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BackgroundThe public often perceives the insanity defense as a “get out of jail free card”. Conversely, several studies demonstrate the substantial control imposed upon these defendants. This study compares Review Boards decisions regarding people found not criminally responsible on account of mental disorder (NCRMD) to criminal courts decisions regarding convicted offenders for similar offenses in Canada.MethodDetention, using logistic regression, and duration under detention and supervision, using Cox regression, were compared between a cohort of 1794 individuals found NCRMD in three Canadian provinces (Quebec, Ontario, and British Columbia) between 2000 and 2005 followed until 2008 from the National Trajectory Project and a national sample of 3,20,919 Canadians convicted of criminal offense from Statistics Canada's Criminal Court Survey.ResultsIndividuals found NCRMD are 3.8 times (95% CI 3.4–4.3) more likely to be detained than convicted offenders as well as 4.8 times (95% CI 4.5–5.3) and 2.9 times (95% CI 2.6–3.1) less likely to be released from detention and supervision, respectively. One year after the verdict, 73% of the NCRMD accused were still under legal supervision and 42% were still in detention, whereas these proportions were, respectively, 41 and 1% for their convicted counterparts. Interaction effects show that sex, age, jurisdiction, number of offenses, and severity of crimes committed have a differential impact on decisions applied to NCRMD accused compared to convicted persons.ConclusionContrary to popular perceptions, the insanity defense is not a loophole. Differences as to factors influencing the trajectories of the two samples confirm that Review Boards are able to distance their practices from the criminal courts and can set aside, at least in part, the principles of proportionality and punitiveness governing the traditional sentencing practices.

Background Schistosomiasis is a parasitic neglected tropical disease that ranks second only to malaria in terms of human suffering in the tropics and subtropics. Biomedical disease control interventions need to be complemented with effective prevention and health education strategies, that address the social and environmental determinants of disease. Malaria Consortium conducted an implementation research study between May 2014 and February 2016, in four districts of Nampula province, Mozambique, to test a Community Dialogue (CD) intervention to enhance schistosomiasis prevention and control. The study aimed to evaluate the acceptability and feasibility of using CD to improve communities’ level of knowledge, attitudes and practices, and engagement in wider schistosomiasis prevention and control efforts. Methods The feasibility and acceptability of the CD intervention was evaluated using qualitative and process evaluation data collected throughout the development and implementation phases. Qualitative data sets included key informant interviews (N = 4) with health system personnel, focus group discussions (N = 22) with Community Dialogue facilitators and participants, field observation visits (N = 11), training reports (N = 7), feedback meeting reports (N = 5), CD monitoring sheets (N = 1,458) and CD planning sheets (N = 152). Findings The CD intervention was found highly acceptable and feasible, particularly well-suited to resource poor settings. Non-specialist community volunteers were able to deliver participatory CDs which resulted in increased knowledge among participants and triggered individual and communal actions for improved disease prevention and control. The visual flipchart was a key aid for learning; the use of participatory communication techniques allowed the correction of misconceptions and positioned correct prevention and control practices as the community recommendations, through consensus building. Conclusion The Community Dialogue Approach should be embedded within neglected tropical disease control programmes and the health system to create long-lasting synergies between the community and health system for increased effectiveness. However, for behavioural change to be feasible, community engagement strategies need to be supported by improved access to treatment services, safer water and sanitation.

Background Across the developing world, countries are increasingly adopting the integrated community case management of childhood illnesses (iCCM) strategy in efforts to reduce child mortality. This intervention’s effectiveness is dependent on community adoption and changes in care-seeking practices. We assessed the implementation process of a theory-driven community dialogue (CD) intervention specifically designed to strengthen the support and uptake of the newly introduced iCCM services and related behaviours in three African countries. Methods A qualitative process evaluation methodology was chosen and used secondary project data and primary data collected in two districts of each of the three countries, in purposefully sampled communities. The final data set included 67 focus group discussions and 57 key informant interviews, totalling 642 respondents, including caregivers, CD facilitators community leaders, and trainers. Thematic analysis of the data followed the ‘Framework Approach’ utilising both a deduction and induction process. Results Results show that CDs contribute to triggering community uptake of and support for iCCM services through filling health information gaps and building cooperation within communities. We found it to be an effective approach for addressing social norms around child care practices. This approach was embraced by communities for its flexibility and value in planning individual and collective change. Conclusions Regular CDs can contribute to the formation of new habits, particularly in relation to seeking timely care in case of child sickness. This study also confirms the value of process evaluation to unwrap the mechanisms of community mobilisation approaches in context and provides key insights for improving the CD approach. Electronic supplementary material The online version of this article (doi:10.1186/s41043-017-0106-0) contains supplementary material, which is available to authorized users.

Nursing clinical approach, listening to the body. In their practice working closely with patients and their families, nurses base their clinical approach on the gathering and analysis of the multiple signals sent by the body of the patient they are caring for. In collaboration with the doctor, the monitoring of vital signs and biological data helps to guide the care and the choice and implementation of therapies. A concrete case illustrates the contribution of nursing sciences to the clinical approach led by the nurse.

