Maternal serum fructosamine levels and stillbirth: a case-control study of the Stillbirth Collaborative Research Network.

OBJECTIVE: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. DESIGN: Secondary analysis of a case-control study. SETTING: Multicentre study of five geographic catchment areas in the USA. POPULATION: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. MAIN OUTCOME MEASURES: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. RESULTS: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 µmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 µmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 µmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605-0.663) overall, 0.713 (0.624-0.802) with diabetes and 0.625 (0.595-0.656) with no diabetes. CONCLUSIONS: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. TWEETABLE ABSTRACT: Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes.

Peri-operative neurological complications.

Brain injury from cardiac surgery is an important source of patient morbidity and mortality. The relationship between risk of brain injury and advanced age portends a rising frequency of these complications due to an increasing proportion of elderly patients undergoing cardiac surgery. This review will explore the aetiology and risk factors for peri-operative stroke, postoperative cognitive dysfunction and postoperative delirium. The prevention of each of these conditions will also be discussed, with a focus on brain protection strategies and the avoidance of cerebral embolism and hypoperfusion.

Association of intraoperative changes in brain-derived neurotrophic factor and postoperative delirium in older adults.

BACKGROUND: Delirium is common after surgery, although the aetiology is poorly defined. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in neurotransmission and neuroplasticity. Decreased levels of BDNF have been associated with poor cognitive outcomes, but few studies have characterized the role of BDNF perioperatively. We hypothesized that intraoperative decreases in BDNF levels are associated with postoperative delirium. METHODS: Patients undergoing spine surgery were enrolled in a prospective cohort study. Plasma BDNF was collected at baseline and at least hourly intraoperatively. Delirium was assessed using rigorous methods, including the Confusion Assessment Method (CAM) and CAM for the intensive care unit. Associations of changes in BDNF and delirium were examined using regression models. RESULTS: Postoperative delirium developed in 32 of 77 (42%) patients. The median baseline BDNF level was 7.6 ng ml -1 [interquartile range (IQR) 3.0-11.2] and generally declined intraoperatively [median decline 61% (IQR 31-80)]. There was no difference in baseline BDNF levels by delirium status. However, the percent decline in BDNF was greater in patients who developed delirium [median 74% (IQR 51-82)] vs in those who did not develop delirium [median 50% (IQR 14-79); P =0.03]. Each 1% decline in BDNF was associated with increased odds of delirium in unadjusted {odds ratio [OR] 1.02 [95% confidence interval (CI) 1.00-1.04]; P =0.01}, multivariable-adjusted [OR 1.02 (95% CI 1.00-1.03); P =0.03], and propensity score-adjusted models [OR 1.02 (95% CI 1.00-1.04); P =0.03]. CONCLUSIONS: We observed an association between intraoperative decline in plasma BDNF and delirium. These preliminary results need to be confirmed but suggest that plasma BDNF levels may be a biomarker for postoperative delirium.

Defining oliguria during cardiopulmonary bypass and its relationship with cardiac surgery-associated acute kidney injury.

BACKGROUND: While urine flow rate ≤0.5 ml kg-1 h-1 is believed to define oliguria during cardiopulmonary bypass (CPB), it is unclear whether this definition identifies risk for acute kidney injury (AKI) . The purpose of this retrospective study was to evaluate if urine flow rate during CPB is associated with AKI. METHODS: Urine flow rate was calculated in 503 patients during CPB. AKI in the first 48 h after surgery was defined by the Kidney Disease: Improving Global Outcomes classification. Adjusted risk factors associated with AKI and urine flow rate were assessed. RESULTS: Patients with AKI [n=149 (29.5%)] had lower urine flow rate than those without AKI (P<0.001). The relationship between urine flow and AKI risk was non-linear, with an inflection point at 1.5 ml kg-1 h-1 Among patients with urine flow <1.5 ml kg-1 h-1, every 0.5 ml kg-1 h-1 higher urine flow reduced the adjusted risk of AKI by 26% (95% CI 13-37; P<0.001). Urine flow rate during CPB was independently associated with the risk for AKI. Age up to 80 years and preoperative diuretic use were inversely associated with urine flow rate; mean arterial pressure on CPB (when <87 mmHg) and CPB flow were positively associated with urine flow rate. CONCLUSIONS: Urine flow rate during CPB <1.5 ml kg-1 h-1 identifies patients at risk for cardiac surgery-associated AKI. Careful monitoring of urine flow rate and optimizing mean arterial pressure and CPB flow might be a means to ensure renal perfusion during CPB. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00769691 and NCT00981474.

Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy.

BACKGROUND: The effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single-session stereotactic radiosurgery (SRS) and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy. PATIENTS AND METHODS: Patients were included if MBMs were treated with single-session SRS within 3 months of receiving systemic therapy. The primary end point of this study was distant MBM control. Secondary end points were local MBM control defined as a >20% volume increase on follow-up MRI, systemic progression-free survival, overall survival (OS) from both SRS and cranial metastases diagnosis, and neurotoxicity. Images were reviewed alongside two neuro-radiologists at our institution. RESULTS: Ninety-six patients were treated to 314 MBMs over 119 SRS treatment sessions between January 2007 and August 2015. No significant differences were noted in age (P = 0.27), gender (P = 0.85), treated gross tumor volume (P = 0.26), or the diagnosis-specific graded prognostic assessment (P = 0.51) between the treatment cohorts. Twelve-month Kaplan-Meier (KM) distant MBM control rates were 38%, 21%, 20%, 8%, and 5% (P = 0.008) for SRS with anti-PD-1 therapies, anti-CTLA-4 therapy, BRAF/MEKi, BRAFi, and conventional chemotherapy, respectively. No significant differences were noted in the KM local MBM control rates among treatment groups (P = 0.25). Treatment with anti-PD-1 therapy, anti-CTLA-4 therapy, or BRAF/MEKi significantly improved OS on both univariate and multivariate analyses when compared with conventional chemotherapy. CONCLUSION: In our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.

Heavy metal accumulation in Lacistorhynchus dollfusi (Trypanorhyncha: Lacistorhynchidae) infecting Citharichthys sordidus (Pleuronectiformes: Bothidae) from Santa Monica Bay, Southern California.

The accumulation of heavy metals in macroparasites of fish has been widely studied in freshwater environments. Less is known about metal uptake in cestodes parasitizing marine fish. Lacistorhynchus dollfusi is a common larval cestode parasite of Pacific sanddab (Citharichthys sordidus), a flatfish species inhabiting Santa Monica Bay. The ability of this cestode to concentrate metals in its tissues was compared with metal levels in its sanddab host. Fish and cestode tissue were analysed for 14 elements using Inductively Coupled Plasma Mass Spectrometry. The elements analysed were silver (Ag), arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), potassium (K), lead (Pb), rubidium (Rb), selenium (Se), strontium (Sr), titanium (Ti) and zinc (Zn). Three of the 14 metals (Cu, Hg and Zn) were significantly greater in concentration in L. dollfusi compared with their levels in the liver, intestine and muscle of their fish host. They ranked in concentration from highest to lowest as follows: Zn > Cu > Hg. The ability of the cestode L. dollfusi to uptake metals at higher concentrations than its host warrants its consideration as a candidate for a heavy metal accumulation indicator of pollution exposure in Pacific sanddab.

Evidence of an association between brain cellular injury and cognitive decline after non-cardiac surgery.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is common after non-cardiac surgery, but the mechanism is unclear. We hypothesized that decrements in cognition 1 month after non-cardiac surgery would be associated with evidence of brain injury detected by elevation of plasma concentrations of S100ß, neuron-specific enolase (NSE), and/or the brain-specific protein glial fibrillary acid protein (GFAP). METHODS: One hundred and forty-nine patients undergoing shoulder surgery underwent neuropsychological testing before and then 1 month after surgery. Plasma was collected before and after anaesthesia. We determined the relationship between plasma biomarker concentrations and individual neuropsychological test results and a composite cognitive functioning score (mean Z-score). RESULTS: POCD (≥-1.5 sd decrement in Z-score from baseline) was present in 10.1% of patients 1 month after surgery. There was a negative relationship between higher plasma GFAP concentrations and lower postoperative composite Z-scores {estimated slope=-0.14 [95% confidence interval (CI) -0.24 to -0.04], P=0.005} and change from baseline in postoperative scores on the Rey Complex Figure Test copy trial (P=0.021), delayed recall trial (P=0.010), and the Symbol Digit Modalities Test (P=0.004) after adjustment for age, sex, history of hypertension and diabetes. A similar relationship was not observed with S100ß or NSE concentrations. CONCLUSIONS: Decline in cognition 1 month after shoulder surgery is associated with brain cellular injury as demonstrated by elevated plasma GFAP concentrations.

A global reference for caesarean section rates (C-Model): a multicountry cross-sectional study.

