Distinct mechanisms control human naive and antigen-experienced CD8+ T lymphocyte proliferation.

Human Ag-specific CD8(+) T lymphocytes are heterogeneous and include functionally distinct populations. In this study, we report that at least two distinct mechanisms control the expansion of circulating naive, memory, and effector CD8(+) T lymphocytes when exposed to mitogen or Ag stimulation. The first one leads to apoptosis and occurs shortly after in vitro stimulation. Susceptibility to cell death is prominent among primed T cell subsets, and it is inversely correlated with the size of the ex vivo Bcl-2(high) population within these subsets. Importantly, the Bcl-2(high) phenotype is associated to the proportion of responsive CD8(+) T cells, independently of their differentiation stage. The second one depends on the expression of newly synthesized cyclin-dependent kinase inhibitor p16(INK4a) that occurs in a significant fraction of T cells that had been actively cycling, leading to their cell cycle arrest upon stimulation. Strikingly, accumulation of p16(INK4a) protein preferentially occurs in naive as opposed to primed derived T lymphocytes and is not related to apoptosis. Significant levels of p16 are readily detectable in a small number of ex vivo CD8(+) T cells. Our observations reveal that activation-induced p16 expression represents an alternative process to apoptosis, limiting the proliferation potential of activated naive derived T lymphocytes.

Why bystanders decline telephone cardiac resuscitation advice.

OBJECTIVES: The aim of this study was to evaluate the rate and reason for refusal of telephone-based cardiopulmonary resuscitation (CPR) instruction by bystanders after the implementation of the dispatch center's systematic telephone CPR protocol. METHODS: Over a 15-month period the authors prospectively collected all case records from the emergency medical services (EMS) dispatch center when CPR had been proposed to the bystander calling in and recorded the reason for declining or not performing that the bystander spontaneously mentioned. All pediatric and adult traumatic and nontraumatic cases were included. Situations when resuscitation had been spontaneously initiated by bystanders were excluded. RESULTS: During the study period, dispatchers proposed CPR on 264 occasions: 232 adult nontraumatic cases, 17 adult traumatic cases, and 15 pediatric (traumatic and nontraumatic) cases. The proposal was accepted in 163 cases (61.7%, 95% confidence interval [CI] = 54.6% to 66.5%), and CPR was eventually performed in 134 cases (51%, 95% CI = 43.2% to 55.3%). In 35 of the cases where resuscitation was not carried out, the condition of the patient or conditions at the scene made this decision medically appropriate. Of the remaining 95 cases, 55 were due to physical limitations of the caller, and 33 were due to emotional distress. CONCLUSIONS: The telephone CPR acceptance rate of 62% in this study is comparable to those of other similar studies. Because bystanders' physical condition is one of the keys to success, the rate may not improve as the population ages.

Assistance circulatoire chronique: le point en 2013 [Long-term mechanical circulatory support: where do we stand in 2013?].

With the advent of new technologies, experience with long-term mechanical circulatory support (MCS) is rapidly growing. Candidates to MCS are selected based on concepts, strategies and classifications that are specific to this indication. As results drastically improve, supported by stronger scientific evidence, the trend is towards earlier implantation. An adequate pre-implant follow-up is mandatory in order to avoid missing the best window of opportunity for implantation. While on chronic support, the hemodynamic profile of patients with continuous-flow ventricular assist devices is unique and remarkably influenced by the hydration status. Optimal management of these patients from the pre-implant phase to the long-term support phase requires a multidisciplinary approach that is similar to that already long validated for organ transplantation.

Anatomie du foie: ce qu'il faut savoir [Anatomy of the liver: what you need to know]

A precise knowledge of arterial, portal, hepatic and biliary anatomical variations is mandatory when a liver intervention is planned. However, only certain variations must be searched when a precise intervention is planned. The basic liver anatomy as well as the most relevant malformations will be precised.

A validated assay for measuring doxorubicin in biological fluids and tissues in an isolated lung perfusion model: matrix effect and heparin interference strongly influence doxorubicin measurements.