Face, content, and construct validity of robotic surgery simulators were confirmed in the literature by several studies, but elements to build a training program are still lacking. The aim of our study was to validate a progressive training program and to assess according to prior surgical experience the amount of training needed with a robotic simulator to complete the program.Exercises using the Da Vinci Skill Simulator were chosen to ensure progressive learning. A new exercise could only be started if a minimal score of 80% was achieved in the prior one. The number of repetitions to achieve an exercise was not limited. We devised a "performance index" by calculating the ratio of the sum of scores for each exercise over the number of repetitions needed to complete the exercise with at least an 80% score.The study took place at the François Baclesse Cancer Center. Participants all work at the primary care university Hospital located next to the cancer center.A total of 32 surgeons participated in the study- 2 experienced surgeons, 8 junior and 8 senior residents in surgery, 6 registrars, and 6 attending surgeons.There was no difference between junior and senior residents, whereas the registrars had better results (p0.0001). The registrars performed less exercise repetitions compared to the junior or senior residents (p = 0.012). Attending surgeons performed significantly more repetitions than registrars (p = 0.024), but they performed fewer repetitions than junior or senior residents with no statistical difference (p = 0.09). The registrars had a performance index of 50, which is the best result among all novice groups. Attending surgeons were between senior and junior residents with an index at 33.85.Choice of basic exercises to manipulate different elements of the robotic surgery console in a specific and progressive order enables rapid progress. The level of prior experience in laparoscopic surgery affects outcomes. More advanced laparoscopic expertise seems to slow down learning, surgeons having to "unlearn" to acquire a new technique.

As operating costs for all academic nanofabrication facilities continue to increase, research groups are finding it more difficult, and in some cases impossible, to fund their efforts. Adding to this difficulty, funding agencies are imposing more stringent funding guidelines as well as significantly increasing the tangible deliverables they demand for initial or continued funding. Furthermore, some academic institutions are cutting back on their direct and indirect subsidies of these efforts. Lastly, the costs to fund students, even before they enter the lab, have risen dramatically over the past several decades. Thus, it is critical that each facility provide not only a competitive recharge model but an explicit justification of recharge rates to enhance the confidence of researchers that they are competitive with their peer institutions. Additionally, a well-defined recharge model will enable researchers and their financial administrators to determine how best to proceed with their proposed research objectives and create an accurate estimate of the research costs. Only then can a researcher confidently make bold proposals that they believe will allow them to succeed scientifically and financially in this highly competitive environment. The reported data illustrate that integrated annual usage costs across the study groups are similar under vastly different fee structures if the subsidy of each site is factored in. There exists a significant range of cost differentials between sites depending on what a research group is working on, the subsidy level of the site, and what emphasis the site's model places on how to distribute the subsidy. We believe that the data further illustrate that the operational costs of each site and the educational experience of users can be significantly affected by the individual site's unique cost model. Lastly, we postulate that regarding resource management between the adviser and student lead to significant operational efficiencies that are critical to controlling costs and maintaining a world-class facility while providing the optimum opportunity for an experiential education for a significantly increased group of students.

Aim To investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma. Methods Multicentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP ±3 concomitant cycles of bevacizumab 15 mg/kg (BCP) followed by IDS. Primary objective is to evaluate the CRR at IDS in the BCP group (reference CRR rate defined as 45% CRR). A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented. Results In the BCP group (N = 58), IDS was performed in 40 (69%) patients, of whom 85% had a complete resection. The CRR of this group was therefore 58.6% (34 patients), statistically over pre-defined 45%. The CRR in the CP group was 51.4%: 22 (60%) patients underwent IDS (85% had a complete resection). Grade ≥3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinal and vascular disorders, without more toxicity with BCP. Postoperative complications (mainly wound, infectious and gastrointestinal complications) occurred in 28% and 36% of the patients, respectively. The pre-specified safety stopping rule was not reached. Conclusion The primary objective was met as the CRR with BCP was significantly higher than the reference rate. Bevacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision. Bevacizumab's role in this setting should be further investigated.

Ovarian cancers are addicted to Bcl-xL and Mcl-1, antiapoptotic members of the Bcl-2 family. Bcl-xL can be inhibited by the BH3-mimetic ABT-737. In vitro, ABT-737 can induce apoptosis of cancer cells, and its activity is potentiated by Mcl-1 inactivation. Herein, we assessed the sensitivity of human ovarian tumor nodes to ABT-737 when combined with carboplatin, which can indirectly inhibit Mcl-1. Fresh samples from 25 patients with high-grade serous ovarian cancer (HGSOC) who were chemo-naive and had undergone surgery were prospectively exposed ex vivo to ABT-737 ± carboplatin. The treatment effect was studied on sliced tumor nodes by assessment of cleaved-caspase 3 immunostaining. We also studied the association between baseline Bcl-2 family protein expression (via immunohistochemistry) and the response of nodes to treatment. ABT-737 induced apoptosis as a single agent but its efficacy was not improved by the addition of carboplatin. Bim was frequently expressed (20/25) and its absence or low expression was associated with the absence of response to ABT-737, p value = 0.019 by Fisher's test and sensitivity = 93%, (95% confidence interval, 66–100). Moreover, we observed that in tumors in which Bim was expressed, a low expression of phospho-Erk1/2 or Mcl-1 improved the proportion of responses. This pilot study showed that ABT-737 has promise as monotherapy for HGSOC in a specific subgroup of tumors. Bim, Mcl-1, and phospho-Erk1/2 appeared to be relevant biomarkers that could be used for the selection of patients in the design of clinical trials using Navitoclax (an orally available compound related to ABT-737).

