, Finnish, Japanese, Sranan, Western Malayo-Polynesian, Yiddish, and a variety of Romance and Native American languages.

Inflammatory markers like C-reactive protein (CRP) have been associated with post-traumatic stress disorder (PTSD) and traumatic experiences, but the underlying mechanisms are unclear. We investigated the relationship among serum CRP, PTSD, and traits related to traumatic events and social support using genetic association data from the Psychiatric Genomics Consortium (23,185 PTSD cases and 151,309 controls), the UK Biobank (UKB; up to 117,900 individuals), and the CHARGE study (Cohorts for Heart and Aging Research in Genomic Epidemiology, 148,164 individual). Linkage disequilibrium score regression, polygenic risk scoring, and two-sample Mendelian randomization (MR) analyses were used to investigate genetic overlap and causal relationships. Genetic correlations of CRP were observed with PTSD (rg = 0.16, p = 0.026) and traits related to traumatic events, and the presence of social support (−0.28 < rg < 0.20; p < 0.008). We observed a bidirectional association between CRP and PTSD (CRP → PTSD: β = 0.065, p = 0.015; PTSD → CRP: β = 0.008, p = 0.009). CRP also showed a negative association with the “felt loved as a child” trait (UKB, β = −0.017, p = 0.008). Owing to the known association of socioeconomic status (SES) on PTSD, a multivariable MR was performed to investigate SES as potential mediator. We found that household income (univariate MR: β = −0.22, p = 1.57 × 10−7; multivariate MR: β = −0.17, p = 0.005) and deprivation index (univariate MR: β = 0.38, p = 1.63 × 10−9; multivariate MR: β = 0.27, p = 0.016) were driving the causal estimates of “felt loved as a child” and CRP on PTSD. The present findings highlight a bidirectional genetic association between PTSD and CRP, also suggesting a potential role of SES in the interplay between childhood support and inflammatory processes with respect to PTSD risk.

In the Anthropocene, in which we now live, climate change is impacting most life on Earth. Microorganisms support the existence of all higher trophic life forms. To understand how humans and other life forms on Earth (including those we are yet to discover) can withstand anthropogenic climate change, it is vital to incorporate knowledge of the microbial ‘unseen majority’. We must learn not just how microorganisms affect climate change (including production and consumption of greenhouse gases) but also how they will be affected by climate change and other human activities. This Consensus Statement documents the central role and global importance of microorganisms in climate change biology. It also puts humanity on notice that the impact of climate change will depend heavily on responses of microorganisms, which are essential for achieving an environmentally sustainable future.

In two randomized trials, evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9), reduced LDL cholesterol levels by 61%. In an exploratory analysis, the incidence of cardiovascular events was reduced in the evolocumab group. Reduction in low-density lipoprotein (LDL) cholesterol levels has proved to be highly effective in reducing rates of major cardiovascular events in numerous large outcome trials. 1 – 3 For this reason, LDL cholesterol reduction has been incorporated into practice guidelines as a fundamental means of reducing cardiovascular morbidity and mortality. 4 – 7 During the past 3 years, monoclonal antibodies that inhibit proprotein convertase subtilisin–kexin type 9 (PCSK9) have emerged as a new class of drugs that very effectively lower LDL cholesterol levels. 8 One of the members of this class is evolocumab, a fully human monoclonal antibody that typically achieves approximately a 60% reduction . . .

In a trial involving 304 veterans with stable PTSD, prazosin did not alleviate distressing dreams and did not improve sleep quality or overall clinical symptoms over 10 or 26 weeks. This result is in contrast to findings in several previous smaller or briefer trials.

JNJ-42165279 is a selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of fatty acid amides (FAA) including anandamide (AEA), palmitoylethanolamide (PEA), and N-oleoylethanolamide (OEA). We assessed the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of treatment with JNJ-42165279 in subjects with social anxiety disorder (SAD). This was a multicenter, double-blind, placebo-controlled study randomizing subjects to 12 weeks of treatment with either JNJ-42165279 (25 mg daily) or placebo (PBO). The primary endpoint was the change in the Liebowitz Social Anxiety Scale (LSAS) total score from baseline to end of study. Secondary endpoints included the Hamilton Anxiety Scale (HAM-A), Hamilton Depression Rating Scale (HDRS17), and the Clinical Global Impression-Improvement (CGI-I). Samples were collected for plasma concentration of AEA, PEA, OEA, and JNJ-42165279. A total of 149 subjects were enrolled with a mean baseline LSAS total score of 102.6 (SD 16.84). The mean change from baseline (SD) in LSAS total score at week 12 was numerically greater for JNJ-42165279: −29.4 (27.47) compared to PBO: −22.4 (23.57) but not significant. The percentage of subjects with ≥30% improvement from baseline in the LSAS total score was significantly higher for JNJ-42165279 (42.4%) compared to PBO (23.6%) (p value = 0.04). The percentage of subjects with a CGI-I score of much or very much improved was also significantly higher for JNJ-42165279 (44.1%) than for PBO (23.6%) (p value = 0.02). The drug was well tolerated. JNJ-42165279 appears to elicit an anxiolytic effect in subjects with SAD although trough concentrations with 25 mg once daily appeared to be insufficient to completely inhibit FAAH activity which may have led to suboptimal efficacy. ClinicalTrials.gov Identifier: NCT02432703.

