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Background Children with perinatal arterial ischemic stroke (PAIS) are at risk for later neurocognitive and behavioral deficits, yet the clinical predictors of these outcomes are understudied. We examined the influence of clinical and infarct characteristics on attention and executive functioning in children following PAIS. Methods Forty children born at term (≥37 weeks' gestation) with PAIS (28 with neonatal arterial ischemic stroke and 12 with presumed PAIS) underwent a comprehensive neuropsychological battery at age three to 16 years (median age 7.2 years; 58% male) to assess attention and executive functioning. Parents also completed questionnaires regarding real-world functioning. Clinical variables including perinatal stroke subtype, infarct characteristics (location, laterality, and volume), and the presence of comorbid epilepsy were ascertained from the medical record. Results Presumed PAIS, larger infarct volume, and comorbid epilepsy negatively influenced the performance on attention and executive functioning measures. These clinical variables were also associated with greater functional problems on parent reports, including a higher frequency of attention-deficit/hyperactivity disorder symptoms and greater difficulties in some subdomains of executive functioning. Infarct location and laterality were not associated with performance measures or parental report of functioning. Conclusion Although all children with PAIS are at risk for later deficits in attention and executive functioning, those with presumed PAIS, larger infarct size, and comorbid epilepsy appear to be the most vulnerable. As they approach and reach school age, these children should undergo neuropsychological assessment to ensure timely implementation of therapeutic interventions and behavioral strategies.

Perinatal arterial ischemic stroke (PAIS) is a form of childhood stroke; the majority of those affected experience neurologic sequelae, including motor, language and neurocognitive impairments. This study examines the attention and executive functioning (EF) profiles of children following PAIS, as well as the impact of age and sex. In this single-center cross-sectional study, 40 children aged 3 to 16 years (median age 7.2 years; 58% male) who have suffered a PAIS underwent a comprehensive neuropsychological battery to assess attention and EF. Parents completed behavioral questionnaires regarding real-world functioning. Composite scores were calculated for seven attention and EF domains (Attention, Working Memory, Verbal Retrieval, Inhibitory Control, Flexibility/Shifting, Planning/Organization, and Processing Speed). The results for all measured domains of attention and EF are significantly lower in the participants compared to the normative samples (p .001), with the exception of Working Memory. However, increasing difficulty with Working Memory is associated with developing age. Older age at time of testing is also associated with a higher incidence of clinically-elevated attention deficit hyperactivity disorder (ADHD) symptoms. Sex is not associated with performance measures or parental report of functioning. The participants demonstrate mild-to-moderate attention and EF impairment compared to the normative population. Clinicians, families, and educators should be informed about the neurocognitive sequelae of PAIS and the need for close developmental surveillance in this population to identify vulnerable children and initiate appropriate therapeutic interventions in a timely fashion.

High pressure ratio, radial-inflow turbines typically experience supersonic expansion in the nozzle section. Accurate estimation of the flow conditions and velocity triangle at the nozzle outlet is of critical importance in correctly predicting the overall turbine performance. The meanline modeling of such a nozzle requires special attention, due to the significantly altered flow field downstream of the throat. In this study, the flow field of a supersonic expansion nozzle is investigated, using a three-dimensional (3D) computational fluid dynamics (CFD) simulation calibrated with test data. Three different CFD configurations are explored: the nozzle alone, the nozzle plus rotor coupled with a mixing plane, and the nozzle plus rotor coupled with the nonlinear harmonic (NLH) method. These configurations are compared to each other to gauge the effect of the rotor and stator interaction and the potential for error in establishing the velocity triangles. The exit vane angle, number of vanes, and expansion ratio across the nozzle are systematically varied to provide the data as the base for nozzle modeling. Finally, a meanline method is proposed to calculate the pressure loss and flow deviation at the nozzle outlet and is compared with CFD results.