e17049 Background: All surgeons have a personalized way of consulting, some deliver information exclusively orally, others through free-form diagrams or anatomical charts. Most patients go home with these patterns that are more or less readable with all the uncertainty of what they really understood or assimilated. Methods: To meet the expectations of patients, we made a computer application to help the surgeon during the consultation.During the consultation, gynecologist surgeons from Center F BACLESSE explained, with the help of the e-consult application, the pathology, surgical intervention, postoperative consequences and potential drug treatments to a cohort of 61 patients admitted for consultation. At the end of the consultation, all the patients received a PDF sheet or an email containing the diagrams constructed in collaboration with the surgeon. Using a questionnaire, we evaluated the satisfaction of the patients. Results: The computer tool was popular with the majority of patients. Regarding the information on the surgical procedure, 86% of the patients judged them as very good, 80% judged the information on adjuvant treatment (radiotherapy, chemotherapy, hormone therapy) as very good and 89% were very satisfied with the information given by the doctor. For the computer tool, 81% of patients found the illustrations very clear, 79% found that the application is a very good help to understanding and 89% found that the interaction with the doctor is sufficient. During the consultation, 100% of the patients were able to ask the desired questions, and 97% think that this computer tool completes the information. For the submitted document, 100% of the patients found it very clear and 100% found that it meets the expectations of the patients. Discussion: E-consult is a unique app created to improve the quality of information delivered to patients during the consultation. The doctor can prove that the information was delivered to the patient, through the development of a PDF during the consultation. A video demonstration is available with the following link: Play the video . Conclusions: e-health is becoming more and more important in medicine. Patients are becoming more connected. E-consult improves the quality of the information received in a simple and personalized way, it is the first application, available at will, designed to improve the understanding of patients. This application integrates with each step in the patient care path.

Background The Community Dialogue Approach is a promising social and behaviour change intervention, which has shown potential for improving health seeking behaviour. To test if this approach can strengthen prevention and control of schistosomiasis at community level, Malaria Consortium implemented a Community Dialogue intervention in four districts of Nampula province, Mozambique, between August 2014 and September 2015. Methodology/Principal findings Cross-sectional household surveys were conducted before (N = 791) and after (N = 792) implementation of the intervention to assess its impact on knowledge, attitudes and practices at population level. At both baseline and endline, awareness of schistosomiasis was high at over 90%. After the intervention, respondents were almost twice as likely to correctly name a risk behaviour associated with schistosomiasis (baseline: 18.02%; endline: 30.11%; adjusted odds ratio: 1.91; 95% confidence interval: 1.14–2.58). Increases were also seen in the proportion of people who knew that schistosomiasis can be spread by infected persons and who could name at least one correct transmission route (baseline: 25.74%; endline: 32.20%; adjusted odds ratio: 1.36; 95% confidence interval: 1.01–1.84), those who knew that there is a drug that treats the disease (baseline: 29.20%, endline: 47.55%; adjusted odds ratio: 2.19; 95% confidence interval: 1.67–2.87) and those who stated that they actively protect themselves from the disease and cited an effective behaviour (baseline: 40.09%, endline: 59.30%; adjusted odds ratio: 2.14; 95% confidence interval: 1.40–3.28). The intervention did not appear to lead to a reduction in misconceptions. In particular, the belief that the disease is sexually transmitted continued to be widespread. Conclusions/Significance Given its overall positive impact on knowledge and behaviour at population level, Community Dialogue can play an important role in schistosomiasis prevention and control. The intervention could be further strengthened by better enabling communities to take suitable action and linking more closely with community governance structures and health system programmes., Author summary Schistosomiasis is a parasitic neglected tropical disease that affects around 190 million people worldwide, causing chronic ill health and disability. Central to its prevention and control are the acceptance of health interventions such as the distribution of drugs on a mass scale and the adoption of good hygiene and sanitation practices in communities where the disease thrives. One promising method for promoting such behaviours is the Community Dialogue Approach, which involves training volunteers to host regular community meetings, where local health concerns are discussed and culturally appropriate solutions are agreed upon. In 2014/15, Malaria Consortium implemented a Community Dialogue intervention in four districts of Nampula province, Mozambique, to improve knowledge, attitudes and practices with regard to schistosomiasis prevention and control. To assess the effectiveness of the approach, two household surveys were conducted. Results show that before the intervention, knowledge of how schistosomiasis is acquired, transmitted, prevented and treated was low. After the intervention, knowledge and self-reported adoption of positive behaviours had improved substantially, demonstrating that Community Dialogue can play a central role in strengthening disease prevention and control. The approach could be strengthened by further empowering communities to take action and reducing deeply-held misconceptions.

