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This paper presents a new algorithm to classify convective clouds and determine their intensity, based on cloud physical properties retrieved from the Spinning Enhanced Visible and Infrared Imager (SEVIRI). The convective rainfall events at 15 min, 4 × 5 km spatial resolution from 2006 to 2012 are analysed over northern Algeria. The convective rain classification methodology makes use of the relationship between cloud spectral characteristics and cloud physical properties such as cloud water path (CWP), cloud phase (CP) and cloud top height (CTH). For this classification, a statistical method based on ‘naive Bayes classifier’ is applied. This is a simple probabilistic classifier based on applying ‘Bayes’ theorem with strong (naive) independent assumptions. For a 9-month period, the ability of SEVIRI to classify the rainfall intensity in the convective clouds is evaluated using weather radar over the northern Algeria. The results indicate an encouraging performance of the new algorithm for intensity differentiation of convective clouds using SEVIRI data.

The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and USA and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies. A single intravenous dose of the glutamatergic modulator ketamine produces a robust and rapid antidepressant effect in persons with TRD; this effect continues to remain significant for 1 week. This observation was a turning point that opened the way for other, more selective glutamatergic modulators (intranasal esketamine, AVP-786, AVP-923, AV-101, and rapastinel). Of the remaining compounds, monoclonal antibodies open highly innovative therapeutic options, based on new pathophysiological approaches to depression. Expert commentary: Promising new agents are emerging for TRD treatment. Glutamatergic modulators likely represent a very promising alternative to monoaminergic antidepressant monotherapy. We could see the arrival of the first robust and rapid acting antidepressant drug in the near future, which would strongly facilitate the ultimate goal of recovery in persons with TRD.

In this review, the authors describe medications in phase III of clinical development for schizophrenia and schizoaffective disorder, and provide an opinion on how current treatment can be improved in the near future.Recent (post 2013) phase III clinical trials of schizophrenia-targeted therapies were found in US and EU clinical trial registries. Two hundred fifty-three trials were identified, that included 16 investigational compounds. The antipsychotics brexpiprazole and cariprazine have been approved in the US, and although both are dopamine D2 receptor partial agonists, they differ markedly in their pharmacodynamic profiles. Encenicline and valbenazine are first-in-class candidates for treatment of cognitive impairment associated with schizophrenia (CIAS) and tardive dyskinesia, respectively. Eleven add-on compounds were previously approved for other therapeutic indications and are for the most part being studied at academic medical centers and smaller pharmaceutical companies for negative symptoms and CIAS or for specific populations (comorbidities, antipsychotic-induced obesity).Promising new agents are emerging for schizophrenia and schizoaffective disorder. In addition to better-tolerated antipsychotics that treat positive symptoms, we could see the arrival of the first effective drug for negative symptoms and CIAS, which would strongly facilitate the ultimate goal of recovery in persons with schizophrenia.

For the last 30 years, drugs targeting serotonin receptors (5-HTR) have been intensively investigated in schizophrenia. New drugs targeting 5-HTRs are under development in patients with schizophrenia.In this review, the authors describe the recent clinical trials for schizophrenia with selective serotonergic agents and provide an opinion on how the investigated drugs can help to fulfil current treatment needs. Clinical trials were found in US and EU clinical trial registries and in the medical literature. Relevant 5-HTR antagonists active in animal models of schizophrenia were also analysed.Antipsychotics reduce positive symptoms of schizophrenia (delusions, hallucinations and disordered thought), but have undesirable side effects. Moreover, satisfactory treatment of negative symptoms (apathy, poverty of speech, lack of interest in social interactions) and cognitive dysfunction is currently not available. The selective 5-HT2CR full agonist vabicaserin showed antipsychotic efficacy with fewer side effects than olanzapine. Adjunctive pimavanserin (a selective 5-HT2AR inverse agonist) facilitated antipsychotic dose and side-effect reductions. Selective 5-HT3R antagonists (ondansetron, tropisetron and granisetron) showed positive results on negative symptoms and/or cognitive impairments in phase II trials. Adjunctive ondansetron has now entered a phase III trial for such indications. Finally, 5-HTA5R and 5-HT7R antagonists have shown procognitive actions in animal models of schizophrenia. These novel serotonergic drugs seem promising for improving the current treatment of schizophrenia.