Fixed-geometry centrifugal compressors have inherent limitations in the off-design operating range and performance that can be delivered. Variable inlet swirl, typically introduced with variable inlet guide vanes, has been a frequent tool implemented across many industries to extend the stable operating range and off-design efficiency. However, a review of available data in the literature reveals a large disparity in the effectiveness of variable inlet swirl for useful map movement. An ideal configuration responds to preswirl with a significant reduction in the mass flow at instability along with increased efficiency. Unfortunately, some cases reveal no movement in the surge line, with increases in inlet swirl only serving to reduce the stage efficiency. This study investigates underlying causes for the variation in sensitivity to inlet swirl amongst various compressor designs, represented by form parameters. An analytical model is established and then verified using CFD and selected test data to explore fundamental causes for decreased sensitivity to inlet swirl. Analytical and computational results suggest a new understanding of the governing parameters for inlet swirl sensitivity, and thus provide insight into the scenarios when inlet swirl is an effective tool for manipulation of performance characteristics. Synthesizing the underlying trends, guidelines are developed for design selections and operational situations when inlet swirl can be effectively implemented as a means to extend the stable operating range and off-design efficiency.

The design of centrifugal stages with an impeller and a downstream diffuser has generally been based on the assumption of axisymmetric flow at the impeller discharge. Flow entering the diffuser has customarily been assumed to also be axisymmetric, at least on a time-averaged basis, while laying out the diffuser vanes, establishing the preferred incidence, and sizing the throat areas. Recent stage studies have shown that the flow is often not fully axisymmetric, that not all diffuser passages perform the same way even at the design or best efficiency points, and that the actual time-averaged diffuser inlet flow conditions (distortion) may be changing from one operating point to another. In this study, comprehensive time-averaged (steady) results from one test rig with a large array of impeller exit pressure taps is examined. Supporting results from five other test rigs are reviewed to broaden the picture of possible flow states. Hypotheses, suitable for future evaluation, are given to begin the explanation of the actual flow states and to guide further research. The current status of CFD to understand these phenomena is discussed.

The current pilot study examined functional magnetic resonance imaging (fMRI) activation in children with mild traumatic brain injury (mTBI) during tasks of working memory and inhibitory control, both of which are vulnerable to impairment following mTBI. Thirteen children with symptomatic mTBI and a group of controls completed a version of the Tasks of Executive Control (TEC) during fMRI scanning. Both groups showed greater prefrontal activation in response to increased working memory load. Activation patterns did not differ between groups on the working memory aspects of the task, but children with mTBI showed greater activation in the posterior cerebellum with the addition of a demand for inhibitory control. Children with mTBI showed greater impairment on symptom report and “real world” measures of executive functioning, but not on traditional “paper and pencil” tasks. Likewise, cognitive testing did not correlate significantly with imaging results, whereas increased report of post-concussive symptoms were correlated with increased cerebellar activation. Overall, results provide some evidence for the utility of symptom report as an indicator of recovery and the hypothesis that children with mTBI may experience disrupted neural circuitry during recovery. Limitations of the study included a small sample size, wide age range, and lack of in-scanner accuracy data. (JINS, 2011, 17, 1143–1152)

Depuis les observations de Pickering et al., il a ete decrit un tableau particulier d’insuffisance cardiaque aigue revelant chez un sujet âge une stenose bilaterale des arteres renales, ou une stenose unilaterale sur rein fonctionnel unique. Ces œdemes aigus pulmonaires (OAP), souvent recidivants, contrastent avec une fonction cardiaque basale conservee. Les rapporter a leur cause permet un traitement endoluminal efficace.

In this paper, turbocharger centrifugal compressors with dual volute design were investigated by using Computational Fluid Dynamics (CFD) method. The numerical simulation focused on the air flow from compressor impeller inlet to volute exit, and the overall performance level and range are predicted. The numerical investigation revealed that the dual volute design could separate the compressor into two operating regions: “high efficiency” and “low efficiency” regions with different air flow characteristics, and treating these two regions separately with dual diffuser design showed extended stable operating range and improved efficiency by comparing with conventional single volute design. The “dual sequential volute” concept also showed the potential to further extend the stable operating range by closing one of the volutes at low air flow rates. Furthermore, by comparing with other alternate designs such as variable diffuser vanes and variable inlet guide vanes, the operation of the dual sequential volute also features relatively simple control and calibration.

In this study, the performance of a turbocharger compressor system for light-duty diesels, encompassing the airflow geometry from impeller inlet to volute exit, has been simulated numerically, and the effects of variable diffuser vane angles on the compressor performance and operating range have been investigated. It is found that the angle of the diffuser vane has significant influence on the compressor operating range, and optimized design of the variable diffuser vane angle can increase the stable operating range and improve the compressor efficiency significantly when compared with fixed diffuser vane angles and vaneless designs. However, changing the diffuser vane angle alone may not achieve the full control of the operating range of a compressor desired. Other technologies (e.g. variable inlet guide vanes, casing treatment, or optimum impeller design) may also be necessary to achieve the widest operating range required.