BACKGROUND: Experience of seasonal malaria chemoprevention (SMC) is growing in the Sahel sub-region of Africa, though there remains insufficient evidence to recommend a standard deployment strategy. In 2012, a project was initiated in Katsina state, northern Nigeria, to design an appropriate and effective community-based delivery approach for SMC, in consultation with local stakeholders. Formative research (FR) was conducted locally to explore the potential feasibility and acceptability of SMC and to highlight information gaps and practical considerations to inform the intervention design. METHODS: The FR adopted qualitative methods; 36 in-depth interviews and 18 focus group discussions were conducted across 13 target groups active across the health system and within the community. Analysis followed the 'framework' approach. The process for incorporating the FR results into the project design was iterative which was initiated by a week-long 'intervention design' workshop with relevant stakeholders. RESULTS: The FR highlighted both supportive and hindering factors to be considered in the intervention design. Malaria control was identified as a community priority, the community health workers were a trusted resource and the local leadership exerted strong influence over household decisions. However, there were perceived challenges with quality of care at both community and health facility levels, referral linkage and supportive supervision were weak, literacy levels lower than anticipated and there was the potential for suspicion of 'outside' interventions. There was broad consensus across target groups that community-based SMC drug delivery would better enable a high coverage of beneficiaries and potentially garner wider community support. A mixed approach was recommended, including both community fixed-point and household-to-household SMC delivery. The FR findings were used to inform the overall distribution strategy, mechanisms for integration into the health system, capacity building and training approaches, supportive interventions to strengthen the health system, and the social mobilization strategy. CONCLUSIONS: Formative research played a valuable role in exploring local socio-cultural contexts and health system realities. Both opportunities and challenges for the introduction of SMC delivery were highlighted, which were appropriately considered in the design of the project.

Background Successful scale-up in the use of malaria rapid diagnostic tests (RDTs) requires that patients accept testing and treatment based on RDT results and that healthcare providers treat according to test results. Patient-provider communication is a key component of quality care, and leads to improved patient satisfaction, higher adherence to treatment and better health outcomes. Voiced or perceived patient expectations are also known to influence treatment decision-making among healthcare providers. While there has been a growth in literature on provider practices around rapid testing for malaria, there has been little analysis of inter-personal communication around the testing process. We investigated how healthcare providers and patients interact and engage throughout the diagnostic and treatment process, and how the testing service is experienced by patients in practice. Methods This research was conducted alongside a larger study which explored determinants of provider treatment decision-making following negative RDT results in a rural district (Kibaale) in mid-western Uganda, ten months after RDT introduction. Fifty-five patients presenting with fever were observed during routine outpatient visits at 12 low-level public health facilities. Observation captured communication practices relating to test purpose, results, diagnosis and treatment. All observed patients or caregivers were immediately followed up with in-depth interview. Analysis followed the ‘framework’ approach. A summative approach was also used to analyse observation data. Results Providers failed to consistently communicate the reasons for carrying out the test, and particularly to RDT-negative patients, a diagnostic outcome or the meaning of test results, also leading to confusion over what the test can detect. Patients appeared to value testing, but were frustrated by the lack of communication on outcomes. RDT-negative patients were dissatisfied by the absence of information on an alternative diagnosis and expressed uncertainty around adequacy of proposed treatment. Conclusions Poor provider communication practices around the testing process, as well as limited inter-personal exchange between providers and patients, impacted on patients’ perceptions of their proposed treatment. Patients have a right to health information and may be more likely to accept and adhere to treatment when they understand their diagnosis and treatment rationale in relation to their perceived health needs and visit expectations.

Hospitalisation is an opportunity for frailty in the elderly to be detected. The collaboration of the assessment and prevention geriatrician-nurse partnership, combined with the skills of the advanced practice nurse in gerontology, helps to instil a culture of frailty prevention in the teams and create adapted care pathways.

This study examines degradation of five tertiary polyamines (di- and triamines) in the presence of CO2 or O2. They were chosen to identify the impact of alkyl chain length between amine functions. Degradation of aqueous amine solutions was evaluated at 140 °C under CO2 or air pressure (2 MPa) in stainless steel batch reactors for 15 days. At the end of the run, most degradation products were identified by gas chromatography (GC)/mass spectrometry; amounts of remaining amine and its degradation products were determined with a quantitative GC method. The main degradation mechanisms are proposed, and some structure−properties relationships are established.

Stearoyl-CoA Desaturase 1 (SCD1) is a central enzyme that catalyzes the biosynthesis of monounsaturated fatty acids from saturated fatty acids. SCD1 is an emerging target in obesity and insulin resistance due to the improved metabolic profile obtained when the enzyme is genetically inactivated. Here, we have investigated if the pharmacological inhibition of SCD1 could elicit the same profile. We have identified a small molecule, GSK993 and characterized it as a potent and orally available SCD1 inhibitor. In Zuckerfa/fa rats, GSK993 exerted a marked reduction in hepatic lipids as well as a significant improvement of glucose tolerance. Furthermore, in a diet-induced insulin resistant rat model, GSK993 induced a very strong reduction in Triton-induced hepatic Very Low Density Lipoprotein-Triglyceride production. In addition, following a hyperinsulinemic–euglycemic clamp in GSK993-treated animals, we observed an improvement in the whole body insulin sensitivity as reflected by an increase in the glucose infusion rate. Taken together, these findings demonstrate that the pharmacological inhibition of SCD1 translates into improved lipid and glucose metabolic profiles and raises the interest of SCD1 inhibitors as potential new drugs for the treatment of insulin resistance.

