Cognitive remediation and professional insertion of people with schizophrenia: RemedRehab, a randomized controlled trial.

BACKGROUND: People suffering from schizophrenia cannot easily access employment in European countries. Different types of vocational programs coexist in France: supported employment, sheltered employment (ShE), and hybrid vocational programs. It is now acknowledged that the frequent cognitive impairments constitute a major obstacle to employment for people with schizophrenia. However, cognitive remediation (CR) is an evidence-based nonpharmacological treatment for these neurocognitive deficits. METHODS: RemedRehab was a multicentric randomized comparative open trial in parallel groups conducted in eight centers in France between 2013 and 2018. Participants were recruited into ShE firms before their insertion in employment (preparation phase). They were randomly assigned to cognitive training Cognitive Remediation for Schizophrenia (RECOS) or Treatment As Usual (TAU). The aim of the study was to compare with the benefits of the RECOS program on access to employment and work attendance for people with schizophrenia, measured by the ratio: number of hours worked on number of hours stipulated in the contract. RESULTS: Seventy-nine patients were included in the study between October 2018 and September 2019. Fifty-three patients completed the study. Hours worked / planned hours equal to 1 or greater than 1 were significantly higher in the RECOS group than in the TAU group. CONCLUSIONS: Participants benefited from a RECOS individualized CR program allows a better rate of work attendance in ShE, compared to the ones benefited from TAU. Traditional vocational rehabilitation enhanced with individualized CR in a population of patients with schizophrenia is efficient on work attendance during the first months of work integration.

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up.

PURPOSE: In the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P < 0.001]. Herein, we report results overall and by subgroups with extended follow-up. METHODS: In this double-blind, phase 3 study, post-menopausal women with ER+/HER2- ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs). RESULTS: After a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib-letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P < 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib-letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients' quality of life was maintained. CONCLUSIONS: With approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2- ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427.

Treatment of scaphotrapeziotrapezoid osteoarthritis with the Pyrocardan® implant: Results with a minimum follow-up of 2 years.

The aim of this study was to report the results of arthroplasty using a mobile pyrocarbon implant (Pyrocardan®) for isolated scaphotrapeziotrapezoid (STT) osteoarthritis. The hypothesis was that this arthroplasty leads to functional improvement without carpal instability. Twenty patients (22 implants) were included with a minimum follow-up of 2 years and an average age of 59.6 years. Outcome criteria were pain (VAS scale), QuickDASH and PRWE scores, strength (grip and pinch), wrist mobility, the Kapandji index, carpal height and the capitolunar angle measured on X-rays. The preoperative data was compared to the postoperative data. The average follow-up was 3.8 years. There was a significant improvement in pain, clinical scores and pinch strength. In terms of range of motion, we found that amplitudes were maintained except for a significant decrease in wrist extension. X-rays did not show any carpal instability; carpal height was maintained and the capitolunar angle was significantly improved. No implant dislocation was reported. The good functional and radiographic outcomes, and the absence of surgical complications are evidence that the Pyrocardan® resurfacing implant is a valid option for treating STT osteoarthritis. If this arthroplasty procedure fails, another procedure can still be done. However, a long-term assessment of this technique is still needed.

[Is the simplification of the immunization schedule applied? Review 2 years after its implementation]. / La simplification du calendrier vaccinal est-elle appliquée ? Bilan 2ans après sa mise en place.

Repeating evaluations of vaccine coverage (VC) is essential to measure the implementation and effectiveness of vaccination policy. We report the results of VC in infants from the Vaccinoscopie® study in 2014 to assess the changes secondary to the new 2013 immunization schedule. METHOD: Study conducted on Internet among a representative sample of mothers reporting their child's vaccination record. RESULTS: The removal of the dose of DTPa-Hib at the age of 3 months was quickly adopted since only 1 % of children aged 6 months had received three doses of DTPa in 2014 compared to 96 % in 2012. The booster dose is administered earlier for the DTPa and hepatitis B components. The shift of MMR vaccination from 9 months of age for children participating in community structures to 12 months for all children was closely followed since only 2 % of 9- to 11-month-old children received a MMR vaccine in 2014 compared to 33 % in 2012. The second dose of MMR recommended at 16-18 months of age rather than between 13 and 24 months was actually followed by an earlier administration of this dose. At 18-20 months of age, 60 % received two doses of MMR in 2014 versus 41 % in 2012. Finally, for meningitis C vaccination, a significant increase of VC was observed in children 15-23 months of age (66 % in 2014 versus 44 % in 2012). CONCLUSION: The simplification of the infant immunization schedule was quickly applied and received excellent support from healthcare professionals. However, this measure alone is still not sufficient to meet the CV objectives defined by the HCSP.