Sunitinib inhibits numerous tyrosine kinase receptors involved in tumor growth, angiogenesis, and metastatic invasion. It is indicated in case of metastatic renal carcinomas and gastrointestinal stromal tumors (GIST) resistant to imatinib. Prospective and retrospective studies have shown association between use of sunitinib and hypothyroidism affecting more than 50% of patients in some series. More amazing, was the non-visualisation of thyroid tissue evaluated with thyroid ultrasonography in two cases. Mechanisms of this side effect are not elucidated. Some studies have suggested destructive thyroiditis but no evidence of autoimmunity has been demonstrated. Anti angiogenic effect could be another hypothesis. Recently antithyroperoxidase activity of sunitinib has been demonstrated. Because hypothyroidism is easily accessible to treatment, screening of thyroid abnormalities is mandatory every three months to improve quality of life of these patients. This unique thyroid side effect of sunitinib with the non-visualisation of thyroid suggests a possible and promising antitumor activity in thyroid cancer.

Hypothalamic-pituitary (HP) sarcoidosis has 2 main endocrine manifestations: diabetes insipidus and hyperprolactinemia. We conducted the current study to investigate pituitary dysfunction and perform imaging of the HP area in patients both immediately following diagnosis and after treatment. The study included 6 men and 3 women, with a mean age of 30 years at the onset of sarcoidosis. All patients had both hormonal and magnetic resonance imaging (MRI) HP disorders. All patients had anterior pituitary dysfunction, 7 of them with associated diabetes insipidus. Nine patients had gonadotropin deficiency and 3 had hyperprolactinemia. MRI revealed infundibulum involvement in 5 patients, pituitary stalk thickness abnormality in 5, and involvement of the pituitary gland in 2, associated with other parenchymal brain or spinal cord lesions in 6 patients. All patients had multiple localizations of sarcoidosis, and 5 had histologically confirmed sinonasal localizations. Mean follow-up of the HP disorder was 7.5 years. All patients received prednisone. There was no correlation between the number of hormonal dysfunctions and the area of the HP axis involved as assessed by MRI. Although corticoid treatment was associated with a reduction of radiologic lesions, only 2 patients had partial recovery of hormonal deficiency. In conclusion, hormonal deficiencies associated with HP sarcoidosis frequently include hypogonadism (all patients) and to a lesser degree diabetes insipidus (7 of 9 patients). MRI abnormalities improved or disappeared in 7 cases under corticosteroid treatment, but most endocrine defects were irreversible despite regression of the granulomatous process. Most cases presented with multivisceral localizations and an abnormally high proportion of sinonasal localizations.

Moderate and severe traumatic brain injuries (TBI) have been known for some time to significantly impact daytime behavioral and adaptive functioning. In recent years, there also has been increasing appreciation of the nocturnal effects of TBI. Sleep problems in adults after a TBI can persist several years post-injury, and include nightmares and dyssomnias that can present as inadequate sleep or as excessive sleep propensity due to poor sleep quality (Bryant, Marosszeky, Crooks, & Gurka, 2000; Masel, Scheibel, Kimbark, & Kuna, 2001; Thaxton & Myers, 2002). As these authors have noted, the etiology of such sleep problems may include pain or discomfort, damage to neural circuits important in the sleep process, and emotional trauma. All of these potential contributors to sleep pathology can occur in childhood TBI, yet very little relevant research has been published. A few studies have identified vaguely defined sleep disturbances after childhood head trauma (Farmer, Singer, Melleits, Hall, & Charney, 1987; Hooper et al., 2004; Nakayama, Gardner, & Rogers, 1990; Pillar et al., 2003). However, sleep problems may follow a wide range of traumatic injuries, including orthopedic injuries (OI) (Kaufman et al., 2001). Moreover, no study has systematically examined sleep across more severe grades of pediatric TBI, despite neuropsychological and behavioral evidence of worse outcomes in the most severely injured children (Yeates et al., 2002, 2004). Finally, the time course of post-injury sleep problems is unknown, as group studies have rarely followed children for more than a few months post-injury. The lack of research on pediatric sleep following TBI is noteworthy in light of evidence of an interrelationship between sleep pathology and the daytime functioning of children and their families. Children who have undergone experimental sleep restriction or have naturally occurring dyssomnias have elevated rates of daytime behavioral disturbances (Blunden & Beebe, 2006). Sleep pathology in children also is a major source of parent and family stress (Mindell & Owens, 2003). Insofar as sleep pathology following pediatric TBI contributes to diminished motivation, caregiver distress, and cognitive and behavioral disturbances, it may pose a significant threat to rehabilitation efforts and functional recovery. In this brief report, we analyze parent-reported sleep data that were collected in the course of a larger prospective study of the neuropsychological and family impact of moderate or severe pediatric TBI. Based upon the adult literature, we hypothesized that children who sustained a TBI, especially a severe TBI, would be reported to display more post-injury sleep problems than children who sustained only OIs. This study also examined the time course of post-injury sleep concerns up to several years post-injury, although we did not have specific hypotheses with regard to change over time.

