North Pacific Surgical Association A predictive model of early mortality in trauma patients

Abstract BACKGROUND: Rapid thrombelastography (rTEG) is a real-time whole-blood viscoelastic coagulation assay. We hypothesized that admission rTEG and clinical data are independent predictors of trauma-related mortality. METHODS: Prospective observational data (patient demographics, admission vital signs, laboratory studies, and injury characteristics) from trauma patients enrolled within 6 hours of injury were collected. Mann-Whitney U test and analysis of variance test assessed significance (P % .05). Logistic regression analyses determined the association of the studied variables with 24-hour mortality. RESULTS: Seven hundred ninety-five trauma patients were enrolled, of which 55 died within 24 hours of admission. Admission variables which independently predicted 24-hour mortality were as follows: Glasgow Coma Scale %8, hemoglobin ,11 g/dL, international normalized ratio .1.5, Ly30 .8%, and penetrating injury (P , .05). This 5-variable model's area under the receiver operator characteristic curve was .88. The Hosmer-Lemeshow goodness-of-fit test was .90. CONCLUSIONS: This 5-variable model provides a rapid prediction of 24-hour mortality. The inclusion of rTEG Ly30 demonstrates the association of fibrinolysis with outcome and may support the early use of antifibrinolytic therapies

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Re-engineering the Resident Applicant Selection Process in Ophthalmology: A Literature Review and Recommendations for Improvement

The current resident selection process for ophthalmology has undergone little change over the last several years and remains highly dependent on the traditional selection factors (i.e., grades, honors, letters of recommendation, and an interview). Unfortunately, these selection factors have not been shown to be consistently predictive of future resident performance. In addition, the Accreditation Council for Graduate Medical Education (ACGME) has mandated implementation of six new competencies in resident training in the USA and the current selection process does not directly recruit for these competencies. We propose an implementation strategy to re-engineer and improve the resident selection process in ophthalmology and potentially develop assessments that would be predictive of actual downstream resident performance that would encompass the ACGME related competencies. An intra-departmental Task Force for the ACGME Competencies reviewed a PubMed literature search regarding resident selection. A content expert (AGL) gleaned selected “good practices” from the literature review and summarized the results. Specific recommendations were reviewed for topicality to ophthalmology and where possible for feasibility, reliability, and validity. We summarize several good practices identified from the literature review and propose an implementation matrix for aligning the resident application process with the ACGME competencies that might include: using a standardized and consolidated academic score for the cognitive domains; converting the letter of recommendation format into a letter of evaluation; standardizing the letters of evaluation, including the “Dean's letter”; using behavior specific interview techniques with standardized questions; and developing a specialty based consensus for the selection of traits specific to ophthalmology that might predict success. The resident selection process for ophthalmology might be improved by implementation of specific good practices from the literature. Ophthalmology should strive to develop applicant selection tools that might be useful for predicting residency performance and that would align with the ACGME competency mandate for tools to predict future performance as a physician

Endoplasmic Reticulum Dynamics, Inheritance, and Cytoskeletal Interactions in Budding Yeast

The endoplasmic reticulum (ER) in Saccharomyces cerevisiae consists of a reticulum underlying the plasma membrane (cortical ER) and ER associated with the nuclear envelope (nuclear ER). We used a Sec63p-green fluorescent protein fusion protein to study motility events associated with inheritance of cortical ER and nuclear ER in living yeast cells. During M phase before nuclear migration, we observed thick, apparently rigid tubular extensions emanating from the nuclear ER that elongate, undergo sweeping motions along the cell cortex, and shorten. Two findings support a role for microtubules in this process. First, extension of tubular structures from the nuclear ER is inhibited by destabilization of microtubules. Second, astral microtubules, structures that undergo similar patterns of extension, cortical surveillance and retraction, colocalize with nuclear ER extensions. During S and G(2) phases of the cell cycle, we observed anchorage of the cortical ER at the site of bud emergence and apical bud growth. Thin tubules of the ER that extend from the anchored cortical ER display undulating, apparently random movement and move into the bud as it grows. Finally, we found that cortical ER morphology is sensitive to a filamentous actin–destabilizing drug, latrunculin-A, and to mutations in the actin-encoding ACT1 gene. Our observations support 1) different mechanisms and cytoskeletal mediators for the inheritance of nuclear and cortical ER elements and 2) a mechanism for cortical ER inheritance that is cytoskeleton dependent but relies on anchorage, not directed movement

Measurement of charged-particle multiplicities in gluon and quark jets in p(p)over-bar collisions at root s=1.8 TeV

We report the first largely model independent measurement of charged particle multiplicities in quark and gluon jets, N-q and N-g, produced at the Fermilab Tevatron in p (p) over bar collisions with a center-of-mass energy of 1.8 TeV and recorded by the Collider Detector at Fermilab. The measurements are made for jets with average energies of 41 and 53 GeV by counting charged particle tracks in cones with opening angles of θ(c)=0.28, 0.36, and 0.47 rad around the jet axis. The corresponding jet hardness Q=E-jetθ(c) varies in the range from 12 to 25 GeV. At Q=19.2 GeV, the ratio of multiplicities r=N-g/N-q is found to be 1.64± 0.17, where statistical and systematic uncertainties are added in quadrature. The results are in agreement with resummed perturbative QCD calculations