Lines of dense nanoparticle colloidal suspensions evaporating on a flat surface: formation of non-uniform dried deposits.
Line evaporation of dense nanoparticle suspensions is studied theoretically and experimentally. The 2-D lines are drawn by a pen-like nozzle continuously dispensing a commercially available concentrated organic suspension (50 wt%; 4.3 vol%) of 5 nm gold nanoparticles in toluene solvent. Such particle-containing lines show promise for industrial applications where circuits are inkjet-printed and heat-treated to dry off the organic solvent and sinter the nanoparticles, thus producing a continuous electrically conducting path. The employed nanosuspension displays spontaneous thickening upon contact with a solid surface in the ambient atmosphere, and thus does not dry according to the well-established coffee-stain forming mechanism applicable to dilute particle suspensions. In the present work, model lines ( approximately 1 mm width) are studied to elucidate the drying peculiarities of such nanoparticle slurries. These scaled-up lines allow detailed spatial measurements of their topography throughout their prolonged evaporation period, and make possible direct comparisons between experiment and theory. The results show the particle deposits formed by evaporative drying of these lines to be of non-uniform thickness with a dent in the middle of the lateral cross-section. Formation of this practically undesirable landscape is attributed to the highly non-uniform evaporative character of sessile or pendent liquid lines, which results in a non-uniform consolidation of the porous phase formed upon contact with the solid surface. The formulated description of the shape changing process, as done in the framework of the consolidation theory, yields predicted deposit speck shapes that compare favorably with the temporally resolved experimental data.


Leukopenia is associated with worse but not prohibitive outcomes following emergent abdominal surgery.
There are little data currently available to guide surgical decision making regarding emergent surgical interventions in leukopenic patients. The purpose of this study was to investigate the impact of leukopenia among patients undergoing emergency abdominal operations to better guide preoperative decision making. The 2005 to 2012 American College of Surgeons' National Surgical Quality Improvement Program database was queried to identify patients who underwent emergent laparotomy. Patients were stratified by preoperative white blood cell (WBC) count (<4.0 × 10(9)/L vs. 4.0-12.0 × 10(9)/L). Baseline demographics, comorbidities, and outcomes were compared. Multivariable logistic regression was performed to estimate the adjusted association between leukopenia and mortality, taking into account the robust array of patient-related factors. Of the 20,443 patients who met study criteria, 2,057 (8.2%) were leukopenic (WBC < 4.0) before surgery. Unadjusted comparison demonstrated significantly increased major morbidity (45.4% vs. 26.9%, p < 0.001) as well as mortality (24.4% vs. 10.8%, p < 0.001) for patients with leukopenia compared with patients with a normal preoperative WBC count. Only 46.0% (n = 947) of patients with leukopenia before surgery were able to avoid major morbidity or mortality compared with 69.4% (n = 15,974) of patients with a normal preoperative WBC count (p < 0.001). After multivariable adjustment for patient-related factors, leukopenia was maintained as a significant predictor of mortality. Although leukopenia remains associated with mortality in patients undergoing emergent laparotomy despite adjustment for other patient-related factors, it is not necessarily prohibitive. Understanding the risk of complications and mortality associated with these procedures is pertinent for preoperative clinical decision making. Prognostic and epidemiologic study, level III.


Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic Parkinson's Disease and Dementia with Lewy Bodies.
Mutations in the GBA gene, encoding the lysosomal hydrolase glucocerebrosidase (GCase), are the most common known genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The present study aims to gain more insight into changes in lysosomal activity in different brain regions of sporadic PD and DLB patients, screened for GBA variants. Enzymatic activities of GCase, β-hexosaminidase, and cathepsin D were measured in the frontal cortex, putamen, and substantia nigra (SN) of a cohort of patients with advanced PD and DLB as well as age-matched non-demented controls (n = 15/group) using fluorometric assays. Decreased activity of GCase (- 21%) and of cathepsin D (- 15%) was found in the SN and frontal cortex of patients with PD and DLB compared to controls, respectively. Population stratification was applied based on GBA genotype, showing substantially lower GCase activity (~ - 40%) in GBA variant carriers in all regions. GCase activity was further significantly decreased in the SN of PD and DLB patients without GBA variants in comparison to controls without GBA variants. Our results show decreased GCase activity in brains of PD and DLB patients with and without GBA variants, most pronounced in the SN. The results of our study confirm findings from previous studies, suggesting a role for GCase in GBA-associated as well as sporadic PD and DLB.


Increased longevity and refractoriness to Ca(2+)-dependent neurodegeneration in Surf1 knockout mice.
Leigh syndrome associated with cytochrome c oxidase (COX) deficiency is a mitochondrial disorder usually caused by mutations of SURF1, a gene encoding a putative COX assembly factor. We present here a Surf1-/- recombinant mouse obtained by inserting a loxP sequence in the open reading frame of the gene. The frequency of -/-, +/+ and +/- genotypes in newborn mice followed a mendelian distribution, indicating that the ablation of Surf1 is compatible with postnatal survival. The biochemical and assembly COX defect was present in Surf1(loxP)-/- mice, but milder than in humans. Surprisingly, not only these animals failed to show spontaneous neurodegeneration at any age, but they also displayed markedly prolonged lifespan, and complete protection from Ca(2+)-dependent neurotoxicity induced by kainic acid. Experiments on primary neuronal cultures showed markedly reduced rise of cytosolic and mitochondrial Ca(2+) in Surf1(loxP)-/- neurons, and reduced mortality, compared to controls. The mitochondrial membrane potential was unchanged in KO versus wild-type neurons, suggesting that the effects of the ablation of Surf1 on Ca(2+) homeostasis, and possibly on longevity, may be independent, at least in part, from those on COX assembly and mitochondrial bioenergetics.


The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber.
Mechanical properties of the nuclear envelope have implications for cell and nuclear architecture as well as gene regulation. Using isolated Xenopus oocyte nuclei, we have established swelling conditions that separate the intact nuclear envelope (membranes, pore complexes and underlying lamin filament network) from nucleoplasm and the majority of chromatin. Swelling proves reversible with addition of high molecular mass dextrans. Micropipette aspiration of swollen and unswollen nuclear envelopes is also reversible and yields a network elastic modulus, unaffected by nucleoplasm, that averages 25 mN/m. Compared to plasma membranes of cells, the nuclear envelope is much stiffer and more resilient. Our results suggest that the nuclear lamina forms a compressed network shell of interconnected rods that is extensible but limited in compressibility from the native state, thus acting as a 'molecular shock absorber'. In light of the conservation of B-type lamins in metazoan evolution, the mechanical properties determined in this investigation suggest physical mechanisms by which mutated lamins can either destabilize nuclear architecture or influence nuclear responses to mechanical signals in Emery-Dreifuss muscular dystrophy, cardiomyopathy, progeria syndromes (premature 'aging') and other laminopathies.


The lower extremity dexterity test as a measure of lower extremity dynamical capability.
The capability of the lower extremity to dynamically interact with the ground is important for skilled locomotor performance. However, there is currently no test method designed to specifically quantify this sensorimotor ability, which we refer to as lower extremity dexterity. We describe a new method to quantify lower extremity dexterity, examine its reliability (n=10), and evaluate the extent to which it is associated with lower extremity strength and anthropometry in healthy young adults (n=38). The lower extremity dexterity test (LED-test)-an adaptation of the Strength-Dexterity test for the fingers-consists of using the isolated lower extremity to compress a slender spring prone to buckling at low forces. The goal of the LED-test is to sustain the highest compression force possible. Applying higher forces makes the spring increasingly unstable, thus achieving higher compression forces represents better ability to dynamically control instability at low force levels. As such, the LED-test provides a novel way to quantify the capability of the lower extremity to regulate dynamic and unstable foot-ground interactions at submaximal forces. LED-test performance ranged between 88.6 and 119.6N, test-retest reliability was excellent (ICC(2,3)=0.94), and the minimal detectable difference was 5.5N. Performance was not correlated with strength or height (r(2)≤0.053, p>0.05), and only weakly with body mass (r(2)=0.116, p=0.04). We propose that the unique lower extremity capability quantified by the LED-test could be informative of skilled locomotor performance and injury risk.


Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF.
We describe a mechanism of tumorigenesis mediated by kinase-dead BRAF in the presence of oncogenic RAS. We show that drugs that selectively inhibit BRAF drive RAS-dependent BRAF binding to CRAF, CRAF activation, and MEK-ERK signaling. This does not occur when oncogenic BRAF is inhibited, demonstrating that BRAF inhibition per se does not drive pathway activation; it only occurs when BRAF is inhibited in the presence of oncogenic RAS. Kinase-dead BRAF mimics the effects of the BRAF-selective drugs and kinase-dead Braf and oncogenic Ras cooperate to induce melanoma in mice. Our data reveal another paradigm of BRAF-mediated signaling that promotes tumor progression. They highlight the importance of understanding pathway signaling in clinical practice and of genotyping tumors prior to administering BRAF-selective drugs, to identify patients who are likely to respond and also to identify patients who may experience adverse effects.


Temperature and atmosphere tunability of the nanoplasmonic resonance of a volumetric eutectic-based Bi₂O₃-Ag metamaterial.
Nanoplasmonic materials are intensively studied due to the advantages they bring in various applied fields such as photonics, optoelectronics, photovoltaics and medicine. However, their large-scale fabrication and tunability are still a challenge. One of the promising ways of combining these two is to use the self-organization mechanism and after-growth engineering as annealing for tuning the properties. This paper reports the development of a bulk nanoplasmonic, Bi2O3-Ag eutectic-based metamaterial with a tunable plasmonic resonance between orange and green wavelengths. The material, obtained by a simple growth technique, exhibits a silver nanoparticle-related localized surface plasmon resonance (LSPR) in the visible wavelength range. We demonstrate the tunability of the LSPR (spectral position, width and intensity) as a function of the annealing temperature, time and the atmosphere. The critical role of the annealing atmosphere is underlined, annealing in vacuum being the most effective option for a broad control of the LSPR. The various potential mechanisms responsible for tuning the localized surface plasmon resonance upon annealing are discussed in relation to the nanostructures of the obtained materials.


