A Neural Network Model for Mortality Prediction in ICU

Abstrac

Contemporary outcomes of vertebral artery injury

ObjectiveVertebral artery injury (VAI) associated with cervical trauma is being increasingly recognized with more aggressive screening. Disparate results from previous literature have led to uncertainty of the significance, natural history, and optimal therapy for VAI.MethodsTo understand the natural history and treatment outcomes from our experience, we performed a retrospective, single-center review from a level I trauma center for the previous 10 years of all VAI. Injuries were identified from search of an administrative trauma database, a resident-run working database, and all radiology dictations for the same period. All VAI were classified according to segmental involvement, Denver grading scale, and laterality. Analysis of associated injuries, demographics, neurologic outcome, mortality, length of stay, treatment plan, and follow-up imaging was also performed.ResultsFifty-one patients with VAI were identified from 2001 to 2011 from a total of 36,942 trauma admissions (0.13% incidence). Associated injuries were significant with an average New Injury Severity Score of 29.6. Penetrating trauma occurred in 14%. Cervical spine fracture was present in 88% with VAI. Diagnosis was obtained with computed tomographic angiography (CTA) in 95%. Screening was prompted by injury pattern or high-risk mechanism in all cases. Injuries classified according to the Denver grading scale were grade I = 24%, grade II = 35%, grade III = 4%, grade IV = 35%, and grade V = 2%. Distribution across segments included V1 = 18%, V2 = 67%, V3 = 31%, and V4 = 6%. Only one posterior circulation stroke was attributable to VAI. Overall mortality was 8%, with each mortality being associated with significant other organ injuries. Treatment rendered for VAI was antiplatelet therapy (50%), observation (31%), warfarin (17%), and stent (2%). There were no significant differences between treatment groups on any variable with the exception of body mass index (P = .047). Follow-up was obtained for 13% (n = 6) of survivors. The CTA demonstrated injury stability in four patients and resolution in two patients. Accuracy of the administrative trauma database was 53% compared with 96% for the resident-run working database.ConclusionsNeurologic sequelae attributable to VAI were rare. Grade of VAI or vertebral artery segment did not correlate with morbidity. We did not observe any differences in short-term outcomes between systemic anticoagulation and antiplatelet therapy. Of those patients seen at follow-up, injury resolution or stability was documented by CTA. A conservative approach with either observation or antithrombotic therapy is suggested. If the natural history of VAI includes a very low stroke rate, then therapies with a lower therapeutic index, such as systemic anticoagulation, in the severely injured trauma patient are not supported. Our search strategy urges awareness of the limitations of administrative databases for retrospective vascular study

Current Status of Nutrition Training in Graduate Medical Education From a Survey of Residency Program Directors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142009/1/jpen0095.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142009/2/jpen0095-sup-0001.pd

Metal ion-dependent, reversible, protein filament formation by designed beta-roll polypeptides

<p>Abstract</p> <p>Background</p> <p>A right-handed, calcium-dependent β-roll structure found in secreted proteases and repeat-in-toxin proteins was used as a template for the design of minimal, soluble, monomeric polypeptides that would fold in the presence of Ca²⁺. Two polypeptides were synthesised to contain two and four metal-binding sites, respectively, and exploit stacked tryptophan pairs to stabilise the fold and report on the conformational state of the polypeptide.</p> <p>Results</p> <p>Initial analysis of the two polypeptides in the presence of calcium suggested the polypeptides were disordered. The addition of lanthanum to these peptides caused aggregation. Upon further study by right angle light scattering and electron microscopy, the aggregates were identified as ordered protein filaments that required lanthanum to polymerize. These filaments could be disassembled by the addition of a chelating agent. A simple head-to-tail model is proposed for filament formation that explains the metal ion-dependency. The model is supported by the capping of one of the polypeptides with biotin, which disrupts filament formation and provides the ability to control the average length of the filaments.</p> <p>Conclusion</p> <p>Metal ion-dependent, reversible protein filament formation is demonstrated for two designed polypeptides. The polypeptides form filaments that are approximately 3 nm in diameter and several hundred nm in length. They are not amyloid-like in nature as demonstrated by their behaviour in the presence of congo red and thioflavin T. A capping strategy allows for the control of filament length and for potential applications including the "decoration" of a protein filament with various functional moieties.</p

