Time constraints, technology, and administrative demands of modern medicine often impede the human connection that is central to clinical care, contributing to physician and patient dissatisfaction.
...To identify evidence and narrative-based practices that promote clinician presence, a state of awareness, focus, and attention with the intent to understand patients.
Preliminary practices were derived through a systematic literature review (from January 1997 to August 2017, with a subsequent bridge search to September 2019) of effective interpersonal interventions; observations of primary care encounters in 3 diverse clinics (n = 27 encounters); and qualitative interviews with physicians (n = 10), patients (n = 27), and nonmedical professionals whose occupations involve intense interpersonal interactions (eg, firefighter, chaplain, social worker; n = 30). After evidence synthesis, promising practices were reviewed in a 3-round modified Delphi process by a panel of 14 researchers, clinicians, patients, caregivers, and health system leaders. Panelists rated each practice using 9-point Likert scales (-4 to +4) that reflected the potential effect on patient and clinician experience and feasibility of implementation; after the third round, panelists selected their "top 5" practices from among those with median ratings of at least +2 for all 3 criteria. Final recommendations incorporate elements from all highly rated practices and emphasize the practices with the greatest number of panelist votes.
The systematic literature review (n = 73 studies) and qualitative research activities yielded 31 preliminary practices. Following evidence synthesis, 13 distinct practices were reviewed by the Delphi panel, 8 of which met criteria for inclusion and were combined into a final set of 5 recommendations: (1) prepare with intention (take a moment to prepare and focus before greeting a patient); (2) listen intently and completely (sit down, lean forward, avoid interruptions); (3) agree on what matters most (find out what the patient cares about and incorporate these priorities into the visit agenda); (4) connect with the patient's story (consider life circumstances that influence the patient's health; acknowledge positive efforts; celebrate successes); and (5) explore emotional cues (notice, name, and validate the patient's emotions).
This mixed-methods study identified 5 practices that have the potential to enhance physician presence and meaningful connection with patients in the clinical encounter. Evaluation and validation of the outcomes associated with implementing the 5 practices is needed, along with system-level interventions to create a supportive environment for implementation.
The study examined the Pygmalion process for creativity among 140 R&D employees. Results generally supported the Pygmalion model. Supervisors holding higher expectations for employee creativity were ...perceived by employees as behaving more supportively of creativity. The effects of these behaviors on employee creative self-efficacy were mediated by employee view of creativity expectations. Creative self-efficacy mediated the effects of supervisor expectations, supervisor behaviors, and employee view, on creative performance. Implications for theory and practice are discussed.
Rett syndrome (RTT) is a complex neurodevelopmental disorder with known behavioral abnormalities, both internalizing (e.g., anxiety, social withdrawal) and externalizing (e.g., aggression, ...self-abuse). However, a broad evaluation of behavioral abnormalities in a large cohort is lacking.
In this report, we describe profiles of internalizing and externalizing behaviors in individuals evaluated in the multi-center U.S. Rett Natural History Study.
Cross-sectional and longitudinal data were collected from 861 females with RTT and from 48 females who have MECP2 mutations without meeting criteria for RTT. Standard statistical methods including linear regression evaluated internalizing behavioral components from the Child Health Questionnaire (CHQ-PF50) and externalizing components from the Motor Behavioral Assessment (MBA).
We found mildly to moderately severe internalizing behaviors in nearly all individuals with RTT, while externalizing behaviors were mild and uncommon. Internalizing behavior in RTT was comparable to groups with psychiatric disorders. Participants with mixed (internalizing and externalizing) behaviors were younger and less affected overall, but showed prominent self-injury and worsening internalizing behaviors over time.
This study revealed that internalizing behaviors are common at a clinically significant level in RTT. Understanding clinical features associated with behavioral profiles could guide treatment strategies.
