Polygenic risk and hostile environments: Links to stable and dynamic antisocial behaviors across adolescence.

Adverse environments are linked to elevated youth antisocial behavior. However, this relation is thought to depend, in part, on genetic susceptibility. The present study investigated whether polygenic risk for antisociality moderates relations between hostile environments and stable as well as dynamic antisocial behaviors across adolescence. We derived two antisocial-linked polygenic risk scores (PRS) (N = 721) based on previous genome-wide association studies. Forms of antisocial behavior (nonaggressive conduct problems, physical aggression, social aggression) and environmental hostility (harsh parenting and school violence) were assessed at age 13, 15, and 17 years. Relations to individual differences stable across adolescence (latent stability) vs. time-specific states (timepoint residual variance) of antisocial behavior were assessed via structural equation models. Higher antisocial PRS, harsh parenting, and school violence were linked to stable elevations in antisocial behaviors across adolescence. We identified a consistent polygenic-environment interaction suggestive of differential susceptibility in late adolescence. At age 17, harsher parenting was linked to higher social aggression in those with higher antisocial PRS, and lower social aggression in those with lower antisocial PRS. This suggests that genetics and environmental hostility relate to stable youth antisocial behaviors, and that genetic susceptibility moderates home environment-antisocial associations specifically in late adolescence.

A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome.

BACKGROUND: Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period. METHOD: Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model. RESULTS: The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA. CONCLUSIONS: Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic-environment correlation (r GE) and interaction (G×E) analyses.

Analysis of variables associated with surgery versus observation in patients with pancreatic cystic lesions referred for endoscopic ultrasound.

BACKGROUND AND STUDY AIM: Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) for cyst fluid analysis (CFA) is often requested for pancreatic cystic lesions, to determine whether to operate or to observe. If this decision is not influenced by the EUS findings, the procedure may be unjustifiable. We aimed to determine whether EUS-CFA results predict surgery or observation in patients with pancreatic cysts referred for EUS. PATIENTS AND METHODS: Consecutive patients referred to a quaternary pancreaticobiliary center for EUS evaluation of pancreatic cysts were eligible. Clinical data, computed tomography (CT) results, EUS findings, and CFA results were reviewed retrospectively. Statistical analysis was performed to determine variables associated with surgery versus observation. RESULTS: Over 33 months, data on 194 consecutive patients referred for EUS for evaluation of pancreatic cysts were analyzed. Of these, 136 (70 %) patients had EUS-FNA. After the initial workup (including EUS with/without CFA), 35 (18 %) underwent surgery. Predictors of surgery were: younger age (< 65 years) (P = 0.0027), malignant appearance at EUS (P = 0.02), and history of EUS-FNA (P = 0.012). Cyst fluid appearance, and carcinoembryonic antigen (CEA), carbohydrate antigen 19­9 (CA 19­9), and amylase levels were not significant determinants of surgery. In 14/50 (28 %) of cases where EUS-CFA clearly suggested benign serous lesions, surgery was still performed and in 9/11 (82 %) of cases with malignant EUS-CFA findings, surgery was not done. CONCLUSIONS: In patients with pancreatic cysts referred for EUS, age and EUS appearance independently predict surgery. The "perceived need for EUS-CFA" also predicts surgery, but not the EUS-CFA results. The clinical value of EUS-CFA requires further study.

A prospective comparison of endoscopic ultrasound-guided fine needle aspiration results obtained in the same lesion, with and without the needle stylet.

BACKGROUND AND STUDY AIMS: The effectiveness of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with (S+) and without (S-) a stylet has never been compared. We prospectively compared the yield for malignancy and sample quality of S+ and S- EUS-FNA. PATIENTS AND METHODS: S+ or S- EUS-FNA was performed on consecutive solid lesions, with a 22-gauge needle, with systematic assignment of S+ or S- passes in a 1 : 2 ratio. Slides were read by a single, blinded cytologist and were rated for bloodiness, adequacy, and presence of malignancy. The yield for malignancy was compared only in lesions in which equal numbers of S+ and S- passes were performed. RESULTS: A total of 309 passes (mean 2.3 passes/lesion, range 1-6, 82% adequate, 38% S+, 62% S-) were performed on 135 lesions (63% malignant, 42% nodes, 58% masses [79% pancreatic]) in 111 patients (mean age 62.9 years, range 30-86). In 46 lesions where an equal number (53 S+ and 53 S-) of passes was performed, there was no difference in the proportion of cases in which S+ FNA was "equal to or better than" S- FNA ([S+] 89% vs. [S-] 87%; P>0.05). The results of the two methods agreed in 80% cases (kappa 0.60). The sensitivities for malignancy were: S+ 87% vs. S- 83%, P>0.05. Specificities were 100%. Sample adequacy was significantly lower in S+ passes (75% vs. 87%, P=0.013), and sample bloodiness was significantly higher (75% vs. 52%, P<0.0001). CONCLUSIONS: Use of the stylet with EUS-FNA does not increase the yield for malignancy and is associated with poorer sample quality. The value of the stylet for EUS-FNA is questionable and requires further investigation.

