How is the trade-off between adverse selection and discrimination risk affected by genetic testing? Theory and experiment.
We develop a theoretical analysis of two widely used regulations of genetic tests, Disclosure Duty and Consent Law, and we run an experiment in order to shed light on both the take-up rate of genetic testing and on the comparison of policyholders' welfare under the two regulations. Disclosure duty forces individuals to reveal their test results to insurers, exposing them to a discrimination risk. Consent Law allows them to hide any detrimental information, resulting in adverse selection. The experiment results in much lower genetic tests take-up rates with Disclosure Duty than with Consent Law, showing that subjects are very sensitive to the discrimination risk. Under Consent Law, take-up rates increase with the adverse selection intensity. A decrease in the test cost, and in adverse selection intensity, both make it more likely that Consent Law is preferred to Disclosure Duty.


Disorder in pentachloronitrobenzene, C(6)Cl(5)NO(2): a diffuse scattering study.
Monte Carlo computer simulation has been used to interpret and model observed single-crystal diffuse X-ray scattering data for pentachloronitrobenzene, C(6)Cl(5)NO(2). Each site in the crystal contains a molecule in one of six different basic orientations with equal probability. However, no short-range order amongst these different orientations has been detected. The strong, detailed and very distinctive diffraction patterns can be accounted for almost entirely on the assumption of random occupancy of each molecular site, but with very large local relaxation displacements that tend to increase the neighbouring distances for contacts involving NO(2)...NO(2) and NO(2)...Cl with a corresponding reduction for those involving Cl...Cl. The results show that the mean NO(2)...NO(2) distance is increased by approximately 0.6 Angstrom, compared with that given by the average structure determination.


Association between type II diabetes and colon cancer among Japanese with reference to changes in food intake.
Many epidemiological studies have provided support for the hypothesis that type II diabetes can increase the risk of colorectal cancer, but time trends, geographical distributions and host factors for the two diseases remain largely to be clarified. To address these issues, we investigated the epidemic pattern of colon cancer and type II diabetes among Japanese in Japan (J-Japanese), with consideration of the westernization of dietary habits. Over the last three decades, the increase in crude mortality rates of colon cancer from the Vital Statistics has closely paralleled the increment in prevalence rates (PRs) from hospital based surveys of diabetes. Age-standardized incidence rates (ASIRs) for colon cancer among Japanese in the United States (US-Japanese) were higher than those among J-Japanese and almost the same as those among US-Whites, while PRs for type II diabetes among US-Japanese were the highest in the three populations. Correlation analysis showed that PRs for type II diabetes had a positive association with ASIRs for colon cancer among the combination of Japanese and US-Japanese (r=0.79, p<0.01). Since 1950, intake of milk, meat, eggs and fat/oil has increased, while that of rice and potatoes has gradually decreased. Our findings indicate that the increment of ASIRs for colon cancer among J-Japanese might be closely associated with the increment of PRs for type II diabetes, reflecting the westernization of food intake.


Student Perceptions of Authoring a Publication Stemming from a Course-Based Undergraduate Research Experience (CURE).
Course-based undergraduate research experiences (CUREs) engage students in authentic research experiences in a course format and can sometimes result in the publication of that research. However, little is known about student-author perceptions of CURE publications. In this study, we examined how students perceive they benefit from authoring a CURE publication and what they believe is required for authorship of a manuscript in a peer-reviewed journal. All 16 students who were enrolled in a molecular genetics CURE during their first year of college participated in semistructured interviews during their fourth year. At the time of the interviews, students had been authors of a CURE publication for a year and a half. Students reported that they benefited personally and professionally from the publication. Students had varying perceptions of what is required for authorship, but every student thought that writing the manuscript was needed, and only two mentioned needing to approve the final draft. Additionally, we identified incomplete conceptions that students had about CURE publications. This work establishes student-perceived benefits from CURE publications and highlights the need for authorship requirements to be explicitly addressed in CUREs.


Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1.
Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 - 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 - 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.


Evaluation of tracking accuracy of the CyberKnife system using a webcam and printed calibrated grid.
Tracking accuracy for the CyberKnife's Synchrony system is commonly evaluated using a film-based verification method. We have evaluated a verification system that uses a webcam and a printed calibrated grid to verify tracking accuracy over three different motion patterns. A box with an attached printed calibrated grid and four fiducial markers was attached to the motion phantom. A target marker was positioned at the grid's center. The box was set up using the other three markers. Target tracking accuracy was evaluated under three conditions: 1) stationary; 2) sinusoidal motion with different amplitudes of 5, 10, 15, and 20 mm for the same cycle of 4 s and different cycles of 2, 4, 6, and 8 s with the same amplitude of 15 mm; and 3) irregular breathing patterns in six human volunteers breathing normally. Infrared markers were placed on the volunteers' abdomens, and their trajectories were used to simulate the target motion. All tests were performed with one-dimensional motion in craniocaudal direction. The webcam captured the grid's motion and a laser beam was used to simulate the CyberKnife's beam. Tracking error was defined as the difference between the grid's center and the laser beam. With a stationary target, mean tracking error was measured at 0.4 mm. For sinusoidal motion, tracking error was less than 2 mm for any amplitude and breathing cycle. For the volunteers' breathing patterns, the mean tracking error range was 0.78-1.67 mm. Therefore, accurate lesion targeting requires individual quality assurance for each patient.


Enantioselective extraction of unprotected amino acids coupled with racemization.
Scalable and economical methods for the production of optically pure amino acids, both natural and unnatural, are essential for their use as synthetic building blocks. Currently, enzymatic dynamic kinetic resolution (DKR) underpins some of the most effective processes. Here we report the development of enantioselective extraction coupled with racemization (EECR) for the chirality conversion of underivatized amino acids. In this process, the catalytic racemization of amino acids in a basic aqueous solution is coupled with the selective extraction of one enantiomer into an organic layer. Back-extraction from the organic layer to an acidic aqueous solution then completes the deracemization of the amino acid. The automation of the EECR process in a recycling flow reactor is also demonstrated. Continuous EECR is made possible by the sterically hindered chiral ketone extractant 5, which prevents the coextraction of the copper racemization catalyst because of its nonplanar geometry. Furthermore, the extractant 5 unexpectedly forms imines with amino acids faster and with greater enantioselectivity than less bulky derivatives, even though 5 cannot participate in intramolecular resonance-assisted hydrogen bonding. These features may allow EECR to challenge the preponderance of enzymatic DKR in the production of enantiomerically enriched amino acids.


ProteoMill: efficient network-based functional analysis portal for proteomics data.
Functional analysis has become a common approach to incorporate biological knowledge into the analysis of omics data, and to explore molecular events that govern a disease state. It is though only one step in a wider analytical pipeline that typically requires use of multiple individual analysis software. There is currently a need for a well-integrated omics analysis tool that performs all the steps. The ProteoMill portal is developed as an R Shiny application and integrates all necessary steps from data-upload, converting identifiers, to quality control, differential expression and network-based functional analysis into a single fast, interactive easy to use workflow. Further, it maintains annotation data sources up to date, overcoming a common problem with use of outdated information and seamlessly integrates multiple R-packages for an improved user-experience. The functionality provided in this software can benefit researchers by facilitating the exploratory analysis of proteomics data. ProteoMill is available at https://proteomill.com.


Effects of varying entry points and trendelenburg positioning degrees in internal jugular vein area measurements of newborns.
Recent guidelines from the National Institute for Clinical Excellence recommend the use of ultrasonography in the central venous catheterization of children. In this study, we aimed to compare area measurements using ultrasonography and efficiency of varying Trendelenburg degrees on the area measurements, for two different entry points used as internal jugular vein (IJV) cannulation points in newborns. Fifty-eight healthy newborns, weighing between 3000 and 3500 g, were recruited for this prospective study. Right IJV (RIJV) consecutive measurements were performed in three different Trendelenburg positions at 0°, 15°, and 30°, at two different entry points: The superior approach and an inferior approach. The landmark used in the superior approach was the top of the triangle formed by the two heads of the sternocleidomastoid muscle with the clavicle; while in the inferior approach, it was taken as the midpoint of the clavicle, as measured from the upper edge of the clavicle. The cross-sectional area (CSA) of the RIJV was significantly increased when using the inferior approach, compared to that in the superior approach, in all Trendelenburg degrees, including the neutral position. Both 15° and 30° Trendelenburg positioning resulted in a significant increase in CSA, both in superior and inferior approaches, when compared to neutral positioning. The use of 15° Trendelenburg positioning may have significant advantage for increasing the CSA when used with the inferior approach.


Amphetamine stereotypy: the influence of environmental factors and prepotent behavioral patterns on its topography and development.
This report describes a series of experiments, all of which demonstrate a strong contribution of the behavioral pattern manifested at the time of initial amphetamine injection to the topography and development of the stereotypy that develops with chronic amphetamine intoxication. These initial behavioral patterns reflect (i) learned behaviors, (ii) species-specific behaviors, (iii) behaviors associated with amphetamine arousal, and (iv) novel behaviors reflecting unique environmental circumstances prevailing at the time of administration. In an experiment using eight dogs administered amphetamine in a situation which allowed interaction between the animals, the behavioral stereotypies that developed were comprised of the social interaction patterns ongoing at the time of initial drug effects. Experiments with rats have demonstrated that the configuration of the enclosure in which they are injected influences the initial behavioral reactions to amphetamine and thus modifies the stereotypy. In experiments with cats pressing a lever to self-administer amphetamine, investigatory behavior at the lever-press operandi becomes incorporated as does the learned behavior response into the stereotypy. The behavioral patterns originally associated with amphetamine arousal eventually supersede the learned response component of the stereotypy. Finally, monkeys incorporate components of the initial behaviors associated with amphetamine administration into a wider range of stereotype patterns over months of chronic intoxication, and eventually the stereotypy may evolve into a specific dyskinesia involving movements of the original behavioral component.