Resume Informer les patients schizophrenes sur leur maladie est suppose ameliorer l’observance medicamenteuse et ainsi diminuer le nombre de rechutes. Toutefois, cette hypothese repose plus sur des elements subjectifs que sur des donnees issues d’essais cliniques methodologiquement adaptes et portant notamment sur l’evaluation et le suivi au long cours des patients soumis a de tels programmes psychoeducatifs comparativement a des patients n’en beneficiant pas. Une etude clinique francaise de phase IV – multicentrique, ouverte, comparative, randomisee – a ete donc destinee a evaluer l’impact d’un programme psychoeducatif (Soleduc ® ) sur le taux de rechutes (nouvelle hospitalisation) a deux ans chez les patients atteints de schizophrenie traites par l’amisulpride, compare a celui du groupe temoin prenant le meme traitement antipsychotique et beneficiant des informations habituelles concernant leur maladie pendant une duree equivalente au programme psychoeducatif. Deux cent vingt patients schizophrenes ont ete recrutes par 51 centres investigateurs. Une reduction significative des risques de rechute a ete observee dans le groupe Soleduc ® lorsque le nombre de seances de formation psychoeducatif etait superieur a cinq. Les mesures educationnelles sont peu couteuses et peuvent etre combinees avec d’autres types d’interventions therapeutiques. L’etude Soleduc ® confirme donc les recommandations de l’American Psychiatric Association, etablissant clairement que la psychoeducation du patient doit faire partie de l’arsenal therapeutique de la schizophrenie.

Bone scintigraphy still is a first line examination to assess bone extension from urological cancers. Technological progress of note has been the arrival of gamma cameras associated with computed tomography with fusion imaging which increases the scintigraphy performance. Nevertheless, bone scintigraphy indications have decreased particularly for the initial assessment of prostate cancer over many years.

Introduction: Despite numerous explanatory hypotheses, few studies have involved a large national clinical sample examining risk factors in the occurrence of rapid cycling during the course of bipolar illness.Methods: From 1,090 manic bipolar I disorder inpatients included in a multicenter national study in France, 958 could be classified as rapid or non-rapid cyclers and assessed for demographic, illness course, clinical, psychometric, temperament, comorbidity, and treatment characteristics.Results: Rapid cycling bipolar disorder occurred in 9% (n=86) of the study group. Compared to nonrapid cyclers (n=872), patients with rapid cycling experienced the onset of their illness at a younger age, a higher number of prior episodes, more depression during the first episode, and more suicide attempts. At study entry, they also experienced manic episodes with more depressive and anxious symptoms, but less psychotic features. The following independent variables were associated with rapid cycling: longer duration of illness, antidepressant treatment, episodes with no free intervals, cyclothymic temperament, lower scores on the Scale for Assessment of Positive Symptoms and presence of thyroid disorder. Retrospective study limited to bipolar I disorder inpatients; several factors previously associated with rapid cycling were not assessed.Conclusion: Our findings may confirm previous descriptions, according to which rapid-cycling develops later in the course of illness following a sensitization process triggered by antidepressant use or thyroid dysfunction, in patients with a depression-mania-free interval course, and cyclothymic temperament.

The antipsychotic and anxiolytic phenothiazine, cyamemazine, was investigated for its effects on the hERG (human ether-à-go-go related gene) channel expressed in HEK 293 cells and on native INa, ICa, Ito, Isus, or IK1 of human atrial myocytes. Moreover, cyamemazine and terfenadine were compared for their effects on the QT interval in anesthetized guinea pigs. Cyamemazine reduced hERG current amplitude with an IC50 value of 470 nM. Cyamemazine 1 microM failed to significantly affect INa, Ito, Isus, or IK1 amplitudes and slightly decreased ICa (18%). For comparison, haloperidol (30 nM) and olanzapine (300 nM) reduced hERG current amplitude by 44.2+/-3.9% and 49.7+/-4.2%, respectively. The cardiac safety ratio of cyamemazine, calculated from the IC50/receptor affinity ratios, is 81 and 313 against dopamine D2 receptors and 5-HT2A receptors, respectively. In guinea pigs, QT and QTcBazett were not significantly modified by intravenous cyamemazine when compared to the effects produced by the vehicle. Conversely, terfenadine (5 mg/kg iv) increased significantly QTcBazett (+58 ms), QTcFrediricia (+83 ms) and QTcVan de Water (+78 ms). In conclusion, cyamemazine concentrations required to inhibit hERG current exceed substantially those necessary to achieve therapeutic activity in humans. Moreover, cyamemazine, in contrast to terfenadine, does not delay cardiac repolarization in the anesthetized guinea pig. These non-clinical findings confirm the excellent cardiac safety records of cyamemazine during its 30 years of extensive therapeutic use.