Doxorubicin is an antineoplasic agent active against sarcoma pulmonary metastasis, but its clinical use is hampered by its myelotoxicity and its cumulative cardiotoxicity, when administered systemically. This limitation may be circumvented using the isolated lung perfusion (ILP) approach, wherein a therapeutic agent is infused locoregionally after vascular isolation of the lung. The influence of the mode of infusion (anterograde (AG): through the pulmonary artery (PA); retrograde (RG): through the pulmonary vein (PV)) on doxorubicin pharmacokinetics and lung distribution was unknown. Therefore, a simple, rapid and sensitive high-performance liquid chromatography method has been developed to quantify doxorubicin in four different biological matrices (infusion effluent, serum, tissues with low or high levels of doxorubicin). The related compound daunorubicin was used as internal standard (I.S.). Following a single-step protein precipitation of 500 microl samples with 250 microl acetone and 50 microl zinc sulfate 70% aqueous solution, the obtained supernatant was evaporated to dryness at 60 degrees C for exactly 45 min under a stream of nitrogen and the solid residue was solubilized in 200 microl of purified water. A 100 microl-volume was subjected to HPLC analysis onto a Nucleosil 100-5 microm C18 AB column equipped with a guard column (Nucleosil 100-5 microm C(6)H(5) (phenyl) end-capped) using a gradient elution of acetonitrile and 1-heptanesulfonic acid 0.2% pH 4: 15/85 at 0 min-->50/50 at 20 min-->100/0 at 22 min-->15/85 at 24 min-->15/85 at 26 min, delivered at 1 ml/min. The analytes were detected by fluorescence detection with excitation and emission wavelength set at 480 and 550 nm, respectively. The calibration curves were linear over the range of 2-1000 ng/ml for effluent and plasma matrices, and 0.1 microg/g-750 microg/g for tissues matrices. The method is precise with inter-day and intra-day relative standard deviation within 0.5 and 6.7% and accurate with inter-day and intra-day deviations between -5.4 and +7.7%. The in vitro stability in all matrices and in processed samples has been studied at -80 degrees C for 1 month, and at 4 degrees C for 48 h, respectively. During initial studies, heparin used as anticoagulant was found to profoundly influence the measurements of doxorubicin in effluents collected from animals under ILP. Moreover, the strong matrix effect observed with tissues samples indicate that it is mandatory to prepare doxorubicin calibration standard samples in biological matrices which would reflect at best the composition of samples to be analyzed. This method was successfully applied in animal studies for the analysis of effluent, serum and tissue samples collected from pigs and rats undergoing ILP.

Psychological transformations in kidney transplantation: A prospective qualitative study

The aim of this IRB-approved study was to prospectively analyze psychological transformations in ESRD patients before and after transplantation (KT). Semi-structured interviews were conducted in 30 patients (mean age = 53±10) after their inclusion on the waiting-list (Gr. A). Follow-up interviews were performed 6 months later in 15 patients still awaiting KT (Gr. B6), and in 15 patients 6 months (Gr. C6) and 12 months (Gr. C12) after KT. Qualitative analysis was performed. Gr: A:All patients underlined loss of freedom, 87% devoted much energy to maintain normality, 57% modified medical directives. All reported emotional fragility related to dialysis and loss of quality of life (QOL), negative (43%) or suicidal thoughts (20%). Professional stigma was underlined (26%). Gr: B6:40% reported no change, 60% mentioned increase of illness intrusiveness, 46% dialysis side-effects, 40% communication problems, 33% tension with medical staff and waiting list handling. Fear of emotional breakdown (40%), couple problems (47%) and worsened professional difficulties (20%) were reported. Gr: C6:All patients mentioned improved QOL and freedom recovery (87%). All expressed concerns about possible acute rejection, 73% were anxious about laboratory results, 93% experienced dependence to immunosuppressants, 47% reported difficulties in handling medication, 21% feared to forget them, 47% were concerned about side-effects, 67% had resumed work but medical constraints led to professional tension (40%). Gr: C12:All mentioned recovered QOL. Medical controls were accepted as a routine (87%) and adherence to medication was mandatory (100%). All mentioned the limited long-term graft survival and 47% were anxious about possible return to dialysis, especially younger patients (27%). Positive identity and existential changes were reported (60%). This prospective qualitative study identifies psychological modifications in the course of KT. It provides a basis to adequately address concerns, but it shows also that KT is clearly associated with positive psychological transformations.

MIBG scintigraphy for the diagnosis and follow-up of children with neuroblastoma.

Neuroblastoma (NBL) is the commonest extra-cranial solid tumor in children and the leading cause of cancer related deaths in childhood between the age of 1 to 4 years. NBL may behave in very different ways, from the less aggressive stage 4S NBL or congenital forms that may resolve without treatment in up to 90% of the children, to the high-risk disseminated stage 4 disease in older children with a cure rate of 35 to 40%. Initial staging is crucial for effective management and radiolabeled metaiodobenzylguanidine (MIBG) with iodine-123 is a powerful tool with a sensitivity around 90% and a specificity close to 100% for the diagnosis of NBL. MIBG scintigraphy is used routinely and is mandatory in most investigational clinical trials both for the initial staging of the disease, the evaluation of the response to treatment, as well as for the detection of recurrence during follow-up. With respect to outcome of children presenting disseminated stage 4 NBL, the role of post-therapeutic [(123)I]MIBG scan has been investigated by several groups but so far there is no consensus whereas a complete or very good partial response as assessed by MIBG may be of prognostic value. NBL needs a multimodality approach at diagnosis and during follow-up and MIBG scintigraphy keeps its pivotal role, in particular with respect to bone marrow involvement and/or cortical bone metastases.