In vivo inhibition of cysteine proteases provides evidence for the involvement of 'senescence-associated vacuoles' in chloroplast protein degradation during dark-induced senescence of tobacco leaves.
Breakdown of leaf proteins, particularly chloroplast proteins, is a massive process in senescing leaves. In spite of its importance in internal N recycling, the mechanism(s) and the enzymes involved are largely unknown. Senescence-associated vacuoles (SAVs) are small, acidic vacuoles with high cysteine peptidase activity. Chloroplast-targeted proteins re-localize to SAVs during senescence, suggesting that SAVs might be involved in chloroplast protein degradation. SAVs were undetectable in mature, non-senescent tobacco leaves. Their abundance, visualized either with the acidotropic marker Lysotracker Red or by green fluorescent protein (GFP) fluorescence in a line expressing the senescence-associated cysteine protease SAG12 fused to GFP, increased during senescence induction in darkness, and peaked after 2-4 d, when chloroplast dismantling was most intense. Increased abundance of SAVs correlated with higher levels of SAG12 mRNA. Activity labelling with a biotinylated derivative of the cysteine protease inhibitor E-64 was used to detect active cysteine proteases. The two apparently most abundant cysteine proteases of senescing leaves, of 40kDa and 33kDa were detected in isolated SAVs. Rubisco degradation in isolated SAVs was completely blocked by E-64. Treatment of leaf disks with E-64 in vivo substantially reduced degradation of Rubisco and leaf proteins. Overall, these results indicate that SAVs contain most of the cysteine protease activity of senescing cells, and that SAV cysteine proteases are at least partly responsible for the degradation of stromal proteins of the chloroplast.


Should two-drug initial therapy for hypertension be recommended for all patients?
Hypertension is a common disorder linked to increases in cardiovascular mortality and morbidity. Effective treatment decreases this excess mortality. Therapy with a single antihypertensive agent fails to achieve blood pressure goals in up to 75 % of patients. Compared to monotherapy, combination antihypertensive therapy, especially with fixed-dose (single pill) formulations, may more effectively control blood pressure and improve medication persistence while decreasing adverse effects, healthcare costs, and physician therapeutic inertia. Certain combinations, such as a calcium channel blocker and angiotensin converting enzyme inhibitor, have been associated with similar or fewer adverse effects and better outcomes than other combinations. In contrast, other combinations such as thiazide diuretics and β-blockers may cause more adverse effects than monotherapy. When choosing a thiazide diuretic, chlorthalidone is preferable to hydrochlorothiazide, given better efficacy and cardiovascular outcomes. Initial combination antihypertensive therapy may benefit patients with stage I or II hypertension and more widespread use should be encouraged.


Photorepair prevents ultraviolet-induced apoptosis in human cells expressing the marsupial photolyase gene.
Photolyase absorbs blue light and employs the energy to remove UV-induced DNA damage, cyclobutane pyrimidine dimers, or pyrimidine pyrimidone (6-4) lesions. These enzymes have been found in many living organisms ranging from bacteria to aplacental mammals, but their photoreactivation effect, such as survival increase of UV-irradiated cells by light-illumination, has not been identified in placental mammals, including humans. Therefore, we introduced a photolyase gene derived from the marsupial rat kangaroo, Potorous tridactylus, into HeLa cells and established the first human cell line capable of photorepairing UV-induced pyrimidine dimers. Several clones were found to increase cell survival after UV irradiation when illuminated by fluorescent light. The induction of apoptosis by UV irradiation was investigated in these photoreactivation-proficient cells. Several typical features of the programmed cell death, such as internucleosomal DNA degradation, presence of subdiploid cells, loss of membrane integrity, and chromosomal condensation, were found to be induced by UV in the HeLa cells, but they can be reduced by photorepair. This implicates that cyclobutane pyrimidine dimers cause UV-induced apoptosis in human cells.


Properties of the primary somatosensory cortex projection to the primary motor cortex in the mouse.
The primary somatosensory (S1) and primary motor (M1) cortices are reciprocally connected, and their interaction has long been hypothesized to contribute to coordinated motor output. Very little is known, however, about the nature and synaptic properties of the S1 input to M1. Here we wanted to take advantage of a previously developed sensorimotor slice preparation that preserves much of the S1-to-M1 connectivity (Rocco MM, Brumberg JC. J Neurosci Methods 162: 139-147, 2007), as well as available optogenetic methodologies, in order to investigate the synaptic profile of this projection. Our data show that S1 input to pyramidal cells of M1 is highly homogeneous, possesses many features of a "driver" pathway, such as paired-pulse depression and lack of metabotropic glutamate receptor activation, and is mediated through axons that terminate in both small and large synaptic boutons. Our data suggest that S1 provides M1 with afferents that possess synaptic and anatomical characteristics ideal for the delivery of strong inputs that can "drive" postsynaptic M1 cells, thereby potentially affecting their output.


Comparison of the fibronectin-binding protein FNE from Streptococcus equi subspecies equi with FNZ from S. equi subspecies zooepidemicus reveals a major and conserved difference.
The gene fnz from Streptococcus equi subspecies zooepidemicus encodes a cell surface protein that binds fibronectin (Fn). Fifty tested isolates of S. equi subspecies equi all contain DNA sequences with similarity to fnz. This work describes the cloning and sequencing of a gene, designated fne, with similarity to fnz from two S. equi subspecies equi isolates. The DNA sequences were found to be identical in the two strains, and sequence comparison of the fne and fnz genes revealed only minor differences. However, one base deletion was found in the middle of the fne gene and eight base pairs downstream of the altered reading frame there is a stop codon. An Fn-binding protein was purified from the growth medium of a subspecies equi culture. Determination of the NH(2)-terminal amino acid sequence and molecular mass, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed that the purified protein is the gene product of the 5'-terminal half of fne. Fn-binding activity has earlier only been found in the COOH-terminal half of FNZ. By the use of a purified recombinant protein containing the NH(2) half of FNZ, we provide here evidence that this half of the protein also harbors an Fn-binding domain.


Hospital pricing: cost shifting and competition.
The issue of cost shifting has taken on enormous policy implications. It is estimated that unsponsored and undercompensated hospital costs--one measure of cost shifting--has totaled $21.5 billion in 1991. The health services research literature indicates that hospitals set different prices for different payers. However, the empirical evidence on hospitals' ability to raise prices to one payer to make up for unsponsored care or lower payments by other payers is mixed at best. No study has concluded that hospitals have raised prices to fully adjust for such actions. The extent of cost shifting is limited by the market. When a hospital has market power, it is able to set prices above marginal costs. However, when a buyer has enough patient/subscribers and a willingness to direct them to particular providers based on price considerations, hospitals have less flexibility in raising prices above costs. Thus, the extent of cost shifting is limited by the market. Cost shifting is not as easy as it may have been in the past because the nature of hospital and insurer competition has changed radically in the last decade. While hospital quality, services, and amenities still matter, some buyers are increasingly concerned about the price they pay. Evidence from studies of PPO and HMO negotiations with hospitals suggests that hospitals' market power is eroding, at least in some areas. In areas with relatively few hospital competitors and little PPO or HMO activity, Medicaid and Medicare price reductions and uncompensated care burdens will be partially absorbed by higher prices paid by private payers. In more price sensitive markets and in markets in which prices to private payers have risen to those commensurate with the market power of local hospitals, such cost shifting will not occur. A market-based approach in hospital pricing requires an explicit policy for the uninsured. In a competitive market, a hospital that traditionally cared for the uninsured by spending some of its profits on them will be unable to do so, at least to the same extent as it did in the past. Increased competition in health care without consideration of the uninsured will decrease the uninsured's access to care.


Dose-finding study of paclitaxel and cyclophosphamide in women with advanced breast cancer.
The primary aim of this study was to define the maximum tolerated doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 3-hour infusion and cyclophosphamide given by intravenous bolus every 3 weeks in patients with breast cancer. Patients had received a maximum of one prior chemotherapy for advanced disease. The maximum tolerated dose of the combination was also determined with granulocyte colony-stimulating factor (G-CSF) support. The 80 women who took part in this study received 347 fully evaluable courses of therapy. Starting doses were paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2; G-CSF support (5 microg/kg subcutaneously) was added at the subsequent cycle if specific dose-limiting toxicities had occurred during the previous cycle. Febrile neutropenia and severe thrombocytopenia defined the maximum tolerated doses as paclitaxel 200 mg/m2 and cyclophosphamide 2,000 mg/m2, with or without G-CSF support, in patients with or without a prior chemotherapy. Recommended doses were paclitaxel 200 mg/m2 and cyclophosphamide 1,750 mg/m2 in these two groups of patients. The overall response rate was 25% among patients who had received prior therapy for metastatic disease and 50% in patients who had not been previously treated. Complete remissions were reported in 9% of patients, but only among those who were previously untreated.


Hospitalization during pregnancy according to childbirth financial coverage: a population-based study.
Objective To analyze the occurrence, profile and main causes of hospitalization during pregnancy according to the type of childbirth financial coverage. Method A cross-sectional population-based study carried out with puerperal women through a stratified sample, calculated according to the hospital and the type of childbirth financial coverage source: public sector (SUS) or private (not SUS). The sociodemographic profile, the rate of obstetric complications and the causes of hospitalization were analyzed, coded according to International Classification of Diseases. Results A total of 928 postpartum women were interviewed, of whom 32.2% reported at least one hospitalization during pregnancy. Those with childbirth covered by SUS were less favored because they were the majority among hospitalized women (57.2%), with a higher percentage of adolescents (18.1%), lower education level (91.8%), low family income (39.3%) and fewer prenatal consultations (25.3%). The most frequent causes of hospitalization were "other maternal diseases that complicate pregnancy" (24.6%) (with emphasis on anemia and influenza), urinary tract infection (13.1%), preterm labor (8.7%) and hypertension (7.2%). Conclusion Anemia, influenza, urinary tract infection, preterm labor and hypertension should especially be prevented and treated to avoid hospital admissions during pregnancy, especially among pregnant women covered by SUS.