The evidence-based approach derived from the health care and medicine disciplines is the explicit and rational use of current best evidence in making decisions about the care of individuals and the population. At present, new technology may enter directly into the people care service without evaluation and without the evidence-based approach. Knowledge and evaluation bypasses will delay the time to market for a rapid and systematic routine use of innovations. Decision making about the purchase of equipment is more problematic when there is less evidence available or when this evidence is of poor quality, because there is no demonstration of efficacy and costeffectiveness before the introduction of new technology. Information and communication technology (ICT) solutions aim to improve health care providers, professional and informal carers, decision makers, and all stakeholders in the field of elderly care. Implementing knowledge and experiences from the medical research and health care fields, we propose some CoNTeNTS Introduction 88 Rationale for an Elderly-Centered ICT Evidence-Based Practice 89 The Concept of Ageing 89 Concept of the Person-Centered Approach 90 Elderly Ecosystem 91 Evidence-Based Practice 94 Appraisal of Evidence-Based Practice 94 Evidence-Based Approach 94 Tracking Down the Evidence: The Value of Information 95 Levels of Evidence 96 Example of Low Evidence: Do We Answer to Carers’ Unmet Needs? 96 Example of High Evidence: Preventing Falls 97 Evidence-Based Practice for AAL Solutions 98 Implementing Best Evidence Practices in AAL Solutions: Guidelines Needed 99 Elderly ICT Ecosystem: An Evidence-Based Approach Proposal for the Future 100 Conclusion 101 References 102 © 2015 by Taylor & Francis Group, LLC 88 Ambient Assisted Living recommendations for an evidence-based approach in gerontotechnology and ICT solutions. The final outcomes of any intervention in the elderly population would ensure well-being and good health and the improvement of quality of life by respecting the autonomy of a potentially frail and vulnerable population. Besides the technology development of ICT solutions, an evidencebased approach including a clinical research–like program would be necessary. Translational research using models from the health care and medicine disciplines will provide added value and also help to spread the use of cost-effective ICT solutions in the elderly. A call to action implementing evidence-based practice into ambient assisted living (AAL) organization and call procedures may be challenging. Let us hope that our desire to use it for the good of the person is stronger than the temptation to use it for our own convenience.

Although the need for rehabilitation services for cancer patients has been known for decades, many individuals with cancer still do not receive appropriate rehabilitation therapies during the course of their care. This has become particularly important for survivors of childhood cancer. As improvements have been made in treatment and mortality rates are decreasing, there are more survivors living with the long term or “late effects” of the cancer and its treatments. Late effects often impact the central nervous system and can impact skills such as mobility, activities of daily living, general physical activity, swallowing, speech production, and cognitive functioning. The focus of this chapter will be on introducing the need for rehabilitation services in this population, a review of some of the common issues that impact physical and speech-language functioning, and tips for when professionals may consider a referral for physical, occupational, or speech-language therapies.

International audience; Glutamic acid decarboxylase antibodies (GAD-abs) are an immunological factor involved in type 1 diabetes and other diseases involving the central nervous system. This report is of a patient with type 1 diabetes and a rare case of non-paraneoplastic limbic encephalitis mediated by anti-GAD65 antibodies that improved with the use of immunosuppressive drugs.

