Total knee replacement (TKR) is a cost-effective treatment option for severe osteoarthritis (OA). While prevalence of OA is higher among blacks than whites, TKR rates are lower among blacks. ...Physicians' implicit preferences might explain racial differences in TKR recommendation. The objective of this study was to evaluate whether the magnitude of implicit racial bias predicts physician recommendation of TKR for black and white patients with OA and to assess the effectiveness of a web-based instrument as an intervention to decrease the effect of implicit racial bias on physician recommendation of TKR.
In this web-based study, 543 family and internal medicine physicians were given a scenario describing either a black or white patient with severe OA refractory to medical treatment. Questionnaires evaluating the likelihood of recommending TKR, perceived medical cooperativeness, and measures of implicit racial bias were administered. The main outcome measures included TKR recommendation, implicit racial preference, and medical cooperativeness stereotypes measured with implicit association tests.
Subjects displayed a strong implicit preference for whites over blacks (P < .0001) and associated "medically cooperative" with whites over blacks (P < .0001). Physicians reported significantly greater liking for whites over blacks (P < .0001) and reported believing whites were more medically cooperative than blacks (P < .0001). Participants reported providing similar care for white and black patients (P = .10) but agreed that subconscious biases could influence their treatment decisions (P < .0001). There was no significant difference in the rate of recommendation for TKR when the patient was black (47%) versus white (38%) (P = .439), and neither implicit nor explicit racial biases predicted differential treatment recommendations by race (all P > .06). Although participants were more likely to recommend TKR when completing the implicit association test before the decision, patient race was not significant in the association (P = .960).
Physicians possessed explicit and implicit racial biases, but those biases did not predict treatment recommendations. Clinicians' biases about the medical cooperativeness of blacks versus whites, however, may have influenced treatment decisions.
Sodium phenylbutyrate (PB) is an aromatic fatty acid with cytostatic and differentiating activity against malignant myeloid
cells (ID 50 , 1–2 m m ). Higher doses induce apoptosis. Patients with ...myelodysplasia ( n = 11) and acute myeloid leukemia ( n = 16) were treated with PB as a 7-day continuous infusion repeated every 28 days in a Phase I dose escalation study. The
maximum tolerated dose was 375 mg/kg/day; higher doses led to dose-limiting reversible neurocortical toxicity. At the maximum
tolerated dose, PB was extremely well tolerated, with no significant toxicities; median steady-state plasma concentration
at this dose was 0.29 ± 0.16 m m . Although no patients achieved complete or partial remission, four patients achieved hematological improvement (neutrophils
in three, platelet transfusion-independence in one). Other patients developed transient increases in neutrophils or platelets
and decrements in circulating blasts. Monitoring of the percentage of clonal cells using centromere fluorescence in situ hybridization over the course of PB administration showed that hematopoiesis remained clonal. Hematological response was
often associated with increases in both colony-forming units-granulocyte-macrophage and leukemic colony-forming units. PB
administration was also associated with increases in fetal erythrocytes. These data document the safety of continuous infusion
PB and provide preliminary evidence of clinical activity in patients with myeloid malignancies.
For nearly a century developmental biologists have recognized that cells from embryos can differ in their potential to differentiate into distinct cell types. Recently, it has been recognized that ...embryonic stem cells derived from both mice and humans exhibit two stable yet epigenetically distinct states of pluripotency: naive and primed. We now show that nicotinamide N-methyltransferase (NNMT) and the metabolic state regulate pluripotency in human embryonic stem cells (hESCs). Specifically, in naive hESCs, NNMT and its enzymatic product 1-methylnicotinamide are highly upregulated, and NNMT is required for low S-adenosyl methionine (SAM) levels and the H3K27me3 repressive state. NNMT consumes SAM in naive cells, making it unavailable for histone methylation that represses Wnt and activates the HIF pathway in primed hESCs. These data support the hypothesis that the metabolome regulates the epigenetic landscape of the earliest steps in human development.
The Sherpa ethnic group living at altitude in Nepal may have experienced natural selection in response to chronic hypoxia. We have previously shown that Sherpa in Kathmandu (1400 m) possess larger ...spleens and a greater apnea-induced splenic contraction compared to lowland Nepalis. This may be significant for exercise capacity at altitude as the human spleen responds to stress-induced catecholamine secretion by an immediate contraction, which results in transiently elevated hemoglobin concentration (Hb).
To investigate splenic contraction in response to exercise at high-altitude (4300 m; P
= ~450 Torr), we recruited 63 acclimatized Sherpa (29F) and 14 Nepali non-Sherpa (7F). Spleen volume was measured before and after maximal exercise on a cycle ergometer by ultrasonography, along with Hb and oxygen saturation (SpO
).