Meter-Scale Chemical and Isotopic Heterogeneities in the Oceanic Mantle, Leka Ophiolite Complex, Norway

Mantle peridotites from three 3 x 3-meter grids sampled at kilometer distances from one another in the ca. 497 Ma Leka Ophiolite Complex (LOC), Norway, are examined to investigate the chemical and isotopic nature of oceanic mantle domains at the centimeter to kilometer scale. The lithology of each grid locality is predominantly harzburgite, but includes layers and lenses of dunite and pyroxenite. Major and lithophile trace element compositions indicate a history of prior melting at pressures at or slightly below the garnet stability field. The common presence of orthopyroxenite veins likely reflects infiltration of silicic melts associated with supra-subduction zone processes. Osmium isotopes and highly siderophile element (HSE) abundance data for centimeter-scale sampling of traverses from the pyroxenites into the harzburgites reveal that the formation of the veins had little effect on Os isotopic compositions, and Os, Ir, Ru and Re abundances in the harzburgites. Adjacent to one of the orthopyroxenite veins studied, however, Pt and Pd abundances appear to have been strongly modified by interactions with vein-forming melts or fluids at distances of as much as 4– 6 cm from the pyroxenite-harzburgite contact. Leka harzburgites have initial gammaOs values (% deviation from a chondritic reference) that range from -4.7 to +2.2 (6.9% variation), with individual uncertainties of 60.2 units. Averaged initial Os isotopic compositions for harzburgites from the three grid sites separated by as much as 6 km, by contrast, differ by only a maximum of 2.6%. Isotopic heterogeneity on the centimeter to meter scale is, therefore, larger than kilometer-scale heterogeneity, indicating that at least some of the Os isotopic heterogeneity commonly observed globally among mantle peridotites is the result of processes that acted on a local scale. The general uniformity of these isotopic compositions among the three grid sites suggests that the portion of the oceanic mantle sampled by the LOC was homogenous at the kilometer scale with respect to the long-term Re/Os ratio. The long-term projected Re/Os for LOC harzburgites is similar to the average required for modern abyssal peridotites. This observation strengthens previous interpretations, based largely on data for abyssal peridotites, that state the Os isotopic evolution of oceanic mantle is consistent with a long-term 187Re/188Os of ~0.38. The present ~3 to 4% difference between the Os isotopic composition of the modern oceanic mantle and estimates for primitive mantle suggests that at least ~6% of the mass of the oceanic mantle has been removed from it in the form of Re- enriched, mafic oceanic crust. Despite the recycling of this crust back into the mantle, most of it has evidently not been mixed back into accessible portions of the upper oceanic peridotite mantle. Compared to composition estimates for the primitive mantle, the median HSE compositions for the three grid sites are moderately to strongly depleted in Pd and Re, consistent with the corresponding lithophile element evidence for 20–30% melt depletion. As with initial cOs values, most harzburgites from a given grid are characterized by greater variations in absolute and relative HSE abundances than the differences between the median abundances of the three grid sampling locales. This observation indicates that as with Os isotopes, the HSE abundance heterogeneity among the harzburgites most strongly reflects centimeter- to meter-scale melting and remobilization effects. Except for Ru, median HSE abundances for grid harzburgites are similar to median abundances for abyssal peridotites. The 30% lower median Ru/Ir in the LOC compared to the median ratio for abyssal peridotites suggests that the abundance of Ru in the oceanic mantle may be more variable than generally thought.This work was supported by National Science Foundation (NSF) Earth Science grants 1423879 (to RJW) and 1447130 (to J.M.D.D.), which are gratefully acknowledged. B.O’D. acknowledges support from a Royal Society Research Grant (RG100528) and from Natural Environment Research Council (NERC) New Investigator grant NE/J00457X/1. J.S.D. gratefully acknowledges a University College Dublin Seed Funding Grant and Science Foundation Ireland Grant No. 13/RC/2092, which was co-funded under the European Regional Development Fund