Sevoflurane preconditioning at 1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bi-centre trial.

BACKGROUND: Volatile agents can mimic ischaemic preconditioning leading to a decrease in myocardial infarct size. The present study investigated if a 15 min sevoflurane administration before cardiopulmonary bypass (CPB) has a cardioprotective effect in patients undergoing coronary surgery. METHODS: Seventy-two patients were randomized in two centres. The intervention group (S) received 1 MAC sevoflurane administrated via the ventilator for 15 min followed by a 15 min washout before CPB, the control group did not. The primary outcome was the postoperative troponin Ic peak. A biopsy of the atrium was taken during canulation for enzyme dosages. Results are expressed as mean (SD). RESULTS: Neither troponin Ic nor tissular enzyme measurement exhibited any difference between the groups: peak of troponin Ic was 4.4 (5.6) in S group vs 5.2 (6.6) ng ml(-1) in control group (ns). Intratissular ecto-5'-nucleotidase activity was 7.1 (4.3) vs 8.5 (11.9), protein kinase C activity was 27.1 (15.7) vs 29.2 (28.7), tyrosine kinase activity was 101 (54.1) vs 98.5 (63.3), and P38 MAPKinase activity was 131.1 (76.1) vs 127.1 (86.8) nmol mg protein(-1) min(-1) in S group and control group, respectively (ns). However there were fewer patients with low postoperative cardiac index in S group (11% in S vs 35% in control group, P < 0.05) when considering the per protocol population. In S group, 25% of patients required an inotropic support during the postoperative period, vs 36% of patients in control group (ns). CONCLUSIONS: This study did not show a significant preconditioning signal after 15 min of sevoflurane administration. The 15 min duration might be too short or the concentration of sevoflurane too low to induce cardioprotection detected by troponin I levels.

[Evaluation of a continuous training program at Bichat hospital for in-hospital cardiac arrest resuscitation]. / Evaluation de la mise en place d'une formation continue du personnel de l'hôpital Bichat à la prise en charge des arrêts cardiocirculatoires intrahospitaliers.

UNLABELLED: Management of in-hospital cardiac arrest is now considered as a hospital quality indicator. Such management actually requires training health care workers (HCWs) for basic life support (BLS). OBJECTIVE: To assess the usefulness and efficacy of a short mandatory BLS training course amongst general ward HCWs in a 1,200 bed teaching hospital. STUDY DESIGN: The in-hospital medical emergency team (MET) established a 45-min BLS training course comprising 10 goals for basic CPR and preparing for the arrival of the MET. Assessment was based on satisfaction questionnaires, cross-sectional evaluation of knowledge and skills of HCWs before and 1 year after the start of the training course. Efficacy of BLS performed on ward was assessed by the MET on scene. RESULTS: One year after, 68 training sessions had been fulfilled and 522 HCWs had been trained (46.27% of total HCWs). HCWs were satisfied with the teaching course. Instant retention of objectives was over 90%. Cross-sectional surveys showed an improvement of BLS knowledge and skills. The knowledge of initial clinical assessment remained low. Knowledge and skills were significantly higher amongst HCWs who had been trained than amongst those who had not. Unfortunately, general ward BLS performance showed no improvement. CONCLUSION: Short mandatory training courses are stimulating and well appreciated amongst HCWs. Although basic knowledge and skills improve dramatically, no improvement of on-scene BLS performance occurs.

[Anesthesia of hypertensive patients]. / Anesthésie du malade hypertendu.