The efficacy of β-lactam antibiotics is threatened by the emergence and global spread of metallo-β-lactamase (MBL) mediated resistance, specifically New Delhi metallo-β-lactamase-1 (NDM-1). By ...utilization of fragment-based drug discovery (FBDD), a new class of inhibitors for NDM-1 and two related β-lactamases, IMP-1 and VIM-2, was identified. On the basis of 2,6-dipicolinic acid (DPA), several libraries were synthesized for structure–activity relationship (SAR) analysis. Inhibitor 36 (IC50 = 80 nM) was identified to be highly selective for MBLs when compared to other Zn(II) metalloenzymes. While DPA displayed a propensity to chelate metal ions from NDM-1, 36 formed a stable NDM-1:Zn(II):inhibitor ternary complex, as demonstrated by 1H NMR, electron paramagnetic resonance (EPR) spectroscopy, equilibrium dialysis, intrinsic tryptophan fluorescence emission, and UV–vis spectroscopy. When coadministered with 36 (at concentrations nontoxic to mammalian cells), the minimum inhibitory concentrations (MICs) of imipenem against clinical isolates of Eschericia coli and Klebsiella pneumoniae harboring NDM-1 were reduced to susceptible levels.
Most subterranean animals are assumed to have evolved from surface ancestors following colonization of a cave system; however, very few studies have raised the possibility of “subterranean ...speciation” in underground habitats (i.e., obligate cave-dwelling organisms troglobionts descended from troglobiotic ancestors). Numerous endemic subterranean diving beetle species from spatially discrete calcrete aquifers in Western Australia (stygobionts) have evolved independently from surface ancestors; however, several cases of sympatric sister species raise the possibility of subterranean speciation. We tested this hypothesis using vision (phototransduction) genes that are evolving under neutral processes in subterranean species and purifying selection in surface species. Using sequence data from 32 subterranean and five surface species in the genus Paroster (Dytiscidae), we identified deleterious mutations in long wavelength opsin (lwop), arrestin 1 (arr1), and arrestin 2 (arr2) shared by a sympatric sister-species triplet, arr1 shared by a sympatric sister-species pair, and lwop and arr2 shared among closely related species in adjacent calcrete aquifers. In all cases, a common ancestor possessed the function-altering mutations, implying they were already adapted to aphotic environments. Our study represents one of the first confirmed cases of subterranean speciation in cave insects. The assessment of genes undergoing pseudogenization provides a novel way of testing modes of speciation and the history of diversification in blind cave animals.
Abstract
Subterranean habitats are generally very stable environments, and as such evolutionary transitions of organisms from surface to subterranean lifestyles may cause considerable shifts in ...physiology, particularly with respect to thermal tolerance. In this study we compared responses to heat shock at the molecular level in a geographically widespread, surface-dwelling water beetle to a congeneric subterranean species restricted to a single aquifer (Dytiscidae: Hydroporinae). The obligate subterranean beetle
Paroster macrosturtensis
is known to have a lower thermal tolerance compared to surface lineages (CT
max
38 °C cf. 42–46 °C), but the genetic basis of this physiological difference has not been characterized. We experimentally manipulated the thermal environment of 24 individuals to demonstrate that both species can mount a heat shock response at high temperatures (35 °C), as determined by comparative transcriptomics. However, genes involved in these responses differ between species and a far greater number were differentially expressed in the surface taxon, suggesting it can mount a more robust heat shock response; these data may underpin its higher thermal tolerance compared to subterranean relatives. In contrast, the subterranean species examined not only differentially expressed fewer genes in response to increasing temperatures, but also in the presence of the experimental setup employed here alone. Our results suggest
P. macrosturtensis
may be comparatively poorly equipped to respond to both thermally induced stress and environmental disturbances more broadly. The molecular findings presented here have conservation implications for
P. macrosturtensis
and contribute to a growing narrative concerning weakened thermal tolerances in obligate subterranean organisms at the molecular level.
Summary Background The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes ...years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. Methods We analysed individual patients' data from 15 071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. Findings In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ2 =0·83, 95% CI 0·83–0·83 in trials without radiotherapy, and 0·87, 0·87–0·87 in trials with radiotherapy) and excellent at trial level ( R2 =0·92, 95% CI 0·88–0·95 in trials without radiotherapy and 0·99, 0·98–1·00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ2 range 0·77–0·85, dependent on the regimen being assessed) and trial level ( R2 range 0·89–0·97). In studies with data on locoregional control, individual-level correlations were good (ρ2 =0·71, 95% CI 0·71–0·71 for concurrent chemotherapy and ρ2 =0·61, 0·61–0·61 for modified vs standard radiotherapy) and trial-level correlations very good ( R2 =0·85, 95% CI 0·77–0·92 for concurrent chemotherapy and R2 =0·95, 0·91–0·98 for modified vs standard radiotherapy). Interpretation We found a high level of evidence that DFS is a valid surrogate endpoint for overall survival in studies of adjuvant chemotherapy involving patients with non-small-cell lung cancers, and PFS in those of chemotherapy and radiotherapy for patients with locally advanced lung cancers. Extrapolation to targeted agents, however, is not automatically warranted. Funding Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le Cancer, British Medical Research Council, Sanofi-Aventis.