2D surface temperature measurement of plasma facing components with modulated active pyrometry.

In nuclear fusion devices, such as Tore Supra, the plasma facing components (PFC) are in carbon. Such components are exposed to very high heat flux and the surface temperature measurement is mandatory for the safety of the device and also for efficient plasma scenario development. Besides this measurement is essential to evaluate these heat fluxes for a better knowledge of the physics of plasma-wall interaction, it is also required to monitor the fatigue of PFCs. Infrared system (IR) is used to manage to measure surface temperature in real time. For carbon PFCs, the emissivity is high and known (ɛ ∼ 0.8), therefore the contribution of the reflected flux from environment and collected by the IR cameras can be neglected. However, the future tokamaks such as WEST and ITER will be equipped with PFCs in metal (W and Be/W, respectively) with low and variable emissivities (ɛ ∼ 0.1-0.4). Consequently, the reflected flux will contribute significantly in the collected flux by IR camera. The modulated active pyrometry, using a bicolor camera, proposed in this paper allows a 2D surface temperature measurement independently of the reflected fluxes and the emissivity. Experimental results with Tungsten sample are reported and compared with simultaneous measurement performed with classical pyrometry (monochromatic and bichromatic) with and without reflective flux demonstrating the efficiency of this method for surface temperature measurement independently of the reflected flux and the emissivity.

Magnetic topology changes induced by lower hybrid waves and their profound effect on edge-localized modes in the EAST tokamak.

Strong mitigation of edge-localized modes has been observed on Experimental Advanced Superconducting Tokamak, when lower hybrid waves (LHWs) are applied to H-mode plasmas with ion cyclotron resonant heating. This has been demonstrated to be due to the formation of helical current filaments flowing along field lines in the scrape-off layer induced by LHW. This leads to the splitting of the outer divertor strike points during LHWs similar to previous observations with resonant magnetic perturbations. The change in the magnetic topology has been qualitatively modeled by considering helical current filaments in a field-line-tracing code.

Modeling of the ITER-like wide-angle infrared thermography view of JET.

Infrared (IR) thermography systems are mandatory to ensure safe plasma operation in fusion devices. However, IR measurements are made much more complicated in metallic environment because of the spurious contributions of the reflected fluxes. This paper presents a full predictive photonic simulation able to assess accurately the surface temperature measurement with classical IR thermography from a given plasma scenario and by taking into account the optical properties of PFCs materials. This simulation has been carried out the ITER-like wide angle infrared camera view of JET in comparing with experimental data. The consequences and the effects of the low emissivity and the bidirectional reflectivity distribution function used in the model for the metallic PFCs on the contribution of the reflected flux in the analysis are discussed.

Analysis of outcome after using high-risk criteria selection to surgery versus endovascular repair in the modern era of abdominal aortic aneurysm treatment.

INTRODUCTION: The concept of high-risk patients suggests that such patients will experience a higher rate of postoperative complications and worse short- and long-term outcomes, and should therefore benefit from the use of endovascular techniques for aortic abdominal aneurysm (AAA) repair. The primary goal of this study was to assess the relevance of the different high-risk criteria, defined by the French health agency Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS) in a single-centre continuous series. Secondary goals were to retrospectively compare the incidence of postoperative complications and short- and long-term survival in three groups of patients. MATERIALS AND METHODS: Between January 1999 and December 2006, details of all the patients undergoing elective surgery for AAA in our hospital were recorded into a prospective registry (n=626). Three groups were considered according to the level of risk and type of repair defined by the AFSSAPS: endovascular aortic aneurysm repair (EVAR) high-risk (HR) (at least one high-risk factor and EVAR, n=138), open HR (at least one high-risk factor and open repair, n=134) and open low-risk (LR) (no high-risk factors and open repair, n=344). None of the low-risk patients were treated using an endovascular approach. The demographics, preoperative risk factors, intra-, postoperative data and short- and long-term survival were compared between the groups. Interrelations among the set of high-risk criteria for mortality were calculated using multiple correspondence analysis (MCA). RESULTS: The distribution of high-risk criteria was similar in both high-risk groups, except for age, heart failure and hostile abdomen, which were significantly more frequent in EVAR HR. Operation time, blood loss and length of stay in an intensive care unit and hospital were significantly lower in the EVAR HR group. The 30-day mortality and survival rates at 5 years were 5.4 and 59.4% for EVAR HR, 3.7 and 70.4% for open HR and 2.3 and 83.7% for open LR, respectively, with no significant difference between the three groups for the mortality, but a significant higher survival at 5 years for the open LR versus both high-risk groups. CONCLUSION: The high-risk AFSSAPS criteria were not predictive of postoperative mortality and should not be used to determine the choice of treatment technique. Other criteria therefore need to be established to determine whether open or EVAR repair should be used.