The economic impact of chronic fatigue syndrome in Georgia: direct and indirect costs.
Chronic fatigue syndrome (CFS) is a debilitating chronic illness affecting at least 4 million people in the United States. Understanding its cost improves decisions regarding resource allocation that may be directed towards treatment and cure, and guides the evaluation of clinical and community interventions designed to reduce the burden of disease. This research estimated direct and indirect costs of CFS and the impact on educational attainment using a population-based, case-control study between September 2004 and July 2005, Georgia, USA. Participants completed a clinical evaluation to confirm CFS, identify other illnesses, and report on socioeconomic factors. We estimated the effect of CFS on direct medical costs (inpatient hospitalizations, provider visits, prescription medication spending, other medical supplies and services) and loss in productivity (employment and earnings) with a stratified sample (n = 500) from metropolitan, urban, and rural Georgia. We adjusted medical costs and earnings for confounders (age, sex, race/ethnicity, education, and geographic strata) using econometric models and weighted estimates to reflect response-rate adjusted sampling rates. Individuals with CFS had mean annual direct medical costs of $5,683. After adjusting for confounding factors, CFS accounted for $3,286 of these costs (p < 0.01), which were driven by increased provider visits and prescription medication use. Nearly one-quarter of these expenses were paid directly out-of pocket by those with CFS. Individuals with CFS reported mean annual household income of $23,076. After adjustment, CFS accounted for $8,554 annually in lost household earnings (p < 0.01). Lower educational attainment accounted for 19% of the reduction in earnings associated with CFS. Study results indicate that chronic fatigue syndrome may lead to substantial increases in healthcare costs and decreases in individual earnings. Studies have estimated up to 2.5% of non-elderly adults may suffer from CFS. In Georgia, a state with roughly 5.5 million people age 18-59, illness could account for $452 million in total healthcare expenditures and $1.2 billion of lost productivity.


Use of minisatellite DNA probes for determination of twin zygosity at birth.
Minisatellite DNA probes that detect highly polymorphic regions of the human genome were used to examine DNA from twelve sets of newborn twins. In the seven cases where the twins were known to be monozygotic or dizygotic, from sex observation or placental examination, the DNA result agreed with these findings. In the other five twin pairs and in two sets of triplets DNA analysis allowed rapid determination of zygosity. Minisatellite DNA probes provide a single genetic test that should allow positive determination of zygosity in all cases of multiple pregnancy.


Attentional control in anterior cingulate cortex based on probabilistic cueing.
In Stroop-like tasks, conflict effects in behavioral measures and ACC activity are smaller on trials following an incongruent trial than following a congruent one. Researchers have found no agreement on whether these sequential effects in ACC can be driven by experienced incongruency only or also by expectations about target types. In the present fMRI experiment, we specifically manipulated the expectancies by using symbolic cues predicting with 75% or 50% certainty the incongruent or congruent targets in a Stroop-like task. Both behavioral and dorsal ACC data replicated previous sequential effects, with conflict effects being smallest for targets following the cues that predicted with 75% certainty the incongruent targets. However, these effects were not driven by experienced conflict but by symbolic cues. These results demonstrate differential attentional control activity in ACC after probabilistic cueing, providing evidence for control adjustments driven by changes in expectation.


Obesity, smoking, alcohol consumption and years lived with disability: a Sullivan life table approach.
To avoid strong declines in the quality of life due to population ageing, and to ensure sustainability of the health care system, reductions in the burden of disability among elderly populations are urgently needed. Life style interventions may help to reduce the years lived with one or more disabilities, but it is not fully understood which life style factor has the largest potential for such reductions. Therefore, the primary aim of this paper is to compare the effect of BMI, smoking and alcohol consumption on life expectancy with disability, using the Sullivan life table method. A secondary aim is to assess potential improvement of the Sullivan method by using information on the association of disability with time to death. Data from the Dutch Permanent Survey of the Living Situation (POLS) 1997-1999 with mortality follow-up until 2006 (n = 6,446) were used. Using estimated relative mortality risks by risk factor exposure, separate life tables were constructed for groups defined in terms of BMI, smoking status and alcohol consumption. Logistic regression models were fitted to predict the prevalence of ADL and mobility disabilities in relationship to age and risk factor exposure. Using the Sullivan method, predicted age-specific prevalence rates were included in the life table to calculate years lived with disability at age 55. In further analysis we assessed whether adding information on time to death in both the regression models and the life table estimates would lead to substantive changes in the results. Life expectancy at age 55 differed by 1.4 years among groups defined in terms of BMI, 4.0 years by smoking status, and 3.0 years by alcohol consumption. Years lived with disability differed by 2.8 years according to BMI, 0.2 years by smoking and 1.6 by alcohol consumption. Obese persons could expect to live more years with disability (5.9 years) than smokers (3.8 years) and drinkers (3.1 years). Employing information on time to death led to lower estimates of years lived with disability, and to smaller differences in these years according to BMI (2.1 years), alcohol (1.2 years), and smoking (0.1 years). Compared with smoking and drinking alcohol, obesity is most strongly associated with an increased risk of spending many years of life with disability. Although employing information on the relation of disability with time to death improves the precision of Sullivan life table estimates, the relative importance of risk factors remained unchanged.


Race-status associations: Distinct effects of three novel measures among White and Black perceivers.
Race is fraught with meaning, but unequal status is central. Race-status associations (RSAs) link White Americans with high status and Black Americans with low status. RSAs could occur via observation of racially distributed jobs, perceived status-related stereotypic attributes, or simple ranking. Nine samples (N = 3,933) validate 3 novel measures of White = high status/Black = low status RSAs-based on jobs, rank, and attributes. First, RSA measures showed clear factor structure, internal validity, and test-retest reliability. Second, these measures differentially corresponded to White Americans' hierarchy-maintaining attitudes, beliefs, and preferences. Potentially based on observation, the more spontaneous Job-based RSAs predicted interracial bias, social dominance orientation, meritocracy beliefs, and hierarchy-maintaining hiring or policy preferences. Preference effects held after controlling for bias and support for the status quo. In contrast, the more deliberate Rank- and Attribute-based RSAs negatively predicted hierarchy-maintaining beliefs and policy preferences; direct inferences of racial inequality linked to preferences for undoing it. Third, Black = low status, rather than White = high status, associations largely drove these effects. Finally, Black Americans also held RSAs; Rank- or Attribute-based RSAs predicted increased perceived discrimination, reduced social dominance, and reduced meritocracy beliefs. Although individuals' RSAs vary, only White Americans' Job-based stratifying associations help maintain racial status hierarchies. Theory-guided evidence of race-status associations introduces powerful new assessment tools. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Malignant Peritoneal Mesothelioma: Characterization of the Inflammatory Response in the Tumor Microenvironment.
Malignant peritoneal mesothelioma (MPM) is a rare cancer arising from mesothelial cells lining the peritoneal surface. Little is known about the tumor microenvironment in regulating MPM oncogenesis. The current study defined the chemokine/cytokine expression profile and inflammatory responses within the MPM microenvironment. Levels of 10 cytokines (Fractalkine, IFNγ, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, TNFα, VEGF) in matched ascites and sera from 15 MPM patients were measured using Milliplex immunoassays. Sera from six normal control sera were included. Statistical analyses included the Wilcoxon signed-rank test, the Mann-Whitney U test, bivariate analysis, and the R (2) coefficient of correlation. The median levels of IL-6 (3190 vs 3.18 ng/ml; p < 0.001), IL-8 (118 vs 4.93 ng/ml; p < 0.001), IP-10 (3923 vs 384 ng/ml; p < 0.001), and MCP-1 (2886 vs 544 ng/ml; p = 0.005) were significantly higher in the MPM ascites than in the matched MPM serum. In the MPM serum samples, the levels of IL-8 (4.93 vs 1.52 ng/ml; p = 0.002), MIP-1β (53.8 vs 22.3; p = 0.016), TNFα (9.97 vs 4.5 ng/ml; p = 0.013), and VEGF (277 vs 105.4 ng/ml; p = 0.036) were significantly higher than in the control sera. The chemokines/cytokines in the MPM tumor microenvironment are distinct from those associated with inflammatory responses to infection or injury (e.g., IL-1, IL-2, TNFα, IFNγ). These local changes reflect active reciprocal communication between tumor and associated stroma, which the authors predict is integral to MPM oncogenesis. Future studies will test this hypothesis and identify potential serum biomarkers for MPM.


The effects of exogenous nitric oxide on smooth muscle cell proliferation following porcine carotid angioplasty.
Nitric oxide reduces platelet adhesion and platelet-thrombus formation following angioplasty and inhibits smooth muscle cell (SMC) proliferation in vitro. In this study we investigated the effects of the nitric oxide donor molsidomine on SMC proliferation and intimal growth following experimental angioplasty. Bilateral carotid angioplasty was performed in 24 anesthetized pigs. Animals were randomized to receive oral molsidomine (whose active metabolite is SIN-1; 0.3 mg/kg every 8 h; n = 12) or placebo (n = 12) for 48 h before angioplasty and until the arteries were removed either 7 or 21 days (n = 12 each group) later. SMC proliferation was quantified by immunocytochemical staining with an antibody to the proliferating cell nuclear antigen (PCNA) and morphometric changes by computerized planimetry. SMC's were identified by alpha-actin staining. After 3 weeks treatment with molsidomine there was a significant prolongation in bleeding time [mean +/- SEM] (151 +/- 6 to 187 +/- 7 s. P < 0.01) and a sustained increase in arterial wall cyclic GMP (6.57 +/- 1.29 to 13.24 +/- 1.02 pmol/mg protein, P < 0.05). Molsidomine significantly reduced intimal proliferation when compared with placebo in arteries with an intact internal elastic lamina at 7 days (4.3 +/- 0.7 vs. 9.6 +/- 1.9 PCNA index, P < 0.005) and medial proliferation at 7 days (2.4 +/- 0.2 vs. 4.2 +/- 0.7 PCNA index, P < 0.05) and at 21 days (1.3 +/- 0.1 vs. 1.9 +/- 0.2 PCNA index, P < 0.05) after angioplasty. In arteries with rupture of the internal elastic lamina, intimal and medial SMC proliferation were similar in molsidomine- and placebo-treated animals. Intimal cell number and intimal area were uninfluenced by treatment with molsidomine in either the presence or absence of rupture of the internal elastic lamina. These results show for the first time that exogenous nitric oxide inhibits SMC proliferation following balloon angioplasty in vivo. The antiproliferative effects of nitric oxide are overwhelmed when injury is severe and are not associated with a reduction in intimal thickening. The inhibitory effects of nitric oxide on platelet adhesion and SMC proliferation identify a possible role for high local concentrations of nitric oxide to modify the vascular response to balloon angioplasty.