Aplasia cutis congenita (ACC) is alleged to be a side effect of antithyroid therapy during pregnancy. This occurrence is uncommon. Only 24 cases have been reported in the literature. In France, there has been no report by the National Center of Pharmacovigilance since 1985. We report a 39-year-old woman with no significant past history in whom Graves disease developed without eye symptoms. She was using methimazole 60 mg daily for 3 months, followed-up by propylthiouracil until delivery. At birth, the newborn had a scalp defect on the vertex, measuring 7- × 2-cm, transient hypothyroidism, and a dysmorphic syndrome (flat face, low-set ears, upper lip retraction, xiphoid funnel, finger-like claws, and low-set fifth finger). At age 1 year, the aplasia cutis was treated surgically. Aplasia cutis is a rare disorder, sometimes associated with other malformations. The mothers with hyperthyroidism who delivered children with reported cases of ACC have used either carbimazole or its active metabolite, methimazole, during early pregnancy. The relationship between methimazole or carbimazole therapy during pregnancy and ACC in the newborn remains to be proven. Nevertheless, to the authors’ knowledge, no case has occurred in which the mother has used only propylthiouracil. Therefore, consideration should be given to the exclusive use of propylthiouracil in pregnancy.

This study examined the effect of traumatic brain injury (TBI) in young children on sleep problems and the relationship of sleep problems to neuropsychological and psychosocial functioning. Participants were drawn from an ongoing longitudinal study of injury in young children recruited from 3 to 6 years of age. They constituted three groups: orthopedic injury (OI; n=92), complicated mild/moderate TBI (mTBI; n=55); and severe TBI (sTBI; n=20). Caregivers completed the Children's Sleep Habits Questionnaire (CSHQ), as well as ratings of behavioral adjustment, adaptive functioning, and everyday executive function at 1, 6, 12, and 18 months postinjury. Retrospective ratings of preinjury sleep and psychosocial functioning were obtained at the initial assessment. Children completed neuropsychological testing at all occasions. Children with complicated mTBI demonstrated more total sleep problems than children with OI at 6 months postinjury, but not at 12 or 18 months. Children with sTBI displayed more bedtime resistance and shorter sleep duration than those with complicated mTBI or OI at several occasions. Across groups, total sleep problems predicted more emotional and behavioral problems and worse everyday executive function as rated by parents across follow-up occasions. In contrast, sleep problems were generally not related to neuropsychological test performance. The results suggest that young children with TBI demonstrate more sleep problems than children with injuries not involving the head. Sleep problems, in turn, significantly increase the risk of poor psychosocial outcomes across time, but are not associated with worse neuropsychological test performance.

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria. We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19–70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14–24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy. In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm3 (range, 4–294); mean CD8: 236/mm3 (range, 1–1293); mean CD19: 113/mm3 (range, 3–547); and mean NK cell count: 122/mm3 (range, 5–416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count

International audience; Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria. We recruited 40 patients (24 female) of mean age 44.2 T 12.2 (19Y70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-F release by natural killer (NK) cell were performed. Mean follow-up was 6.9 T 6.7 (0.14Y24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy. In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm 3 (range, 4Y294); mean CD8: 236/mm 3 (range, 1Y1293); mean CD19: 113/mm 3 (range, 3Y547); and mean NK cell count: 122/mm 3 (range, 5Y416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count G150/mm 3 and NK cell count G100/mm 3 were predictors of death. In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.

BACKGROUND Medullary thyroid carcinoma is a rare tumour derived from the thyroid parafollicular calcitonin-secreting cells. Calcitonin is a very specific marker of this cancer that allows preoperative diagnosis. Serum calcitonin assay is particularly useful to define the postoperative state of patients (cured, apparently cured, not cured) and, because of its great sensitivity, it has a major place in the postoperative follow-up. OBJECTIVE To identify, among patients thyroidectomized for medullary thyroid carcinoma (MTC), the characteristics of authentic recurrent MTC [re-elevation of stimulated serum calcitonin (CT) level measured by a sensitive immunoradiometric assay, after postoperative normalization]. PATIENTS AND METHODS We first collected, through the national registry of the French Calcitonin Tumour Study Group (GETC), patients who had undergone a total thyroidectomy with or without lymph node surgery and who were not cured at the last follow-up visit. Among 453 such patients included in the database, 15 patients met the criteria for authentic recurrence as defined in previous studies: they had been first considered as cured during the 6 months following the initial surgical procedure (basal and pentagastrin-stimulated serum calcitonin level ≤ 10 ng/l) but had a secondary rerise of their pentagastrin-stimulated calcitonin level, over 10 ng/l. Eight of them even had an undetectable (

