Characteristics of blood plasma proteome changes associated with the hemorrhagic purpura of cosmonauts on the first day after long-term space missions.

The interest in the role of the gravitational factor during landing after long-term space flights (SF) leads to the search for various innovative approaches to assessing the compliance of external changes observed by clinicians. The results of special research methods such as Omics technologies that may reflect physiological responses to the conditions created during landing are of great interest. Our purpose is to compare the blood plasma proteome changes associated with the trauma and endothelial dysfunction processes prior to launch and on the day of landing, as well as the groups of cosmonauts with and without the secondary hemorrhagic purpura. In our study, the concentrations of 125 plasma proteins in 18 Russian cosmonauts, measured using targeted proteomic analysis based on liquid chromatography and tandem mass spectrometry were analyzed. The results reveal the trends of 12 proteins participating in the processes that trigger hemorrhagic purpura under the effect of re-entry g-forces. Exposure to intense g-forces and return to the gravity are the key factors for external manifestations of changes in the body systems induced by a long-term stay in space microgravity. Our results may be useful for further research to experts in gravitational physiology, aviation and space medicine.

Correction: Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease.

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Probing the mechanism for hydrogel-based stasis induction in human pluripotent stem cells: is the chemical functionality of the hydrogel important?

It is well-known that pluripotent human embryonic stem cells (hPSC) can differentiate into any cell type. Recently, we reported that hPSC colonies enter stasis when immersed in an extremely soft hydrogel comprising hydroxyl-functional block copolymer worms (I. Canton, N. J. Warren, A. Chahal, K. Amps, A. Wood, R. Weightman, E. Wang, H. Moore and S. P. Armes, ACS Centr. Sci., 2016, 2, 65-74). The gel modulus and chemical structure of this synthetic hydrogel are similar to that of natural mucins, which are implicated in the mechanism of diapause for mammalian embryos. Does stasis induction occur merely because of the very soft nature of such hydrogels or does chemical functionality also play a role? Herein, we address this key question by designing a new hydrogel of comparable softness in which the PGMA stabilizer chains are replaced with non-hydroxylated poly(ethylene glycol) [PEG]. Immunolabeling studies confirm that hPSC colonies immersed in such PEG-based hydrogels do not enter stasis but instead proliferate (and differentiate if no adhesion substrate is present). However, pluripotency is retained if an appropriate adhesion substrate is provided. Thus, the chemical functionality of the hydrogel clearly plays a decisive role in the stasis induction mechanism.

How iMALDI can improve clinical diagnostics.

Protein mass spectrometry (MS) is an indispensable tool to detect molecular signatures that can be associated with cellular dysregulation and disease. Despite its huge success in the life sciences, where it has led to novel insights into disease mechanisms and the identification of potential protein biomarkers, protein MS is rarely used for clinical protein assays. While conventional matrix-assisted laser desorption/ionization (MALDI) MS is not compatible with complex samples, liquid chromatography-MS (LC-MS)-based assays may be too complex and may lack the robustness and ease of automation required for routine use in the clinic. Therefore, clinical protein assays are dominated by immunohistochemistry and immunoassays which, however, often lack standardization and fully depend on antibody specificity. Immuno-MALDI (iMALDI) MS may overcome these hurdles by utilizing anti-peptide antibodies for the specific enrichment of targeted analytes and on-target detection of the captured analytes, thus combining the unique properties of MS for the unambiguous detection and quantitation of analytes with a workflow that can be fully automated. Here we discuss the requirements for clinical protein assays, the pitfalls of existing methods, how iMALDI has been successfully used to quantify endogenous peptides and proteins from clinical samples, as well as its potential as a powerful tool for companion diagnostics in the light of precision medicine.

Differential Proteomics for Distinguishing Ischemic Stroke from Controls: a Pilot Study of the SpecTRA Project.