OBJECTIVE: To generate a global reference for caesarean section (CS) rates at health facilities. DESIGN: Cross-sectional study. SETTING: Health facilities from 43 countries. POPULATION/SAMPLE: Thirty eight thousand three hundred and twenty-four women giving birth from 22 countries for model building and 10,045,875 women giving birth from 43 countries for model testing. METHODS: We hypothesised that mathematical models could determine the relationship between clinical-obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three-step approach to generate the global benchmark of CS rates at health facilities: creation of a multi-country reference population, building mathematical models, and testing these models. MAIN OUTCOME MEASURES: Area under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate. RESULTS: According to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C-Model, with summary estimates ranging from 0.832 to 0.844. The C-Model was able to generate expected CS rates adjusted for the case-mix of the obstetric population. We have also prepared an e-calculator to facilitate use of C-Model (www.who.int/reproductivehealth/publications/maternal_perinatal_health/c-model/en/). CONCLUSIONS: This article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C-Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS. TWEETABLE ABSTRACT: The C-Model provides a customized benchmark for caesarean section rates in health facilities and systems.

Apparent diffusion coefficient scalars correlate with near-infrared spectroscopy markers of cerebrovascular autoregulation in neonates cooled for perinatal hypoxic-ischemic injury.

BACKGROUND AND PURPOSE: Neurologic morbidity remains high in neonates with perinatal hypoxic-ischemic injury despite therapeutic hypothermia. DTI provides qualitative and quantitative information about the microstructure of the brain, and a near-infrared spectroscopy index can assess cerebrovascular autoregulation. We hypothesized that lower ADC values would correlate with worse autoregulatory function. MATERIALS AND METHODS: Thirty-one neonates with hypoxic-ischemic injury were enrolled. ADC scalars were measured in 27 neonates (age range, 4-15 days) in the anterior and posterior centrum semiovale, basal ganglia, thalamus, posterior limb of the internal capsule, pons, and middle cerebellar peduncle on MRI obtained after completion of therapeutic hypothermia. The blood pressure range of each neonate with the most robust autoregulation was identified by using a near-infrared spectroscopy index. Autoregulatory function was measured by blood pressure deviation below the range with optimal autoregulation. RESULTS: In neonates who had MRI on day of life ≥10, lower ADC scalars in the posterior centrum semiovale (r = -0.87, P = .003, n = 9) and the posterior limb of the internal capsule (r = -0.68, P = .04, n = 9) correlated with blood pressure deviation below the range with optimal autoregulation during hypothermia. Lower ADC scalars in the basal ganglia correlated with worse autoregulation during rewarming (r = -0.71, P = .05, n = 8). CONCLUSIONS: Blood pressure deviation from the optimal autoregulatory range may be an early biomarker of injury in the posterior centrum semiovale, posterior limb of the internal capsule, and basal ganglia. Optimizing blood pressure to support autoregulation may decrease the risk of brain injury in cooled neonates with hypoxic-ischemic injury.

Arterial pressure above the upper cerebral autoregulation limit during cardiopulmonary bypass is associated with postoperative delirium.

BACKGROUND: Mean arterial pressure (MAP) below the lower limit of cerebral autoregulation during cardiopulmonary bypass (CPB) is associated with complications after cardiac surgery. However, simply raising empiric MAP targets during CPB might result in MAP above the upper limit of autoregulation (ULA), causing cerebral hyperperfusion in some patients and predisposing them to cerebral dysfunction after surgery. We hypothesized that MAP above an ULA during CPB is associated with postoperative delirium. METHODS: Autoregulation during CPB was monitored continuously in 491 patients with the cerebral oximetry index (COx) in this prospective observational study. COx represents Pearson's correlation coefficient between low-frequency changes in regional cerebral oxygen saturation (measured with near-infrared spectroscopy) and MAP. Delirium was defined throughout the postoperative hospitalization based on clinical detection with prospectively defined methods. RESULTS: Delirium was observed in 45 (9.2%) patients. Mechanical ventilation for >48 h [odds ratio (OR), 3.94; 95% confidence interval (CI), 1.72-9.03], preoperative antidepressant use (OR, 3.0; 95% CI, 1.29-6.96), prior stroke (OR, 2.79; 95% CI, 1.12-6.96), congestive heart failure (OR, 2.68; 95% CI, 1.28-5.62), the product of the magnitude and duration of MAP above an ULA (mm Hg h; OR, 1.09; 95% CI, 1.03-1.15), and age (per year of age; OR, 1.01; 95% CI, 1.01-1.07) were independently associated with postoperative delirium. CONCLUSIONS: Excursions of MAP above the upper limit of cerebral autoregulation during CPB are associated with risk for delirium. Optimizing MAP during CPB to remain within the cerebral autoregulation range might reduce risk of delirium. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT00769691 and NCT00981474.