Investigation of designated eye position and viewing zone for a two-view autostereoscopic display.
Designated eye position (DEP) and viewing zone (VZ) are important optical parameters for designing a two-view autostereoscopic display. Although much research has been done to date, little empirical evidence has been found to establish a direct relationship between design and measurement. More rigorous studies and verifications to investigate DEP and to ascertain the VZ criterion will be valuable. We propose evaluation metrics based on equivalent luminance (EL) and binocular luminance (BL) to figure out DEP and VZ for a two-view autostereoscopic display. Simulation and experimental results prove that our proposed evaluation metrics can be used to find the DEP and VZ accurately.


Host nuclear factor-kappaB activation potentiates lung cancer metastasis.
Epidemiologic and experimental evidence suggests that a link exists between inflammation and cancer, although this relationship has only recently begun to be elucidated for lung cancer, the most frequently fatal human tumor. Nuclear factor-kappaB (NF-kappaB), a transcription factor that controls innate immune responses in the lungs, has been implicated as an important determinant of cancer cell proliferative and metastatic potential; however, its role in lung tumorigenesis is uncertain. Here, we specifically examine the role of NF-kappaB-induced airway inflammation in lung cancer metastasis using a model of intravenous injection of Lewis lung carcinoma cells into immunocompetent C57Bl/6 mice. Induction of lung inflammation by direct and specific NF-kappaB activation in airway epithelial cells potentiates lung adenocarcinoma metastasis. Moreover, we identify resident lung macrophages as crucial effectors of lung susceptibility to metastatic cancer growth. We conclude that NF-kappaB activity in host tissue is a significant factor in the development of lung metastasis.


Genetic susceptibility in diabetes mellitus: analysis of the HLA association.
Two hundred and eighty-eight patients with insulin-dependent diabetes w,o were aged 30 or under at onset and 150 patients with late-onset diabetes, 50 of them dependent on insulin and 100 not dependent on insulin, were HLA-typed. There was a significant positive association between the young-onset insulin-dependent patients and HLA-B8, BW15, and B18 and a significant negative association with B7. These data were combined with those from two other centres. There was a significant concordance for the distribution of all the HLA antigens among these three series, producing evidence in favour of an HLA-linked diabetogenic gene (or genes) having a major role in all cases of juvenile-onset insulin-dependent diabetes. There was a positive association between late-onset insulin-dependent diabetes and B8, but no association between non-insulin-dependent diabetes and the HLA system. This provides further evidence for the existence of different pathogenetic mechanisms in the two major clinical forms of diabetes mellitus.


Use of Pelvic Corrective Force With Visual Feedback Improves Paretic Leg Muscle Activities and Gait Performance After Stroke.
The purpose of this study was to examine the effects of combined pelvic corrective force and visual feedback during treadmill walking on paretic leg muscle activity and gait characteristics in individuals with post-stroke hemiparesis. Fifteen chronic stroke participants completed visual feedback only and combined pelvic corrective force and visual feedback conditions during treadmill walking. Each condition included: 1-minute baseline, 7-minute training with visual feedback only or additional pelvic corrective force, 1-minute post training, 1-minute standing break, and another 5-minute training. EMGs from the paretic leg muscles and step length were measured. Overground walking was evaluated before treadmill walking, immediately and 10 minutes after treadmill walking. Greater increases in integrated EMG of all muscles, except vastus medialis and tibialis anterior, were observed with the application of additional pelvic corrective force compared to visual feedback only during treadmill walking. Overground walking speed significantly increased after treadmill training with combined pelvic correction force and visual feedback, but was not significant for the visual feedback only condition. Voluntary weight shifting with additional pelvic corrective force enhanced paretic leg muscle activities and improved gait characteristics during walking. Individuals with post-stroke hemiparesis could adapt feedforward control and generalize the adaptation to overground walking.


Long-term natural history of intracranial arterial stenosis: an MRA follow-up study.
Intracranial arterial stenosis (ICAS) is a major cause of ischemic stroke in Asians. Despite the clinical importance of ICAS, the literature on the natural history of ICAS has been less enlightening. The aims of our study were to evaluate a long-term natural course of symptomatic and asymptomatic ICAS. 102 subjects (37 symptomatic and 65 asymptomatic) underwent follow-up MR angiography (MRA) with a median time interval between initial and follow-up MRA of 5.7 years (range 3.6-8.5 years). For each patient, the extent of stenosis of five arteries (both middle cerebral arteries, both intracranial internal carotid arteries, and basilar artery) was classified according to five grades, by consensus: normal, mild (signal reduction <50%), moderate (signal reduction ≥50%), severe (focal signal loss with the presence of a distal signal), and occlusion. Because the sample size was too small to adjust for multiple confounders, we applied the propensity score. Mean (Standard deviation) age at initial MRA was 63.5 (9.6) and 54% were men. The progression rate of ICAS differed significantly between symptomatic and asymptomatic patients (22 vs. 8%, p < 0.01), indicating a 3-fold risk of progression for symptomatic stenosis compared with asymptomatic stenosis [odds ratio (OR) 3.27, 95% confidence interval (CI) 1.08-9.95]. After adjustment for propensity score, the OR was 4.84 (95% CI, 1.40-16.7). In the matched cohort, the relative risk of stenosis progression was 5.20 for symptomatic stenosis (95% CI 1.00-27.23) compared with asymptomatic stenosis. We found a greater risk of progression for symptomatic stenosis compared with asymptomatic stenosis.


The role of prophylactic cholecystectomy versus deferral in the care of patients after endoscopic sphincterotomy.
Prophylactic cholecystectomy (PC) is advised after ES and clearance of ductal calculi on the basis of a randomized controlled trial that showed a requirement for cholecystectomy in 36% of patients who defer surgery. Other studies suggest the cholecystectomy rate to be as low as 8%. To determine the proportion of patients who deferred cholecystectomy and the outcome, we reviewed 870 consecutive patients who underwent endoscopic retrograde cholangiography and sphincterotomy; the gallbladder of 420 of these remained in situ. Patients were assigned to PC or deferred cholecystectomy (DC) groups. Cholecystectomy was deferred in 180 of 310 eligible patients. DC patients were significantly older (66.4 v. 49.8 yr) and sicker (according to the American Society of Anesthesiology [ASA] physiological status score) and had a significantly higher mortality rate than did PC patients. Deaths were principally cardiovascular and not biliary related. After a follow-up of 24.2 (<1-82.3) months, eventual cholecystectomy was required in 46 (24.7%) DC patients at a mean of 6 months after ES. The subgroup undergoing eventual cholecystectomy was younger (57.6 v. 69.4 yr; p<0.001) fitter (ASA score of 1.98 v. 2.26; p=0.015) and more likely to have residual cholecystolithiasis than were those who continued deferral. Recurrent pancreatitis was more common in DC (30%) than in PC (4.8%) patients if pancreatitis was the indication for sphincterotomy. PC is advised for patients with residual cholecystolithiasis after ES. In patients with relative contraindications, the choice is balanced in favour of cholecystectomy if there is a history of pancreatitis and in favour of deferral if more than 6 months have elapsed since ES.


Some consequences of early harsh discipline: child aggression and a maladaptive social information processing style.
Although a number of studies have reported a relation between abusive parental behavior and later aggressive behavior in the victim, many of these investigations have had methodological limitations that make precise interpretation of their results problematic. In the present study, we attempted to determine whether harsh parental discipline occurring early in life was associated with later aggression and internalizing behavior in children, using a prospective design with randomly selected samples to avoid some of these methodological difficulties. Structural equation modeling indicated a consistent relation between harsh discipline and aggression in 2 separate cohorts of children. This relation did not appear to be due to possible confounding factors such as child temperament, SES, and marital violence, although there was some indication in our data that the latter variables were related to child aggression. In addition, our analyses suggested that the effect of harsh discipline on child aggression may be mediated at least in part by maladaptive social information processing patterns that develop in response to the harsh discipline.


Veteran Experiences Seeking Non-pharmacologic Approaches for Pain.
Pain is a longstanding and growing concern among US military veterans. Although many individuals rely on medications, a growing body of literature supports the use of complementary non-pharmacologic approaches when treating pain. Our objective is to characterize veteran experiences with and barriers to accessing alternatives to medication (e.g., non-pharmacologic treatments or non-pharmacologic approaches) for pain in primary care. Data for this qualitative analysis were collected as part of the Effective Screening for Pain (ESP) study (2012-2017), a national randomized controlled trial of pain screening and assessment methods. This study was approved by the Veterans Affairs (VA) Central IRB and veteran participants signed written informed consent. We recruited a convenience sample of US military veterans in four primary care clinics and conducted semi-structured interviews (25-65 min) elucidating veteran experiences with assessment and management of pain in VA Healthcare Systems. We completed interviews with 36 veterans, including 7 females and 29 males, from three VA health care systems. They ranged in age from 28 to 94 yr and had pain intensity ratings ranging from 0 to 9 on the "pain now" numeric rating scale at the time of the interviews. We analyzed interview transcripts using constant comparison and produced mutually agreed upon themes. Veteran experiences with and barriers to accessing complementary non-pharmacologic approaches for pain clustered into five main themes: communication with provider about complementary approaches ("one of the best things the VA has ever given me was pain education and it was through my occupational therapist"), care coordination ("I have friends that go to small clinic in [area A] and I still see them down in [facility in area B] and they're going through headaches upon headaches in trying to get their information to their primary care docs"), veteran expectations about pain experience ("I think as a society we have shifted the focus to if this doctor doesn't relieve me of my pain I will find someone who does"), veteran knowledge and beliefs about various complementary non-pharmacologic approaches ("how many people know that tai chi will help with pain?… Probably none. I saw them doing tai chi down here at the VA clinic and the only reason I knew about it was because I saw it being done"), and access ("the only physical therapy I ever did… it helped…but it was a two-and-a-half-hour drive to get there three times a week… I can't do this"). Specific access barriers included local availability, time, distance, scheduling flexibility, enrollment, and reimbursement. The veterans in this qualitative study expressed interest in using non-pharmacologic approaches to manage pain, but voiced complex multi-level barriers. Limitations of our study include that interviews were conducted only in five clinics and with seven female veterans. These limitations are minimized in that the clinics covered are diverse ranging to include urban, suburban, and rural residents. Future implementation efforts can learn from the veterans' voice to appropriately target veteran concerns and achieve more patient-centered pain care.