Hypertension is a frequent condition among adults. It is one of the major risk factors of atherosclerotic diseases. Anesthetologists are frequently confronted to the management of treated or untreated hypertensive patients whose major risk during that period concerns the potential association with coronary artery disease. Therefore, the preoperative assessment should be insured of an adequate control of blood pressure, the presence of potential target organ damage and especially the detection an underlying coronary disease and its importance. The risk of cardiovascular complications and consecutively the preoperative check-up depend of the type of surgery scheduled. Preoperative systolic blood pressures (SBP) below 180 mmHg and diastolic blood pressures (DBP) below 110 mmHg are recommended. Due to their efficacy, tolerability and the easiness of their use, dihydropyridins and beta-blockers are the most frequent drugs used in the peri-operative period. Many studies evidenced the benefit of beta-blocking agents in patients with definite or potential coronary artery disease during the immediate period of major surgery, with not only a decrease of serious cardiac complications and post-operative mortality but also an improvement of mid- and longterm prognosis. There is no evidence to privilege any type of anesthesia. A respect of hemodynamic conditions (avoidance of severe hypotension and tachycardia) reduces the incidence of ischemic complications. The hemodynamic stability is obtained with an adapted anesthesia and the use of intravenous vasoconstrictive or vasodilator agents as well as beta-blockers (esmolol). The diagnosis of perioperative myocardial infarction is based on the measurement of seric concentrations of cardiac Troponin isoforms (TnI or TnT).

The security of urban women: practice, research, and partnerships.

All public bodies whose mandate includes responsibility for the quality of urban life cannot ignore the question of security. On a global level, it is agreed that action needs to be taken locally, with the input of everyone involved. Since women have more at stake where safety issues are concerned, it is logical that security plans be drawn up that prioritize them. The interaction of public bodies, community organizations, and individual women is in itself innovative, enriching everyone involved, despite the inherent drawbacks and demands. International information networks on women's security are expanding and can help the new partnerships refine their working methods, to the benefit of all, regardless of gender. Still, the transfer of knowledge between partners and among the population is fundamental and demanding. The same applies to the need to develop methods and criteria of evaluation that are adapted to the specific realities of the partnership for prevention of crime and violence towards women.

Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide-stimulated whole blood cells: roles of interleukin-10 and the extracorporeal circuit.

OBJECTIVE: To determine whether cardiopulmonary bypass (CPB) alters the ex vivo cytokine production of whole blood cells stimulated by lipopolysaccharide (LPS) and to assess the roles of interleukin (IL)-10 and an extracorporeal circuit (ECC) in the alteration. DESIGN: Prospective, controlled study. SETTING: Biochemistry laboratory and surgical intensive care unit in a university hospital. PATIENTS: Seventeen consecutive adult patients undergoing coronary artery bypass grafting or valve surgery with normothermic CPB and eight healthy volunteers. INTERVENTIONS: Blood samples for cytokine measurement were drawn from patients before and during (at 60, 90, 120, 180 and 360 mins) CPB and were cultured with and without LPS and with and without anti-IL-10 antibodies. Blood was also drawn from healthy subjects and sampled for cytokine analysis before and during circulation in an isolated ECC. MEASUREMENTS AND MAIN RESULTS: The concentrations of ex vivo tumor necrosis factor (TNF)-alpha, IL-6, IL-8, and IL-10, measured by enzyme-linked immunosorbent assay, were reduced in both experimental settings. In patients on CPB, LPS hyporesponsiveness was detected at 60 mins after the onset of CPB and was maximal at 120 mins (78% to 86% decreases from pre-CPB levels) but was transient, except for TNF-alpha. The plasma concentration of IL-10 peaked at 90 mins after the start of CPB, but the role of IL-10 in LPS hyporesponsiveness appears limited because anti-IL-10 antibodies significantly increased ex vivo production of IL-6 but not TNF-alpha or IL-8. In the isolated ECC study, no IL-10 was detected in plasma, yet the ex vivo production of the cytokines (except IL-8) was decreased (by 66% to 95%). CONCLUSION: Our results demonstrate the following: a) CPB induces an early and transient LPS hyporesponsiveness of whole blood as measured by cytokine production; b) IL-10 seems only partly involved in this process, and its role is restricted to an in vivo situation; and c) contact of blood with an ECC is sufficient to induce LPS hyporesponsiveness.