On the reliability of scrape-off layer ion temperature measurements by retarding field analyzers.

The retarding field analyzer (RFA) is one of the only widely accepted diagnostics for measurements of ion temperature Ti in the tokamak scrape-off layer. In this paper we analyze some instrumental effects of the RFA and their influence on Ti measurements. It is shown that selective ion transmission through the RFA slit is responsible for an overestimation of Ti by less than 14%, even for a relatively thick slit plate. Therefore, thicker slit plates are preferable, since they reduce, e.g., the risk of melting during off-normal events, and the effect of positive space charge inside the cavity. The influence of the electron repelling grid, as well as misalignment of the slit with respect to the magnetic field on Ti measurements are negligible.

Role of Lu/BCAM in abnormal adhesion of sickle red blood cells to vascular endothelium.

Lutheran (Lu) blood group and Basal Cell Adhesion Molecule (BCAM) antigens are both carried by two glycoprotein (gp) isoforms of the immunoglobulin superfamily representing receptors for laminin alpha5 chain. They are expressed in red blood cells, in endothelial cells of vascular capillaries and in epithelial cells of several tissues. Lu/BCAM gps are overexpressed in sickle red blood cells (SS RBCs). Stimulation of SS RBCs by epinephrine activates the PKA depending signaling pathway and induces reinforced Lu/BCAM-mediated adhesion to laminin10/11. We have analyzed the phosphorylation state of Lu/BCAM long isoform cytoplasmic tail and showed that it is phosphorylated by CKII, GSK3b and PKA. Phosphorylation of this isoform in transfected K562 cells is stimulated by effectors of the PKA pathway and induces cell adhesion to laminin10/11. Lu/BCAM gps are highly expressed in endothelial cells and exhibit potential integrin binding motifs. We showed that they interact with integrin alpha4beta1, the unique integrin expressed on the surface of young reticulocytes. Adhesion assays under flow conditions showed that SS RBCs adhere to primary human endothelial cells (HUVEC) after selective activation of intergin alpha4beta1 and that this adhesion is mediated by endothelial Lu/BCAM gps. Our studies show that Lu/BCAM gps expressed either on erythroid or on endothelial cells are involved in SS RBC-endothelium interactions and could play a role in the abnormal adhesion of SS RBCs to vascular endothelium contributing to the vaso-occlusive crises reported for sickle cell disease patients.

Morphometric evidence for impairment of renal autoregulation in advanced essential hypertension.

A morphometric study was performed on 22 renal biopsies from hypertensive patients with proteinuria and/or azotemia, with no evidence of other renal disease. These results were compared with our earlier study of normotensive aging kidneys. Afferent arterioles in hypertensive kidneys showed a significant increase in lumen diameter (15.7+/-4.9 vs 13.4+/-4.7 microm, P=0.0007) and wall area (1234+/-769 vs 998+/-445 microm(2), P=0.037), due primarily to shift in the distribution of arteriolar types, from predominantly normal toward predominantly hyaline arterioles in hypertension. Glomeruli were divided into four basic types: normal, hypertrophic, focal segmental glomerulosclerosis (FSGS) type, and sclerosing. Overall, glomeruli in hypertensive kidneys were much larger than in normotensive aging kidneys, for example, total capillary area (16 247+/-10 681 vs 11 624+/-5702 microm(2), P<0.00001). This increase was due primarily to an increase in size of each type, for example, for hypertrophic glomeruli: total capillary area (22 205+/-10 426 vs 15 349+/-4577 microm(2), P=0.0038). There was an excellent correlation between arteriolar lumen diameter and mean glomerular capillary area for hypertrophic/FSGS-type glomeruli (r=0.4778, P=0.0013), such that as arteriolar diameter increases the mean glomerular capillary area increases, consistent with loss of autoregulation. The morphologic correlates of loss of autoregulation, with afferent arteriolar dilatation and increase in glomerular capillary size, glomerular hypertrophy, and subsequent FSGS, are present on a focal basis in aging kidneys and, much more extensively, although still focally, in hypertensive kidneys.

Molecular identification and expression of differentially regulated genes of the European flounder, Platichthys flesus, submitted to pesticide exposure.