Comparative construct validity of three presenteeism instruments in workers with musculoskeletal complaints: a prospective cohort study.
To compare the construct validity of three presenteeism instruments, using health and economic outcomes as external references, among working persons reporting musculoskeletal complaints. Data from the prospective Study on Transitions in Employment, Ability and Motivation were used. Presenteeism measurement comprised a global rating of work-ability, and two instruments indicating at-work productivity, and was assessed yearly over 6 years of follow-up. Longitudinal associations between measures of health and subsequent presenteeism, and between presenteeism and subsequent days of sick leave were assessed using generalised estimating equation models. The effect of groups of contextual factors (socio-demographic, lifestyle, personal and work-related factors) was investigated by assessing the change in explained variability. In total, 4523 persons were analysed. The association between physical health and work-ability was stronger than both at-work productivity measures; 10 points increase in physical health (0-100, higher is better) was associated with 0.79 points (95% CI 0.75 to 0.84) better work-ability (0-10, higher is better) in the subsequent year. Besides, work-ability best predicted sick leave; one point higher work-ability was associated with 4 days less sick leave (95% CI -5.09 to -3.63) the subsequent year. Personal factors improved model fit for models on health and work-ability, but conflicting results were seen for both at-work productivity instruments. Work-ability showed higher construct validity against health and economic outcomes as compared to at-work productivity, which shows that work-ability is different to productivity (losses). Personal factors are especially relevant when interpreting the relation between health and work-ability or self-reported quantity of work.


5-Fluorouracil alters dihydrofolate reductase pre-mRNA splicing as determined by quantitative polymerase chain reaction.
A quantitative polymerase chain reaction (PCR) assay has been developed to determine the absolute and relative amounts of each dihydrofolate reductase RNA species present at different stages of splicing (i.e., pre-mRNA, splicing intermediate, and mRNA). The ratios of each RNA species as measured by quantitative PCR have been confirmed by S1 nuclease mapping analysis. Quantitative PCR studies reveal a concentration-dependent decrease in the levels of dihydrofolate reductase mRNA and a splicing intermediate but little change in pre-mRNA levels after long term exposure of cells to 5-fluorouracil (FUra). The observed changes correlate with the extent of FUra incorporation into RNA and with cytotoxicity. These results, together with previous data from our laboratory, provide the first direct evidence that FUra incorporation into RNA can cause inhibition of pre-mRNA splicing in vivo. Inhibition of pre-mRNA splicing is thus a likely additional mechanism by which FUra incorporation into RNA may lead to growth inhibition and cell death.


RNA Sequencing Reveals Widespread Transcription of Natural Antisense RNAs in Entamoeba Species.
Entamoeba is a genus of Amoebozoa that includes the intestine-colonizing pathogenic species Entamoeba histolytica. To understand the basis of gene regulation in E. histolytica from an evolutionary perspective, we have profiled the transcriptomes of its closely related species E. dispar, E. moshkovskii and E. invadens. Genome-wide identification of transcription start sites (TSS) and polyadenylation sites (PAS) revealed the similarities and differences of their gene regulatory sequences. In particular, we found the widespread initiation of antisense transcription from within the gene coding sequences is a common feature among all Entamoeba species. Interestingly, we observed the enrichment of antisense transcription in genes involved in several processes that are common to species infecting the human intestine, e.g., the metabolism of phospholipids. These results suggest a potentially conserved and compact gene regulatory system in Entamoeba.


An international review of projects on hospital performance assessment.
Assessing the quality of health care has become increasingly important in health care in response to growing demands from purchasers, providers, clinicians and the public. Given the increase in projects and programs to assess performance in health care in the last 15 years, the purpose of this paper is to review current indicator projects for hospital performance assessment and compare them to the Performance Assessment Tool for Quality Improvement in Hospitals (PATH), an initiative by the WHO Regional Office for Europe. We identified current indicator projects through a systematic literature search and through contact with experts. Using an inductive approach based on a review of the literature, we identified 10 criteria for the comparison of indicator projects. We extracted data and contacted the coordinators of each indicator project to validate this information. In addition, we carried out interviews with coordinators to gather additional information on the evaluation of the respective projects. We included 11 projects that appear to have adopted a common methodology for the design and selection of indicators; however, major differences exist with regard to the philosophy, scope and coverage of the projects. This relates in particular to criteria such as participation, disclosure of results and dimensions of hospital performance assessed. Hospital performance assessment projects have become common worldwide, and initiatives such as the WHO PATH project need to be well coordinated with existing projects. Our review raised questions regarding the impact of hospital performance assessment that should be pursued in further research.


HRG/HER2/HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer.
Colorectal cancer (CRC) is a complex disease with still unsatisfactory prognosis even in western societies, although substantial progress has been made in pre-screening programs, surgical techniques and targeted therapy options. Mediator of motility-1 (Memo-1) was previously recognized as an important effector of cell migration downstream of receptor tyrosine kinase signaling in breast cancer. This study identified Memo-1 as frequently overexpressed in CRC and established a close link between extracellular HER2 activation, AhR/ARNT transcriptional activity and Memo-1 expression. Dissection of the hMemo-1 gene promoter using reporter assays and chromatin IP techniques revealed recruitment of Aryl hydrocarbon receptor (AhR)/Aryl hydrocarbon receptor nuclear-translocator (ARNT) complex, which positively influenced Memo-1 expression in cancer cells. We found that Memo-1 depletion negatively influenced the cellular actin network and that its expression is required for HER2-mediated cell migration and invasion. Moreover, analyses of Memo-1 expression in primary CRC revealed correlation with clinical parameters that point to Memo-1 as a new prognostic factor of aggressive disease in CRC patients. Altogether, these observations demonstrate that Memo-1 is an important downstream regulator of HER2-driven CRC cell migration and invasion through connecting extracellular signals from membrane to the cytoskeletal actin network.


Live cell imaging and biophotonic methods reveal two types of mutant huntingtin inclusions.
Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder that can be characterized by the presence of protein inclusions containing mutant huntingtin within a subset of neurons in the brain. Since their discovery, the relevance of inclusions to disease pathology has been controversial. We show using super-resolution fluorescence imaging and Förster resonance energy transfer (FRET) in live cells, that mutant huntingtin fragments can form two morphologically and conformationally distinct inclusion types. Using fluorescence recovery after photobleaching (FRAP), we demonstrate that the two huntingtin inclusion types have unique dynamic properties. The ability to form one or the other type of inclusion can be influenced by the phosphorylation state of serine residues at amino acid positions 13 and 16 within the huntingtin protein. We can define two types of inclusions: fibrillar, which are tightly packed, do not exchange protein with the soluble phase, and result from phospho-modification at serines 13 and 16 of the N17 domain, and globular, which are loosely packed, can readily exchange with the soluble phase, and are not phosphorylated in N17. We hypothesize that the protective effect of N17 phosphorylation or phospho-mimicry seen in animal models, at the level of protein inclusions with elevated huntingtin levels, is to induce a conformation of the huntingtin amino-terminus that causes fragments to form tightly packed inclusions that do not exit the insoluble phase, and hence exert less toxicity. The identification of these sub-types of huntingtin inclusions could allow for drug discovery to promote protective inclusions of mutant huntingtin protein in HD.


The influence of recent experience on perceptions of attractiveness.
Adults rate average faces as more attractive than most of the faces used in the creation of the average. One explanation for this is that average faces appear as both more familiar and more attractive because they resemble internal face prototypes formed from experience. Here we evaluated that explanation by examining the influence of recent experience on participants' subsequent judgments of attractiveness. Participants first performed a memory task lasting 8 min in which all of the female faces to be remembered had their features placed in a low, average, or high position, depending on experimental condition. In what was described as a separate experiment, participants then moved the features of a female face with averaged features to their most attractive vertical location. The most attractive location was affected by the faces seen during the memory task, with participants who saw faces with features in the high position placing features in higher locations than participants who saw faces with features in either the low or average positions. The results demonstrate that perceptions of attractiveness are influenced by recent experience, and suggest that internal face prototypes are constantly being updated by experience.


Cell-targeted platinum nanoparticles and nanoparticle clusters.
Herein, we report the facile preparation of cell-targeted platinum nanoparticles (PtNPs), through the design of peptides that, as a single molecule added in small concentration during the synthesis, control the size of PtNP clusters during their growth, stabilise the PtNPs in aqueous suspension and enable the functionalisation of the PtNPs with a versatile range of cell-targeting ligands. Water-soluble PtNPs targeted respectively at blood group antigens and at integrin receptors are demonstrated.