Thermostat Influence on the Structural Development and Material Removal during Abrasion of Nanocrystalline Ferrite.
We consider a nanomachining process of hard, abrasive particles grinding on the rough surface of a polycrystalline ferritic work piece. Using extensive large-scale molecular dynamics (MD) simulations, we show that the mode of thermostating, i.e., the way that the heat generated through deformation and friction is removed from the system, has crucial impact on tribological and materials related phenomena. By adopting an electron-phonon coupling approach to parametrize the thermostat of the system, thus including the electronic contribution to the thermal conductivity of iron, we can reproduce the experimentally measured values that yield realistic temperature gradients in the work piece. We compare these results to those obtained by assuming the two extreme cases of only phononic heat conduction and instantaneous removal of the heat generated in the machining interface. Our discussion of the differences between these three cases reveals that although the average shear stress is virtually temperature independent up to a normal pressure of approximately 1 GPa, the grain and chip morphology as well as most relevant quantities depend heavily on the mode of thermostating beyond a normal pressure of 0.4 GPa. These pronounced differences can be explained by the thermally activated processes that guide the reaction of the Fe lattice to the external mechanical and thermal loads caused by nanomachining.


Inhibition of prolactin secretion delays extinction of circadian LH surges in ovariectomized rats bearing estradiol implants.
Ovariectomized rats bearing Silastic capsules containing estradiol exhibit a daily afternoon surge of luteinizing hormone (LH) which decreases with time until it is undetectable by Day 10 after implantation of estradiol. Increases in basal prolactin levels as well as afternoon surges are also observed. To determine if increased prolactin secretion contributed to the extinction of the circadian LH surges, we examined the patterns of LH and prolactin secretion in rats in which prolactin was suppressed by bromocriptine treatment. In vehicle-treated control rats, the magnitude of the LH surges decreased with time. Large LH surges were observed on Days 2 and 4. A significant decrease in the surge occurred on Day 6, and it disappeared by Day 10. Animals treated with bromocriptine also exhibited large LH surges on Days 2 and 4, and in addition, secreted a greater amount of LH than the control group on Days 6, 8, and 10. In ovariectomized rats bearing estradiol implants, large afternoon surges in prolactin were observed and by Day 6, basal prolactin levels were also elevated. Bromocriptine treatment completely suppressed prolactin secretion through Day 6, but a small afternoon rise was observed on Days 8 and 10. These findings suggest that elevated prolactin secretion may be one factor contributing to the extinction of circadian LH surges in the estrogen-treated rat.


Adherence to a Mediterranean-type diet and reduced prevalence of clustered cardiovascular risk factors in a cohort of 3,204 high-risk patients.
The Mediterranean food pattern (MeDiet) has been suggested to have beneficial effects on cardiovascular risk factors. Scarcity of assessment of this effect on large samples of patients at high risk is, however, observed. Our objective was to estimate the association between adherence to MeDiet and the prevalence of risk factors in 3,204 asymptomatic high-risk patients. Cross-sectional assessment of baseline characteristics of participants in a primary prevention trial. Participants were assessed by their usual primary-care physicians to ascertain the prevalence of diet-related cardiovascular risk factors (diabetes, hypertension, dyslipidemia, or obesity) using standard diagnostic criteria. A dietitian interviewed each participant to obtain a 14-point score measuring the degree of adherence to MeDiet. Adherence to MeDiet was inversely associated with individual risk factors and, above all, with the clustering of them. The multivariate adjusted odds ratio to present simultaneously the four risk factors for those above the median value of the MeDiet score was 0.67 (95% confidence interval: 0.53-0.85). The multivariate odds ratios for successive categories of adherence to MeDiet were 1 (ref.), 1.03, 0.85, 0.70 and 0.54 (P for trend <0.001). Following a MeDiet was inversely associated with the clustering of hypertension, diabetes, obesity, and hypercholesterolemia among high-risk patients.


Recirculation of biomass ashes onto forest soils: ash composition, mineralogy and leaching properties.
In Denmark, increasing amounts of wood ashes are generated from biomass combustion for energy production. The utilisation of ashes on top of forest soil for liming purposes has been proposed asan alternative to landfilling. Danish wood ash samples were collected and characterised with respect to chemical composition, mineralogy and leaching properties (batch leaching at L/S 2 and 10L/kg, and pH-dependent leaching at 10L/kg). Large variations in the ash liming properties were observed (ANC7.5: 1.8-6.4meqH+/g), indicating that similar soil application dosages may result in different liming effects. High contents of Ca, Si, P, K and Mg were observed in all samples, while the highest contents of S and N were found in fly ashes and mixed ashes (combination of fly and bottom ashes). Similarly, the highest contents of some trace metals, e.g. Cd, Mo and Se, were observed for fly ash. Releases of major, minor and trace elements were affected significantly by pH: high releases of PO43-, Mg, Zn, Cu and Cd were found for acidic conditions relevant to forest soils, while the highest releases of Mo and Cr were observed in alkaline conditions. Mineral phases were selected based on XRD analyses and the existing literature, and they were applied as inputs for the geochemical modelling of pH-dependent leaching. Mineral dissolution was found adequate for a wide range of major elements and nutrients, while the description of trace elements could be done only for parts of the pH-range. Content and leaching of PAHs were observed below detection limits. The source-term release of Ca, K, Mg, Mn, and P in acidic conditions relevant to forest soils was higher than ten years of atmospheric deposition, in contrast to the relatively low release of Al, Fe and Na. The potential release of Cd was found to be the most critical element compared with soil quality criteria, whereas the maximum theoretical loads of Ba, Cd, Cr, Sr, Mo, Ni, Pb, Sb, Se, Sn and V were relatively low.


Genomic organization of the S core region and the S flanking regions of a class-II S haplotype in Brassica rapa.
The nucleotide sequence of an 86.4-kb region that includes the SP11, SRK, and SLG genes of Brassica rapa S-60 (a class-II S haplotype) was determined. In the sequenced region, 13 putative genes were found besides SP11-60, SRK-60, and SLG-60. Five of these sequences were isolated as cDNAs, five were homologues of known genes, cDNAs, or ORFs, and three are hypothetical ORFs. Based on their nucleotide sequences, however, some of them are thought to be non-functional. Two regions of colinearity between the class-II S-60 and Brassica class-I S haplotypes were identified, i.e., S flanking region 1 which shows partial colinearity of non-genic sequences and S flanking region 2 which shows a high level of colinearity. The observed colinearity made it possible to compare the order of SP-11, SRK, and SLG genes in the S locus between the five sequenced S haplotypes. It emerged that the order of SRK and SLG in class-II S-60 is the reverse of that in the four class-I S haplotypes reported so far, and the order of SP11, SRK and SLG is the opposite of that in the class-I haplotype S-910. The possible gene designated as SAN1 (S locus Anther-expressed Non-coding RNA like-1), which is located in the region between SP11-60 and SRK-60, has features reminiscent of genes for non-coding RNAs (ncRNAs), but no homologous sequences were found in the databases. This sequence is transcribed in anthers but not in stigmas or leaves. These features of the genomic structure of S-60 are discussed with special reference to the characteristics of class-II S haplotypes.


A provincial adaptation of clinical practice guidelines for depression in primary care: a case illustration of the ADAPTE method.
Mental health services for patients with a major depressive disorder are commonly delivered by primary care. To support the uptake of clinical practice guidelines in primary care, we developed and disseminated a practice protocol for depression tailored for a multidisciplinary audience of primary mental health care providers with the ADAPTE methodology. The research questions addressed in this study aimed at examining the experience of the development process of a mental health practice protocol in terms of adaptation, facilitation and implementation. We present a descriptive case study of the development and implementation of a practice protocol for major depressive disorder for primary mental health care in the organizational and cultural context of the province of Québec (Canada), following the steps of the ADAPTE methodology. An expert committee composed of general practitioners, mental health specialists, health care administrators and decision makers at regional and provincial levels participated in the protocol development process. The practice protocol was based on two clinical practice guidelines: the NICE guideline on the treatment and management of depression in adults (2009, 2010) and the Canadian Network for Mood and Anxiety Treatments clinical guidelines for the management of major depressive disorder in adults (2009). A stepped care model was embedded in the protocol to facilitate the implementation of clinical recommendations in primary mental health care. A multifaceted dissemination strategy was used to support the uptake of the protocol recommendations in clinical practice. The ADAPTE methodology provided structure, rigour and efficiency to the trans-contextual adaptation of guideline recommendations. We will share the challenges associated with the adaptation of clinical recommendations and organizational strategies for a mental health guideline, and the dissemination of the practice protocol in primary care.


Cardiac catheterization and postoperative acute kidney failure in congenital heart pediatric patients.
Acute renal failure (ARF) is a severe complication of cardiac operations in pediatric patients. Angiography with the exposure to contrast media is a risk factor for ARF. In the present study, we explored the association between timing of angiography, dose of contrast media, and the incidence of ARF after cardiac operations in pediatric patients. We performed a retrospective analysis of prospectively collected data. Angiographic data and other covariates were collected in 277 patients aged ≤12 years receiving angiography and cardiac operations during the same hospital stay. Renal outcome was assessed according to the pediatric Risk, Injury, Failure, Loss of function, End stage score (pRIFLE). One hundred seventy-seven (64%) patients suffered some degree of postoperative renal dysfunction, and 55 (20%) had ARF (pRIFLE stage Failure). Patients with ARF received a significantly (P < 0.001) larger dose of iodine contrast media (4.6 ± 2.6 g/kg) with respect to the other patients (2.8 ± 2.2 g/kg), with a relative risk increase for ARF of 31% per each incremental iodine dose of 1 g/kg at the univariate analysis. A multivariable risk model demonstrated that the risk for ARF is 20 times higher in patients aged younger than 2 years and 3 times higher in case of postoperative low cardiac output. Within this model, the iodine dose on angiography is confirmed as an independent risk factor for ARF, with a relative risk increase for ARF of 16% per each incremental iodine dose of 1 g/kg. Angiography before cardiac surgery is an important risk factor for ARF in pediatric patients. Being a modifiable risk factor, the contrast media dose should be limited to the lowest possible value, avoiding large doses of iodine which, together with other factors (age and postoperative low cardiac output), concur in the determinism of postoperative ARF.


