Baseline low ALT activity is associated with increased long-term mortality after COPD exacerbations.

BACKGROUND: COPD exacerbations have negative impact on patients' survival. Several risk factors for grave outcomes of such exacerbations have been descried. Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival. Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival. METHODS: This is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation. RESULTS: Included were 232 consecutive COPD exacerbation patients. The median time of follow-up was 34.9 months (IQR 23.13-41.73 months). During this period 104 (44.8%) patients died. All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatic tissue damage (ALT > 40 IU)). The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached. For ALT < 11 IU; 12-16 IU; 17-20 IU and > 21 IU the mortality rates were 69%; 40.9%; 36.3 and 25% respectively (p <  0.001 for comparison of lower quartile with upper three quartiles). The crude hazard ratio for mortality amongst patients with ALT levels lower than 11 IU was 2.37 (95% CI; 1.6-3.5). This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08-3.1, p <  0.05). CONCLUSIONS: Low ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation.

Reducing drug prescription errors and adverse drug events by application of a probabilistic, machine-learning based clinical decision support system in an inpatient setting.

BACKGROUND: Drug prescription errors are made, worldwide, on a daily basis, resulting in a high burden of morbidity and mortality. Existing rule-based systems for prevention of such errors are unsuccessful and associated with substantial burden of false alerts. OBJECTIVE: In this prospective study, we evaluated the accuracy, validity, and clinical usefulness of medication error alerts generated by a novel system using outlier detection screening algorithms, used on top of a legacy standard system, in a real-life inpatient setting. MATERIALS AND METHODS: We integrated a novel outlier system into an existing electronic medical record system, in a single medical ward in a tertiary medical center. The system monitored all drug prescriptions written during 16 months. The department's staff assessed all alerts for accuracy, clinical validity, and usefulness. We recorded all physician's real-time responses to alerts generated. RESULTS: The alert burden generated by the system was low, with alerts generated for 0.4% of all medication orders. Sixty percent of the alerts were flagged after the medication was already dispensed following changes in patients' status which necessitated medication changes (eg, changes in vital signs). Eighty-five percent of the alerts were confirmed clinically valid, and 80% were considered clinically useful. Forty-three percent of the alerts caused changes in subsequent medical orders. CONCLUSION: A clinical decision support system that used a probabilistic, machine-learning approach based on statistically derived outliers to detect medication errors generated clinically useful alerts. The system had high accuracy, low alert burden and low false-positive rate, and led to changes in subsequent orders.

A critical study of the generality of the two step two electron pathway for water splitting by application of a C3N4/MnO2 photocatalyst.

A novel C3N4-CDot composite photocatalyst was very recently shown to be highly efficient and very stable in water splitting by solar radiation without using any sacrificial reagent (J. Liu, et al., Science, 2015, 347(6225), 970). This photocatalyst utilizes a two-electron/two-step process in which the production of H2O2 and H2 is photocatalyzed by using C3N4 in the first step and H2O2 is decomposed by using CDots in the second step. The present work is a study on the generality of this approach by application of a C3N4/MnO2 catalyst. This new catalyst indeed splits water by a two step process in a stable way, without any sacrificial agent. It was however found that though the absorbance of the new catalyst in the visible range of 500-600 nm is much larger than that of the C3N4-CDot catalyst, its water splitting efficiency is much lower. These findings add insight into and assist in the further optimization of this new class of photocatalysts to meet the requirements of commercial water splitting systems.

Sub-chronic (13-week) oral toxicity study, preceded by an in utero exposure phase and genotoxicity studies with fish source phosphatidylserine in rats.