Prostate cancer gene 3 score predicts prostate biopsy outcome in men receiving dutasteride for prevention of prostate cancer: results from the REDUCE trial.
To examine the ability of the urinary prostate cancer gene 3 (PCA3) assay to predict biopsy-detected cancers in men receiving dutasteride in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study cohort. Urine and serum samples from 930 men in the active arm were acquired at years 2 and 4 of the biopsy visits. In addition to univariate logistic regression and receiver operating characteristic analysis, multivariate analysis for association with biopsy outcome was performed for PCA3 score in the presence of serum prostate-specific antigen (PSA), age, prostate volume, and family history of prostate cancer. At year 2, the univariate PCA3 score area under the receiver operating characteristic curve (AUC) was 0.668 versus 0.603 for PSA. At year 4, the PCA3 assay significantly predicted the biopsy outcome (AUC 0.628, 95% confidence interval 0.556-0.700), and the PSA level was not predictive (AUC 0.556, 95% confidence interval 0.469-0.642). The year 2 multivariate model yielded an AUC of 0.712. Removing the PCA3 score decreased the AUC to 0.660 (P = .0166 vs the full model). The median PCA3 scores in the dutasteride arm were not different from those in the 1072 men in the placebo arm (16.2 and 17.2 at year 2, P = .1755; and 18.8 and 18.1 at year 4, P = .2340, respectively). However, the PSA values were reduced >50% in the dutasteride arm at both visits (both P < .0001 vs placebo). At a PCA3 score cutoff of 35, the sensitivity and specificity were equivalent between the 2 arms. In the present study, the PCA3 assay outperformed PSA for cancer detection in men undergoing dutasteride treatment and improved the diagnostic accuracy when combined with the PSA level and other clinical variables. In addition, no adjustment in PCA3 score was needed to yield equivalent clinical performance between the dutasteride and placebo arms. These findings are particularly important in light of the potential role of dutasteride for prostate cancer chemoprevention.


Factors related to induced abortion among young women in Edo State, Nigeria.
Sub-Saharan Africa has the highest death rate from induced abortion in the world, and young women in southern Nigeria are particularly likely to terminate their pregnancies. This study assesses the prevalence of and factors associated with induced abortion among 602 young women aged 15-24 who were surveyed in Edo State, Nigeria, in 2002. We find that 41 percent of all pregnancies reported by the young women surveyed were terminated, and we estimate the age-specific abortion rate for 15-19-year-olds in Edo State at 49 abortions per 1,000 women, which is slightly higher than previous local estimates and nearly double the countrywide estimate for women aged 15-49. We construct explanatory multivariate models to predict the likelihood that a young woman has experienced sexual intercourse, has become pregnant, and has undergone an induced abortion, controlling for important demographic and risk-behavior factors. Young women unmarried at the time of the interview are found to be significantly more likely than married women to have had an abortion. Young women who have experienced transactional or forced sex are also significantly more likely to report ever having had an abortion, as are young women who have experienced more than one pregnancy. We conclude with suggestions for modifying the content and target populations of behavioral change messages and programs in the area.


The Effects of Direct Oral Anticoagulants, Warfarin, Aspirin and Thienopyridine on the Performance of Immunochemical, Faecal, Occult Blood Tests.
To clarify whether antithrombotic drugs affect diagnosis using the immunochemical faecal occult blood test -(iFOBT) of colorectal neoplasia. Using the Japan Endoscopy Database from 8 centres between 2015 and 2017, we analyzed data about patients who were iFOBT positive and had received direct oral anticoagulants (DOAC), warfarin, aspirin or thienopyridine. One-to-one matching-analogue propensity score weighted analyses were performed to compare the positive predictive value (PPV) of all neoplasms, invasive and non-invasive colorectal cancers and adenomas between drug users and non-users. All neoplasms included invasive and non-invasive colorectal cancer, and adenomas. We analyzed 197 DOAC users and 196 non-users, 153 warfarin users and 153 non-users, 408 aspirin users and 415 non-users, and 97 thienopyridine users and 97 non-users. No significant differences were observed in the PPV for all neoplasms (56.67 vs. 50.43%), invasive cancer (4.32 vs. 3.53%), non-invasive cancer (15.58 vs. 15.56%) or adenoma (53.13 vs. 48.09%) between the DOAC user and non-user groups. No significant differences were observed in the PPV for all neoplasia, invasive and non-invasive cancer, or adenoma between warfarin, aspirin and thienopyridine use and non-users. DOAC, warfarin, aspirin and thienopyridine use did not decrease the PPVs of the iFOBT used to evaluate all colorectal neoplasia.


Power relations in qualitative research.
This article focuses on the tensions between the commitment to power redistribution of the qualitative paradigm and the ethical and methodological complexity inherent in clinical research. Qualitative inquiry, in general, though there are significant variations between its different paradigms and traditions, proposes to reduce power differences and encourages disclosure and authenticity between researchers and participants. It clearly departs from the traditional conception of quantitative research, whereby the researcher is the ultimate source of authority and promotes the participants' equal participation in the research process. But it is precisely this admirable desire to democratize the research process, and the tendency to question traditional role boundaries, that raises multiple ethical dilemmas and serious methodological challenges. In this article, we offer a conceptual frame for addressing questions of power distribution in qualitative research through a developmental analysis of power relations across the different stages of the research process. We discuss ethical and methodological issues.


Detection of mutant free circulating tumor DNA in the plasma of patients with gastrointestinal stromal tumor harboring activating mutations of CKIT or PDGFRA.
In gastrointestinal stromal tumor (GIST), there is no biomarker available that indicates success or failure of therapy. We hypothesized that tumor-specific v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (CKIT)- or platelet-derived growth factor receptor-α (PDGFRA)-mutant DNA fragments can be detected and quantified in plasma samples of patients with GIST. We prospectively collected 291 plasma samples from 38 subjects with GIST harboring activating mutations of CKIT or PDGFRA detected in tumor tissue, irrespective of current disease status or treatment. We used allele-specific ligation PCR to detect mutant free circulating DNA (fcDNA). We were able to detect fcDNA harboring the tumor mutation in 15 of 38 patients. Patients with active disease displayed significantly higher amounts of mutant fcDNA compared with patients in complete remission (CR). The amount of mutant fcDNA correlated with disease course. We observed repeated positive test results or an increase of mutant fcDNA in five patients with progressive disease or relapse. A decline of tumor fcDNA or conversion from positive to negative was seen in five patients responding to treatment. A negative to positive conversion was seen in two patients with relapse and one patient with progression. In two cases, we aimed to identify additional mutations and found four additional exchanges, including mutations not known from sequentially conducted tumor biopsies. Our results indicate that fcDNA harboring tumor-specific mutations in the plasma of patients with GIST can be used as tumor-specific biomarker. The detection of resistance mutations in plasma samples might allow earlier treatment changes and obviates the need for repeated tumor biopsies.


The outcome and cost of alcohol and drug treatment in an HMO: day hospital versus traditional outpatient regimens.
To compare outcome and cost-effectiveness of the two primary addiction treatment options, day hospitals (DH) and traditional outpatient programs (OP) in a managed care organization, in a population large enough to examine patient subgroups. Interviews with new admissions to a large HMO's chemical dependency program in Sacramento, California between April 1994 and April 1996, with follow-up interviews eight months later. Computerized utilization and cost data were collected from 1993 to 1997. Design was a randomized control trial of adult patients entering the HMO's alcohol and drug treatment program (N = 668). To examine the generalizability of findings as well as self-selection factors, we also studied patients presenting during the same period who were unable or unwilling to be randomized (N = 405). Baseline interviews characterized type of substance use, addiction severity, psychiatric status, and motivation. Follow-up interviews were conducted at eight months following intake. Breathanalysis and urinalysis were conducted. Program costs were calculated. Interview data were merged with computerized utilization and cost data. Among randomized subjects, both study arms showed significant improvement in all drug and alcohol measures. There were no differences overall in outcomes between DH and OP, but DH subjects with midlevel psychiatric severity had significantly better outcomes, particularly in regard to alcohol abstinence (OR = 2.4; 95% CI = 1.2, 4.9). The average treatment costs were $1,640 and $895 for DH and OP programs, respectively. In the midlevel psychiatric severity group, the cost of obtaining an additional person abstinent from alcohol in the DH cohort was approximately $5,464. Among the 405 self-selected subjects, DH was related to abstinence (OR = 2.1; 95% CI = 1.3, 3.5). Although significant benefits of the DH program were not found in the randomized study, DH treatment was associated with better outcomes in the self-selected group. However, for subjects with mid-level psychiatric severity in both the randomized and self-selected samples, the DH program produced higher rates of abstention and was more cost-effective. Self-selection in studies that randomize patients to services requiring very different levels of commitment may be important in interpreting findings for clinical practice.


Delving into the complexity of hereditary spastic paraplegias: how unexpected phenotypes and inheritance modes are revolutionizing their nosology.
Hereditary spastic paraplegias (HSP) are rare neurodegenerative diseases sharing the degeneration of the corticospinal tracts as the main pathological characteristic. They are considered one of the most heterogeneous neurological disorders. All modes of inheritance have been described for the 84 different loci and 67 known causative genes implicated up to now. Recent advances in molecular genetics have revealed clinico-genetic heterogeneity of these disorders including their clinical and genetic overlap with other diseases of the nervous system. The systematic analysis of a large set of genes, including exome sequencing, is unmasking unusual phenotypes or inheritance modes associated with mutations in HSP genes and related genes involved in various neurological diseases. A new nosology may emerge after integration and understanding of these new data to replace the current classification. Collectively, functions of the known genes implicate the disturbance of intracellular membrane dynamics and trafficking as the consequence of alterations of cytoskeletal dynamics, lipid metabolism and organelle structures, which represent in fact a relatively small number of cellular processes that could help to find common curative approaches, which are still lacking.


Sex differences in visual evoked potentials in school-age children: what is the evidence beyond the checkerboard?
Visual evoked potentials (VEPs) are known to be influenced by several biological variables, including sex. In adult populations studies using conventional high-contrast checkerboard have shown that females display larger amplitudes and shorter latencies than males. To date, few studies have been conducted in children; the available data suggests that girls display significantly larger amplitudes than boys but the effect on latency is absent or negligible. We investigated sex-related VEP differences in 149 school-age (11.3 ± 0.6 years) children from Northern Quebec using several VEP protocols: achromatic pattern-reversal VEPs at high (95%) and low contrast (30%, 12% and 4%), as well as motion-onset VEPs and isoluminant pattern-reversal VEPs. Girls showed significantly larger amplitudes in achromatic VEPs for most of the contrast levels as well as in N2 response to motion-onset. No significant difference was found regarding the amplitude of isoluminant VEPs. In addition, girls showed shorter latencies for the achromatic N75 and a trend (p<0.1) for the P100, regardless of the contrast level. Interestingly, this latency effect appeared mostly due to head size, not sex. No differences in latency were found for motion or isoluminant responses. Overall, these findings show that sex-related differences are present in children mostly in VEP amplitude not only for high contrast achromatic pattern-reversal but also for low contrast levels and motion-onset VEPs, suggesting that sex affects VEP responses in a general fashion.