High-resolution mass spectrometric identification and quantification of glucocorticoid compounds in various wastewaters in the Netherlands.
In the past two decades much research effort has focused on the occurrence, effects, and risks of estrogenic compounds. However, increasing emissions of new emerging compounds may also affect the action of hormonal pathways other than the estrogenic hormonal axis. Recently, a suite of novel CALUX bioassays has become available that enables looking further than estrogenic effects only. By employing these bioassays, we recently showed high glucocorticogenic activity in wastewaters collected at various sites in The Netherlands. However, since bioassays provide an integrated biological response, the identity of the responsible biological compounds remained unknown. Therefore, our current objective was to elucidate the chemical composition of the wastewater extracts used in our previous study by means of LC-high-resolution Orbitrap MS/MS and to determine if the compounds quantified could account for the observed glucocorticoid responsive (GR) CALUX bioassay response. The mass spectrometric analysis revealed the presence of various glucocorticoids in the range of 13-1900 ng/L. In extracts of hospital wastewater-collected prior to sewage treatment-several glucocorticoids were identified (cortisol 275-301 ng/L, cortisone 381-472 ng/L, prednisone 117-545 ng/L, prednisolone 315-1918 ng/L, and triamcinolone acetonide 14-41 ng/L) which are used to treat a great number of human pathologies. A potency balance calculation based on the instrumental analyses and relative potencies (REPs) of the individual glucocorticoids supports the conclusion that triamcinolone acetonide (REP = 1.3), dexamethasone (REP = 1), and prednisolone (REP = 0.2) are the main contributors to the glucocorticogenic activity in the investigated wastewater extracts. The action of these compounds is concentration additive and the overall glucocorticogenic activity can be explained to a fairly large extent by their contribution.


The absence of the mitochondrial ATP synthase delta subunit promotes a slow growth phenotype of rho- yeast cells by a lack of assembly of the catalytic sector F1.
In the yeast Saccharomyces cerevisiae, inactivation of the gene encoding the delta subunit of the ATP synthase led to a lack of assembly of the catalytic sector. In addition a slow-growth phenotype was observed on fermentable medium. This alteration appears in strains lacking intact mitochondrial DNA and showing a defect in the assembly of the catalytic sector, such as the yeast strain inactivated in the gene encoding the epsilon subunit. In rho mitochondria having an intact F1, the ion movement resulting from the exchange of ADP formed in the organelle and ATP entering the mitochondrial compartment led to a mitochondrial transmembranous potential delta psi that was sensitive to carboxyactractyloside. This ion movement was dramatically decreased in rho mitochondria lacking the delta subunit and thus the F1 sector, whereas a cell devoid of delta subunit and complemented with a plasmid harboring the ATPdelta gene displayed an assembled F1, a normal generation time and a fully restored mitochondrial potential. This result could be linked to the involvement of the membrane potential delta psi which is indispensible for mitochondrial biogenesis.


Bioaccumulation, toxicokinetics, and effects of copper from sediment spiked with aqueous Cu, nano-CuO, or micro-CuO in the deposit-feeding snail, Potamopyrgus antipodarum.
The present study examined the relative importance of copper (aqueous Cu and CuO particles of different sizes) added to sediment to determine the bioaccumulation, toxicokinetics, and effects in the deposit feeder Potamopyrgus antipodarum. In experiment 1, the bioaccumulation of Cu (240 µg Cu/g dry wt of sediment) added as aqueous Cu (CuCl2 ), nano- (6 nm, 100 nm), or micro- (<5 µm) CuO particles in adult snails was measured. In experiment 2, a more comprehensive analysis of the toxicokinetics of Cu (aqueous Cu, 6 nm, or 100 nm) was conducted. In experiment 3, the effects of Cu form (aqueous Cu and 6 nm CuO) on juvenile growth and survival at 0, 30, 60, 120, and 240 µg Cu/g dry weight sediment were assessed. Snails took up less of the 5-µm CuO particles than nano-CuO or aqueous Cu. A substantial fraction of Cu taken up was associated with shell, and this was rapidly lost when snails were transferred to clean sediment. Net uptake rates from sediment amended with 6 nm CuO and aqueous Cu were significantly higher (∼40-50%) than from sediment amended with 100 nm CuO. During 2 wk of depuration, there were no significant differences in depuration rates (kd ) among forms (aqueous Cu: kd = -0.12 wk(-1) ; 6 nm CuO: kd = -0.22 wk(-1) ; 100 nm CuO: kd = -0.2 wk(-1) ). Average juvenile growth was reduced by 0.11 mm (41%) at measured exposure concentrations of 127.2 µg Cu/g dry weight sediment for aqueous Cu and 71.9 µg Cu/g dry weight sediment for 6 nm CuO compared with control; however, differences between forms were not statistically significant. Juvenile snails in the highest exposure concentrations (aqueous Cu and 6-nm CuO groups pooled) reduced their growth by 0.18 mm on average (67%) compared with the control group. Although we observed minor differences in toxicity among Cu forms, effects on juvenile snail growth occurred at bulk sediment concentrations lower than those in the Canadian interim sediment quality guidelines. Characterization of the CuO particles showed that particle size distributions of commercially prepared particles deviated substantially from the manufacturers' specifications and highlighted the importance of fully characterizing particles when using them in toxicity tests.


Effects of starvation in infancy (pyloric stenosis) on subsequent learning abilities.
The model of starvation in this study was the medical condition of congenital hypertrophic pyloric stenosis. Pyloric stenosis involves a period of brief starvation in early infancy, is unrelated to socioeconomic conditions, and is easily correctable. A number of specific learning abilities together with the general adjustment of 50 subjects, 5 to 14 years old, who had PS were studied and compared to those of 44 siblings and 50 matched controls. Learning ability was negatively correlated with the degree of severity of the starvation. Starvation resulting in reduction of more than 10% of the expected body weight in infancy was associated with poorer learning abilities, especially those involving short-term memory and attention.


Effect of 5'-deoxy-5'-isobutylthioadenosine on putrescine uptake and polyamine biosynthesis by chick embryo fibroblasts.
The effect of 5'-deoxy-5'-S-isobutylthioadenosine (SIBA) on polyamine biosynthesis has been studied by using cultured chick embryo fibroblasts. It has been shown that the drug inhibits the uptake of [14C]putrescine and its conversion into labelled spermidine or spermine. The inhibitory effect is reversed by removing the inhibitor after exposing the cells to the drug for 24 h. SIBA also caused a significant decrease in cellular spermine levels and an accumulation of putrescine. These changes are reversed by removing the inhibitor. SIBA had the same effect on chick embryo fibroblasts transformed by Rous sarcoma virus; a decrease in cellular spermine levels in SIBA-treated cells was observed. In all the experiments SIBA caused a reduction in the spermine/putrescine and spermidine/putrescine ratios. It is suggested that SIBA is not only an inhibitor of transmethylation but also interferes with polyamine biosynthesis, probably by blocking aminopropyltransferase.


[The variable picture of gastric carcinoid].
Carcinoids are endocrine tumors which develop from enterochromaffin cells and will be found in more than 80% in the gastrointestinal tract. Only 2-3% of these carcinoids is located in the stomach. The rarity of their occurrence and the wide variety of radiographic features (intramural defects, multiple gastric polyps, large gastric ulcers and polypoid intraluminal lesions) make their recognition difficult. We report 3 cases of gastric carcinoid, one of them presented with pernicious anemia, which has been reported more frequently in literature. One patient showed the unusual combination of adenocarcinoma and a carcinoid with a stalk in the stomach.


Physician-assisted suicide and older patients' perceived duty to die.
Physician-assisted suicide (PAS) may soon be legal in the United States. The legal option of PAS will place certain hardships on older persons. Many older individuals may feel a duty to die to avoid becoming a burden to their families. Moreover, the suicide option becomes attractive because medical care at the end of life is often fragmented, impersonal, and unable to meet the needs of the dying individual. To make suicide less attractive, nurses must help restructure the care of the dying to help meet their needs and reduce the burdens of caregivers.


[Diarrhea in the elderly].
The causes of acute and chronic diarrheal disorders and their underlying pathophysiologic mechanisms are common at all ages. The impact of diarrhea, however, may be more pronounced in the elderly due to various causes, such as age-related structural and functional intestinal changes, concomittant illnesses, consume of preventive and therapeutic drugs, impaired sense of hunger and thirst, compromised nutrition and hydration to withstand the effect of diarrhea, more frequent hospital admissions and courses of antibiotics, and more subtle clinical presentation than in younger patients. These aspects have to be considered when investigating and treating diarrhea of older patients. Diarrhea may have a devastating effect on quality of life in the elderly and above all, fecal incontinence is a common consequence. In elderly institutionalized persons, fecal impaction in the rectum with liquid stool leaking around the hard, dry fecal mass is often associated with fecal incontinence. In this article, general aspects of diarrhea in the elderly, clostridium difficile infection, ischemic colitis, microscopic colitis and incontinence due to fecal impaction are discussed.


High-Resolution Imaging of Mitochondria and Mitochondrial Nucleoids in Differentiated SH-SY5Y Cells.
Mitochondria are highly dynamic organelles which form intricate networks with complex dynamics. Mitochondrial transport and distribution are essential to ensure proper cell function, especially in cells with an extremely polarised morphology such as neurons. A layer of complexity is added when considering mitochondria have their own genome, packaged into nucleoids. Major mitochondrial morphological transitions, for example mitochondrial division, often occur in conjunction with mitochondrial DNA (mtDNA) replication and changes in the dynamic behaviour of the nucleoids. However, the relationship between mtDNA dynamics and mitochondrial motility in the processes of neurons has been largely overlooked. In this chapter, we describe a method for live imaging of mitochondria and nucleoids in differentiated SH-SY5Y cells by instant structured illumination microscopy (iSIM). We also include a detailed protocol for the differentiation of SH-SY5Y cells into cells with a pronounced neuronal-like morphology and show examples of coordinated mitochondrial and nucleoid motility in the long processes of these cells.


Regional brain changes in aging healthy adults: general trends, individual differences and modifiers.
Brain aging research relies mostly on cross-sectional studies, which infer true changes from age differences. We present longitudinal measures of five-year change in the regional brain volumes in healthy adults. Average and individual differences in volume changes and the effects of age, sex and hypertension were assessed with latent difference score modeling. The caudate, the cerebellum, the hippocampus and the association cortices shrunk substantially. There was minimal change in the entorhinal and none in the primary visual cortex. Longitudinal measures of shrinkage exceeded cross-sectional estimates. All regions except the inferior parietal lobule showed individual differences in change. Shrinkage of the cerebellum decreased from young to middle adulthood, and increased from middle adulthood to old age. Shrinkage of the hippocampus, the entorhinal cortices, the inferior temporal cortex and the prefrontal white matter increased with age. Moreover, shrinkage in the hippocampus and the cerebellum accelerated with age. In the hippocampus, both linear and quadratic trends in incremental age-related shrinkage were limited to the hypertensive participants. Individual differences in shrinkage correlated across some regions, suggesting common causes. No sex differences in age trends except for the caudate were observed. We found no evidence of neuroprotective effects of larger brain size or educational attainment.