Factors affecting the quality of cardiopulmonary resuscitation in inpatient units: perception of nurses

Abstract OBJECTIVE To identify, in the perception of nurses, the factors that affect the quality of cardiopulmonary resuscitation (CPR) in adult inpatient units, and investigate the influence of both work shifts and professional experience length of time in the perception of these factors. METHOD A descriptive, exploratory study conducted at a hospital specialized in cardiology and pneumology with the application of a questionnaire to 49 nurses working in inpatient units. RESULTS The majority of nurses reported that the high number of professionals in the scenario (75.5%), the lack of harmony (77.6%) or stress of any member of staff (67.3%), lack of material and/or equipment failure (57.1%), lack of familiarity with the emergency trolleys (98.0%) and presence of family members at the beginning of the cardiopulmonary arrest assistance (57.1%) are factors that adversely affect the quality of care provided during CPR. Professional experience length of time and the shift of nurses did not influence the perception of these factors. CONCLUSION The identification of factors that affect the quality of CPR in the perception of nurses serves as parameter to implement improvements and training of the staff working in inpatient units.

Milloria de cumplementació de l´estil Utstein. Incorporació d´un sistema de registre d´audio durant l´aturada cardíaca intrahospitalària

El registre precís de l´aturada cardíaca intrahospitalària seguint les recomanacions segons l´estil Utstein i mesurar els intèrvals de temps entre les diferents accions és difícil. L´estudi demostra que l'ús d'una gravadora amb temporitzador incorporat durant les maniobres de ressussitació cardiopulmonar en l´aturada cardíaca intrahospitalària permet el registre de més ítems per pacients i el càlcul dels intèrvals de temps entre les diferents accions durant les maniobres de reanimació cardiopulmonar de forma precisa i objectiva. Estudi observacional prospectiu entre gener de 2008 i desembre de 2009. S´inclouen pacients hospitalitzats i no hospitalitzats atesos per l´equip d´aturada cardíaca.

Oxidized LDL modulates apoptosis of regulatory T cells in patients with ESRD.

Increased levels of oxidized low-density lipoproteins (oxLDL) contribute to the increased risk for atherosclerosis, which persists even after adjusting for traditional risk factors, among patients with ESRD. Regulatory T cells (CD4+/CD25+ Tregs), which down-regulate T cell responses to foreign and self-antigens, are protective in murine atherogenesis, but whether similar immunoregulation occurs in humans with ESRD is unknown. Because cellular defense systems against oxLDL involve proteolytic degradation, the authors investigated the role of oxLDL on proteasome activity of CD4+/CD25+ Tregs in patients with ESRD. CD4+/CD25+ Tregs isolated from uremic patients' peripheral blood, especially that of chronically hemodialyzed patients, failed to suppress cell proliferation, exhibited cell-cycle arrest, and entered apoptosis by altering proteasome activity. Treating CD4+/CD25+ Tregs with oxLDL or uremic serum ex vivo decreased the number and suppressive capacity of CD4+/CD25+ Tregs. In vitro, oxLDL promoted the accumulation of p27Kip1, the cyclin-dependent kinase inhibitor responsible for G1 cell cycle arrest, and increased apoptosis in a time- and concentration-dependent manner. In summary, proteasome inhibition by oxLDL leads to cell cycle arrest and apoptosis, dramatically affecting the number and suppressive capacity of CD4+/CD25+ Tregs in chronically hemodialyzed patients. This response may contribute to the immune dysfunction, microinflammation, and atherogenesis observed in patients with ESRD.

Utilité des biomarqueurs du sepsis en réanimation [Usefulness of biomarkers of sepsis in the ICU].

Despite some progress, the mortality of severe sepsis and septic shock remains high. Immunotherapy directed against inflammatory mediators failed, but new treatments more specifically tailored to individual situations are actively investigated. C-reactive protein (CRP) and procalcitonin (PCT) have not demonstrated to be useful for individual prognostic stratification. New biomarkers such as pancreatic stone protein (PSP) or growth arrest specific protein 6 (Gas6) could improve this prediction. Combined with the clinical course, "PCT" allows to tailor individually the duration of antibiotic therapy in ICU patients. This still contested innovative approach significantly reduces overall exposure to antibiotics.