Consistency in the reporting of sexual behaviour by adolescent girls in Kenya: a comparison of interviewing methods.
To investigate in a district in Kenya the level and consistency of reporting of sexual behaviour among adolescent girls randomly assigned to two modes of survey interview: face to face interview and audio computer assisted self-interview (ACASI). The analysis is based on a subsample of over 700 never married girls aged 15-21 years in Kisumu, Kenya, drawn from a population based survey of over 2100 respondents. A questionnaire with 69 questions was used, two thirds of which were considered sensitive, including questions about risky sexual behaviour, alcohol and drug use, contraceptive practice, pregnancy, induced abortions, and births. ACASI produced significantly higher reporting of sex with a relative, stranger, or older man, and higher reporting of coerced sex. However, differences by mode for ever had sex and sex with a boyfriend were not significant. Relative to ACASI, the interviewer administered mode produced highly consistent reporting of sexual activity, both within the main interview and between the main and exit interviews. Both the mode of survey administration and the probing for various behaviours significantly affect the observed prevalence of sexual activity. The ACASI results suggest that adolescent girls in Kenya have more complex and perilous sex lives than traditional face to face surveys of sexual activity indicate. The level of consistency in the interviewer mode is argued to be suspect, particularly given the much lower levels of reporting, relative to ACASI, for types of sexual partners and coerced sexual activity.


Male origin microchimerism and ovarian cancer.
Reduced risk of ovarian cancer is commonly ascribed to reduced exposure to endogenous hormones during pregnancy, using oral contraceptives or not using hormone replacement therapy. However, exposure to hormones alone account for less than half of all cases. Many women carry small amounts of male cells-known as male origin microchimerism-in their circulation and remarkable impacts of these cells on women's health are being published. Here, we pursue the possibility that male origin microchimerism has a role in reducing ovarian cancer risk. We conducted a prospective case-cohort study using blood samples and questionnaire data from 700 women participating in the Danish Diet, Cancer, and Health cohort. Blood samples were analysed for Y chromosome presence as a marker of male microchimerism. We evaluated the association between male microchimerism and ovarian cancer, using weighted Cox regression models reporting hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Male microchimerism was detected in 46% of cases and 65.9% of controls. Women testing positive for male microchimerism had a reduced hazard rate of ovarian cancer compared with women testing negative (HR = 0.44, 95% CI: 0.29-0.68). We found no evidence of interaction with measures of hormonal exposures (P = 0.50). For the first time we report that women who test positive for male microchimerism in their circulation have reduced rates of ovarian cancer compared with women who test negative. Although the underlying mechanisms are presently unknown, we believe male microchimerism is potent in preventing ovarian cancer.


Effects on the monocyte-macrophage system and antitumor activity against L1210 leukemia of cis-bis-cyclopentenecarboxylato-trans-R,R-1,2-diaminocyclohexane -platinum (II) encapsulated in multilamellar vesicles.
Multilamellar vesicles (MLVs) composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol at a molar ratio of 7:3 were used as carriers of cis-bis-cyclopentenecarboxylato-trans-R,R-1,2-diaminocyclohexane-p latinum (II) (CPDP). The encapsulation efficiency of liposomal CPDP (L-CPDP) was 87.6%, and its stability in normal saline at 14 days was 94.4%. The in vitro and in vivo effects on the function of the monocyte-macrophage system and the antitumor activity against L1210 leukemia were investigated in CD-1 and (C57BL/6J X DBA/2J)F1 mice. L-CPDP and cisplatin (CDDP) caused a comparable inhibition of murine-resident peritoneal macrophage (PM) protein and RNA synthesis and superoxide anion release. PM-mediated tumor cell cytotoxicity was completely inhibited at a concentration of 10 micrograms CDDP and L-CPDP/ml but not at concentrations of 1 and 5 micrograms/ml. The differences in plasma clearance of 99mTc-labeled MLV and phagocytic capacity of the liver among animals pretreated with the maximum tolerated doses of L-CPDP (25 mg/kg), empty liposomes, or CDDP (10 mg/kg) were not statistically significant (plasma clearance % of control: 105, 110, and 100, respectively: P greater than .05; liver uptake % of control: 87, 96, and 104, respectively: P greater than .05). At the maximum tolerated doses, the antitumor activity of L-CPDP against L1210 leukemia was similar to that of CDDP when a single dose was administered [median survival of treated mice/median survival of control mice X 100 (%T/C): 181 vs. 175] and slightly higher with the use of a triple-dose schedule (%T/C: 275 vs. 225). L-CPDP is easy to prepare, has a high-encapsulation efficiency and stability, is not more toxic than CDDP to the monocyte-macrophage system, and is at least as effective as CDDP against L1210 leukemia.


XTandem Parser: an open-source library to parse and analyse X!Tandem MS/MS search results.
Identification of proteins by MS plays an important role in proteomics. A crucial step concerns the identification of peptides from MS/MS spectra. The X!Tandem Project (http://www.thegpm.org/tandem) supplies an open-source search engine for this purpose. In this study, we present an open-source Java library called XTandem Parser that parses X!Tandem XML result files into an easily accessible and fully functional object model (http://xtandem-parser.googlecode.com). In addition, a graphical user interface is provided that functions as a usage example and an end-user visualization tool.


Impacts of waste from concentrated animal feeding operations on water quality.
Waste from agricultural livestock operations has been a long-standing concern with respect to contamination of water resources, particularly in terms of nutrient pollution. However, the recent growth of concentrated animal feeding operations (CAFOs) presents a greater risk to water quality because of both the increased volume of waste and to contaminants that may be present (e.g., antibiotics and other veterinary drugs) that may have both environmental and public health importance. Based on available data, generally accepted livestock waste management practices do not adequately or effectively protect water resources from contamination with excessive nutrients, microbial pathogens, and pharmaceuticals present in the waste. Impacts on surface water sources and wildlife have been documented in many agricultural areas in the United States. Potential impacts on human and environmental health from long-term inadvertent exposure to water contaminated with pharmaceuticals and other compounds are a growing public concern. This work-group, which is part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards--Searching for Solutions, identified needs for rigorous ecosystem monitoring in the vicinity of CAFOs and for improved characterization of major toxicants affecting the environment and human health. Last, there is a need to promote and enforce best practices to minimize inputs of nutrients and toxicants from CAFOs into freshwater and marine ecosystems.


Electrowetting of nonwetting liquids and liquid marbles.
Transport of a water droplet on a solid surface can be achieved by differentially modifying the contact angles at either side of the droplet using capacitive charging of the solid-liquid interface (i.e., electrowetting-on-dielectric) to create a driving force. Improved droplet mobility can be achieved by modifying the surface topography to enhance the effects of a hydrophobic surface chemistry and so achieve an almost complete roll-up into a superhydrophobic droplet where the contact angle is greater than 150 degrees . When electrowetting is attempted on such a surface, an electrocapillary pressure arises which causes water penetration into the surface features and an irreversible conversion to a state in which the droplet loses its mobility. Irreversibility occurs because the surface tension of the liquid does not allow the liquid to retract from these fixed surface features on removal of the actuating voltage. In this work, we show that this irreversibility can be overcome by attaching the solid surface features to the liquid surface to create a liquid marble. The solid topographic surface features then become a conformable "skin" on the water droplet both enabling it to become highly mobile and providing a reversible liquid marble-on-solid system for electrowetting. In our system, hydrophobic silica particles and hydrophobic grains of lycopodium are used as the skin. In the region corresponding to the solid-marble contact area, the liquid marble can be viewed as a liquid droplet resting on the attached solid grains (or particles) in a manner similar to a superhydrophobic droplet resting upon posts fixed on a solid substrate. When a marble is placed on a flat solid surface and electrowetting performed it spreads but with the water remaining effectively suspended on the grains as it would if the system were a droplet of water on a surface consisting of solid posts. When the electrowetting voltage is removed, the surface tension of the water droplet causes it to ball up from the surface but carrying with it the conformable skin. A theoretical basis for this electrowetting of a liquid marble is developed using a surface free energy approach.


Clinical Practice Guideline on Screening for Colorectal Cancer in Individuals With a Family History of Nonhereditary Colorectal Cancer or Adenoma: The Canadian Association of Gastroenterology Banff Consensus.
A family history (FH) of colorectal cancer (CRC) increases the risk of developing CRC. These consensus recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on screening these high-risk individuals. Multiple parallel systematic review streams, informed by 10 literature searches, assembled evidence on 5 principal questions around the effect of an FH of CRC or adenomas on the risk of CRC, the age to initiate screening, and the optimal tests and testing intervals. The GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach was used to develop the recommendations. Based on the evidence, the Consensus Group was able to strongly recommend CRC screening for all individuals with an FH of CRC or documented adenoma. However, because most of the evidence was very-low quality, the majority of the remaining statements were conditional ("we suggest"). Colonoscopy is suggested (recommended in individuals with ≥2 first-degree relatives [FDRs]), with fecal immunochemical test as an alternative. The elevated risk associated with an FH of ≥1 FDRs with CRC or documented advanced adenoma suggests initiating screening at a younger age (eg, 40-50 years or 10 years younger than age of diagnosis of FDR). In addition, a shorter interval of every 5 years between screening tests was suggested for individuals with ≥2 FDRs, and every 5-10 years for those with FH of 1 FDR with CRC or documented advanced adenoma compared to average-risk individuals. Choosing screening parameters for an individual patient should consider the age of the affected FDR and local resources. It is suggested that individuals with an FH of ≥1 second-degree relatives only, or of nonadvanced adenoma or polyp of unknown histology, be screened according to average-risk guidelines. The increased risk of CRC associated with an FH of CRC or advanced adenoma warrants more intense screening for CRC. Well-designed prospective studies are needed in order to make definitive evidence-based recommendations about the age to commence screening and appropriate interval between screening tests.