We present a method of extracting the field-effect mobility from the transfer characteristics of organic polymer thin-film transistors (OP-TFTs), in both the linear and saturation regimes, by accounting for the dependence of the mobility on the gate bias, which translates to a dependence on the accumulated density of majority charge carriers in the channel. This method is compared to the commonly used extraction methods, which are based on the standard MOSFET square-law drain current equations that do not account for the variation of mobility with the applied gate bias. We show that by using the standard MOSFET equations, the extracted field-effect mobility can be significantly overestimated. We also demonstrate the use of the proposed method to extract the field-effect mobility at different measurement temperatures and present the dependence of the extracted parameters on temperature.

We have studied the electrical performance of organic polymer thin-film transistors (OP-TFTs) under steady-state white-light illumination, as well as the performance of these devices as photodetectors. The off-state drain current of the OP-TFT is significantly increased due to the illumination, while a smaller relative effect is observed on the drain current in the strong-accumulation regime. The illumination effectively decreases the threshold voltage of the device and increases the apparent subthreshold swing, while the field-effect mobility of the charge carriers in the polymer channel is unchanged. We have observed full recovery of our devices after the illumination is removed at room temperature. These observations are explained in terms of the photogeneration of excitons due to the absorbed photons. The photogenerated excitons subsequently diffuse and dissociate into free charge carriers, thereby enhancing the carrier density in the channel of the device. We have found broadband responsivities of approximately 0.7 mA/W for devices biased in the strong-accumulation regime and gate-to-source voltage-independent photosensitivities of approximately 10/sup 3/ for devices in the off-state. We also determine, for the first time, the flatband voltage of these devices to be about -2.3 V.

AIMS: Although the prevalence of alcohol problems amongst detainees is suspected to be high, often only more flagrant problems are detected, restricting the possibilities for intervention in alcohol misuse and reducing opportunities for preventive efforts. This study examined the re-test reliability of AUDIT (the Alcohol Use Disorder Identification Test) in screening prisoners METHODS: AUDIT was administered for the first time on the day of entry to prison and again about 15 days later. The results were analysed according to two AUDIT thresholds: a score of 8 or higher and 12 or higher. RESULTS: Of 75 consecutive entrants tested, 47 male prisoners completed the study. At the first administration, 19.1% of these 47 men met criteria for a probable alcohol problem but this percentage rose to 59.6% on the second occasion (P = 0.0001). The proportion of subjects with a score 12 or higher (probably dependent) was 10.6% the first time versus 42.6% the second time (P = 0.0001). In the 19 who scored positive at the second administration only, changes in answers to the 10 items were coherent with a total score growing from 3.0 to 18.1 (P = 0.0001). No prisoner had a lower AUDIT score on the second administration. As alcohol problems are not routinely considered during the medical and biological examination at entry, no confirmation of the AUDIT results could be obtained, although those obtained at the second administration fitted well with the prevalence rates in previous reports. CONCLUSIONS: AUDIT, for the purpose of giving a prevalence estimate or to enter appropriate prisoners into more detailed assessment or interventions, should not be conducted immediately at entry, but some weeks later.

This paper describes syntheses of new chiral cyclopentadienes and indenes derived from a disaccharide (trehalose) and a nucleoside (uridine). The reaction of lithium cyclopentadienide and indenide with a disaccharide, derived from trehalose, bearing methylated secondary hydroxyls and primary triflate groups, affords the trehalose bis-cyclopentadiene (5) and the trehalose bis-indene (6).These compounds have been fully characterized by NMR spectroscopy and the molecular structure of the trehalose bis-indene has been determined by X-ray diffraction. From uridine, a nucleoside in which secondary hydroxyls have been protected with isopropylidene groups and the free primary hydroxyl function transformed into the tosylate derivative, the reaction with lithium cyclopentadienide or lithium indenide under sonication conditions leads to either uridine cyclopentadiene (9) or uridine indene (10). The molybdenum(II) complex 7 has been obtained from trehalose bis-cyclopentadiene and its molecular structure determined by X-ray diffraction. From the uridine cyclopentadiene the molybdenum(II) complex 11 has been prepared and characterized.

We report in this paper the fabrication and characterization of a new gate-planarized organic polymer thin-film transistor (GP OP-TFT). We describe in detail the effects of the measurement procedure on the GP OP-TFT electrical characteristics and extracted parameters and show that it is extremely critical to carefully control the electrical measurement conditions to obtain accurate and meaningful results, before any material optimization is undertaken. We also describe the importance of normalization of electrical characteristics and extracted parameters for a proper comparison of different devices. Finally, we report and analyze the gate voltage and channel length dependence of the TFT field-effect mobility.