Le syndrome de Lymphopenie CD4+ Idiopathique (LCI) se definit par une depletion stable des lymphocytes T CD4+ en l’absence de cause connue de deficit immunitaire. Il s’agit d’un syndrome rare chez l’adulte. Des deficits de proliferation aux mitogenes T ont ete decrits chez certains de ces patients qui presentaient en outre des signes cliniques d’infection opportuniste. Nous avons emis l’hypothese que des anomalies d’activation des lymphocytes T pourraient expliquer a la fois la depletion CD4+ et le deficit immunitaire. Nous avons donc analyse, chez trois de ces patients, les evenements biochimiques de la voie de signalisation CD3-TCR. Le patient 1 presentait une lymphopenie globale CD4+ et CD8+, alors que les patients 2 et 3 avaient une lymphopenie CD4+ selective. Nous avons observe, chez tous les patients, un deficit proliferatif affectant uniquement la sous-population lymphocytaire T qui apparaissait depletee. De plus, nous avons mis en evidence chez les patients 1 et 3 un defaut d’induction (d’intensite variable) des tyrosine phosphorylations proteiques dans les lymphocytes T CD4+, suggerant un deficit d’activation des tyrosine kinases, alors que les cellules T du patient 2 repondent normalement a la stimulation du CD3-TCR. Au total, ce travail demontre que l’heterogeneite du syndrome de LCI se situe au niveau intracellulaire, et implique, dans deux des cas etudies, des anomalies de proteines de la voie de signalisation CD3-TCR.

During recent decades, undeniable progress has been made with regard to the management of arterial hypertension. Larger numbers of patients are aware they have hypertension, receive treatment and benefit from this therapy. Furthermore, significant reductions have been observed in morbidity and mortality resulting from cardiovascular diseases. The objectives of hypertension treatment have been formulated on the basis of results of extensive epidemiological studies. Only a few patients receiving monotherapy actually achieve and maintain acceptable blood pressure levels. The complex pathogenesis of essential hypertension, the implications of nervous and humoral counter-regulatory effects, the heterogeneous character of individual responses to any given class of antihypertensive treatment and the onset of adverse effects all account for these failures. The search for a simple, effective and well-tolerated treatment based on a low dose combination of 2 classes of antihypertensive agents is consequently legitimate. The fixed combination of atenolol 50 mg and sustained release nifedipine 20 mg enables patients to benefit from the antihypertensive synergy of a beta-blocker and a calcium antagonist (dihydropyridine). Several open-ended or double-blind, controlled studies have shown that this combination produces a more marked antihypertensive effect than the individual components used alone or other reference monotherapies. Furthermore, it has been shown that this effect persists throughout the entire 24-hour period; this has been confirmed by 24-hour blood pressure monitoring. Short and medium term tolerability is significantly improved: the side effects commonly associated with the 2 drugs when used alone are reduced with the combination formulation since the 2 active substances have different and complementary mechanisms of action. In addition, long term studies have shown that therapeutic efficacy and tolerability remain stable and have even been seen to improve over a 12-month period. The fixed combination of atenolol-nifedipine has a role in strategies for the treatment of mild to moderate hypertension, particularly under the following conditions: when first-line monotherapy has failed to attain specific clearly defined objectives, including stabilised blood pressure levels together with acceptable tolerability. when patient compliance is jeopardised as a result of undesirable side effects. when the vascular burden is aggravated through lack of attention to individual risk factors in hypertensive patients. In more serious forms of hypertension, the atenolol-nifedipine combination can replace sequential monotherapies or other combination treatments that have failed to comply with the various criteria of therapeutic efficacy. Controlling arterial hypertension commonly requires polytherapy with 3 or even 4 different drugs in conjunction with particularly strict rules governing hygiene and diet. The addition of the fixed combination of atenolol-nifedipine simplifies the treatment of patients with arterial hypertension by limiting the daily doses and reducing laboratory monitoring.