Resting spleen volume was larger in the Sherpa compared with Nepali non-Sherpa (237 ± 62 vs. 165 ± 34 mL, p < .001), as was the exercise-induced splenic contraction (Δspleen volume, 91 ± 40 vs. 38 ± 32 mL, p < .001). From rest to exercise, Hb increased (1.2 to 1.4 g.dl
), SpO
decreased (~9%) and calculated arterial oxygen content (CaO
) remained stable, but there were no significant differences between groups. In Sherpa, both resting spleen volume and the Δspleen volume were modest positive predictors of the change (Δ) in Hb and CaO
with exercise (p-values from .026 to .037 and R
values from 0.059 to 0.067 for the predictor variable).
Larger spleens and greater splenic contraction may be an adaptive characteristic of Nepali Sherpa to increase CaO
during exercise at altitude, but the direct link between spleen size/function and hypoxia tolerance remains unclear.
To evaluate the genetic findings, demographic features and clinical presentation of tumour necrosis factor receptor-associated autoinflammatory syndrome (TRAPS) in patients from the ...Eurofever/EUROTRAPS international registry.
A web-based registry collected retrospective data on patients with TNFRSF1A sequence variants and inflammatory symptoms. Participating hospitals included paediatric rheumatology centres and adult centres with a specific interest in autoinflammatory diseases. Cases were independently validated by experts in the disease.
Complete information on 158 validated patients was available. The most common TNFRSF1A variant was R92Q (34% of cases), followed by T50M (10%). Cysteine residues were disrupted in 27% of cases, accounting for 39% of sequence variants. A family history was present in 19% of patients with R92Q and 64% of those with other variants. The median age at which symptoms began was 4.3 years but 9.1% of patients presented after 30 years of age. Attacks were recurrent in 88% and the commonest features associated with the pathogenic variants were fever (88%), limb pain (85%), abdominal pain (74%), rash (63%) and eye manifestations (45%). Disease associated with R92Q presented slightly later at a median of 5.7 years with significantly less rash or eye signs and more headaches. Children were more likely than adults to present with lymphadenopathy, periorbital oedema and abdominal pains. AA amyloidosis has developed in 16 (10%) patients at a median age of 43 years.
In this, the largest reported case series to date, the genetic heterogeneity of TRAPS is accompanied by a variable phenotype at presentation. Patients had a median 70 symptomatic days a year, with fever, limb and abdominal pain and rash the commonest symptoms. Overall, there is little evidence of a significant effect of age or genotype on disease features at presentation.
Fusions involving tropomyosin receptor genes are noted in cancers affecting children and adults. The TRK inhibitor larotrectinib induced a response in 75% of patients, regardless of age, tissue of ...origin, or
TRK
fusion partner. Toxic effects were generally mild.
In a randomized trial involving patients with limb ischemia, the incidence of a major adverse limb event or death at 2.7 years was lower in the surgical group than in the endovascular group.
Measles was eliminated in the United States in 2000. However, an outbreak occurred in New York City from 2018 to 2019 that was associated with the importation of measles into an undervaccinated ...community, leading to 649 confirmed cases, with 49 patients being hospitalized and 20 receiving care in an intensive care unit.
Background
Bundle branch block (BBB) is a powerful independent predictor of cardiovascular mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The ...prognostic implications in HF with preserved systolic function (HF-PSF) are less well understood.
Methods
The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomised 7599 patients with symptomatic HF to receive candesartan or placebo. The primary outcome comprised cardiovascular death or HF hospitalisation. The relative risk conveyed by BBB relative to a normal electrocardiogram was examined.
Results
The prevalence of BBB was significantly lower in patients with preserved compared with reduced systolic function (CHARM-Preserved 14.4%, Alternative 29.6%, Added 30.5%), p<0.0001. Overall, the adjusted hazard ratio for the primary outcome was 1.48 (95% confidence interval 1.22-1.78), p<0.0001, reflecting increased risk in patients with reduced LVEF (1.72 1.28-2.31, p=0.0003). The apparently more modest risk among patients with HF-PSF was significant in unadjusted (1.80 1.37-2.37, p<0.0001) but not adjusted analysis (1.16 0.88-1.54, p=0.2897). However, no formal statistical difference was observed between the two cohorts, and interpretation is limited by the unknown prevalence of left and right BBB morphologies in each. Comparing BBB presence with absence yielded qualitatively similar results.
Conclusion
The simple clinical finding of BBB is a powerful independent predictor of worse clinical outcomes in patients with HF and reduced LVEF. It is less frequent, with a more modest predictive effect, in patients with preserved systolic function.
SNAPSHOT USA 2019 Cove, Michael V.; Bontrager, Helen; Bresnan, Claire ...
Ecology,
June 2021, Letnik:
102, Številka:
6
Journal Article
Recenzirano
Odprti dostop
With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To ...address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14‐week period (17 August–24 November of 2019). We sampled wildlife at 1,509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian’s eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the United States. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban–wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot‐usa, as will future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species‐specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.
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