A diagnostic blood test for stroke is desirable but will likely require multiple proteins rather than a single "troponin." Validating large protein panels requires large patient numbers. Mass spectrometry (MS) is a cost-effective tool for this task. We compared differences in the abundance of 147 protein markers to distinguish 20 acute cerebrovascular syndrome (ACVS) patients who presented to the Emergency Department of one urban hospital within < 24 h from onset) and from 20 control patients who were enrolled via an outpatient neurology clinic. We targeted proteins from the stroke literature plus cardiovascular markers previously studied in our lab. One hundred forty-one proteins were quantified using MS, 8 were quantified using antibody protein enrichment with MS, and 32 were measured using ELISA, with some proteins measured by multiple techniques. Thirty proteins (4 by ELISA and 26 by the MS techniques) were differentially abundant between mimic and stroke after adjusting for age in robust regression analyses (FDR < 0.20). A logistic regression model using the first two principal components of the proteins significantly improved discrimination between strokes and controls compared to a model based on age alone (p < 0.001, cross-validated AUC 0.93 vs. 0.78). Significant proteins included markers of inflammation (47%), coagulation (40%), atrial fibrillation (7%), neurovascular unit injury (3%), and other (3%). These results suggest the potential value of plasma proteins as biomarkers for ACVS diagnosis and the role of plasma-based MS in this area.

Current trends in quantitative proteomics - an update.

Proteins can provide insights into biological processes at the functional level, so they are very promising biomarker candidates. The quantification of proteins in biological samples has been routinely used for the diagnosis of diseases and monitoring the treatment. Although large-scale protein quantification in complex samples is still a challenging task, a great amount of effort has been made to advance the technologies that enable quantitative proteomics. Seven years ago, in 2009, we wrote an article about the current trends in quantitative proteomics. In writing this current paper, we realized that, today, we have an even wider selection of potential tools for quantitative proteomics. These tools include new derivatization reagents, novel sampling formats, new types of analyzers and scanning techniques, and recently developed software to assist in assay development and data analysis. In this review article, we will discuss these innovative methods, and their current and potential applications in proteomics. Copyright © 2017 John Wiley & Sons, Ltd.

Prognostic parameters and outcome after re-irradiation for progressive glioblastoma.

OBJECTIVES: In progressive glioblastoma, salvage treatment remains unstandardized, response is highly variable, and detailed analysis of individual approaches is mandatory. Re-irradiation is an established option in the therapy of progressive glioblastoma. Thus, we analysed outcome and prognostic parameters of patients with re-irradiated glioblastoma treated at our institution since 1998. MATERIALS AND METHODS: In a total of 51 patients, clinical and treatment parameters were collected and analysed retrospectively. Re-irradiation protocols included radiosurgery, hypofractionated radiotherapy or normofractionated radiotherapy. Outcome was analysed regarding prognostic factors in this highly selected cohort. RESULTS: Median overall survival after primary diagnosis was 28.8 months. Patients re-irradiated with single-dose stereotactic radiosurgery or hypofractionated regimes showed a superior overall survival after primary diagnosis compared to normofractionated treatment. Positive prognostic factors included a smaller gross tumour volume and younger age. A methylated MGMT promoter approached statistical significance as a positive factor regarding overall survival after re-irradiation. Further well-known prognostic factors as extension of the initial resection and the concomitance of temozolomide with the initial radiation treatment only appeared relevant in a subgroup of four long-term survivors. CONCLUSIONS: The favourable results regarding overall survival are probably due to patient selection for re-irradiation. If technically feasible, stereotactic radiosurgery or hypofractionated regimes should be preferred. In this highly selected re-irradiation cohort, only some of the well-known prognostic factors of the primary tumour setting were found to influence overall survival significantly. In contrast, also some patients presenting with unfavourable predictive parameters showed an encouraging course of disease and thus should not be excluded from re-irradiation.

Architecture of the RNA polymerase II-Mediator core initiation complex.

The conserved co-activator complex Mediator enables regulated transcription initiation by RNA polymerase (Pol) II. Here we reconstitute an active 15-subunit core Mediator (cMed) comprising all essential Mediator subunits from Saccharomyces cerevisiae. The cryo-electron microscopic structure of cMed bound to a core initiation complex was determined at 9.7 Å resolution. cMed binds Pol II around the Rpb4-Rpb7 stalk near the carboxy-terminal domain (CTD). The Mediator head module binds the Pol II dock and the TFIIB ribbon and stabilizes the initiation complex. The Mediator middle module extends to the Pol II foot with a 'plank' that may influence polymerase conformation. The Mediator subunit Med14 forms a 'beam' between the head and middle modules and connects to the tail module that is predicted to bind transcription activators located on upstream DNA. The Mediator 'arm' and 'hook' domains contribute to a 'cradle' that may position the CTD and TFIIH kinase to stimulate Pol II phosphorylation.

The Human Proteome Organization Chromosome 6 Consortium: integrating chromosome-centric and biology/disease driven strategies.