One-dimensional SDS gel electrophoresis of proteins.
Electrophoresis is used to separate complex mixtures of proteins (e.g., from cells, subcellular fractions, column fractions, or immunoprecipitates), to investigate subunit compositions, and to verify homogeneity of protein samples. It can also serve to purify proteins for use in further applications. In polyacrylamide gel electrophoresis, proteins migrate in response to an electrical field through pores in a polyacrylamide gel matrix; pore size decreases with increasing acrylamide concentration. The combination of pore size and protein charge, size, and shape determines the migration rate of the protein. In this unit, the standard Laemmli method is described for discontinuous gel electrophoresis under denaturing conditions, that is, in the presence of sodium dodecyl sulfate (SDS). Both full-size and minigel formats are detailed. Several modifications are provided for specific applications. For separation of peptides and small proteins, the standard buffers are replaced with either a Tris-tricine buffer system or a modified Tris buffer in the absence of urea. Continuous SDS-PAGE is a simplified method in which the same buffer is used for both the gel and the electrode solutions and the stacking gel is omitted. Other protocols cover the preparation and use of ultrathin gels and gradient gels, and the simultaneous preparation of multiple gels.


Predictors of the quality of life of older people with heart failure recruited from primary care.
Current understanding of quality of life in heart failure is largely derived from clinical trials. Older people, women and those with co-morbidities are underrepresented in these. Little is known about factors predictive of quality of life amongst older people with heart failure recruited from community settings. To identify factors predictive of quality of life amongst older people recruited from community settings. prospective questionnaire survey. General practice surgeries located in four areas of the UK: Bradford, Barnsley, East Devon and West Hampshire. A total of 542 people aged >60 years with heart failure. Participants completed a postal questionnaire, which included a disease-specific measure (Kansas City Cardiomyopathy Questionnaire), a generic quality-of-life measure (SF-36) and sociodemographic information. A multiple linear regression analysis identified the following factors as predictive of decreased quality of life: being female, being in New York Heart Association (NYHA) functional class III or IV, showing evidence of depression, being in socioeconomic groups III-V and experiencing two or more co-morbidities. Older age was associated with decreased quality of life, as measured by a generic health-related quality-of-life tool (the SF-36 mental and physical health functioning scales) but not by a disease-specific tool (the Kansas City Cardiomyopathy Questionnaire). Findings from the study suggest that quality of life for older people with heart failure can be described as challenging and difficult, particularly for women, those in a high NYHA class, patients showing evidence of depression, patients in socioeconomic groups III-V, those experiencing two or more co-morbidities and the 'oldest old'. Such information can help clinicians working with older people identify those at risk of reduced quality of life and target interventions appropriately.


Plant-based FRET biosensor discriminates environmental zinc levels.
Heavy metal accumulation in the environment poses great risks to flora and fauna. However, monitoring sites prone to accumulation poses scale and economic challenges. In this study, we present and test a method for monitoring these sites using fluorescent resonance energy transfer (FRET) change in response to zinc (Zn) accumulation in plants as a proxy for environmental health. We modified a plant Zn transport protein by adding flanking fluorescent proteins (FPs) and deploying the construct into two different species. In Arabidopsis thaliana, FRET was monitored by a confocal microscope and had a 1.4-fold increase in intensity as the metal concentration increased. This led to a 16.7% overall error-rate when discriminating between a control (1μm Zn) and high (10mm Zn) treatment after 96h. The second host plant (Populus tremula×Populu salba) also had greater FRET values (1.3-fold increase) when exposed to the higher concentration of Zn, while overall error-rates were greater at 22.4%. These results indicate that as plants accumulate Zn, protein conformational changes occur in response to Zn causing differing interaction between FPs. This results in greater FRET values when exposed to greater amounts of Zn and monitored with appropriate light sources and filters. We also demonstrate how this construct can be moved into different host plants effectively including one tree species. This chimeric protein potentially offers a method for monitoring large areas of land for Zn accumulation, is transferable among species, and could be modified to monitor other specific heavy metals that pose environmental risks.


Protection and spontaneous recovery from cisplatin-induced hearing loss.
Cisplatin [cis-diamminechloroplatinum(II)] has proved itself as a potent antineoplastic agent. However, nephrotoxicity, neurotoxicity, gastrointestinal toxicity, myelosuppression, and ototoxicity interfere with its therapeutical efficacy. Forced diuresis reduces nephrotoxicity, effectively leaving neurotoxicity and ototoxicity as the major side effects of concern, and gastrointestinal toxicity and myelosuppression as the secondary side effects. So far, attempts to reduce these side effects by developing equally potent platinum analogs have been unsuccessful. Some success has been achieved, however, by co-treatment with protective agents. Nearly all these agents are sulfur- or sulfhydryl-containing compounds (thio compounds), known as antioxidants and potent heavy metal chelators. These thio compounds may provide protection from cisplatin toxicity either (1) by direct interaction between the cisplatin and the thio moiety, (2) by displacing platinum from its site of toxic action, (3) by preventing platinum from interfering with superoxide dismutase, or (4) by scavenging of cisplatin-induced free radicals. In particular the first two protective mechanisms bear the risk of reducing the antineoplastic activity of cisplatin. Since nephrotoxicity can be controlled effectively by forced diuresis, a more specific approach of coping with ototoxicity by focusing on protection at the sensorineural level was chosen. Being familiar with the neuro-protective and neurotrophic properties of ACTH-related neuropeptides, specifically against cisplatin-induced peripheral neuropathies, it was judged expedient to test for a possible otoprotective action of these neuropeptides. The results were positive, although tainted with high interanimal variability. When testing for the possibility that the neuropeptides would merely delay cisplatin-induced ototoxicity rather than reduce it, it was discovered in control series without neuropeptide co-treatment that the ear can recover spontaneously from cisplatin-induced hearing loss. This was found both electrophysiologically and in outer hair cell (OHC) counts. Although these preliminary findings require further investigation, they strongly suggest that spontaneous recovery of cochlear injury can occur in the mature mammalian cochlea. Moreover, the otoprotective action of the ACTH-related neuropeptides suggests that it may be possible to stimulate recovery from acute hearing loss using neuropeptides.


Enhanced priming for trauma-related words predicts posttraumatic stress disorder.
There is preliminary evidence that enhanced priming for trauma-related cues plays a role in posttraumatic stress disorder (PTSD). A prospective study of 119 motor vehicle accident survivors investigated whether priming for trauma-related stimuli predicts PTSD. Participants completed a modified word-stem completion test comprising accident-related, traffic-related, general threat, and neutral words at 2 weeks post-trauma. Priming for accident-related words predicted PTSD at 6 months follow-up, even when initial symptom levels of PTSD and depression and priming for other words were controlled. The results are in line with the hypothesis that enhanced priming for traumatic material contributes to the development of chronic PTSD.


Absence of Fms-like tyrosine kinase 3 ligand (Flt3L) signalling protects against collagen-induced arthritis.
Comprehending the mechanisms that regulate activation of autoreactive T cells and B cell antibody production is fundamental for understanding the breakdown in self-tolerance and development of autoimmunity. Here we studied the role of Fms-like tyrosine kinase 3 ligand (Flt3L) signalling in the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in mice lacking Flt3L (Flt3L(-/-)) and wild-type (WT) littermates (C57/BL6, 8-10 weeks old). Mice were killed in the initial phase (acute phase: experiment 1) and late phase (chronic phase: experiment 2) of the disease. Arthritis severity was assessed using a semiquantitative scoring system (0-4), and histological analysis of cellular infiltration, cartilage destruction and peptidoglycan loss was performed. Phenotypic and functional analysis of T and B cells, FoxP3 expression, activation and lymphocyte costimulatory markers, and cytokine production were performed ex vivo by flow cytometry in lymph nodes. Serum collagen type II (CII)-specific antibodies were measured by ELISA. Flt3L(-/-) mice showed a marked decrease in clinical arthritis scores and incidence of arthritis in both acute and chronic phases of CIA compared with WT mice. Moreover, decreased synovial inflammation and joint destruction was observed. Both the magnitude and quality of T cell responses were altered in Flt3L(-/-). In the acute phase, the amount of CII-specific IgG2a antibodies was lower in Flt3L(-/-) than WT mice. These results strongly suggest a role for Flt3L signalling in the development of arthritis.


Lifetime Measurements of Excited States in ^{172}Pt and the Variation of Quadrupole Transition Strength with Angular Momentum.
Lifetimes of the first excited 2^{+} and 4^{+} states in the extremely neutron-deficient nuclide ^{172}Pt have been measured for the first time using the recoil-distance Doppler shift and recoil-decay tagging techniques. An unusually low value of the ratio B(E2:4_{1}^{+}→2_{1}^{+})/B(E2:2_{1}^{+}→0_{gs}^{+})=0.55(19) was found, similar to a handful of other such anomalous cases observed in the entire Segré chart. The observation adds to a cluster of a few extremely neutron-deficient nuclides of the heavy transition metals with neutron numbers N≈90-94 featuring the effect. No theoretical model calculations reported to date have been able to explain the anomalously low B(E2:4_{1}^{+}→2_{1}^{+})/B(E2:2_{1}^{+}→0_{gs}^{+}) ratios observed in these cases. Such low values cannot, e.g., be explained within the framework of the geometrical collective model or by algebraic approaches within the interacting boson model framework. It is proposed that the group of B(E2:4_{1}^{+}→2_{1}^{+})/B(E2:2_{1}^{+}→0_{gs}^{+}) ratios in the extremely neutron-deficient even-even W, Os, and Pt nuclei around neutron numbers N≈90-94 reveal a quantum phase transition from a seniority-conserving structure to a collective regime as a function of neutron number. Although a system governed by seniority symmetry is the only theoretical framework for which such an effect may naturally occur, the phenomenon is highly unexpected for these nuclei that are not situated near closed shells.