Risk factors for spontaneous and provider-initiated preterm delivery in high and low Human Development Index countries: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To evaluate how the effect of maternal complications on preterm birth varies between spontaneous and provider-initiated births, as well as among different countries. DESIGN: Secondary analysis of a cross-sectional study. SETTING: Twenty-nine countries participating in the World Health Organization Multicountry Survey on Maternal and Newborn Health. POPULATION: 299 878 singleton deliveries of live neonates or fresh stillbirths. METHODS: Countries were categorised into very high, high, medium and low developed countries using the Human Development Index (HDI) of 2012 by the World Bank. We described the prevalence and risk of maternal complications, their effect on outcomes and their variability by country development. MAIN OUTCOME MEASURES: Preterm birth, fresh stillbirth and early neonatal death. RESULTS: The proportion of provider-initiated births among preterm deliveries increased with development: 19% in low to 40% in very high HDI countries. Among preterm deliveries, the socially disadvantaged were less likely, and the medically high risk were more likely, to have a provider-initiated delivery. The effects of anaemia [adjusted odds ratio (AOR), 2.03; 95% confidence interval (CI), 1.84; 2.25], chronic hypertension (AOR, 2.28; 95% CI, 1.94; 2.68) and pre-eclampsia/eclampsia (AOR, 5.03; 95% CI, 4.72; 5.37) on preterm birth were similar among all four HDI subgroups. CONCLUSIONS: The provision of adequate obstetric care, including optimal timing for delivery in high-risk pregnancies, especially to the socially disadvantaged, could improve pregnancy outcomes. Avoiding preterm delivery in women when maternal complications, such as anaemia or hypertensive disorders, are present is important for countries at various stages of development, but may be more challenging to achieve.

Risks for impaired cerebral autoregulation during cardiopulmonary bypass and postoperative stroke.

BACKGROUND: Impaired cerebral autoregulation may predispose patients to cerebral hypoperfusion during cardiopulmonary bypass (CPB). The purpose of this study was to identify risk factors for impaired autoregulation during coronary artery bypass graft, valve surgery with CPB, or both and to evaluate whether near-infrared spectroscopy (NIRS) autoregulation monitoring could be used to identify this condition. METHODS: Two hundred and thirty-four patients were monitored with transcranial Doppler and NIRS. A continuous, moving Pearson's correlation coefficient was calculated between mean arterial pressure (MAP) and cerebral blood flow (CBF) velocity, and between MAP and NIRS data, to generate the mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Functional autoregulation is indicated by an Mx and COx that approach zero (no correlation between CBF and MAP); impaired autoregulation is indicated by an Mx and COx approaching 1. Impaired autoregulation was defined as an Mx ≥0.40 at all MAPs during CPB. RESULTS: Twenty per cent of patients demonstrated impaired autoregulation during CPB. Based on multivariate logistic regression analysis, time-averaged COx during CPB, male gender, Pa(CO(2)), CBF velocity, and preoperative aspirin use were independently associated with impaired CBF autoregulation. Perioperative stroke occurred in six of 47 (12.8%) patients with impaired autoregulation compared with five of 187 (2.7%) patients with preserved autoregulation (P=0.011). CONCLUSIONS: Impaired CBF autoregulation occurs in 20% of patients during CPB. Patients with impaired autoregulation are more likely than those with functional autoregulation to have perioperative stroke. Non-invasive monitoring autoregulation may provide an accurate means to predict impaired autoregulation. Clinical trials registration. www.clinicaltrials.gov (NCT00769691).

Multiple primary tumours in women following breast cancer, 1973-2000.

We investigated the predictors of the risk of developing a second primary cancer after breast cancer, this occurring in about 12% of affected women. The analysis included 335 191 females, registered in the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database, who had been diagnosed with breast cancer. Observed numbers of subsequent cancers in the SEER database with a first breast cancer diagnosed from 1973 to 2000 were compared with the expected numbers based on age-adjusted incidence rates to calculate standardised incidence ratios. Kaplan-Meier curves were conducted to determine the median time until the second primary cancer diagnosis. Average number of years until diagnosis varied by site and by age as well as median years until second cancer diagnosis. Most cancer risks decreased with age, but there was an increase in aging-related cancers such as lung cancer. The median years of follow-up were well beyond the 5-year mark. Breast cancer survivors should be advised of their increased risk for developing certain cancers in their lifetime.