The Human Proteome Project (HPP) is designed to generate a comprehensive map of the protein-based molecular architecture of the human body, to provide a resource to help elucidate biological and molecular function, and to advance diagnosis and treatment of diseases. Within this framework, the chromosome-based HPP (C-HPP) has allocated responsibility for mapping individual chromosomes by country or region, while the biology/disease HPP (B/D-HPP) coordinates these teams in cross-functional disease-based groups. Chromosome 6 (Ch6) provides an excellent model for integration of these two tasks. This metacentric chromosome has a complement of 1002-1034 genes that code for known, novel or putative proteins. Ch6 is functionally associated with more than 120 major human diseases, many with high population prevalence, devastating clinical impact and profound societal consequences. The unique combination of genomic, proteomic, metabolomic, phenomic and health services data being drawn together within the Ch6 program has enormous potential to advance personalized medicine by promoting robust biomarkers, subunit vaccines and new drug targets. The strong liaison between the clinical and laboratory teams, and the structured framework for technology transfer and health policy decisions within Canada will increase the speed and efficacy of this transition, and the value of this translational research. BIOLOGICAL SIGNIFICANCE: Canada has been selected to play a leading role in the international Human Proteome Project, the global counterpart of the Human Genome Project designed to understand the structure and function of the human proteome in health and disease. Canada will lead an international team focusing on chromosome 6, which is functionally associated with more than 120 major human diseases, including immune and inflammatory disorders affecting the brain, skeletal system, heart and blood vessels, lungs, kidney, liver, gastrointestinal tract and endocrine system. Many of these chronic and persistent diseases have a high population prevalence, devastating clinical impact and profound societal consequences. As a result, they impose a multi-billion dollar economic burden on Canada and on all advanced societies through direct costs of patient care, the loss of health and productivity, and extensive caregiver burden. There is no definitive treatment at the present time for any of these disorders. The manuscript outlines the research which will involve a systematic assessment of all chromosome 6 genes, development of a knowledge base, and development of assays and reagents for all chromosome 6 proteins. We feel that the informatic infrastructure and MRM assays developed will place the chromosome 6 consortium in an excellent position to be a leading player in this major international research initiative. This article is part of a Special Issue: Can Proteomics Fill the Gap Between Genomics and Phenotypes?

Chemical fingerprinting of naphthenic acids and oil sands process waters-A review of analytical methods for environmental samples.

This article provides a review of the routine methods currently utilized for total naphthenic acid analyses. There is a growing need to develop chemical methods that can selectively distinguish compounds found within industrially derived oil sands process affected waters (OSPW) from those derived from the natural weathering of oil sands deposits. Attention is thus given to the characterization of other OSPW components such as oil sands polar organic compounds, PAHs, and heavy metals along with characterization of chemical additives such as polyacrylamide polymers and trace levels of boron species. Environmental samples discussed cover the following matrices: OSPW containments, on-lease interceptor well systems, on- and off-lease groundwater, and river and lake surface waters. There are diverse ranges of methods available for analyses of total naphthenic acids. However, there is a need for inter-laboratory studies to compare their accuracy and precision for routine analyses. Recent advances in high- and medium-resolution mass spectrometry, concomitant with comprehensive mass spectrometry techniques following multi-dimensional chromatography or ion-mobility separations, have allowed for the speciation of monocarboxylic naphthenic acids along with a wide range of other species including humics. The distributions of oil sands polar organic compounds, particularly the sulphur containing species (i.e., OxS and OxS2) may allow for distinguishing sources of OSPW. The ratios of oxygen- (i.e., Ox) and nitrogen-containing species (i.e., NOx, and N2Ox) are useful for differentiating organic components derived from OSPW from natural components found within receiving waters. Synchronous fluorescence spectroscopy also provides a powerful screening technique capable of quickly detecting the presence of aromatic organic acids contained within oil sands naphthenic acid mixtures. Synchronous fluorescence spectroscopy provides diagnostic profiles for OSPW and potentially impacted groundwater that can be compared against reference groundwater and surface water samples. Novel applications of X-ray absorption near edge spectroscopy (XANES) are emerging for speciation of sulphur-containing species (both organic and inorganic components) as well as industrially derived boron-containing species. There is strong potential for an environmental forensics application of XANES for chemical fingerprinting of weathered sulphur-containing species and industrial additives in OSPW.

Atomic scale investigation of redistribution of alloying elements in pearlitic steel wires upon cold-drawing and annealing.