Placenta accreta is recognized as a catastrophic disease in obstetrics. Diagnosed incidentally, it has been a rare disease in previous decades prior indiscriminate use of cesarean delivery. The World Health Organization has recently highlighted this disease as a new pandemic, which is directly related to patients who have two or more caesarean sections. Our country keeps high rates of caesarean section and therefore this problem will be increasing in diagnosis. It is necessary that medical units made ad hoc clinical guidelines, for prompt intervention in these cases. Early diagnosis should be given priority in women with these risk characteristics. With the advent of high-resolution sonography, specific images have been identified supporting the diagnosis during pregnancy; likewise, multidisciplinary treatments are especially of interest. The interventional radiology offers treatments semiconservative that have proven to reduce morbidity and mortality.

Influenza A H1N1 is an acute respiratory illness caused by a new strain of H1N1. Human influenza is a subtype of influenza Avirus, from the family of Orthomyxoviridae. This strain is the cause of new influenza pandemic declared by the World Health Organization in June, 2009. This paper reports the first case occurred in Mexico: a 39-year-old woman with a history of diabetes mellitus type 2 and obesity grade II, which suffered atypical and aggressive pneumonia positive to coronavirus. Patient died 98 hours after her admission to the hospital unit. Due to the clinical presentation of the case, the doctors sent samples to the Instituto Nacional de Diagnóstico y Referencia Epidemiológica that sent an aliquot of the National Center for Immunization and Respiratory Diseases of theAgency of Public Health in Canada, that reported positivity to influenza virus, and catalogued it as a new global strain called influenza A virus H1N1. The notice of 229E/NL63 coronavirus and its relationship to the recent outbreaks of avian influenza in humans and the clinical presentation of the case were the epidemiological circumstances that prevented the nation epidemiology system to establish global containment strategies to prevent the spread of this emerging infection. The consequence was the declaration of WHO pandemic alert level 6. Its behavior in pregnancy, reported by Assistant General Direction of Epidemiology in Mexico, has placed this infection as a risk factor for women.

International audience; OBJECTIVES: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.

Urea cycle disorders (UCD) are rare inborn errors of metabolism which result from mutations in the genes encoding for one of six enzymes or two transporters necessary for normal function of the urea cycle and are characterized by hyperammonemia and life-threatening hyperammonemic crises1,2. Hyperammonemia-related neurologic injury ranges from lethal cerebral edema to mild or subclinical cognitive impairment among individuals with milder genetic defects3. Abnormalities in executive function, manifested by difficulty in goal setting, planning, monitoring progress and purposeful problem solving significantly impair day-to-day function among children with UCDs, even those with milder disease who present beyond the neonatal period4. Management of UCD patients typically involves dietary protein restriction, dietary supplements and, when dietary management alone is insufficient, sodium phenylbutyrate (NaPBA), which is the only approved drug (Ucyclyd Pharma, US trade name: BUPHENYL®, EU: AMMONAPS®) for treatment of UCDs2,5. Glycerol phenylbutyrate is an investigational agent being developed for UCDs 6,7,8. Like NaPBA, it contains phenylbutyric acid (PBA), a pro-drug that is converted via β-oxidation to the active moiety, phenylacetic acid (PAA), which conjugates with glutamine to form phenylacetylglutamine (PAGN). PAGN is excreted in the urine and mediates waste nitrogen excretion. Unlike NaPBA, glycerol phenylbutyrate consists of three molecules of PBA joined to glycerol in ester linkage that is hydrolyzed in the small intestine by pancreatic lipases to release PBA, contains no sodium, has minimal taste and no odor, and 17.4 mL contains the same amount of PBA as 40 tablets of NaPBA, the maximal approved daily dose 6,7,8. The development of glycerol phenylbutyrate for UCD, rare disorders with fewer than 500 patients in the US currently estimated to be treated with NaPBA, has involved a cooperative effort among investigators of the NIH-funded UCD Consortium, the National Urea Cycle Disorders Foundation and Hyperion Therapeutics 2,9,10. This report describes the results of the pivotal phase 3 study of glycerol phenylbutyrate for UCD, as well as short and long-term ammonia control and neurocognitive outcomes among a total of 91 UCD patients participating in four clinical trials.