Psycho-Cognitive Intervention for ASD from Cross-Species Behavioral Analyses of Infants, Chicks and Common Marmosets.
Educational treatment to support social development of children with autism spectrum disorder (ASD) is an important topic in developmental psychiatry. However, it remains difficult to objectively quantify the socio-emotional development of ASD children. To address this problem, we developed a novel analytical method that assesses subjects' complex behaviors using multivariate analysis, 'Behavior Output analysis for Quantitative Emotional State Translation' (BOUQUET). Here, we examine the potential for psycho-cognitive ASD therapy based on comparative evaluations of clinical (human) and experimental (animal) models. Our observations of ASD children (vs. their normally developing siblings) and the domestic chick in socio-sensory deprivation models show the importance of unimodal sensory stimulation, particularly important for tactile- and auditory-biased socialization. Identifying psycho-cognitive elements in early neural development, human newborn infants in neonatal intensive care unit as well as a New World monkey, the common marmoset, also prompted us to focus on the development of voluntary movement against gravity. In summary, striking behavioral similarities between children with ASD and domestic chicks' socio-sensory deprivation models support the role of multimodal sensory-motor integration as a prerequisite step for normal development of socio-emotional and psycho-cognitive functions. Data obtained in the common marmoset model also suggest that switching from primitive anti-gravity reflexes to complex voluntary movement may be a critical milestone for psycho-cognitive development. Combining clinical findings with these animal models, and using multivariate integrative analyses may facilitate the development of effective interventions to improve social functions in infants and in children with neurodevelopmental disorders.


[A case of chronic pesticide poisoning in a storehouse worker].
The article narrates on a female worker's chronic intoxication case with a set of chemical weed- and pest-killers. The clinical picture predominantly displayed the CNS hypothalamic sections' damages which became apparent through sympatho-adrenal crises and the symptoms of the intoxication characteristic of phosphorus compounds, hypotension, bradycardia and gastric juice hyperacidity.


High-frequency stimulation selectively blocks different types of fibers in frog sciatic nerve.
Conduction block using high-frequency alternating current (HFAC) stimulation has been shown to reversibly block conduction through various nerves. However, unlike simulations and experiments on myelinated fibers, prior experimental work in our lab on the sea-slug, Aplysia, found a nonmonotonic relationship between frequency and blocking thresholds in the unmyelinated fibers. To resolve this discrepancy, we investigated the effect of HFAC waveforms on the compound action potential of the sciatic nerve of frogs. Maximal stimulation of the nerve produces a compound action potential consisting of the A-fiber and C-fiber components corresponding to the myelinated and unmyelinated fibers' response. In our study, HFAC waveforms were found to induce reversible block in the A-fibers and C-fibers for frequencies in the range of 5-50 kHz and for amplitudes from 0.1-1 mA. Although the A-fibers demonstrated the monotonically increasing threshold behavior observed in published literature, the C-fibers displayed a nonmonotonic relationship, analogous to that observed in the unmyelinated fibers of Aplysia. This differential blocking behavior observed in myelinated and unmyelinated fibers during application of HFAC waveforms has diverse implications for the fields of selective stimulation and pain management.


The non-surgical management for hemorrhoidal disease. A systematic review.
The non-surgical treatments for hemorrhoids are cost and time-saving techniques usually performed in patients suffering early hemorrhoidal disease. The most used are rubber band ligation (RBL), injection sclerotherapy (IS), and infrared coagulation (IRC). We performed a systematic review in order to evaluate: do these procedures really help to avoid further more aggressive treatments? What are the common harms? What are the rare harms? How many recurrences there are? A total of 21 RCTs were included in this review: 12 on RBL, 4 on IRC and 5 on IS. In RBL bleeding stops in up to 90% and III degree hemorrhoids improves in 78%-83.8%. IV degree prolapse should have a more invasive treatment. The commonest complications are bleeding and pain (8-80%). IRC related improvement is 78%, 51% and 22% for I, II and III degree. Post-operative pain occurs in 15-100% and post-operative bleeding ranges from 15% to 44%. Recurrence rate is 13% at a three months follow-up. IS brings to the resolution of prolapse in 90%-100% of II degree and allows good results for III degree even if reported only by case series. The post-procedural pain is 36%-49%. Bleeding is a very rare harm. Even if not definitive, these treatments could be an alternative for mild symptomatic patients after a clear explanation of recurrence rates and possible complications.


[The videolaparoscopic splenectomy by spleen injuries].
The results of 9 videolaparoscopic splenectomies were analyzed. Indications and contraindications to the procedure were formulated, as well as the operative technique. The videolaparoscopic splenectomy proved to be more safe and effective in comparison with the traditional method.


Structural basis for two efficient modes of agropinic acid opine import into the bacterial pathogen Agrobacterium tumefaciens.
Agrobacterium tumefaciens pathogens genetically modify their host plants to drive the synthesis of opines in plant tumors. The mannityl-opine family encompasses mannopine, mannopinic acid, agropine and agropinic acid. These opines serve as nutrients and are imported into bacteria via periplasmic-binding proteins (PBPs) in association with ABC transporters. Structural and affinity data on agropine and agropinic acid opines bound to PBPs are currently lacking. Here, we investigated the molecular basis of AgtB and AgaA, proposed as the specific PBP for agropine and agropinic acid import, respectively. Using genetic approaches and affinity measurements, we identified AgtB and its transporter as responsible for agropine uptake in agropine-assimilating agrobacteria. Nonetheless, we showed that AgtB binds agropinic acid with a higher affinity than agropine, and we structurally characterized the agropinic acid-binding mode through three crystal structures at 1.4, 1.74 and 1.9 Å resolution. In the crystallization time course, obtaining a crystal structure of AgtB with agropine was unsuccessful due to the spontaneous lactamization of agropine into agropinic acid. AgaA binds agropinic acid only with a similar affinity in nanomolar range as AgtB. The structure of AgaA bound to agropinic acid at 1.65 Å resolution defines a different agropinic acid-binding signature. Our work highlights the structural and functional characteristics of two efficient agropinic acid assimilation pathways, of which one is also involved in agropine assimilation.


Developing a Preoperative Algorithm for the Diagnosis of Uterine Leiomyosarcoma.
Early diagnosis of the rare and life-threatening uterine leiomyosarcoma (LMS) is essential for prompt treatment, to improve survival. Preoperative distinction of LMS from benign leiomyoma remains a challenge, and thus LMS is often diagnosed post-operatively. This retrospective observational study evaluated the predictive diagnostic utility of 32 preoperative variables in 190 women who underwent a hysterectomy, with a postoperative diagnosis of leiomyoma (n = 159) or LMS (n = 31), at the Liverpool Women's National Health Service (NHS) Foundation Trust, between 2010 and 2019. A total of 7 preoperative variables were associated with increased odds of LMS, including postmenopausal status (p < 0.001, OR 3.08), symptoms of pressure (p = 0.002, OR 2.7), postmenopausal bleeding (p = 0.001, OR 5.01), neutrophil count ≥7.5 × 109/L (p < 0.001, OR 5.72), haemoglobin level <118 g/L (p = 0.037, OR 2.22), endometrial biopsy results of cellular atypia or neoplasia (p = 0.001, OR 9.6), and a mass size of ≥10 cm on radiological imaging (p < 0.0001, OR 8.52). This study has identified readily available and easily identifiable preoperative clinical variables that can be implemented into clinical practice to discern those with high risk of LMS, for further specialist investigations in women presenting with symptoms of leiomyoma.


Optimizing percutaneous coronary revascularization in diabetic women: analysis from the EPISTENT trial.
Clinical studies have demonstrated that diabetic women have an increased risk of death and nonfatal myocardial infarction (MI) after percutaneous coronary intervention (PCI). However, there have been few data regarding the outcome of diabetic women in the current era of percutaneous coronary revascularization. Using the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial (EPISTENT) database, we determined morbidity and mortality for diabetic women undergoing PCT in the current era using stents and the glycoprotein IIb/IIIa inhibitor, abciximab. There were no mortality differences in the diabetic women treated with stent-placebo, stent-abciximab, or balloon-abciximab at 30 days and 6 months. However, the primary end point of 1-year death, MI, or target vessel revascularization (TVR) was lowered in the diabetic women from 34.5% in the stent-placebo group and 28.9% in the balloon-abciximab group to 13. 3% in the stent-abciximab group (p = 0.02 for stent-stent comparison, and p = 0.09 for stent-abciximab vs. balloon-abciximab comparison). Also, 1-year TVR rates were lowered from 21.1% in the stent-placebo group and 26.7% in the balloon-abciximab group to 4.5% in the stent-abciximab group (p = 0.02 for stent-stent comparison, and p = 0.004 for stent-abciximab vs. balloon-abciximab comparison). The combination of stenting and abciximab therapy among diabetic women resulted in a significant reduction in 1-year rate of death, MI, or TVR compared with stent-placebo or balloon-abciximab therapy.