The orientation of ice crystals affects their microphysical behaviour, growth, and precipitation. Orientation also affects interaction with electromagnetic radiation, and through this it influences remote sensing signals, in situ observations, and optical effects. Fall behaviours of a variety of 3D-printed plate-like ice crystal analogues in a tank of water–glycerine mixture are observed with multi-view cameras and digitally reconstructed to simulate the falling of ice crystals in the atmosphere. Four main falling regimes were observed: stable, zigzag, transitional, and spiralling. Stable motion is characterised by no resolvable fluctuations in velocity or orientation, with the maximum dimension oriented horizontally. The zigzagging regime is characterised by a back-and-forth swing in a constant vertical plane, corresponding to a time series of inclination angle approximated by a rectified sine wave. In the spiralling regime, analogues consistently incline at an angle between 7 and 28°, depending on particle shape. Transitional behaviour exhibits motion in between spiral and zigzag, similar to that of a falling spherical pendulum. The inclination angles that unstable planar ice crystals make with the horizontal plane are found to have a non-zero mode. This observed behaviour does not fit the commonly used Gaussian model of inclination angle. The typical Reynolds number when oscillations start is strongly dependent on shape: solid hexagonal plates begin to oscillate at Re =237, whereas several dendritic shapes remain stable throughout all experiments, even at Re > 1000. These results should be considered within remote sensing applications wherein the orientation characteristics of ice crystals are used to retrieve their properties.

Targeting oncogenic pathways holds promise for brain tumor treatment, but inhibition of Sonic Hedgehog (SHH) signaling has failed in SHH-driven medulloblastoma. Cellular diversity within tumors and reduced lineage commitment can undermine targeted therapy by increasing the probability of treatment-resistant populations. Using single-cell RNA-seq and lineage tracing, we analyzed cellular diversity in medulloblastomas in transgenic, medulloblastoma-prone mice, and responses to the SHH-pathway inhibitor vismodegib. In untreated tumors, we find expected stromal cells and tumor-derived cells showing either a spectrum of neural progenitor-differentiation states or glial and stem cell markers. Vismodegib reduces the proliferative population and increases differentiation. However, specific cell types in vismodegib-treated tumors remain proliferative, showing either persistent SHH-pathway activation or stem cell characteristics. Our data show that even in tumors with a single pathway-activating mutation, diverse mechanisms drive tumor growth. This diversity confers early resistance to targeted inhibitor therapy, demonstrating the need to target multiple pathways simultaneously. Although the hedgehog (HH) pathway is known to be deregulated in medulloblastoma, inhibitors of the pathway have shown disappointing clinical benefit. Using single-cell sequencing in a mouse model of the disease, the authors show that the response to the HH pathway inhibitor vismodegib is cell-type specific.

Targeting critical epigenetic regulators reverses aberrant transcription in cancer, thereby restoring normal tissue function 1 – 3 . The interaction of menin with lysine methyltransferase 2A (KMT2A), an epigenetic regulator, is a dependence in acute leukaemia caused by either rearrangement of KMT2A or mutation of the nucleophosmin 1 gene ( NPM1 ) 4 – 6 . KMT2A rearrangements occur in up to 10% of acute leukaemias and have an adverse prognosis, whereas NPM1 mutations occur in up to 30%, forming the most common genetic alteration in acute myeloid leukaemia 7 , 8 . Here, we describe the results of the first-in-human phase 1 clinical trial investigating revumenib (SNDX-5613), a potent and selective oral inhibitor of the menin–KMT2A interaction, in patients with relapsed or refractory acute leukaemia (ClinicalTrials.gov, NCT04065399). We show that therapy with revumenib was associated with a low frequency of grade 3 or higher treatment-related adverse events and a 30% rate of complete remission or complete remission with partial haematologic recovery (CR/CRh) in the efficacy analysis population. Asymptomatic prolongation of the QT interval on electrocardiography was identified as the only dose-limiting toxicity. Remissions occurred in leukaemias refractory to multiple previous lines of therapy. We demonstrate clearance of residual disease using sensitive clinical assays and identify hallmarks of differentiation into normal haematopoietic cells, including differentiation syndrome. These data establish menin inhibition as a therapeutic strategy for susceptible acute leukaemia subtypes. Revumenib, a potent and selective oral inhibitor of the menin–KMT2A interaction, is associated with a low frequency of treatment-related adverse events and promising clinical activity in patients with relapsed or refractory acute leukaemia.