Elastic vibrations in seamless microtubules.

Parameters characterizing elastic properties of microtubules, measured in several recent experiments, reflect an anisotropic character. We describe the microscopic dynamical properties of microtubules using a discrete model based on an appropriate lattice of dimers. Adopting a harmonic approximation for the dimer-dimer interactions and estimating the lattice elastic constants, we make predictions regarding vibration dispersion relations and vibration propagation velocities. Vibration frequencies and velocities are expressed as functions of the elastic constants and of the geometrical characteristics of the microtubules. We show that vibrations which propagate along the protofilament do so significantly faster than those along the helix.

Systematic genetic analysis with ordered arrays of yeast deletion mutants.

In Saccharomyces cerevisiae, more than 80% of the approximately 6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of approximately 4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1, ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.

Mechanisms and attenuation of hemostatic activation during extracorporeal circulation.

Patients undergoing cardiac surgery with cardiopulmonary bypass are at risk for excessive microvascular bleeding, which often leads to transfusion of allogeneic blood and blood components as well as reexploration in a smaller subset of patients. Excessive bleeding after cardiac surgery is generally related to a combination of several alterations in the hemostatic system pertaining to hemodilution, excessive activation of the hemostatic system, and potentially the use of newer, longer-acting antiplatelet or antithrombotic agents. Although several nonpharmacologic strategies have been proposed, this review summarizes the role of pharmacologic interventions as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Specifically, agents that inhibit platelets, fibrinolysis, factor Xa and thrombin, as well as broad-spectrum agents, have been investigated with respect to their role in reducing consumption of clotting factors and better preservation of platelet function. Prophylactic administration of agents with antifibrinolytic, anticoagulant, and possibly antiinflammatory properties can decrease blood loss and transfusion. Although aprotinin seems to be the most effective blood conservation agent (which is most likely related to its broad-spectrum nature), agents with isolated antifibrinolytic properties may be as effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.

Cardiac and neurologic complications identify risks for mortality for both men and women undergoing coronary artery bypass graft surgery.

BACKGROUND: Despite a number of studies showing that women and men respond to coronary artery bypass graft surgery differently, it is not known whether variables associated with mortality are the same for women and men. The purpose of this study was to identify variables independently associated with mortality for women undergoing coronary artery bypass graft surgery. METHODS: Single-institutional data were prospectively collected from 5,113 patients (1,558 or 30.5% women) undergoing coronary artery bypass graft surgery. The database was reviewed for patient characteristics and operative outcomes based on sex. Complications evaluated included low cardiac output syndrome (cardiac index < 2.0 l x min(-1) x m(-2) for > 8 h, regardless of treatment), stroke (new permanent global or focal motor deficits), Q-wave myocardial infarction, postoperative atrial fibrillation, and operative mortality. RESULTS: Women were older than men, and they were more likely to have preexisting hypertension, diabetes, and a history of stroke. Operative mortality for women was higher than for men (3.5% vs. 2.5%, P < 0.05). Compared with men, women were more likely to experience a postoperative myocardial infarction, stroke, and low cardiac output syndrome. When performing analysis on data from both sexes separately, low cardiac output syndrome, new stroke, myocardial infarction, and duration of cardiopulmonary bypass were independently associated with mortality for women and men both. Patient age was not independently associated with risk for mortality for women, but it was for men. However, when the authors combined both sexes in the logistic regression analysis, the age-sex interaction was not significant (P = 0.266), indicating that there was insufficient evidence to assert that age has a different effect on mortality for men and women. CONCLUSIONS: These data confirm that women have higher perioperative mortality after coronary artery bypass graft surgery compared with men. A higher frequency of cardiac and neurologic complications seem to account to a large extent for the higher operative mortality for women. Factors independently associated with perioperative mortality are generally similar for women and men.

VISTRAJ: exploring protein conformational space.

UNLABELLED: VISTRAJ is an application which allows 3D visualization, manipulation and editing of protein conformational space using probabilistic maps of this space called 'trajectory distributions'. Trajectory distributions serve as input to FOLDTRAJ which samples protein structures based on the represented conformational space. VISTRAJ also allows FOLDTRAJ to be used as a tool for homology model creation, and structures may be generated containing post-translationally modified amino acids. AVAILABILITY: Binaries are freely available for non-profit use as part of the FOLDTRAJ package at ftp://ftp.mshri.on.ca/pub/TraDES/foldtraj/.