A local electrode atom probe has been employed to analyze the redistribution of alloying elements including Si, Mn, and Cr in pearlitic steel wires upon cold-drawing and subsequent annealing. It has been found that the three elements undergo mechanical mixing upon cold-drawing at large strains, where Mn and Cr exhibit a nearly homogeneous distribution throughout both ferrite and cementite, whereas Si only dissolves slightly in cementite. Annealing at elevated temperatures leads to a reversion of the mechanical alloying. Si atoms mainly segregate at well-defined ferrite (sub)grain boundaries formed during annealing. Cr and Mn are strongly concentrated in cementite adjacent to the ferrite/cementite interface due to their lower diffusivities in cementite than in ferrite.

Arsenic contamination of coarse-grained and nanostructured nitinol surfaces induced by chemical treatment in hydrofluoric acid.

XPS measurements of coarse-grained and nanostructured nitinol (Ni(50.2)Ti(49.8)) before and after chemical treatment in hydrofluoric acid (40% HF, 1 min) are presented. The nanostructured state, providing the excellent mechanical properties of nitinol, is achieved by severe plastic deformation. The near-surface layers of nitinol were studied by XPS depth profiling. According to the obtained results, a chemical treatment in hydrofluoric acid reduces the thickness of the protective TiO(2) oxide layer and induces a nickel release from the nitinol surface and an arsenic contamination, and can therefore not be recommended as conditioning to increase the roughness of NiTi-implants. A detailed evaluation of the resulting toxicological risks is given.

Bronchoalveolar lavage in the diagnosis of ventilator-associated pneumonia: to quantitate or not, that is the question.

Quantitative bronchoalveolar lavage (BAL) is used to diagnose ventilator-associated pneumonia (VAP). We prospectively compared semiquantitative (SQ) and quantitative (Qu) culture of BAL for VAP diagnosis. Ventilated patients suspected of VAP underwent bronchoscopic BAL. BAL fluid was examined by both Qu (colony-forming units [CFUs]/mL) and SQ culture (none, sparse, moderate, or heavy) and results were compared. VAP was defined as 105 CFU/mL or greater on Qu culture. Over 36 months, 319 BALs were performed. Sixty-three of 319 (20%) showed diagnostic growth by Qu culture identifying a total of 81 organisms causing VAP. All 63 specimens showed growth of some organism(s) on SQ culture with 79 of 81 causative organisms identified and two (Pseudomonas, one; Corynebacterium, one) not identified. The remaining 256 specimens did not meet the threshold for VAP by the Qu method. Among these, 79 did not show any growth on SQ culture. Among the 240 specimens showing some growth on SQ culture, a total of 384 organisms were identified. VAP rates in relation to strength of growth on SQ culture were: sparse, 10 of 140 (7%); moderate, 24 of 147 (16%); and heavy, 45 of 97 (46%). Sensitivity (Sn), specificity (Sp), positive (PPV), and negative (NPV) predictive values of SQ culture of BAL fluid for the diagnosis of VAP were 97, 21, 21, and 97 per cent, respectively. Nonquantitative culture of BAL fluid is fairly accurate in ruling out VAP (high Sn and NPV). It however has poor Sp and PPV and using this method will lead to unnecessary antimicrobial use with its attendant complications of toxicity, cost, and resistance.

Multiple levels of gene regulation mediate differentiation of the intracellular pathogen Leishmania.

For many years, mRNA abundance has been used as the surrogate measure of gene expression in biological systems. However, recent genome-scale analyses in both bacteria and eukaryotes have revealed that mRNA levels correlate with steady-state protein abundance for only 50-70% of genes, indicating that translation and post-translation processes also play important roles in determining gene expression. What is not yet clear is whether dynamic processes such as cell cycle progression, differentiation, or response to environmental changes change the relationship between mRNA and protein abundance. Here, we describe a systems approach to interrogate promastigote-to-amastigote differentiation in the obligatory intracellular parasitic protozoan Leishmania donovani. Our results indicate that regulation of mRNA levels plays a major role early in the differentiation process, while translation and post-translational regulation are more important in the latter part. In addition, it appears that the differentiation signal causes a transient global increase in the rate of protein synthesis, which is subsequently down-regulated by phosphorylation of α-subunit of translation initiation factor 2. Thus, Leishmania dynamically changes the relationship between mRNA and protein abundance as it adapts to new environmental circumstances. It is likely that similar mechanisms play a more important role than previously recognized in regulation of gene expression in other organisms.