The credit ratings game

The spectacular failure of top-rated structured finance products has broughtrenewed attention to the conflicts of interest of Credit Rating Agencies (CRAs). We modelboth the CRA conflict of understating credit risk to attract more business, and the issuerconflict of purchasing only the most favorable ratings (issuer shopping), and examine theeffectiveness of a number of proposed regulatory solutions of CRAs. We find that CRAs aremore prone to inflate ratings when there is a larger fraction of naive investors in the marketwho take ratings at face value, or when CRA expected reputation costs are lower. To theextent that in booms the fraction of naive investors is higher, and the reputation risk forCRAs of getting caught understating credit risk is lower, our model predicts that CRAs aremore likely to understate credit risk in booms than in recessions. We also show that, due toissuer shopping, competition among CRAs in a duopoly is less efficient (conditional on thesame equilibrium CRA rating policy) than having a monopoly CRA, in terms of both totalex-ante surplus and investor surplus. Allowing tranching decreases total surplus further.We argue that regulatory intervention requiring upfront payments for rating services (beforeCRAs propose a rating to the issuer) combined with mandatory disclosure of any ratingproduced by CRAs can substantially mitigate the con.icts of interest of both CRAs andissuers.

Archives curieuses de l'histoire de France.... 1re série. Tome 8e

Comprend : Histoire contenant un abrégé de la vie, moeurs et vertus du roy... Charles IX... ; La Prinse du Comte de Montgommery, dedans le chasteau de Donfron, par monsieur de Matignon, lieutenant en la basse Normandie, en l'absence du Duc de Bouillon, le Ieudy XXVII de May, mil cinq cens soixante et quatorze. A Paris, pour Nicolas du Mont demeurant auprès le Collège de Reims 1574 ; Arrest contre Geoffroy Vallée. 8 février 1574. (Extrait des Registres du Parlement) ; Discours de la mort et exécution de Gabriel Comte de Montgommery, par arrest de la Court, pour les conspirations et menées par luy commises, contre le Roy et son estat, qui fut à Paris, le vingsixième de Iuing, 1574. A Paris, par Michel Buffet... 1574 ; Choses notables et qui semblent digne de l'histoire, advenues aux premiers troubles et qui peuvent estre adjoustées aux discours qui en on esté escrits ; Histoire de Charles IX ; Le Tumulte de Bassigni... ; Discours de la famine de Sancerre. Mars 1573 ; Lettre... au roy, 27 septembre 1572 ; Des mines d'argent trouvées en France, ouvrage et police d'icelles... ; Ordonnances... sur la discipline militaire

Gross – to – Net Payroll Calculation Program Human Resources Information System (HRIS), 2000

Gross-to-Net is a payroll calculator modeled after the actual payroll calculation used for state employees’ paychecks. This calculator can be used to project changes in net pay when there are changes in pay amounts, hours worked, mandatory and voluntary deductions, including all pre-tax deductions such as retirement, insurances, deferred compensation or flexible spending plans. Federal and state tax withholding, retirement rates, OASDI and Medicare (FICA) are calculated using current rates.

Efficacy of brief motivational intervention at army conscription to address alcohol use and related problems: a randomized controlled trial

Objectives: The aim of this study was to evaluate the efficacy of brief motivational intervention (BMI) in reducing alcohol use and related problems among binge drinkers randomly selected from a census of 20 year-old French speaking Swiss men and to test the hypothesis that BMI contributes to maintain low-risk drinking among non-bingers. Methods: Randomized controlled trial comparing the impact of BMI on weekly alcohol use, frequency of binge drinking and occurrence of alcohol-related problems. Setting: Army recruitment center. Participants: A random sample of 622 men were asked to participate, 178 either refused, or missed appointment, or had to follow military assessment procedures instead, resulting in 418 men randomized into BMI or control conditions, 88.7% completing the 6-month follow-up assessment. Intervention: A single face-to-face BMI session exploring alcohol use and related problems in order to stimulate behaviour change perspective in a non-judgmental, empathic manner based on the principles of motivational interviewing (MI). Main outcome measures: Weekly alcohol use, binge drinking frequency and the occurrence of 12 alcohol-related consequences. Results: Among binge drinkers, we observed a 20% change in drinking induced by BMI, with a reduction in weekly drinking of 1.5 drink in the BMI group, compared to an increase of 0.8 drink per week in the control group (incidence rate ratio 0.8, 95% confidence interval 0,66 to 0,98, p = 0.03). BMI did not influence the frequency of binge drinking and the occurrence of 12 possible alcohol-related consequences. However, BMI induced a reduction in the alcohol use of participants who, after drinking over the past 12 months, experienced alcohol-related consequences, i.e., hangover (-20%), missed a class (-53%), got behind at school (-54%), argued with friends (-38%), engaged in unplanned sex (-45%) or did not use protection when having sex (-64%). BMI did not reduce weekly drinking in those who experienced the six other problems screened. Among non-bingers, BMI did not contribute to maintain low-risk drinking. Conclusions: At army conscription, BMI reduced alcohol use in binge drinkers, particularly in those who recently experienced alcohol-related adverse consequences. No preventive effect of BMI was observed among non-bingers. BMI is an interesting preventive option in young binge drinkers, particularly in countries with mandatory army recruitment.