In this paper, we present a 2D numerical computer program for amorphous silicon thin film transistors (a-Si:H TFTs) simulation, and its application to the bidimensional study of the parasitic channel access resistances. The program solves the transport equation set under non-equilibrium steady state conditions, for given applied voltages. The values of physical parameters describing the internal state of the transistor are calculated at each node of a bidimensionnal mesh and the resulting drain current can therefore be related to the physical characteristics of the materials and to the geometrical and technological parameters of the device. The program allowed us to perform the evaluation of parasitic channel access resistances and their sensitivity to physical and geometrical parameters.

International audience; The industrial development of active immunotherapy based on live-attenuated bacterial vectors has matured. We developed a microsyringe for antigen delivery based on the type III secretion system (T3SS) of P. aeruginosa. We applied the "killed but metabolically active" (KBMA) attenuation strategy to make this bacterial vector suitable for human use. We demonstrate that attenuated P. aeruginosa has the potential to deliver antigens to human antigen-presenting cells in vitro via T3SS with considerable attenuated cytotoxicity as compared with the wild-type vector. In a mouse model of cancer, we demonstrate that this KBMA strain, which cannot replicate in its host, efficiently disseminates into lymphoid organs and delivers its heterologous antigen. The attenuated strain effectively induces a cellular immune response to the cancerous cells while lowering the systemic inflammatory response. Hence, a KBMA P. aeruginosa microsyringe is an efficient and safe tool for in vivo antigen delivery.

Trifluoromethanesulfonates derived from acetal protected α-D-galactopyranose 1 c and α-D-glucofuranose 3 c react with cyclopentadienyl and indenyl lithium to give optically active carbohydrate-substituted cyclopentadienes 2a and 4a and indenes 2b and 4b in good to moderate yields; because of the double bonds tautomerism of the cyclopentadiene unit 2a and 4a have been characterised as their cyclopentadienyl molybdenum complexes 6 and 7 and the X-ray structure of 7 is reported.

International audience; Degradation of 22 compounds was evaluated in stainless steel batch reactors at 140 °C for 14 days under a pressure of 0.5 MPa (mixture of 75% CO2, 20% N2, and 5% O2). For each run, two corrosion coupons, one carbon steel (XC38) and one stainless steel (304Ti), were immersed in aqueous solutions of amines to determine corrosion due to degraded solutions. Two additional coupons were put in the vapor phase above solutions. At the end of the run, corrosion rates were evaluated through weight-loss measurements. The amounts of remaining starting material were determined with a quantitative gas chromatography method. Corrosion and degradation data were compared with those of a benchmark molecule (MEA, monoethanolamine), tested under the same conditions. Results indicate that some molecules are less corrosive and have a better chemical stability than MEA. In addition, a quantitative structure property relationship (QSPR) model was built that can be applied to predict compound degradation.

Rationale: A noninvasive tool allowing the detection of vulnerable atherosclerotic plaques is highly needed. By combining nanomolar affinities and fast blood clearance, nanobodies represent potential radiotracers for cardiovascular molecular imaging. Vascular cell adhesion molecule-1 (VCAM1) constitutes a relevant target for molecular imaging of atherosclerotic lesions. Objective: We aimed to generate, radiolabel, and evaluate anti-VCAM1 nanobodies for noninvasive detection of atherosclerotic lesions. Methods and Results: Ten anti-VCAM1 nanobodies were generated, radiolabeled with technetium-99m, and screened in vitro on mouse and human recombinant VCAM1 proteins and endothelial cells and in vivo in apolipoprotein E–deficient (ApoE −/− ) mice. A nontargeting control nanobody was used in all experiments to demonstrate specificity. All nanobodies displayed nanomolar affinities for murine VCAM1. Flow cytometry analyses using human human umbilical vein endothelial cells indicated murine and human VCAM1 cross-reactivity for 6 of 10 nanobodies. The lead compound cAbVCAM1-5 was cross-reactive for human VCAM1 and exhibited high lesion-to-control (4.95±0.85), lesion-to-heart (8.30±1.11), and lesion-to-blood ratios (4.32±0.48) ( P −/− mice were successfully identified by single-photon emission computed tomography imaging. 99m Tc-cAbVCAM1-5 binding specificity was demonstrated by in vivo competition experiments. Autoradiography and immunohistochemistry further confirmed cAbVCAM1-5 uptake in VCAM1-positive lesions. Conclusions: The 99m Tc-labeled, anti-VCAM1 nanobody cAbVCAM1-5 allowed noninvasive detection of VCAM1 expression and displayed mouse and human cross-reactivity. Therefore, this study demonstrates the potential of nanobodies as a new class of radiotracers for cardiovascular applications. The nanobody technology might evolve into an important research tool for targeted imaging of atherosclerotic lesions and has the potential for fast clinical translation.

The discovery, synthesis and biological evaluation of a novel series of 7-isoxazoloquinolines is described. Several analogs are shown to increase ApoA1 expression within the nanomolar range in the human hepatic cell line HepG2.