Atom probe tomography characterization of heavily cold drawn pearlitic steel wire.

Atom Probe Tomography (APT) was used to analyze the carbon distribution in a heavily cold drawn pearlitic steel wire with a true strain of 6.02. The carbon concentrations in cementite and ferrite were separately measured by a sub-volume method and compared with the literature data. It is found that the carbon concentration in ferrite saturates with strain. The carbon concentration in cementite decreases with the lamellar thickness, while the carbon atoms segregate at dislocations or cell/grain boundaries in ferrite. The mechanism of cementite decomposition is discussed in terms of the evolution of dislocation structure during severe plastic deformation.

A central venous line protocol decreases bloodstream infections and length of stay in a trauma intensive care unit population.

We evaluated the benefit of a central venous line (CVL) protocol on bloodstream infections (BSIs) and outcome in a trauma intensive care unit (ICU) population. We prospectively compared three groups: Group 1 (January 2003 to June 2004) preprotocol; Group 2 (July 2004 to June 2005) after the start of the protocol that included minimizing CVL use and strict universal precautions; and Group 3 (July 2005 to December 2006) after the addition of a line supply cart and nursing checklist. There were 1622 trauma patients admitted to the trauma ICU during the study period of whom 542 had a CVL. Group 3 had a higher Injury Severity Score (ISS) compared with both Groups 2 and 1 (28.3 +/- 13.0 vs 23.5 +/- 11.7 vs 22.8 +/- 12.0, P = 0.0002) but had a lower BSI rate/1000 line days (Group 1: 16.5; Group 2: 15.0; Group 3: 7.7). Adjusting for ISS group, three had shorter ICU length of stay (LOS) compared with Group 1 (12.11 +/- 1.46 vs 18.16 +/- 1.51, P = 0.01). Logistic regression showed ISS (P = 0.04; OR, 1.025; CI, 1.001-1.050) and a lack of CVL protocol (P = 0.01; OR, 0.31; CI, 0.13-0.76) to be independent predictors of BSI. CVL protocols decrease both BSI and LOS in trauma patients. Strict enforcement by a nurse preserves the integrity of the protocol.

Predictive value of broncho-alveolar lavage fluid Gram's stain in the diagnosis of ventilator-associated pneumonia: a prospective study.

BACKGROUND: Quantitative broncho-alveolar lavage (qBAL) is increasingly being used for diagnosing ventilator-associated pneumonia (VAP). The current study prospectively evaluates the accuracy of broncho-alveolar lavage fluid Gram's stain (GS) in predicting both the presence of VAP and the class of causative microorganism in patients suspected of VAP. METHODS: Patients suspected of VAP in a trauma or surgical intensive care unit underwent bronchoscopic qBAL with GS. Presence and class of organisms seen on GS were correlated respectively with the presence of VAP, as diagnosed by qBAL, and class of causative microorganism. VAP was defined as qBAL >10(5) colony forming units/mL. All data were gathered prospectively. RESULTS: During a 28-month study period, 229 patients underwent 309 qBALs for suspected VAP. Seventy-one (23%) specimens were positive for VAP (qBAL>10(5) CFU/mL). Fifty-four specimens (77%) had one causative microorganism, 13 (18%) had two, 3 (4%) had three, and 1 (1%) demonstrated four microorganisms giving a total of 93 VAPs. Forty-one (62%) of 66 specimens showing moderate or many microorganisms on GS were positive for VAP. However, 7 (4%) of 167 specimens showing none and 23 (30%) of 76 showing few microorganisms on GS were also positive for VAP. Of the 64 qBAL specimens positive for VAP and where the GS showed microorganisms, 6 (23%) of 26 showing only G+ microorganisms on GS had G- VAP (G- alone, 4; G+ and G-, 2), and 1 (8%) of 12 showing G- microorganisms only had G+ and G- VAP. Of the seven qBAL specimens positive for VAP where the GS did not show microorganisms, one had G+ and six had G- VAP. With the threshold of positivity of GS at more than none, the sensitivity, specificity, positive, and negative predictive values of GS for the presence of VAP were 90%, 67%, 45%, and 96% respectively. CONCLUSIONS: Broncho-alveolar lavage fluid GS is poor in predicting the presence of VAP and predicting the class of causative microorganism. Using GS to determine necessity of and to select class of antimicrobial therapy will result in delayed or inappropriate VAP therapy or both.