The Mg/Ca ratio of planktic foraminifera is a widely used proxy for sea‐surface temperature but is also sensitive to other environmental factors. Previous work has relied on correcting Mg/Ca for ...nonthermal influences. Here, we develop a set of Bayesian models for Mg/Ca in four major planktic groups—Globigerinoides ruber (including both pink and white chromotypes), Trilobatus sacculifer, Globigerina bulloides, and Neogloboquadrina pachyderma (including N. incompta)—that account for the multivariate influences on this proxy in an integrated framework. We use a hierarchical model design that leverages information from both laboratory culture studies and globally distributed core top data, allowing us to include environmental sensitivities that are poorly constrained by core top observations alone. For applications over longer geological timescales, we develop a version of the model that incorporates changes in the Mg/Ca ratio of seawater. We test our models—collectively referred to as BAYMAG—on sediment trap data and on representative paleoclimate time series and demonstrate good agreement with observations and independent sea‐surface temperature proxies. BAYMAG provides probabilistic estimates of past temperatures that can accommodate uncertainties in other environmental influences, enhancing our ability to interpret signals encoded in Mg/Ca.
Plain Language Summary
The amount of magnesium (Mg) incorporated into the calcite shells of tiny protists called foraminifera is determined by the temperature of the water in which they grew. This allows paleoclimatologists to measure the magnesium‐to‐calcium (Mg/Ca) ratio of fossil foraminiferal shells and determine how past sea‐surface temperatures have changed. However, other factors can influence Mg/Ca, like the salinity and pH of seawater. Here, we develop Bayesian models of foraminiferal Mg/Ca that account for all of the influences on Mg/Ca and show how we can use these to improve our interpretations of Mg/Ca data.
Key Points
We introduce Mg/Ca Bayesian calibrations for planktic foraminifera
Hierarchical modeling is used to constrain multivariate Mg/Ca sensitivities
For deep‐time applications, we incorporate estimates of Mg/Ca of seawater
Abstract Recent evidence from neuropsychological patients with focalized lesions and functional brain imaging studies indicate that processing of self is distinguishable from processing of ...information about others (e.g., recognizing a familiar face). Here, we conduct an effect-location meta-analysis (Fox et al., 1998) of 9 functional neuroimaging studies of self-face recognition. The evidence provides support for a right-dominated, but largely bilaterally distributed model for self-face processing. Four areas are consistently activated: the left fusiform gyrus, bilateral middle and inferior frontal gyri, and right precuneus. The evidence is interpreted in light of a developing model of self-face recognition as part of a larger social cognitive stream of processing.
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•Independently evolved subterranean beetles in Australia have lost eyes.•Independent parallel loss of eight phototransduction genes in 32 species.•A relaxation of selection on these ...genes can explain vision loss in these beetles.
In the framework of neutral theory of molecular evolution, genes specific to the development and function of eyes in subterranean animals living in permanent darkness are expected to evolve by relaxed selection, ultimately becoming pseudogenes. However, definitive empirical evidence for the role of neutral processes in the loss of vision over evolutionary time remains controversial. In previous studies, we characterized an assemblage of independently-evolved water beetle (Dytiscidae) species from a subterranean archipelago in Western Australia, where parallel vision and eye loss have occurred. Using a combination of transcriptomics and exon capture, we present evidence of parallel coding sequence decay, resulting from the accumulation of frameshift mutations and premature stop codons, in eight phototransduction genes (arrestins, opsins, ninaC and transient receptor potential channel genes) in 32 subterranean species in contrast to surface species, where these genes have open reading frames. Our results provide strong evidence to support neutral evolutionary processes as a major contributing factor to the loss of phototransduction genes in subterranean animals, with the ultimate fate being the irreversible loss of a light detection system.
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