Epigenetic mechanisms of gene regulation have a profound role in normal development and disease processes. An integral part of this mechanism occurs through lysine acetylation of histone tails which are recognized by bromodomains. While the biological and structural characterization of many bromodomain containing proteins has advanced considerably, the therapeutic tractability of this protein family is only now becoming understood. This paper describes the discovery and molecular characterization of potent (nM) small molecule inhibitors that disrupt the function of the BET family of bromodomains (Brd2, Brd3, and Brd4). By using a combination of phenotypic screening, chemoproteomics, and biophysical studies, we have discovered that the protein-protein interactions between bromodomains and acetylated histones can be antagonized by selective small molecules that bind at the acetylated lysine recognition pocket. X-ray crystal structures of compounds bound into bromodomains of Brd2 and Brd4 elucidate the molecular interactions of binding and explain the precisely defined stereochemistry required for activity.

Trifluoromethanesulfonates derived from acetal protected α-D-galactopyranose 1 c and α-D-glucofuranose 3 c react with cyclopentadienyl and indenyl lithium to give optically active carbohydrate-substituted cyclopentadienes 2a and 4a and indenes 2b and 4b in good to moderate yields; because of the double bonds tautomerism of the cyclopentadiene unit 2a and 4a have been characterised as their cyclopentadienyl molybdenum complexes 6 and 7 and the X-ray structure of 7 is reported.

5538 Background: ANTHALYA study is a randomized non comparative clinical trial to evaluate the efficacy and safety of neoadjuvant chemotherapy associated with bevacizumab. It was a 2:1 randomization to receive carboplatin, paclitaxel with (experimental arm) or without (control arm) bevacizumab in the neoadjuvant setting. The extent of initial carcinomatosis is a major determinant of complete resection but is rarely well described. We report here the extent of carcinomatosis explored by laparoscopy of patients included in Anthalya and its correlation with baseline characteristics. Methods: Non-optimally resectable stage IIIC or IV ovarian cancer patients were eligible for this study. Disease extent was evaluated by a standardized form and the Fagotti score was calculated. Baseline clinical characteristics were compared to trials comparing primary debulking surgery and IDS. Results: This multicenter study was conducted in 15 centers: 205 patients have been screened and 95 patients were included. Median age ...

Interaction of lithium cyclopentadienide with a suitable partially protected alpha-D-allofuranose triflate, 4, epimer at C3 of glucose, gives as a major product, besides the expected glucose-cyclopentadiene, 5, a glucose-disubstituted cyclopentadiene, 6. This unprecedented behaviour, which does not occur with alpha-D-glucofuranose and other sugars, is tentatively explained by a complexation of LiCp and the oxygen atoms of the isopropylidene function of one molecule of 4 and one of 5, giving a termolecular structure as the result of a template effect. The results of other experiments, such as the use of MgCp2 in place of LiCp or the complexation of oxygen atoms by lithium triflate, which changed the selectivity of the reaction largely in favour of the monosubstitution product 5, support this hypothesis. When lithium indenide is reacted with 4, glucose-monosubstituted and glucose-disubstituted indenes, 8 and 9, respectively, are formed, and 9 is obtained with almost total diastereoselectivity. This result can also be rationalised by a stereoselective complexation of lithium, as shown by separate experiments and by molecular mechanics calculations. Methyltricarbonyl molybdenum(II) complexes have been synthesised and characterised from glucose-monosubstituted 5 and glucose-disubstituted 6 cyclopentadienes.

Background In France outpatient centres for the care of alcoholics are healthcare establishments providing medical, psychological and social support. Although they meet the practical needs of these patients, their degree of use in each of these domains and the respective mobilisation of different skills by the care team are not well understood. Our aim was therefore to determine in detail the management involved as a function of the severity of alcohol dependence. For this purpose, all the procedures involved were compiled in a thesaurus describing its type (psychological, medical, social, reception), its scheduled or unscheduled nature, its method (face-to-face, telephone, letter) and its duration. The severity of dependence was evaluated using the Addiction Severity Index (ASI). Results 45 patients were included and followed-up during 291 ± 114 days. The mean initial ASI scores (± SD) were: medical (M) = 0.39 ± 0.3, working-income (ER) = 0.5 ± 0.3, alcohol (A) = 0.51 ± 0.2, illicit drugs (D) = 0.07 ± 0.08, legal (L) = 0.06 ± 0.13, familial and social environment (FS) = 0.34 ± 0.26, psychological (P) = 0.39 ± 0.22. The total number of procedures was 1341 (29.8 per patient) corresponding to 754.4 hours (16.7 per patient). The intensity of management peaked during the first month of treatment, and then declined rapidly; the maximum incidence of abstinence was observed during the 3rd month of management. Interviews with patients, group therapy and staff meetings represented 68.7%, 9.9% and 13.9% of all procedures, respectively. In patients with severe dependence, as compared to moderate, management was twice as intense in the psychological and social domains, but not in the medical domain. The ASI questionnaire was completed a second time by 24 patients, after an average of 3.2 months. The improvement was significant in the M, A, D and P domains only. Conclusion This study provided an overview of the methods employed in managing a sample of patients consulting an alcoholism centre in line with standards for medical, psychological and social establishments. The predominance of the social and psychological domains over the medical domain was clearly established. Relapses were common after the third month of treatment, but a remobilisation of teams made it possible to contain them. These results provide a framework for discussions on the organisation of healthcare systems and highly suggest that staff need to maintain a constant level of care throughout the treatment process.