Protocol of a randomized controlled trial of the fear of recurrence therapy (FORT) intervention for women with breast or gynecological cancer.
Clinically significant levels of fear of cancer recurrence (FCR) affect up to 49% of cancer survivors and are more prevalent among women. FCR is associated with psychological distress, lower quality of life, and increased use of medical resources. Despite its prevalence, FCR is poorly addressed in clinical care. To address this problem, we first developed, and pilot tested a 6-week, 2 h, Cognitive-existential group intervention therapy that targeted FCR in survivors of breast or gynecological cancer. Following the positive outcome of the pilot, we are now testing this approach in a randomized clinical trial (RCT). Goal and hypotheses: This multicenter, prospective RCT aims to test the efficacy of the intervention. The study hypotheses are that, compared to a control group, cancer survivors participating in the intervention (1) will have less FCR, (2) will show more favorable outcomes on the following measures: cancer-specific distress, quality of life, illness uncertainty, intolerance of uncertainty, perceived risk of cancer recurrence, and coping skills. We further postulate that the between-group differences will persist three and 6 months post-intervention. Sixteen groups of seven to nine women are being allocated to the intervention or the control group. The control group receives a 6-week, 2 h, structurally equivalent support group. We are recruiting 144 cancer survivors from four hospital sites in three Canadian cities. The sample size was based on the moderate pre/post-test changes found in our pilot study and adjusted to the drop-out rates. The primary outcome, FCR, is measured by the Fear of Cancer Recurrence Inventory. Secondary outcomes measured include cancer-specific distress, perceived risk of cancer recurrence, illness uncertainty, intolerance of uncertainty, coping, and quality of life. We use reliable and recognized valid scales. Participants are to complete the questionnaire package at four times: before the first group session (baseline), immediately after the sixth session, and 3 and 6 months post-intervention. In the descriptive analysis, comparison of group equivalent baseline variables, identification of confounding/intermediate variables and univariate analysis are planned. Each participant's trajectory is calculated using Generalized Estimating Equation models to determine the time and group effects, after considering the correlation structures of the groups. An intent-to-treat analysis approach may be adopted. Our Fear of Recurrence Therapy (FORT) intervention has direct implications for clinical service development to improve the quality of life for patients with breast (BC) and gynecological cancer (GC). Based on our pilot data, we are confident that the FORT intervention can guide the development of effective psychosocial cancer survivorship interventions to reduce FCR and improve psychological functioning among women with BC or GC. Dr. Christine Maheu registered the trial with ISRCTN registry (Registration number: ISRCTN83539618, date assigned 03/09/2014).


Minimal immersions of spheres into spheres.
In this paper we announce a qualitative description of an important class of closed n-dimensional submanifolds of the m-dimensional sphere, namely, those which locally minimize the n-area in the same way that geodesics minimize the arc length and are themselves locally n-spheres of constant radius r; those r that may appear are called admissible. It is known that for n = 2 each admissible r determines a unique element of the above class. The main result here is that for each n >/= 3 and each admissible r >/= [unk]8 there exists a continuum of distinct such submanifolds.


Trends and outcomes of concurrent carotid revascularization and coronary bypass.
The management of concurrent carotid and coronary artery disease is controversial. Although single-center observational studies have revealed acceptable outcomes of combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG), community-based outcomes have been substantially inferior. Recently, carotid artery stenting (CAS) has been introduced for the management of high-risk patients with carotid stenosis, including those with severe coronary artery disease. This study was undertaken to evaluate the nationwide trends and outcomes of CAS before CABG vs combined CEA and CABG and to assess the risk for adverse events. The Nationwide Inpatient Sample (NIS) was used to identify patients discharged after concurrent carotid and coronary revascularization procedures. All patients that underwent CAS before CABG and combined CEA-CABG during the years 2000 to 2004 were included. The type of revascularization and major adverse events (ie, in-hospital stroke and death rates) were determined by cross-tabulating discharge diagnostic and procedural codes. Risk stratification was performed using the Charlson Comorbidity Index. Weighted exact Cochrane-Armitage trend test and multivariate logistic regression were used to assess the association between types of revascularization, comorbidities, complications, and risk-adjusted mortality. During the 5-year period, 27,084 concurrent carotid revascularizations and CABG were done. Of these, 96.7% underwent CEA-CABG, whereas only 3.3% (887 patients) had CAS-CABG. From 2000 to 2004, the proportion of patients undergoing CAS-CABG vs CEA-CABG did not significantly changed (P = .27). Patients undergoing CAS-CABG had fewer major adverse events than those undergoing CEA-CABG. CAS-CABG patients had a lower incidence of postoperative stroke (2.4% vs 3.9%), and combined stroke and death (6.9% v. 8.6%) than the combined CEA-CABG group (P < .001), although in-hospital death rates were similar (5.2% vs 5.4%). After risk-stratification, CEA-CABG patients had a 62% increased risk of postoperative stroke compared with patients undergoing CAS before CABG (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.1-2.5; P = .02). However, no differences in the risk of combined stroke and death were observed (OR, 1.26; 95% CI, 0.9-1.6; P = NS). Although CAS may currently be performed for high-risk patients, it is still infrequently used in patients who require concurrent carotid and coronary interventions. In the United States, patients who undergo CAS-CABG have significantly decreased in-hospital stroke rates compared with patients undergoing CEA-CABG but similar in-hospital mortality. CAS may provide a safer carotid revascularization option for patients who require CABG.


Chemical and structural insights into the regioversatility of the aminoglycoside acetyltransferase Eis.
A recently discovered cause of tuberculosis resistance to a drug of last resort, the aminoglycoside kanamycin, results from modification of this drug by the enhanced intracellular survival (Eis) protein. Eis is a structurally and functionally unique acetyltransferase with an unusual capability of acetylating aminoglycosides at multiple positions. The extent of this regioversatility and its defining protein features are unclear. Herein, we determined the positions and order of acetylation of five aminoglycosides by NMR spectroscopy. This analysis revealed unprecedented acetylation of the 3''-amine of kanamycin, amikacin, and tobramycin, and the γ-amine of the 4-amino-2-hydroxybutyryl group of amikacin. A crystal structure of Eis in complex with coenzyme A and tobramycin revealed how tobramycin can be accommodated in the Eis active site in two binding modes, consistent with its diacetylation. These studies, describing chemical and structural details of acetylation, will guide future efforts towards designing aminoglycosides and Eis inhibitors to overcome resistance in tuberculosis.


Passive air sampling of VOCs, O3, NO2, and SO2 in the large industrial city of Ulsan, South Korea: spatial-temporal variations, source identification, and ozone formation potential.
Concerns about volatile organic compounds (VOCs) have increased due to their toxicity and secondary reaction with nitrogen oxides (NOX) to form ozone (O3). In this study, passive air sampling of VOCs, O3, NO2, and SO2 was conducted in summer, fall, winter, and spring from 2019 to 2020 at six industrial and ten urban sites in Ulsan, the largest industrial city in South Korea. Over the entire sampling period, the concentration of toluene (mean: 8.75 μg/m3) was the highest of the 50 target VOCs, followed by m,p-xylenes (4.52 μg/m3), ethylbenzene (4.48 μg/m3), 3-methylpentane (4.40 μg/m3), and n-octane (4.26 μg/m3). Total (Σ50) VOC levels did not statistically differ between seasons, indicating that large amounts of VOCs are emitted into the atmosphere throughout the year. On the other hand, O3, NO2, and SO2 exhibited strong seasonal variation depending on the meteorological conditions and emission sources. The spatial distribution of Σ50 VOCs, NO2, and SO2 indicated that industrial complexes were major sources in Ulsan, while O3 had the opposite spatial distribution. Using a positive matrix factorization model, five major sources were identified, with industrial effects dominant. Aromatic compounds, such as m,p,o-xylenes, toluene, and 1,2,4-trimethylbenzene, significantly contributed to O3 formation. The VOC/NO2 ratio and O3 concentrations suggested that reducing VOC emissions is more effective than reducing NO2 emissions in terms of preventing the secondary formation of O3. The findings of this study allow for a better understanding of the relationship between VOCs, O3, NO2, and SO2 in industrial cities.


Vasomotor oscillation in vibration-induced white finger.
Vasomotor oscillation at different ambient temperatures, with and without anesthesia of the finger nerves, was studied in six persons with vibration-induced white finger (VWF) and in 10 referents. The power spectral density (PSD) of the Fourier transform of the laser-Doppler flowmeter signal from the finger pad vessels was analyzed. In both groups, the PSD of the vasomotor oscillation in the frequency range of 0.05-0.25 Hz was more pronounced in a cold than in a hot environment. Without finger nerve anesthesia, the oscillations of the referents were significantly greater (p less than 0.01) than those of the VWF subjects (PSD -34.4 dB and -41.6 dB, respectively). With anesthesia of the finger vasomotor nerves, the PSD was reduced in both groups. In the anesthetized finger there was no statistically significant group difference. Thus the myogenic component of the vasomotor activity was the same in the referents as in the VWF subjects. The results show that the autonomic neural influence on vasomotor oscillation in skin of the finger pad is weaker in persons with VWF. This weakness may be a sign of peripheral neuropathy, which may lead to a denervation syndrome causing hypersensitivity of the adrenoceptors to cold.


Right robotic-assisted thoracoscopic lower lobectomy.
The right lower lobectomy is considered one of the easier resection operations performed by an open technique. The posterior approach for the video-assisted thoracoscopic surgery (VATS) version of this is similar, as instruments and staplers pass up the fissure. When moving to the robotic platform with the camera and instruments entering from caudal ports, the equal view of the lobe, fissure and both hila allow for a more balanced operation. This article aims to discuss the technology of robotic-assisted surgery and the optimal surgical techniques to enable precise and safe resection of the lower lobe.


Obesity risks: towards an emerging Inuit pattern.
The aim of this study was to provide analytical overviews of anthropometric measurements and their relationships with type 2 diabetes and cardiovascular disease (CVD) risk factors within the Inuit population, given that few studies have focused on this issue. Study design. Cross-sectional study. Anthropometric and biological data were obtained from 867 Inuit participants from Nunavik (≥18 years). Obesity prevalence for men and women, respectively, was 25.1% and 31.3% according to body mass index (BMI: >30 kg/m2); 20.2% and 55.3% according to waist circumference (WC: >102 cm for men and >88 cm for women); 22.4% and 22.5% according to body fat percentage (%BF: ≥30 in men and ≥40 in women). There was substantial agreement between anthropometric obesity measurements, except for the waist-to-hip ratio (WHR) which showed the lowest agreement with the other measurements. All risk factors were significantly associated with anthropometry. The prevalence of abnormal values for risk factors increased across quartiles of BMI and WC. Among obese participants, as defined by the WC cutoff, 22% had metabolic syndrome based on the National Cholesterol Education Program in the Adult Treatment Panel III (NCEP-ATPIII) definition and 64.8% of them were also insulin resistant. Obesity rates among Inuit are high, especially among women. Inuit women display especially high rates of abdominal obesity. Further longitudinal work is needed to evaluate the effects of central and global obesity among Inuit.