This study assessed the effect of a fixed combination of nifedipine sustained release (SR) 20 mg + atenolol 50 mg on the blood pressure values of partial responders to treatment with a calcium channel blocker. Sixty hypertensive patients who had a diastolic blood pressure (DBP) >90 mm Hg throughout a period of monotherapy with a calcium channel blocker were included in the trial. After a 2-week run-in period with nifedipine SR 20 mg twice daily, 53 patients were randomly assigned to receive either the fixed combination nifedipine SR 20 mg + atenolol 50 mg once daily or nifedipine SR 20 mg twice daily. Mean systolic blood pressure was significantly lower (148 ± 13 mm Hg vs 156 ± 14 mm Hg) at 12 hours postdose in the combination group than in the nifedipine-only group. Responder patients (DBP

The requirements for higher fuel economy and better diesel and gasoline engines demand a wider range in turbocharger compressor operation. Ported shroud compressor housing is one of the most commonly used techniques for compressor map width enhancement. Although the general mechanism of such a flow feature is well understood, there are no readily available design tools to guide the engineers at the preliminary design stage. Designers have had to rely on three-dimensional (3D) CFD tools to sort out many design variables, but these tools can be prohibitively expensive. This paper explains how to develop a ported shroud compressor model on top of a commercial meanline compressor design program. The model considers some basic parameters, such as bleed location and geometry, which drive the recirculation or bypass flow through the bleed channel. The effects of the secondary flow on the compressor performance, such as pressure rise, efficiency, and stall and choke margins are also analyzed. The model prediction is validated with CFD simulation and test data.

Human immunodeficiency virus (HIV) infection and protease inhibitor (PI)-based antiretroviral treatment might increase large artery (aortic) stiffness compared with healthy untreated controls. To clarify the role of PI therapy in the progression of subclinical arteriosclerosis in patients with HIV, we investigated the impact of PI treatment on arterial stiffness.In our single-centre, cross-sectional study, normotensive male HIV patients free from overt cardiovascular disease received PI treatment (n=60) or no PI treatment (n=42). The PI group had a significantly higher pulse wave velocity (PWV) than the PI-free group (9.0 ± 1.4 vs. 8.1 ± 1.3m/s; P=0.016). There was a significant positive correlation between age and PWV in the PI-free group (R(2) 0.310; P0.0001) and, to a lesser extent, in the PI group (R(2) 0.181; P0.0001). PI treatment was associated with a significant increase in the adjusted slope of the curve relating age to PWV as compared with no PI treatment.In normotensive HIV patients, PI treatment significantly increases both aortic stiffness and the positive correlation between PWV and age. Aortic stiffness predicts cardiovascular mortality, thus these results provide new insight on the relationship between PI treatment, mechanical arteriosclerotic and cardiovascular risk.

The polymerase chain reaction (PCR) was used to detect hepatitis D (HD) viremia in patients infected with the human immunodeficiency virus (HIV). Nineteen (9%) of 206 such patients, unselected for liver disease or HBV infection, were found prospectively to be infected by HDV. Thirty-one anti-HIV-positive patients were studied by means of PCR, and the results were analyzed according to HDV and hepatitis B virus (HBV) serological status. HDV-PCR was positive in 5 patients. Two had detectable serum HDV antigen. Four patients had anti-HD IgM and IgG antibodies. All these patients were HBs antigen-positive, and 3 were HBV-DNA-positive. All the other patients were HDV-PCR-negative. Statistical analysis suggested more extensive liver damage and immunological impairment in HDV-PCR-positive patients. In this unselected HIV-infected population, HDV-RNA detection by PCR was restricted to HDV infected patients in whom 5/19 were positive. This test permitted direct diagnosis of HDV viremia and will be useful for monitoring HDV infection.

The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism workshop was designed to address challenges in translating potential therapies for these rare disorders, and to highlight novel therapeutic strategies and innovative approaches to CNS delivery, assessment of effects and directions for the future in the treatment of these diseases. Therapies for the brain in inborn errors represent some of the greatest challenges to translational research due to the special properties of the brain, and of inborn errors themselves. This review covers the proceedings of this workshop as submitted by participants. Scientific, ethical and regulatory issues are discussed, along with ways to measure outcomes and the conduct of clinical trials. Participants included regulatory and funding agencies, clinicians, scientists, industry and advocacy groups.

The Urea Cycle Disorders Consortium (UCDC) was created as part of a larger network established by the National Institutes of Health to study rare diseases. This paper reviews the UCDC’s accomplishments over the first six years, including how the Consortium was developed and organized, clinical research studies initiated, and the importance of creating partnerships with patient advocacy groups, philanthropic foundations and biotech and pharmaceutical companies.