The safety of fish phosphatidylserine (PS) conjugated to DHA (InCog™) was examined in a series of toxicology studies as first step to support future use in infants and general population using in vitro genotoxicity tests and in a sub-chronic toxicity study with an in-utero exposure phase. PS is a major lipid in the cell membrane, active in various membrane-mediated processes. PS-DHA, present in human milk, has been suggested to be important for early brain development. Rats were exposed to diets containing 1.5%, 3% or 4.5% InCog or two control diets. Parental (F0) animals were fed throughout mating, gestation and lactation. Subsequently, a subchronic, 13-week study was conducted on the F1 animals followed by 4 weeks of recovery. The genotoxicity tests showed no mutagenicity potential. No significant toxicological findings were found in the F0 rats or the F1 pups. In the 13-weeks study, an increase in the presence of renal minimal-mild multifocal corticomedullary mineralization was noted in nine females of the high-dose group. This change was not associated with any inflammatory or degenerative changes in the kidneys. The no-observed-adverse-effect level (NOAEL) in the present study was placed at 3% in the diet (mid-dose group), equivalent to an overall intake of at least 2.1 g InCog/kg bw/day in the F1 generation.

Structures and energetics of hydrogen-terminated silicon nanowire surfaces.

The analysis and density-functional tight-binding simulations of possible configurations of silicon nanowires (SiNWs) enclosed by low-index surfaces reveal a number of remarkable features. For wires along <100>, <110>, and <111> directions, many low-index facet configurations and cross sections are possible, making their controlled growth difficult. The 112 wires are the most attractive for research and applications because they have only one configuration of enclosing low-index facets with a rectangular cross section, enclosed with the most stable (111) facet and the (110) facet next to it. In general, the stability of the SiNWs is determined by a balance between (1) minimization of the surface energy gamma(111)svr(rectangular)>svr(triangular)]. The energy band gaps follow the order of <100>wires > <112>wires > <111>wires > <110>wires. The results are compared with our recent scanning tunneling microscopy and transmission electron microscopy data.

Visualization of diamond nucleation and growth from energetic species.

The mystery of diamond nucleation by energetic species is resolved via a special deposition scheme. The evolution of the precursor material for diamond nucleation and the development of the nanodiamond crystallites are visualized by high resolution electron microscopy and other spectroscopies. The diamond precipitation and growth are explained in terms of our recently proposed mechanism [Science 297, 1531 (2002)]]: (i) precipitation of sp(3) clusters a small fraction of which are perfect diamond; (ii) growth of diamond crystallites by preferential displacement of amorphous carbon atoms leaving diamond atoms intact. This general scheme is applicable to other materials such as cubic boron nitride.

The mechanism of diamond nucleation from energetic species.

A model for diamond nucleation by energetic species (for example, bias-enhanced nucleation) is proposed. It involves spontaneous bulk nucleation of a diamond embryo cluster in a dense, amorphous carbon hydrogenated matrix; stabilization of the cluster by favorable boundary conditions of nucleation sites and hydrogen termination; and ion bombardment-induced growth through a preferential displacement mechanism. The model is substantiated by density functional tight-binding molecular dynamics simulations and an experimental study of the structure of bias-enhanced and ion beam-nucleated films. The model is also applicable to the nucleation of other materials by energetic species, such as cubic boron nitride.

Nanostructure. Epitaxial diamond polytypes on silicon.

Carbon is unique in the variety of configurations it can adopt with itself and other elements. Here we show how ion beams can be used to nanostructure various diamond polytypes, epitaxially aligning them to a silicon substrate. The ready controllability of ion beams, which are already used to manufacture submicrometre-scale devices, means that our findings should enable new carbon and non-carbon materials to be nanostructured for a host of applications.

Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis leading to renal failure is the most severe complication in untreated patients. In Israel FMF is most frequent among Jews of North African origin. Recently the causative gene (MEFV) has been found and the common mutations characterised. The aim of this study was to investigate the carrier rates of the common MEFV mutations among 400 healthy members of four different ethnic groups (100 in each group) in Israel, and to compare the distribution of the different mutations between FMF carriers and patients. We found a high frequency of carriers among Jews from the various ethnic groups. In North African Jews it was 22%, in Iraqi Jews 39%, in Ashkenazi Jews 21%, and in Iranian Jews 6%. The distribution of the four most common MEFV mutations among healthy individuals (M694V 29%, V726A 16%, M6801 2% and E148Q 53%) was significantly different (P < 0.003) from that found in patients (M694V 84.4%, V726A 9.0%, M6801 0% and E148Q 6.6%). Six healthy asymptomatic individuals were found to carry mutations in both alleles: two homozygotes for E148Q and four compound heterozygotes E148Q/other. These results demonstrate a very high carrier rate among all Jewish ethnic groups. They confirm that mutation E148Q is associated with a milder phenotype, which explains the lower prevalence of FMF among the Ashkenazi and Iraqi Jews. This study raises the question of the need for molecular screening for M694V homozygotes in the Israeli North African Jewish community.