Effects of pesticide exposure on the European flounder, Platichthys flesus, were investigated using a suppression subtractive hybridization method (SSH) to identify up- and down-regulated genes after a 30-day exposure to herbicides (a cocktail of atrazine, diuron, and isoproturon, and a single herbicide, glyphosate). A total of 256 expressed gene sequences were identified as having the potential for being differentially expressed, of which 116 could be identified by homology with databased sequences. The metabolic functions with which they are associated include energy production, general metabolism, signaling, transport, immune system, and structure. Expression of 14 of these genes was analyzed in liver, muscle, and gills by reverse transcriptase-polymerase chain reaction (RT-PCR) under experimental conditions (0, 15, and 30 days of exposure) and under field conditions (sampling in two estuaries displaying different levels of pesticide contamination). This study provides a first basis for studying the response of fish to pesticide exposure and allows the characterization of new potential genetic markers of pesticide contamination in the field.

[A global intervention program for institutionalized demented patients]. / Méthode de prise en charge globale non médicamenteuse des patients déments institutionnalisés.

INTRODUCTION: Over the last decades many approaches have been developed to manage cognitive and behavioral disturbances in dementia. The present work describes a global intervention program carried out with moderately to severely demented institutionalized patients. The aims of the intervention program are to stimulate and maintain the preserved abilities of demented patients in a supportive context, to decrease the behavioral disturbance and to avoid burnout of care-unit staff. METHODS: This intervention combines different means: psychosocial care (validation therapy, social interaction), cognitive stimulation (memory and verbal training), and motor and sensitive stimulation. The global intervention program requires a special trained team composed of a supervisor, six aid-nurses, an occupational therapist, a speech therapist, a psychomotor therapist and a psychologist. The team cared for the patients five days per week over a three-month period. Assessments were conducted before and after the intervention program to measure the benefit. RESULTS: Positive effects were shown for cognitive abilities, nutritional problems and staff burnout. However, due to the small sample size for this study, more research is needed to verify the effectiveness of this global intervention program, particularly the implications for nutrition. CONCLUSION: This global intervention combined with pharmacological treatment seems to be useful for managing psychological and behavioral disorders of institutionalized demented patients.

Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition.

AIMS/HYPOTHESIS: The acute-phase proteins, serum amyloid As (SAA), are precursors of amyloid A, involved in the pathogenesis of AA amyloidosis. This work started with the characterisation of systemic AA amyloidosis concurrent with SAA overexpression in the subcutaneous white adipose tissue (sWAT) of an obese patient with a leptin receptor deficiency. In the present study a series of histopathological, cellular and gene expression studies was performed to assess the importance of SAA in common obesity and its possible production by mature adipocytes. MATERIALS AND METHODS: Gene expression profiling was performed in the sWAT of two extremely obese patients with a leptin receptor deficiency. Levels of the mRNAs of the different SAA isoforms were quantified in sWAT cellular fractions from lean subjects and from obese subjects before and after a very-low-calorie diet. These values were subsequently compared with serum levels of SAA in these individuals. In addition, histopathological analyses of sWAT were performed in lean and obese subjects. RESULTS: In sWAT, the expression of SAA is more than 20-fold higher in mature adipocytes than in the cells of the stroma vascular fraction (p<0.01). Levels of SAA mRNA expression and circulating levels of the protein are sixfold (p<0.001) and 3.5-fold (p<0.01) higher in obese subjects than in lean subjects, respectively. In lean subjects, 5% of adipocytes are immunoreactive for SAA, whereas the corresponding value is greater than 20% in obese subjects. Caloric restriction results in decreases of 45-75% in levels of the transcripts for the SAA isoforms and in circulating levels of the protein. CONCLUSIONS/INTERPRETATION: The results of the present study indicate that SAA is expressed by sWAT, and its production at this site is regulated by nutritional status. If amyloidosis is seen in the context of obesity, it is possible that production of SAA by adipocytes could be a contributory factor.

Breast cancer risk associated with being treated for infertility: results from the French E3N cohort study.

BACKGROUND: The use of fertility drugs (FDs) is steadily increasing in Western countries and concern has been raised as to the possible impact of fertility treatments on breast cancer risk. METHODS: We analysed this association in the French E3N study. In this prospective cohort, data on treatment against infertility, duration and time of administration were collected at entry through self-administered questionnaires. Cox regression analysis was used to estimate adjusted relative risks (RRs). RESULTS: Among the 92 555 women from the study population, 6602 women were treated for infertility. During the 10 year follow-up period, 2571 cases of primary invasive breast cancer were diagnosed (183 in treated women). Our study showed no overall significant association between breast cancer risk and treatment for infertility (RR = 0.95, confidence interval 0.82-1.11), after surgery or FDs, and whatever the type, the duration of use and the age at first use of FDs. However, infertility treatment was associated with an increased risk, of borderline significance, of breast cancer among women with a family history of breast cancer. This last result had limited statistical power. CONCLUSIONS: Our study provides evidence that treatment for infertility does not influence breast cancer risk overall. An interaction with a familial history of breast cancer is possible but should be investigated further.