Genetic Variation in Cell Death Genes and Risk of Non-Hodgkin Lymphoma

Background Non-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5th highest cause of cancer mortality in the United States and Canada. Poor control of cell death in lymphocytes can lead to autoimmune disease or cancer, making genes involved in programmed cell death of lymphocytes logical candidate genes for lymphoma susceptibility. Materials and Methods We tested for genetic association with NHL and NHL subtypes, of SNPs in lymphocyte cell death genes using an established population-based study. 17 candidate genes were chosen based on biological function, with 123 SNPs tested. These included tagSNPs from HapMap and novel SNPs discovered by re-sequencing 47 cases in genes for which SNP representation was judged to be low. The main analysis, which estimated odds ratios by fitting data to an additive logistic regression model, used European ancestry samples that passed quality control measures (569 cases and 547 controls). A two-tiered approach for multiple testing correction was used: correction for number of tests within each gene by permutation-based methodology, followed by correction for the number of genes tested using the false discovery rate. Results Variant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63–4.82]; pF = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing. Conclusions This is the first reported association between a germline polymorphism at a miRNA locus and lymphoma

Elevated vascular transformation blood biomarkers in Long-COVID indicate angiogenesis as a key pathophysiological mechanism

Background: Long-COVID is characterized by prolonged, diffuse symptoms months after acute COVID-19. Accurate diagnosis and targeted therapies for Long-COVID are lacking. We investigated vascular transformation biomarkers in Long-COVID patients. Methods: A case–control study utilizing Long-COVID patients, one to six months (median 98.5 days) post-infection, with multiplex immunoassay measurement of sixteen blood biomarkers of vascular transformation, including ANG-1, P-SEL, MMP-1, VE-Cad, Syn-1, Endoglin, PECAM-1, VEGF-A, ICAM-1, VLA-4, E-SEL, thrombomodulin, VEGF-R2, VEGF-R3, VCAM-1 and VEGF-D. Results: Fourteen vasculature transformation blood biomarkers were significantly elevated in Long-COVID outpatients, versus acutely ill COVID-19 inpatients and healthy controls subjects (P \u3c 0.05). A unique two biomarker profile consisting of ANG-1/P-SEL was developed with machine learning, providing a classification accuracy for Long-COVID status of 96%. Individually, ANG-1 and P-SEL had excellent sensitivity and specificity for Long-COVID status (AUC = 1.00, P \u3c 0.0001; validated in a secondary cohort). Specific to Long-COVID, ANG-1 levels were associated with female sex and a lack of disease interventions at follow-up (P \u3c 0.05). Conclusions: Long-COVID patients suffer prolonged, diffuse symptoms and poorer health. Vascular transformation blood biomarkers were significantly elevated in Long-COVID, with angiogenesis markers (ANG-1/P-SEL) providing classification accuracy of 96%. Vascular transformation blood biomarkers hold potential for diagnostics, and modulators of angiogenesis may have therapeutic efficacy

Elevated vascular transformation blood biomarkers in Long-COVID indicate angiogenesis as a key pathophysiological mechanism

