Would you be surprised if this patient died?: Preliminary exploration of first and second year residents' approach to care decisions in critically ill patients

BACKGROUND: How physicians approach decision-making when caring for critically ill patients is poorly understood. This study aims to explore how residents think about prognosis and approach care decisions when caring for seriously ill, hospitalized patients. METHODS: Qualitative study where we conducted structured discussions with first and second year internal medicine residents (n = 8) caring for critically ill patients during Medical Intensive Care Unit Ethics and Discharge Planning Rounds. Residents were asked to respond to questions beginning with "Would you be surprised if this patient died?" RESULTS: An equal number of residents responded that they would (n = 4) or would not (n = 4) be surprised if their patient died. Reasons for being surprised included the rapid onset of an acute illness, reversible disease, improving clinical course and the patient's prior survival under similar circumstances. Residents reported no surprise with worsening clinical course. Based on the realization that their patient might die, residents cited potential changes in management that included clarifying treatment goals, improving communication with families, spending more time with patients and ordering fewer laboratory tests. Perceived or implied barriers to changes in management included limited time, competing clinical priorities, "not knowing" a patient, limited knowledge and experience, presence of diagnostic or prognostic uncertainty and unclear treatment goals. CONCLUSIONS: These junior-level residents appear to rely on clinical course, among other factors, when assessing prognosis and the possibility for death in severely ill patients. Further investigation is needed to understand how these factors impact decision-making and whether perceived barriers to changes in patient management influence approaches to care

Pac13 is a small, monomeric dehydratase that mediates the formation of the 3′-deoxy nucleoside of pacidamycins

This work was supported by the EPSRC council (Grant number 1398501), Wellcome Trust (Investigator Award) and GlaxoSmithKline.The uridyl peptide antibiotics (UPAs), of which pacidamycin is a member, have a clinically unexploited mode of action and an unusual assembly. Perhaps the most striking feature of these molecules is the biosynthetically unique 3′-deoxyuridine that they share. This moiety is generated by an unusual, small and monomeric dehydratase, Pac13, which catalyses the dehydration of uridine-5’-aldehyde. Here we report the structural characterisation of Pac13 with a series of ligands, and gain insight into the enzyme’s mechanism demonstrating that H42 is critical to the enzyme’s activity and that the reaction is likely to proceed via an E1cB mechanism. The resemblance of the 3′-deoxy pacidamycin moiety with the synthetic anti-retrovirals, presents a potential opportunity for the utilisation of Pac13 in the biocatalytic generation of antiviral compounds.Publisher PDFPeer reviewe

Genetic variation and gene expression across multiple tissues and developmental stages in a non-human primate

By analyzing multitissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalog of expression quantitative trait loci (eQTLs) in a nonhuman primate model. This catalog contains more genome-wide significant eQTLs per sample than comparable human resources and identifies sex- and age-related expression patterns. Findings include a master regulatory locus that likely has a role in immune function and a locus regulating hippocampal long noncoding RNAs (lncRNAs), whose expression correlates with hippocampal volume. This resource will facilitate genetic investigation of quantitative traits, including brain and behavioral phenotypes relevant to neuropsychiatric disorders

Timing of therapy for latent tuberculosis infection among immigrants presenting to a U.S. public health clinic: a retrospective study

<p>Abstract</p> <p>Background</p> <p>In the U.S. more than half of incident tuberculosis (TB) cases occur in immigrants. Current guidelines recommend screening and treatment for latent TB infection (LTBI) within 5 years of arrival to the U.S. This study evaluates the timing of LTBI therapy among immigrants presenting for care to a public health TB clinic.</p> <p>Methods</p> <p>Retrospective chart review of patients prescribed LTBI treatment based on medical records from Prince Georges County Health Department.</p> <p>Results</p> <p>1882 immigrants received LTBI therapy at Prince Georges County Health Department between 1999 and 2004. 417 of these patients were diagnosed with LTBI through contact investigations and were excluded from the analysis. Among the remaining 1465 individuals, median time from arrival to the U.S. until initiation of LTBI therapy was 5 months (range 0–42.4 years). 16% of all immigrants initiated therapy more than 5 years after arrival to the U.S. A logistic regression model using risks identified on univariate analysis revealed that referral for therapy by non-immigration proceedings was the strongest predictor of initiation of therapy more than 5 years after arrival to the U.S. Other factors associated with > 5 year U.S. residence prior to initiation of LTBI therapy included female gender (adjusted odds ratio (AOR) 1.8, 95% CI 1.2–2.6), age ≥ 35 (AOR = 4.1, 95% 2.5–6.6), and originating from Latin American and the Caribbean (AOR = 1.9, 95% CI 1.3–3.0).</p> <p>Conclusion</p> <p>Foreign-born individuals who are not referred for LTBI therapy through immigration proceedings are less likely to receive LTBI therapy within 5 years of arrival to the U.S. These data highlight the need to explore other mechanisms for timely LTBI screening beyond services provided by immigration.</p