A nucleation site and mechanism leading to epitaxial growth of diamond films

A diamond nucleation site responsible for epitaxial growth of diamond on silicon by chemical vapor deposition (CVD) is identified in high-resolution transmission electron microscopic images. Other sites in the same sample leading to polycrystalline growth, but deleterious to epitaxial CVD growth, are also described. A mechanism for the heteroepitaxial growth of diamond is suggested, in which etching of the nondiamond carbon binder exposes and removes nonadherent nanodiamond nuclei, leaving intact only those directly nucleated on the silicon substrate. This work enhances our understanding of diamond nucleation and heteroepitaxial growth and its potential applications.

Role of metal ions in coupling between chemical catalysis and conformational changes in ATP synthase.

Isolated chloroplast ATP synthase (CF0F1) was used for determination of the structure-function relation by measuring the effect of divalent metal ions on the properties of ATPase. Mg2+ ions were more efficient catalysts than Ca2+ ions as indicated by Kcat/Km of 55.2 and 5.4, respectively. Other activity parameters related to binding, such as the Km of MATP and Ki of MADP, indicated a stronger binding in the presence of Mg2+ as seen from a Mg2+/Ca2+ ratio of 2.8 and 3.8, respectively. Strong binding of Ca2+ ions with a Kd of 0.03 +/- 00.6 microM-1 was detected only in the presence of ADP probably because of the positive interactive effect of CaADP as indicated in the inhibition properties. Mg2+ ions were more efficient catalysts also in other forms of the enzyme such as in the thylakoid membrane, in isolated CF0F1 and in CF1. The Mg2+/Ca2+ ratio of Kcat/Km was 5.3, 10.2 and 1.5 for the thylakoid membrane enzyme, the isolated CF0F1 and the soluble CF1 respectively. This indicated that Ca2+ ions became less efficient catalysts in the more intact and integrated enzyme while Mg2+ ions were as efficient in all forms of the enzyme. Unlike Mg2+, Ca2+ ions also did not support proton-coupled ATP synthesis and ATP driven proton pumping. It is suggested that the differences in the ligand structure of these two ions might be the reason for the differential function. An average 0.3 A shorter bond length of octahedral first coordination in Ca2+ ions caused a weaker binding of CaATP than that of MgATP. The effect of differential binding is discussed in relation to the binding of the transition state intermediate and to the rate of product release.

The effect of typing frequency and speed on the incidence of upper extremity cumulative trauma disorder.

Typing in the work setting, with its emphasis on speed, force and repetitive movements and its tendency to be performed under less than optimum conditions has been one of the major causes of upper extremity cumulative trauma disorder (CTD). This disorder, also known as overuse syndrome, is a chronic condition believed to result from habitual overuse of the digits, hands or arms. The objective of this study was to examine the relationship between typing habits, specifically the influence of typing frequency, speed and style, on the incidence of injury. One hundred Israeli female typists aged between 20 and 60 years with no prior history of orthopedic or neurological disease participated in the study. Data collection took place at the work setting and consisted of a clinical evaluation of the upper extremities and trunk, a typing test, and a questionnaire which included questions concerning demographic information, occupational history, and upper extremity usage in the home and at work. Subjects were asked whether they had suffered from pain or other symptoms in the upper extremity (shoulder, arm, forearm, elbow or hand) on more than three occasions in the last year or on one occasion lasting more than a week. Subjects who answered no to this question were designated as 'non-sufferers'. Those who answered yes to the question were designated 'sufferers'. The 100 women who participated in the study represented a wide range of ages and educational levels. The variables describing on-the-job performance showed a wide range of values. Similar variability was found in the anthropometric variables. On the basis of the subjective criterion, 40 of the women belonged to the group labeled 'sufferers'. The remaining 60 subjects belonged to the group of 'non-sufferers'. The Odd's ratio test (OR), a common statistical procedure for risk factor estimation, was used to determine threshold levels associated with the development of CTD. Age, hours worked per week, typing speed, and years worked as a typist were variables in which at least one cut-off value generated a significant OR. The delineation of factors associated with typists who are classified as 'sufferers' establishes a portrait of the typical worker at risk for the development of CTD and provides insight into ways in which employers, clinicians and workers themselves could reduce the risk of CTD.