Initial characterization of new bacteria degrading high-molecular weight polycyclic aromatic hydrocarbons isolated from a 2-year enrichment in a two-liquid-phase culture system.

AIMS: To characterize some polycyclic aromatic hydrocarbons (PAH)-degrading microorganisms isolated from an enriched consortium degrading high molecular weight (HMW) PAHs in a two-liquid-phase (TLP) soil slurry bioreactor, and to determine the effect of low molecular weight (LMW) PAH on their growth and HMW PAH-degrading activity. METHODS AND RESULTS: Several microorganisms were isolated from a HMW-PAH (pyrene, chrysene, benzo[a]pyrene and perylene) degrading consortium enriched in TLP cultures using silicone oil as the organic phase. From 16S rRNA analysis, four isolates were identified as Mycobacterium gilvum B1 (99% identity),Bacillus pumilus B44 (99% identity), Microbacterium esteraromaticum B21 (98% identity), and to the genus Porphyrobacter B51 (96% identity). The two latter isolates have not previously been associated with PAH degradation. Isolate B51 grew strongly in the interfacial fraction in the presence of naphthalene vapours and phenanthrene compared with cultures without LMW PAHs. Benzo[a]pyrene was degraded in cultures containing a HMW PAH mixture but pyrene had no effect on its degradation. The growth of isolates B1 and B21 was improved in the aqueous phase than in the interfacial fraction for cultures with naphthalene vapours. Pyrene was required for benzo[a]pyrene degradation by isolate B1. For isolate B21, pyrene and chrysene were degraded only in cultures without naphthalene vapours. CONCLUSION: Consortium enriched in a TLP culture is composed of microorganisms with different abilities to grow at the interface or in the aqueous phase according to the culture conditions and the PAH that are present. Naphthalene vapours increased the growth of the microorganisms in TLP cultures but did not stimulate the HMW PAH degradation. SIGNIFICANCE AND IMPACT OF THE STUDY: New HMW PAH-degrading microorganisms and a better understanding of the mechanisms involved in HMW PAH degradation in TLP cultures.

Environmental pesticide exposure as a risk factor for Alzheimer's disease: a case-control study.

The aim of this study was to evaluate the influence of pesticide exposure on the development of Alzheimer's disease (AD), taking into account the potentially confounding factors (genetic, occupational exposure, and sociodemographic). The 1924 study participants (>70 years old) were randomly selected in the Saguenay-Lac Saint-Jean region (Quebec, Canada). The AD diagnosis was established in three steps according to recognized criteria. Sixty-eight cases were paired with a nondemented control for age (+/-2 years) and sex. Structured questionnaires addressed to subjects and proxy respondents allowed a description of the sociodemographic characteristics, lifestyle characteristics, and residential, occupational, familial, and medical histories. Assessment of environmental exposure to pesticides was based on residential histories and the agriculture census histories of Statistics Canada (1971-1991) for herbicide and insecticide spraying in the area. Statistical analyses were performed with a logistic regression, adjusting for potential confounding factors. The results failed to show a significant risk of AD with an exposure to herbicides, insecticides, and pesticides. However, future investigations are needed to establish more precisely the identification, measurement, mobility, and bioavailability of neurotoxic pesticide residues in relation to AD.

Congenital erythropoietic porphyria: prenatal diagnosis and autopsy findings in two sibling fetuses.

Congenital erythropoietic porphyria is an autosomal recessive disease characterized by a deficiency of uroporphyrinogen III cosynthetase activity, with diffuse tissue accumulation of specific type I porphyrins. The diagnosis of this disease was made in two fetuses, who were siblings, and from a Caucasian nonconsanguinous family. The first fetus died in utero with hydrops fetalis and anemia, but without an etiopathogenic diagnosis. In the second case, the diagnosis was based on pink fluorescence of the amniotic fluid examined fortuitously in sunlight. DNA analysis showed that the fetus was heteroallelic for the mutation C73R. The autopsy showed brown skin, and at histological examination, porphyrin pigment was deposited in many tissues. Retrospectively, similar deposits were found in the tissues of the first fetus.