Geoacoustic inversion with ships as sources.
Estimation of geoacoustic parameters using acoustic data from a surface ship was performed for a shallow water region in the Gulf of Mexico. The data were recorded from hydrophones in a bottom mounted, horizontal line array (HLA). The techniques developed to produce the geoacoustic inversion are described, and an efficient method for geoacoustic inversion with broadband beam cross-spectral data is demonstrated. The performance of cost functions that involve coherent or incoherent sums over frequency and one or multiple time segments is discussed. Successful inversions for the first sediment layer sound speed and thickness and some of the parameters for the deeper layers were obtained with the surface ship at nominal ranges of 20, 30, or 50 water depths. The data for these inversions were beam cross-spectra from four subapertures of the HLA spanning a little more than two water depths. The subaperture beams included ten frequencies equally spaced in the 120-200 Hz band. The values of the geoacoustic parameters from the inversions are validated by comparisons with geophysical observations and with the parameter values from previous inversions by other invesigators, and by comparing transmission loss (TL) measured in the experiment with modeled TL based on the inverted geoacoustic parameters.


Comparative analysis of diguanylate cyclase and phosphodiesterase genes in Klebsiella pneumoniae.
Klebsiella pneumoniae can be found in environmental habitats as well as in hospital settings where it is commonly associated with nosocomial infections. One of the factors that contribute to virulence is its capacity to form biofilms on diverse biotic and abiotic surfaces. The second messenger Bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is a ubiquitous signal in bacteria that controls biofilm formation as well as several other cellular processes. The cellular levels of this messenger are controlled by c-di-GMP synthesis and degradation catalyzed by diguanylate cyclase (DGC) and phophodiesterase (PDE) enzymes, respectively. Many bacteria contain multiple copies of these proteins with diverse organizational structure that highlight the complex regulatory mechanisms of this signaling network. This work was undertaken to identify DGCs and PDEs and analyze the domain structure of these proteins in K. pneumoniae. A search for conserved GGDEF and EAL domains in three sequenced K. pneumoniae genomes showed that there were multiple copies of GGDEF and EAL containing proteins. Both single domain and hybrid GGDEF proteins were identified: 21 in K. pneumoniae Kp342, 18 in K. pneumoniae MGH 78578 and 17 in K. pneumoniae NTUH-K2044. The majority had only the GGDEF domain, most with the GGEEF motif, and hybrid proteins containing both GGDEF and EAL domains were also found. The I site for allosteric control was identified only in single GGDEF domain proteins and not in hybrid proteins. EAL-only proteins, containing either intact or degenerate domains, were also identified: 15 in Kp342, 15 in MGH 78578 and 10 in NTUH-K2044. Several input sensory domains and transmembrane segments were identified, which together indicate complex regulatory circuits that in many cases can be membrane associated. The comparative analysis of proteins containing GGDEF/EAL domains in K. pneumoniae showed that most copies were shared among the three strains and that some were unique to a particular strain. The multiplicity of these proteins and the diversity of structural characteristics suggest that the c-di-GMP network in this enteric bacterium is highly complex and reflects the importance of having diverse mechanisms to control cellular processes in environments as diverse as soils or plants and clinical settings.


The role of NK cells during in vivo antigen-specific antibody responses.
Investigations into the role of NK cells in regulating Ab responses have yielded variable results, some suggesting that NK cells can down-regulate Ag-specific Ig production and others proposing an enhancing effect. These apparently inconsistent findings may stem partially from the specificity of reagents used in purifying cell populations and/or the nature of the in vitro systems used to study these events. We chose to investigate the ability of either resting or poly(I:C)-activated NK cells to alter an in vivo Ab response in mice given a T-independent (TNP-LPS) or T-dependent (TNP-keyhole limpet hemocyanin (KLH)) Ag. By using a more specific Ab, anti-NK-1.1, to deplete NK cells, we were able to clearly show that resting, endogenous NK cells do not affect either type of response, as measured by serum Ag-specific Ig levels quantitated by isotype-specific ELISA. In contrast, activation of NK cells by poly(I:C) increased Ag-specific IgC2a as well as IgG1 levels. Interestingly, only the effect on IgG2a production is reversible by depletion of NK cells.


Lysines and Arginines play non-redundant roles in mediating chemokine-glycosaminoglycan interactions.
Glycosaminoglycans (GAGs) bind a large array of proteins and mediate fundamental and diverse roles in human physiology. Ion pair interactions between protein lysines/arginines and GAG sulfates/carboxylates mediate binding. Neutrophil-activating chemokines (NAC) are GAG-binding proteins, and their sequences reveal high selectivity for lysines over arginines indicating they are functionally not equivalent. NAC binding to GAGs impacts gradient formation, receptor functions, and endothelial activation, which together regulate different components of neutrophil migration. We characterized the consequence of mutating lysine to arginine in NAC CXCL8, a well-characterized GAG-binding protein. We chose three lysines - two highly conserved lysines (K20 and K64) and a CXCL8-specific lysine (K67). Interestingly, the double K64R/K20R and K64R/K67R mutants are highly impaired in recruiting neutrophils in a mouse model. Further, both the mutants bind GAG heparin with higher affinity but show similar receptor activity. NMR and MD studies indicate that the structures are essentially identical to the WT, but the mutations alter the network of intramolecular ion pair interactions. These observations collectively indicate that the reduced in vivo recruitment is due to altered GAG interactions, higher GAG binding affinity can be detrimental, and specificity of lysines fine-tunes in vivo GAG interactions and function.


(S)-FTY720-vinylphosphonate, an analogue of the immunosuppressive agent FTY720, is a pan-antagonist of sphingosine 1-phosphate GPCR signaling and inhibits autotaxin activity.
FTY720 (Fingolimod), a synthetic analogue of sphingosine 1-phosphate (S1P), activates four of the five EDG-family S1P receptors and is in a phase-III clinical study for the treatment of multiple sclerosis. (S)-FTY720-phosphate (FTY720-P) causes S1P(1) receptor internalization and targeting to the proteasomal degradative pathway, and thus functions as an antagonist of S1P(1) by depleting the functional S1P(1) receptor from the plasma membrane. Here we describe the pharmacological characterization of two unsaturated phosphonate enantiomers of FTY720, (R)- and (S)-FTY720-vinylphosphonate. (R)-FTY720-vinylphosphonate was a full agonist of S1P(1) (EC(50) 20+/-3 nM). In contrast, the (S) enantiomer failed to activate any of the five S1P GPCRs and was a full antagonist of S1P(1,3,4) (K(i) 384 nM, 39 nM, and 1190 nM, respectively) and a partial antagonist of S1P(2), and S1P(5). Both enantiomers dose-dependently inhibited lysophospholipase D (recombinant autotaxin) with K(i) values in the low micromolar range, although with different enzyme kinetic mechanisms. When injected into mice, both enantiomers caused transient peripheral lymphopenia. (R)- and (S)-FTY720-vinylphosphonates activated ERK1/2, AKT, and exerted an antiapoptotic effect in camptothecin-treated IEC-6 intestinal epithelial cells, which primarily express S1P(2) transcripts and traces of S1P(5). (S)-FTY720-vinylphosphonate is the first pan-antagonist of S1P receptors and offers utility in probing S1P responses in vitro and in vivo. The biological effects of the (R)- and (S)-FTY720-vinylphosphonate analogues underscore the complexity of FTY720 cellular targets.


The roles of garment design and scene complexity in the daytime conspicuity of high-visibility safety apparel.
This study examines the effects of high-visibility garment design on daytime pedestrian conspicuity in work zones. Factors assessed were garment color, amount of background material, pedestrian arm motion, scene complexity, and driver age. The study was conducted in naturalistic conditions on public roads in real traffic. Drivers drove two passes on a 31-km route and indicated when they detected pedestrians outfitted in the fluorescent garments. The locations of the vehicle and the pedestrian were recorded. Detection distances between fluorescent yellow-green and fluorescent red-orange garments were not significantly different, nor were there any significant two-way interactions involving garment color. Pedestrians were detected at longer distances in lower complexity scenes. Arm motion significantly increased detection distances for pedestrians wearing a Class 2 vest, but had little added benefit on detection distances for pedestrians wearing a Class 2 jacket. Daytime detection distances for pedestrians wearing Class 2 or Class 3 garments are longest when the complexity of the surround is low. The more background information a driver has to search through, the longer it is likely to take the driver to locate a pedestrian--even when wearing a high-visibility garment. These findings will provide information to safety garment manufacturers about characteristics of high-visibility safety garments which make them effective for daytime use.


The role of sentinel lymph-node biopsy (SLNB) in the treatment of breast cancer.
Sentinel lymph-node biopsy is an innovative method for axillary staging in breast cancer patients, based on the concept that information about the status of the entire lymphatic drainage from a tumour site could be obtained by identification and sampling of a "sentinel node". The aim of the study was to evaluate the impact of sentinel lymph-node biopsy in the management of patients with early invasive breast carcinoma. Three hundred and forty-one patients with primary invasive breast carcinoma measuring less than 2 cm (less than 3 cm from January 2001) and clinically negative axillary nodes were recruited into the study. Sentinel lymph-nodes were positive for metastases in 108/341 cases (31.7%). Micrometastases were found in 22 patients and isolated tumour cells in 1 case. The mean number of sentinel lymph-nodes removed was 1.8 per patient. The sentinel lymph-node was the only positive node in 57 of 108 patients (52.8%). The percentage of axillary recurrence in sentinel lymph-node-negative patients was 0%. The accuracy of sentinel lymph-node biopsy for axillary staging has been confirmed in many studies. Axillary recurrences after sentinel lymph-node biopsy range from 0 to 1.6% in many series, while axillary recurrence after axillary lymph-node dissection is about 0-3%. In our experience we observed no axillary recurrences in 233 patients with sentinel lymph-node biopsy alone, with a median follow-up of 33 months, confirming the accuracy of the procedure, and sentinel lymph-node-negative patients with sentinel lymph-node biopsy alone are no more at risk for axillary recurrences than those undergoing axillary lymph-node dissection.