[Prostatic specific antigen for detection and monitoring of prostatic cancer].

Prostatic specific antigen (PSA) can be detected in normal and benign hypertrophic prostates, as well as in prostatic cancer and its metastases. Since it appears in the serum, this glycoprotein has become an established marker for the detection and monitoring of prostate cancer. Using a radioimmunoassay (CIS--Biointernational, France), we found serum PSA levels higher than 4 ng/ml in 55 of 58 patients with prostatic cancer. The concentrations were proportional to tumor stage: significantly higher in stages C and D than in stages A and B (p less than 0.002). In all 6 cases with occult prostatic carcinoma (stage A), levels were higher than 15 ng/ml. PSA was found to be a good indicator of response to therapy, as well as a marker of tumor progression during follow-up. After radical prostatectomy serum PSA levels decreased to below 1 ng/ml. Following radiotherapy levels returned to normal within 1-6 months in 8 of 11 patients. In 21 of 23 with metastases serum PSA decreased during hormonal treatment. In 3 who responded initially to hormonal therapy, levels increased before clinical manifestation of tumor progression. We conclude that PSA is a sensitive serum marker for the diagnosis of prostatic cancer in cases of metastatic disease of unknown origin, as well as for monitoring the response to treatment of prostatic carcinoma. The use of PSA serum levels for screening for prostatic cancer is still controversial.

Inhibition of chloroplast CF1-ATPase by vanadate.

Inhibition of ATPase activity by vanadate, having K1/2 of 0.5 mM, was demonstrated in the CF1-ATPase. The Ca(2+)-dependent ATPase activity of the isolated enzyme was inhibited in an allosteric manner by vanadate with a Hill coefficient of 3.19 +/- 0.6. Vanadate also inhibited ATPase and Pi-ATP exchange activities of the chloroplast membrane-bound enzyme. Using 51V NMR it was demonstrated that ATP caused partial release of about 1.87 equivalents while ADP caused additional binding of approximately 1.46 equivalents of vanadate, when added to a solution containing CF1 equilibrated with vanadate. The relevance of these results to a possible involvement of a pentacovalent phosphate as transition state intermediate in the hydrolysis of ATP by CF1-ATPase is discussed.

Spheroplast-derived membrane vesicles from Rhodobacter capsulatus cells catalyzing nucleotide transport.

Rodobacter capsulatus cells, which were cultured anaerobically in high light intensity, had fewer foldings in the cytoplasmic membrane than those which were grown in lower light intensities. Spheroplast-derived membrane fractions obtained from cells cultured under high light intensity contained a high yield of large right-side-out membrane vesicles. The right-side-out vesicles catalyzed reversible light-induced proton efflux as did intact cells. Nucleotide transport activity was also catalyzed by these membrane vesicles. This activity was indirectly monitored by measurement of photophosphorylation or hydrolysis of externally added diphospho- and triphosphonucleosides. These enzymatic activities occur inside the cytoplasmic membrane of spheroplasts and membrane vesicles and therefore require the transport of the externally added reagents. The indirect measurements of transport were complemented by the demonstration of direct uptake of radiolabeled nucleotides into the membrane vesicles. These data support the suggestion that a nucleotide transporter located in the cytoplasmic membrane of R. capsulatus bacteria mediates these activities.