Background: Long-COVID is characterized by prolonged, diffuse symptoms months after acute COVID-19. Accurate diagnosis and targeted therapies for Long-COVID are lacking. We investigated vascular transformation biomarkers in Long-COVID patients. Methods: A case–control study utilizing Long-COVID patients, one to six months (median 98.5 days) post-infection, with multiplex immunoassay measurement of sixteen blood biomarkers of vascular transformation, including ANG-1, P-SEL, MMP-1, VE-Cad, Syn-1, Endoglin, PECAM-1, VEGF-A, ICAM-1, VLA-4, E-SEL, thrombomodulin, VEGF-R2, VEGF-R3, VCAM-1 and VEGF-D. Results: Fourteen vasculature transformation blood biomarkers were significantly elevated in Long-COVID outpatients, versus acutely ill COVID-19 inpatients and healthy controls subjects (P \u3c 0.05). A unique two biomarker profile consisting of ANG-1/P-SEL was developed with machine learning, providing a classification accuracy for Long-COVID status of 96%. Individually, ANG-1 and P-SEL had excellent sensitivity and specificity for Long-COVID status (AUC = 1.00, P \u3c 0.0001; validated in a secondary cohort). Specific to Long-COVID, ANG-1 levels were associated with female sex and a lack of disease interventions at follow-up (P \u3c 0.05). Conclusions: Long-COVID patients suffer prolonged, diffuse symptoms and poorer health. Vascular transformation blood biomarkers were significantly elevated in Long-COVID, with angiogenesis markers (ANG-1/P-SEL) providing classification accuracy of 96%. Vascular transformation blood biomarkers hold potential for diagnostics, and modulators of angiogenesis may have therapeutic efficacy

Rapid effects of extrafine beclomethasone dipropionate/formoterol fixed combination inhaler on airway inflammation and bronchoconstriction in asthma: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The dose-dependent anti-inflammatory effects of a recent fixed combination of extrafine beclomethasone dipropionate/formoterol (BDP/F) were investigated using non-invasive markers of inflammation, exhaled nitric oxide (NO) and adenosine monophosphate (AMP) provocative challenge. The aim was to assess the onset of the anti-inflammatory action of low and high doses and evaluate the suitability of non-invasive assessments to demonstrate dose response.</p> <p>Methods</p> <p>Steroid naïve adult out-patients with mild asthma, sensitive to AMP with baseline exhaled NO > 25 parts per billion entered a double-blind, placebo-controlled, 3-way, cross-over study. Patients were randomised to low dose (1 actuation) or high dose (4 actuations) extrafine BDP/F 100/6 μg, or placebo administered twice daily on Days 1 and 2 and once in the morning on Day 3 of each period. Exhaled NO was measured pre-dose on Day 1, then 2 and 4 hours post-administration on Day 3. The AMP challenge was performed 4 hours post-administration on Day 3 and forced expiratory volume in 1 second (FEV₁, L) was measured from 0 to 4 hours post-dose on Day 1. Endpoints were NO at 2 and 4 hours, AMP challenge at 4 hours after the fifth dose on Day 3 and FEV₁area under the curve from 0 to 4 h post-dose on Day 1. Analysis of covariance was performed for NO and FEV₁and analysis of variance for AMP challenge.</p> <p>Results</p> <p>Eighteen patients were randomised and completed the study. Exhaled NO was significantly lower for both doses of extrafine BDP/F versus placebo at 2 and 4 hours (high dose LS mean difference: -22.5 ppb, p < 0.0001 and -20.5 ppb, p < 0.0001; low dose: -14.1 ppb, p = 0.0006 and -12.1 ppb, p = 0.0043) with a significant dose response (p = 0.0342 and p = 0.0423). Likewise, AMP challenge revealed statistically significant differences between both doses of extrafine BDP/F and placebo (high dose LS mean difference: 4.8 mg/mL, p < 0.0001; low dose: 3.7 mg/mL, p < 0.0001), and a significant dose response (p = 0.0185). FEV₁was significantly improved versus placebo for both doses (high dose LS mean difference: 0.2 L, p = 0.0001; low dose: 0.2 L p = 0.0001), but without a significant dose response.</p> <p>Conclusions</p> <p>The fixed combination inhaler of extrafine BDP/F has early dose-dependent anti-inflammatory effects with a rapid onset of bronchodilatation in mild asthmatic patients.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01343745">NCT01343745</a></p