The All-Data-Based Evolutionary Hypothesis of Ciliated Protists with a Revised Classification of the Phylum Ciliophora (Eukaryota, Alveolata)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ The file attached is the published version of the article

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

Cosmic Flows on 100 Mpc/h Scales: Standardized Minimum Variance Bulk Flow, Shear and Octupole Moments

The low order moments, such as the bulk flow and shear, of the large scale peculiar velocity field are sensitive probes of the matter density fluctuations on very large scales. In practice, however, peculiar velocity surveys are usually sparse and noisy, which can lead to the aliasing of small scale power into what is meant to be a probe of the largest scales. Previously, we developed an optimal ``minimum variance'' (MV) weighting scheme, designed to overcome this problem by minimizing the difference between the measured bulk flow (BF) and that which would be measured by an ideal survey. Here we extend this MV analysis to include the shear and octupole moments, which are designed to have almost no correlations between them so that they are virtually orthogonal. We apply this MV analysis to a compilation of all major peculiar velocity surveys, consisting of 4536 measurements. Our estimate of the BF on scales of ~ 100 Mpc/h has a magnitude of |v|= 416 +/- 78 km/s towards Galactic l = 282 degree +/- 11 degree and b = 6 degree +/- 6 degree. This result is in disagreement with LCDM with WMAP5 cosmological parameters at a high confidence level, but is in good agreement with our previous MV result without an orthogonality constraint, showing that the shear and octupole moments did not contaminate the previous BF measurement. The shear and octupole moments are consistent with WMAP5 power spectrum, although the measurement noise is larger for these moments than for the BF. The relatively low shear moments suggest that the sources responsible for the BF are at large distances.Comment: 13 Pages, 7 figures, 4 tables. Some changes to reflect the published versio

Case-mix & patients' reports of outcome in Independent Sector Treatment Centres: Comparison with NHS providers

BACKGROUND: There has been considerable concern expressed about the outcomes achieved in Independent Sector Treatment Centres (ISTCs) introduced in England since 2003. Our aim was to compare the case-mix and patients' reported outcomes of surgery in ISTCs and in NHS providers. METHODS: Prospective cohort study of 769 patients treated in six ISTCs and 1895 treated in 20 NHS providers (acute hospitals and treatment centres) in England during 2006-07. Participants underwent one of three day surgery procedures (inguinal hernia repair, varicose vein surgery, cataract extraction) or hip or knee replacement. Change in patient-reported health status and health related quality of life (measured using a disease-specific and a generic (EQ-5D) instrument) was assessed either 3-months (day surgery) or 6-months (hip/knee) after surgery. In addition patient-reported post-operative complications and an overall assessment of success of surgery were collected. Outcome measures were adjusted (using multivariable regression) for patient characteristics (disease severity, duration of symptoms, age, sex, socioeconomic status, general health, previous similar surgery, comorbidity). RESULTS: Post-operative response rates varied by procedure (73%-88%) and were similar for those treated in ISTCs and NHS facilities. Patients treated in ISTCs were healthier, were less likely to have any comorbidity and, for those undergoing cataract surgery or joint replacement, their primary condition was less severe. Those undergoing hernia repair or joint replacement were less likely to have had similar surgery before. When adjustment was made for pre-operative characteristics, patients undergoing cataract surgery or hip replacement in ISTCs achieved a slightly greater improvement in functional status and quality of life than those treated in NHS facilities, while the opposite was true of patients undergoing hernia repair. No significant differences were found for the two other procedures. Patients treated in ISTCs were less likely to report post-operative problems than those treated in NHS facilities for cataract surgery (Adjusted Odds Ratio 0.35; 95% CI 0.17-0.70), hernia repair (0.42; 0.28-0.63) and knee replacement (0.44; 0.28-0.69). Most patients described the result of their operation as excellent, very good or good, regardless of where they were treated. CONCLUSION: The case-mix of patients treated in ISTCs differs from that in NHS providers, in line with the intention of the contracts. Caution is needed in interpreting the observation that patients treated in ISTCs reported slightly better outcomes as very few ISTCs participated, case-mix adjustment might have been insufficient, and patients' reports might have been biased as they were more likely to be satisfied with the way they were treated

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV

The results from the STAR Collaboration on directed flow (v_1), elliptic flow (v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a Blast Wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v_2, scaling with the number of constituent quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures modified, but data the same. However, in Fig. 35 the hydro calculations are corrected in this version. The data tables are available at http://www.star.bnl.gov/central/publications/ by searching for "flow" and then this pape