[Determining thorium level in urine with its preliminary chromatographic extraction].
The contributors propose a radiometric technique of detecting thorium in urine. The technique is based on a prior concentrating of the nuclide on phosphate residues, with its further separation in extraction-chromatographic vessel filled with diethylhexylphosphorus acid, and reextraction with oxalic acid. Measurements were made in the hard scintillator layer at 90 percent effectiveness. Thorium chemical output was at 85 +/- 3 percent, sensitivity at 5 mBk for a sample. If the sample contained an equal quantity of uranium, the percentage of cleaning thorium from uranium was 100. The proposed technique is economical, simple to perform, and is designed for natural thorium content measurements in human organism.


Development of 2D band-target entropy minimization and application to the deconvolution of multicomponent 2D nuclear magnetic resonance spectra.
Spectral reconstruction from multicomponent spectroscopic data is the frequent primary goal in chemical system identification and exploratory chemometric studies. Various methods and techniques have been reported in the literature. However, few algorithms/methods have been devised for spectral recovery without the use of any a priori information. In the present studies, a higher dimensional entropy minimization method based on the BTEM algorithm (Widjaja, E.; Li, C.; Garland, M. Organometallics 2002, 21, 1991-1997.) and related techniques were extended to large-scale arrays, namely, 2D NMR spectroscopy. The performance of this novel method had been successfully verified on various real experimental mixture spectra from a series of randomized 2D NMR mixtures (COSY NMR and HSQC NMR). With the new algorithm and raw multicomponent NMR alone, it was possible to reconstruct the pure spectroscopic patterns and calculate the relative concentration of each species without recourse to any libraries or any other a priori information. The potential advantages of this novel algorithm and its implications for general chemical system identification of unknown mixtures are discussed.


Prognostic importance of physical examination for heart failure in non-ST-elevation acute coronary syndromes: the enduring value of Killip classification.
In acute myocardial infarction, the presence and severity of heart failure at the time of initial presentation have been formally categorized by the Killip classification. Although well studied in ST-elevation myocardial infarction, the prognostic importance of Killip classification in non-ST-elevation acute coronary syndromes is not well established. To determine the prognostic importance of physical examination for heart failure analyzed according to Killip classification in non-ST-elevation acute coronary syndromes and to understand its predictive value relative to other variables. From April 2001 to September 2003, We analyzed information from 26 090 patients with non-ST-elevation acute coronary syndromes enrolled in the GUSTO IIb, PURSUIT, PARAGON A, and PARAGON B trials. Demographic information was categorized by Killip class. Killip classes III and IV were combined into 1 category. Multivariate Cox proportional hazard models were developed to determine the prognostic importance of Killip classification in comparison with other variables. Association between Killip classification and all-cause mortality at 30 days and 6 months. Patients in Killip class II (n = 2513) and III/IV (n = 390) were older than those in Killip class I (n = 23 187), with higher rates of diabetes, prior myocardial infarction, ST depression, and elevated cardiac enzymes (all P<.001). Higher Killip class was associated with higher mortality at 30 days (2.8% in Killip class I vs 8.8% in class II vs 14.4% in class III/IV; P<.001) and 6 months (5.0% vs 14.7% vs 23.0%, respectively; P<.001). Patients with Killip class II, III, or IV constituted 11% of the overall population but accounted for approximately 30% of the deaths at both time points. In multivariate analysis, Killip class III/IV was the most powerful predictor of mortality at 30 days (hazard ratio [HR], 2.35; 95% confidence interval [CI], 1.69-3.26; P<.001) and 6 months (HR, 2.12; 95% CI, 1.63-2.75; P<.001). Killip class II was predictive of mortality at 30 days (HR, 1.73; 95% CI, 1.44-2.09; P<.001) and 6 months (HR, 1.52; 95% CI, 1.31-1.76; P<.001). Five factors-age, Killip classification, heart rate, systolic blood pressure, and ST depression-provided more than 70% of the prognostic information for 30-day and 6-month mortality. Killip classification is a powerful independent predictor of all-cause mortality in patients with non-ST-elevation acute coronary syndromes. Age, Killip classification, heart rate, systolic blood pressure, and ST depression should receive particular attention in the initial assessment of these patients.


Survival and confinement under quenched disorder.
We study the survival and confinement of random walkers under quenched disorder characterized by spatially-varying waiting times and decay rates. Spatial heterogeneity and segregation lead to a dynamic coupling between transport and reaction, resulting in history-dependent dynamics exhibiting long survivals and confinement. The survival probability decays as a power law, in contrast to the classical exponential law for decay at a homogeneous rate. The mean squared displacement shows dimension-dependent subdiffusive growth followed by localization, with stronger confinement in higher dimensions.


Age, smoking, and negative affectivity as predictors of sleep patterns among shiftworkers in two environments.
Although adaptation to shiftwork has been widely studied, little is known about how individual and environmental factors combine to influence sleep among shiftworkers. This study examined age, smoking, and negative affectivity (NA) as predictors of sleep duration and quality for 3 work phases (day shifts, DS; night shifts, NS; and leave periods, LP). Data were collected from personnel working 12-hr shifts, onshore (n = 330) or offshore (n = 456). Individual factors predicted patterns of sleep measures across the DS, NS, and LP phases onshore, but not offshore; onshore, work phase interacted with smoking and with age to predict sleep duration and with NA to predict sleep quality. The role of the offshore environment in shiftwork adaptation is discussed.


Enhanced third-order nonlinear effects in optical AlGaAs nanowires.
We report the first observation of enhanced third-order nonlinear effects in AlGaAs nanowires. AlGaAs nanowaveguides with widths varying from 100 to 600nm were fabricated and characterized. Nonlinear phase shifts of approximately pi were experimentally observed at 1.55mum with peak powers of 30-40W in 600mum long, 550nm wide guides.


Vitronectin mediates internalization of Neisseria gonorrhoeae by Chinese hamster ovary cells.
Gonococci producing a distinct opacity protein (OpaA in strain MS11) adhere to and are efficiently internalized by cultured epithelial cells such as the Chang conjunctiva cell line. Both adherence and uptake require interactions between OpaA and heparan sulfate proteoglycans on the mammalian cell surface. Chinese hamster ovary (CHO) cells also support adherence of gonococci through interactions of OpaA with cell surface heparan sulfate proteoglycans. However, despite this similarity in the requirements for adherence, CHO cells are not capable of internalizing gonococci. In this report, we characterized this apparent deficiency and identified a factor in fetal calf serum (FCS) which is capable of mediating uptake of gonococci by CHO cells. In the absence of FCS, OpaA+ gonococci adhered to but were not internalized by CHO cells, whereas in the presence of up to 15% FCS, the bacteria were efficiently internalized by the cells. Preincubation of bacteria, but not cells, with FCS also stimulated internalization, suggesting that a factor present in FCS was binding to the surface of gonococci and subsequently stimulating entry. Using a combination of chromatographic purification procedures, we identified the adhesive glycoprotein vitronectin as the serum factor which mediates the internalization of gonococci by CHO cells. Vitronectin-depleted serum did not support gonococcal entry, and this deficiency was restored by the addition of purified vitronectin. Further experiments using a set of gonococcal recombinants, each expressing a single member of the family of Opa outer membrane proteins, demonstrated that vitronectin bound to the surface of OpaA-producing gonococci only and that the vitronectin-mediated uptake by the CHO cells was limited to this bacterial phenotype. To our knowledge, our data are the first example that vitronectin can serve as a molecule that drives bacterial entry into epithelial cells.


Significance of retrograde diastolic uterine artery blood flow during regional anesthesia in instrumented pregnant sheep.
We studied the interactions between uterine and placental hemodynamics during maternal hypotension in chronically instrumented fetal sheep. In addition, we investigated maternal hemodynamic characteristics, fetoplacental hemodynamics and fetal acid-base status when a retrograde diastolic uterine artery blood flow pattern is present during maternal hypotension. Invasive maternal and fetal hemodynamic parameters, uterine (Q(UtA)) and placental (Q(UA)) volume blood flows and acid-base values were examined in 24 chronically instrumented sheep at baseline and during epidural-induced maternal hypotension at 117-132 (term 145) days of gestation. Uterine artery blood flow velocity waveforms were obtained by Doppler ultrasonography. Maternal hypotension decreased Q(UtA) without affecting Q(UA). During hypotension, eight out of 24 sheep demonstrated a retrograde diastolic blood flow velocity waveform pattern in the uterine artery. Maternal systolic, diastolic and mean arterial blood pressures were significantly lower in the retrograde group than in the antegrade group. No statistically significant differences in Q(UtA), Q(UA) and fetal blood gas values were detected between the two groups during hypotension. An acute decrease in uterine artery volume blood flow during maternal hypotension is not compensated by increased placental volume blood flow. A retrograde diastolic blood flow pattern in the uterine artery is related to lower maternal arterial pressures, especially during diastole. A uterine artery retrograde diastolic blood flow pattern does not have any additional detrimental short-term effects on fetal acid-base status.


Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory.
Mutations in the Autism susceptibility candidate 2 gene (AUTS2) have been associated with a broad range of psychiatric illnesses including autism spectrum disorders, intellectual disability and schizophrenia. We previously demonstrated that the cytoplasmic AUTS2 acts as an upstream factor for the Rho family small GTPase Rac1 and Cdc42 that regulate the cytoskeletal rearrangements in neural cells. Moreover, genetic ablation of the Auts2 gene in mice has resulted in defects in neuronal migration and neuritogenesis in the developing cerebral cortex caused by inactivation of Rac1-signaling pathway, suggesting that AUTS2 is required for neural development. In this study, we conducted a battery of behavioral analyses on Auts2 heterozygous mutant mice to examine the involvement of Auts2 in adult cognitive brain functions. Auts2-deficient mice displayed a decrease in exploratory behavior as well as lower anxiety-like behaviors in the absence of any motor dysfunction. Furthermore, the capability for novel object recognition and cued associative memory were impaired in Auts2 mutant mice. Social behavior and sensory motor gating functions were, however, normal in the mutant mice as assessed by the three-chamber test and prepulse inhibition test, respectively. Together, our findings indicate that AUTS2 is critical for the acquisition of neurocognitive function.