Effect of the expression of a hepatocyte-specific MHC molecule in transgenic mice on T cell tolerance.
A hybrid murine class I gene, Q10/L, was injected into C3H/HeJ fertilized ova to produce transgenic (TG) mice. This fusion gene contained 414 bp of Q10 promoter sequences which was sufficient to direct liver-specific expression in two lines of animals. Animals from these lines did not have Q10/L mRNA in 10 nonhepatic tissues examined including thymus, spleen, and bone marrow. The ontogeny of Q10/Ld expression in both liver and yolk sac paralleled expression of endogenous Q10. Analysis of liver cells from these lines by flow cytometry and immunofluorescence demonstrated the presence of the Q10/L Ag solely on hepatocytes. TG animals showed no signs of hepatic disease as evidenced by an absence of cellular infiltrates in the liver and a normal profile of serum enzymes that are elevated in association with hepatic disease. When spleen cells from TG animals were cocultured with splenocytes that express Ag cross-reactive with Q10/L, CTL were generated that recognized and lysed L cells which express Q10/L. However, the extent of lysis was less than that generated from non-TG control littermates. That these cross-reactive T cells were physiologically significant was demonstrated by adoptive transfer of in vivo primed T cell enriched spleen cells which produced a mononuclear infiltration of the liver of TG recipients. However, inoculation of Q10/L L cells or splenocytes expressing Q10/L cross-reactive Ag into TG mice did not induce cellular infiltration or overt hepatic disease. Whereas inoculation of normal C3H mice with these cells led to priming of Q10/L reactive CTL, anti-Q10/L CTL could not be primed in TG mice. This suggests that Ag expression solely on hepatocytes can lead to inactivation of specific CTL clones and thus account for the observed in vivo tolerance.


Growth parameters and childhood epilepsy in Hai District, Tanzania: a community-based study.
This cross-sectional study examined whether growth parameters were associated with epilepsy in children living in a rural community in sub-Saharan Africa (SSA). A cross-sectional study was performed in the Hai District Demographic Surveillance Site (HDSS), Tanzania in which 6-14 year old children with epilepsy (CWE) were identified. Age matched controls were randomly selected from the Hai census database for comparison. Anthropometric measurements were used to assess the nutritional status of the children and body mass index (BMI) calculated. Associations between social, demographic and nutritional factors and epilepsy were assessed using multivariable logistic regression. 112 CWE were identified and were compared with 113 controls. There was no significant difference in the BMI between cases and controls (T-test, p-value of 0.117). Amongst cases, there were no significant associations between BMI and motor difficulties, antiepileptic drug use, cognitive or behavioural problems, early-onset epilepsy or seizure frequency. In the whole group, BMI was significantly associated with socio-economic status (p=0.037) and age. There was no significant difference found between CWE and matched controls with respect to nutritional status. This suggests that there is no causal association between under nutrition and epilepsy in this community. Nutritional assessment is still important as part of the comprehensive care of CWE.


Comparison of Temperature-Index Snowmelt Models for Use within an Operational Water Quality Model.
The accurate prediction of snowmelt runoff is a critical component of integrated hydrological and water quality models in regions where snowfall constitutes a significant portion of the annual precipitation. In cold regions, the accumulation of a snowpack and the subsequent spring snowmelt generally constitutes a major proportion of the annual water yield. Furthermore, the snowmelt runoff transports significant quantities of sediment and nutrients to receiving streams and strongly influences downstream water quality. Temperature-index models are commonly used in operational hydrological and water quality models to predict snowmelt runoff. Due to their simplicity, computational efficiency, low data requirements, and ability to consistently achieve good results, numerous temperature-index models of varying complexity have been developed in the past few decades. The objective of this study was to determine how temperature-index models of varying complexity would affect the performance of the water quality model SWAT (a modified version of SWAT that was developed for watersheds dominated by boreal forest) for predicting runoff. Temperature-index models used by several operational hydrological models were incorporated into SWAT. Model performance was tested on five watersheds on the Canadian Boreal Plain whose hydrologic response is dominated by snowmelt runoff. The results of this study indicate that simpler temperature-index models can perform as well as more complex temperature-index models for predicting runoff from the study watersheds. The outcome of this study has important implications because the incorporation of simpler temperature-index snowmelt models into hydrological and water quality models can lead to a reduction in the number of parameters that need to be optimized without sacrificing predictive accuracy.


Mortality and Operative Management for Patients Undergoing Repair of Coarctation of the Aorta: A Retrospective Review of the Pediatric Cardiac Care Consortium.
The surgical mortality associated with repair of coarctation of the aorta (CoA) over a 25-year period was examined. Risk factors for discharge mortality were evaluated as well as the surgical techniques and its evolution over the period studied. Utilizing the pediatric cardiac care consortium, we conducted a retrospective review of patients less than 18 years of age submitted between 1982 and 2007. Variables reviewed included weight at birth, age and weight at the operation, type of coarctation repair, associated cardiac anomalies, year of repair, center-specific volume, postoperative length of stay, and in-hospital mortality. There were 7,860 patients submitted with the procedural code for repair of CoA. Forty-five percent underwent repair within 30 days of life (n = 3,549), including 1,444 patients who were operated upon within the first 7 days of life (18% of all patients). Seventy percent (n = 5,528) of patients had an isolated CoA (iCoA). The overall mortality for the entire group was 4.2% (n = 331), decreasing to 2.0% (n = 114) for iCoA (P < .0001). A hypoplastic aortic arch occurred in 4.6%, with a mortality of 10.6%. Coarctectomy with an end-to-end reconstruction was the most common procedure performed. Multivariable modeling for discharge mortality was significant for diagnosis of ventricular septal defect, operative weight, operative year, and diagnosis of aortic arch hypoplasia. Operative repair of CoA is accomplished with a low mortality, although certain subgroups have persistently inferior outcomes. The techniques utilized for aortic reconstruction have evolved, with coarctectomy and an end-to-end anastomosis becoming the dominant surgical procedures.


Long-Term clinical outcomes according to initial management and thrombolysis in myocardial infarction risk score in patients with acute non-ST-segment elevation myocardial infarction.
There is still debate about the timing of revascularization in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI). We analyzed the long-term clinical outcomes of the timing of revascularization in patients with acute NSTEMI obtained from the Korea Acute Myocardial Infarction Registry (KAMIR). 2,845 patients with acute NSTEMI (65.6 +/- 12.5 years, 1,836 males) who were enrolled in KAMIR were included in the present study. The therapeutic strategy of NSTEMI was categorized into early invasive (within 48 hours, 65.8 +/- 12.6 years, 856 males) and late invasive treatment (65.3 +/- 12.1 years, 979 males). The initial- and long-term clinical outcomes were compared between two groups according to the level of Thrombolysis In Myocardial Infarction (TIMI) risk score. There were significant differences in-hospital mortality and the incidence of major adverse cardiac events during one-year clinical follow-up between two groups (2.1% vs. 4.8%, p < 0.001, 10.0% vs. 13.5%, p = 0.004, respectively). According to the TIMI risk score, there was no significant difference of long-term clinical outcomes in patients with low to moderate TIMI risk score, but significant difference in patients with high TIMI risk score (>or= 5 points). The old age, high Killip class, low ejection fraction, high TIMI risk score, and late invasive treatment strategy are the independent predictors for the long-term clinical outcomes in patients with NSTEMI.


The effect of application sustained seating pressure on adhesive luting procedure.
To evaluate the effect of short versus long application seating pressure on the bond strength of resin blocks, luted with a dual-cured resin cement (Panavia F) to pre-coated or non pre-coated dentin with an hydrophobic light-cured adhesive (Clearfil Protect Bond). Sixteen non-carious human third molars were randomly divided into six Groups (four teeth each). Cylindrical composite blocks were luted with Panavia F (Group Ia) and with Clearfil Protect Bond with Panavia F (Group IIa) and seating pressure was applied for 5s. In Groups Ib and IIb, the two bonding procedures were respectively repeated, but the resin cylinder was maintained under constant pressure during the entire 3min polymerization period for the resin cement. After storing in distilled water for 24h, 0.9mmx0.9mm sticks were produced from these luted specimens for microtensile bond testing and SEM examination. The use of Clearfil Protect Bond with Panavia F produced higher bond strengths than the use of Panavia F (p<0.05). Extending the time of pressure application up to 3min increased the bond strength (p<0.001) and improved the integrity of the interfacial quality. The application of sustained seating pressure during luting procedures and the additional use of a hydrophobic light-cured adhesive both improve the final bond strength of the resin cement.


Fractionation, solid-phase immobilization and chemical degradation of long pectin oligogalacturonides. Initial steps towards sequencing of oligosaccharides.
This work presents the optimized separation of pectin oligomers, their analysis by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), their subsequent immobilization to supports, and our initial steps towards solid-support assisted sequencing. The ambient pressure strong anion-exchange resin Source 15Q combined with ammonium formate buffer (AF) was used for the separation of unsaturated and saturated pectic oligogalacturonides (OGAs) derived from enzymatic digestion of pectin. Routinely, multi-milligram quantities of defined sizes OGAs with DPs from 5 to 19 were produced in excellent purity (>95%). Elution of OGAs followed by direct analysis of the peak fractions by MALDI-TOF MS. Purified OGAs (DP 5-7) were chemoselectively immobilized onto aminooxy-terminated polyethylene glycol polyacrylamide (PEGA) supports. Solid-phase anchoring took place at the reducing end of the oligosaccharide and resulted in the formation of an oxime linkage. The very high coupling yields confirmed the general suitability of aminooxy-PEGA resins for the immobilization of OGAs of different lengths. The OGA-functionalized PEGA supports were subsequently treated with aq TFA at 40 or 60 degrees C, and the chemical degradation products released from the support were analyzed by ESIMS. In all cases, the original OGA was degraded into smaller oligomers of various sizes down to the monomer. This work illustrates some of the basic principles underlying a strategy ultimately aimed at solid-support assisted sequencing of oligosaccharides.