Computed tomographic angiography for the diagnosis of blunt carotid/vertebral artery injury: a note of caution.

OBJECTIVE: Computed tomographic angiography (CTA) by 16-channel multidetector scanner is increasingly replacing conventional digital subtraction angiography (DSA) for diagnosing or excluding blunt carotid/vertebral injuries (BCVI). To date there has been only 1 study in which all patients received both examinations. That study reported a high accuracy for 16-detector CTA. The current prospective parallel comparative study aims at validating this high accuracy and examining the rates of evaluability of CTA performed with a 16-detector scanner with image reconstruction by modern imaging software. METHODS: Patients at risk for BCVI (facial/cervical-spinal fractures; unexplained neurologic deficit; anisocoria; lateral neck soft tissue injury; clinical suspicion) underwent both CTA (16-channel multidetector scanner) and DSA. Results of the 2 studies and the clinical course were prospectively recorded. RESULTS: During the 40-month study period ending March 2007, approximately 7000 blunt trauma patients were evaluated and of these 119 (1.7%) consecutive patients meeting inclusion criteria were screened by CTA. Ninety-two patients underwent confirmatory DSA. Twenty-three (22%) DSA identified 26 BCVI (vertebral, 13; carotid, 13). Among these 23 CTAs, 17 identified 19 BCVIs (vertebral, 10; carotid, 9) (true positives), and 6 failed to identify 7 BCVIs (vertebral, 3; carotid, 4) (false negatives). Sixty-nine of the 92 DSA were normal. Of these 69 CTAs, 10 were falsely suspicious for 11 BCVIs (vertebral, 7; carotid, 4) (false positives), and 56 were normal (true negatives). The remaining 3 CTAs were nonevaluable (mistimed contrast, 1; streak artifact, 2). Sixteen of 89 (18%) evaluable CTAs, were suboptimal (mistimed contrast, 9; streak artifacts, 4; motion artifact, 2; body habitus, 1). Excluding the 3 nonevaluable CTAs, the sensitivity, specificity, positive and negative predictive values of CTA for diagnosing or excluding BCVI were 74%, 86%, 65%, and 90% respectively. One patient with grade II carotid artery injuries (by CTA and DSA) on antiplatelet agent developed stroke related to carotid artery injuries. CONCLUSIONS: Current CTA technology cannot reliably diagnose or exclude BCVI. Twenty percent of CTAs are either nonevaluable or suboptimal. Until more data are available and the technique is standardized, the current trend towards using CTA to screen for and/or diagnose these rare but potentially devastating injuries is dangerous.

Prospective evaluation of an extubation protocol in a trauma intensive care unit population.

Little data exists regarding extubation protocols in critically injured trauma patients. The objective of the current study was to prospectively examine the impact of implementing an extubation protocol on the outcomes of ventilated trauma patients in a surgical intensive care unit (STICU). Trauma patients admitted to the STICU over a 15-month period at a Level 1 trauma center were prospectively evaluated. The total period was divided into an education and institution period (April 2002-November 2003) and an evaluation period (December 2003-July 2003). Patient demographics, hospital course, complications, and outcomes from period I were compared with those obtained during period II. From April 8, 2002 through July 5, 2003, 69 patients intubated for greater than 24 hours were included in our analysis. Thirty-three were treated during period I and 36 were treated during period II. Both groups were well matched in terms of age, sex, Injury Severity Score, and chest Abbreviated Injury Score. Ventilation days significantly decreased from a mean of 16.3 to 8.2 days (P = 0.04). ICU length of stay also decreased, nearly meeting significance. A rigorously enforced extubation protocol significantly decreased ventilator days in STICU patients. Continued education of health care providers is key to the success of the protocol.

Catalyst-nanostructure interaction in the growth of 1-D ZnO nanostructures.

Vapor-liquid-solid is a well-established process in catalyst guided growth of 1-D nanostructures, i.e., nanobelts and nanowires. The catalyst particle is generally believed to be in the liquid state during growth, and is the site for impinging molecules. The crystalline structure of the catalyst may not have any influence on the structure of the grown nanostructures. In this work, using Au guided growth of ZnO, we show that the interfaces between the catalyst droplet and the nanostructure grow in well-defined mutual crystallographic relationships. The nanostructure defines the crystallographic orientation of the solidifying Au droplet. Possible alloy, intermetallic, or eutectic phase formation during catalysis are elucidated with the help of a proposed ternary Au-Zn-O phase diagram.