We analysed liver histology findings in a large cohort of patients with chronic hepatitis C and in roughly half of them their response to interferon-alpha-based on iron parameters and HFE status. Histological activity and virological response to antiviral therapy (n = 146) were analysed in 273 immunocompetent and nonalcoholic patients with chronic hepatitis C, in terms of serum iron load, intrahepatic iron load (n = 110) and HFE mutations. Patients who were heterozygous for the C282Y and H63D mutations exhibited higher iron serum parameters than subjects without these mutations. The intrahepatic iron load was higher in H63D patients only. No association was observed between HFE mutations and histological activity. Increased iron parameters were associated with liver disease severity by univariate analysis only. Genotype 1 and ferritinaemia were associated with a poor response to antiviral therapy, whereas the H63D mutation emerged as a positive predictive factor for end of treatment and sustained antiviral response. Therefore, in chronic hepatitis C patients serum and intrahepatic iron levels were weakly correlated with histological activity, while HFE mutations were not. As for the response to interferon-alpha, elevated ferritinaemia constituted a negative predictive factor whereas the H63D mutation was a positive one. The H63D mutation might form part of an immunogenetic profile influencing the response to interferon therapy.

The first studies of organic semiconductors date back nearly 100 years with the observation of photoconductivity in anthracene by Pochettino1 and the study of its dark conductivity by Koenigsberger and Schilling.2 While the physical properties of organic semiconductors have been the subject of intense study since these early findings, it has only been within the last 20 years that organic semiconductors for use as the active layer in organic thin film transistors (OTFTs) have been a topic of study. Despite the recent finding of scientific misconduct of a researcher at Bell Labs investigating single-crystal organic materials and OTFTs3 which has invalidated published results, showing unprecedented behavior in crystalline organic semiconductors (such as, high-temperature superconductivity, quantum Hall effect, ballistic transport, injection lasing, and exceedingly large carrier mobility at low temperatures), their remains tremendous interest in OTFTs, and organic electronics in general.

AIMS: Although the prevalence of alcohol problems amongst detainees is suspected to be high, often only more flagrant problems are detected, restricting the possibilities for intervention in alcohol misuse and reducing opportunities for preventive efforts. This study examined the re-test reliability of AUDIT (the Alcohol Use Disorder Identification Test) in screening prisoners METHODS: AUDIT was administered for the first time on the day of entry to prison and again about 15 days later. The results were analysed according to two AUDIT thresholds: a score of 8 or higher and 12 or higher. RESULTS: Of 75 consecutive entrants tested, 47 male prisoners completed the study. At the first administration, 19.1% of these 47 men met criteria for a probable alcohol problem but this percentage rose to 59.6% on the second occasion (P = 0.0001). The proportion of subjects with a score 12 or higher (probably dependent) was 10.6% the first time versus 42.6% the second time (P = 0.0001). In the 19 who scored positive at the second administration only, changes in answers to the 10 items were coherent with a total score growing from 3.0 to 18.1 (P = 0.0001). No prisoner had a lower AUDIT score on the second administration. As alcohol problems are not routinely considered during the medical and biological examination at entry, no confirmation of the AUDIT results could be obtained, although those obtained at the second administration fitted well with the prevalence rates in previous reports. CONCLUSIONS: AUDIT, for the purpose of giving a prevalence estimate or to enter appropriate prisoners into more detailed assessment or interventions, should not be conducted immediately at entry, but some weeks later.

We present results on the electrical characterization of gate-planarized organic polymer thin-film transistors (OP-TFTs). We investigated the time dependence of the OP-TFT current. Over a relatively short time range (several 100ms), we observed a decrease of the OP-TFT current corresponding to the establishment of the steady-state regime, and is slower when the transistor is in the weak accumulation regime or in the OFF-state. We believe that this is associated with carrier thermalization in the organic semiconductor. Over longer time scales, the decrease of the OP-TFT current is due to device aging and can be associated with a threshold voltage shift, up to 20V after an electrical stress at V GS =-30V for 30min at room temperature. This shift is fully reversible once the gate polarization is removed and might be associated with charge trapping in the semiconductor.

We have investigated the effects of illumination, both broadband and monochromatic, on the electrical performance of organic polymer thin-film transistors (OP-TFTs). In each case, providing the illumination is sufficiently absorbed by the organic polymer, the drain current of a device biased in the OFF-state is significantly increased. We have observed increases in the OFF-state drain current as large as several orders of magnitude depending on the intensity of the incident illumination. Whereas, the drain current of a device biased in the strong accumulation regime is relatively unaffected by the incident illumination. The illumination also serves to decrease the threshold voltage and increase the subthreshold slope, but has little effect on the field-effect mobility of the charge carriers. We explain these effects in terms of the photo-carrier generation in the channel region of the device due to the incident illumination. We have also studied how our OP-TFTs respond to the turn-on and turn-off of gate bias under illumination and to the turn-on and turn-off of illumination at certain gate biases.