Because of a high prevalence of Pseudomonas aeruginosa infections, we conducted an epidemiological study to assess the need for systematic surveillance, as well as the value of applying barrier precautions toP. aeruginosa carriers. From July 1997 to February 1998, we conducted a prospective cohort study in an 18-bed medical intensive care unit (ICU), which is part of the infectious diseases department in a 1200-bed tertiary-care teaching hospital. Rectal and oropharyngeal swabs were obtained on admission and twice weekly. Acquired strains were genotypically characterized by pulsed-field gel electrophoresis (PFGE). A risk factor analysis for carriage, colonization and infection was performed. Among 269 eligible patients, 116 (43%) were P. aeruginosa carriers, with 46 (17%) detected on admission and 70 (26%) who acquired carriage during their stay in ICU. Among these 70 patients, 29 became colonized (N=13) or developed infection (N=16). Conversely, in the 121 patients who remained free of carriage, no colonization or infection were detected. Genotyping analysis using PFGE was performed for 81/85 (95%) acquired strains in 67 patients. The same genotype I was observed for 58/81 (70%) of these strains issued from 47 patients, and a distinct genotype II affected two other patients (three strains). The last 20 strains were not genetically related. In a multivariate model, mechanical ventilation was associated with the acquisition of P. aeruginosa carriage. Antibiotics ineffective against P. aeruginosa significantly increased the risk of colonization or infection in ICU. Although several recent studies concluded that endogenous sources account for the majority of P. aeruginosa colonizations or infections, we conclude that epidemiology may vary according to the ICU, and that cross-colonization (i.e., exogenous source) may occur and warrant reinforced barrier precautions.

Anxiety is a frequent symptom of schizophrenia, which is highly associated with an increased risk of relapse and suicide. The effect of antipsychotics on this clinical dimension is not specific and the common practice of prescribing benzodiazepines remains unsatisfactory.The authors review recent well-designed clinical trials for anxiety in patients with schizophrenia. The content includes information derived from trial databases, regulatory authorities and scientific literature.Anxiety in schizophrenia has severe consequences and specific clinical features, which require a specific therapy, beyond benzodiazepines. In these past 2 years, two compounds (the anticonvulsant/anxiolytic pregabalin and the atypical antipsychotic quetiapine) were on Phase III/IV clinical trials for schizophrenia, with comorbid anxiety as a primary outcome measure. Potential for success is high, given their strong rationale and the clinical experience with both drugs. Anxiety (as a symptom) was a secondary outcome measure in trials for schizophrenia involving seven other compounds (lurasidone, amisulpride, bitopertin, oxytocin, famotidine, cannabidiol and the L-theanine and pregnenolone combination). Primary completion date is expected in the next 2 years. In spite of ancient positive results and a strong rationale, aripiprazole and related compounds were not in recent clinical trials. The authors believe that these compounds deserve more attention.

International audience; Bipolar disorder (BD) is one of the world's ten most disabling conditions. More options are urgently needed for treating bipolar depressive episodes and for safer, more tolerable long-term maintenance treatment. We reviewed 30 recent clinical trials in depressive episodes (eight tested compounds) and 14 clinical trials in maintenance treatment (ten tested compounds). Positive results in Phase III trials, regulatory approval and/or new therapeutic indications were obtained with some of the developing drugs, particularly for depressive episodes. The current BD pipeline is encouraging with promising new compounds, acting on novel pharmacological targets and on specific aspects of bipolar depression.

SummaryAs specific assays used to identify defects in the protein C (PC) anticoagulant pathway are laborious and expensive, we describe here a global test to screen for these defects. This assay is expressed as the ratio of two activated partial thomboplastin times, one in the absence and one in the presence of 0,125 U/ml of the PC activator of Agkistrodon contortrix venom (ACV). Eight of the 168 healthy volunteers of the control group exhibited an ACV ratio below the lower normal limit of 3.37 [6 subjects with the mutation Arg 506 to Gin in their factor V gene (FV R506Q) and one with PS deficiency]. 128 patients who have had at least one episode of deep-vein thrombosis were retrospectively studied. All patients carrying FV Q506R (n = 48), PC deficiency (n = 14) or combined defects, i. e. FV Q506R and PC deficiency (n = 4) or FV Q506R and PS deficiency (n = 3), had ACV ratios < 3.37. PS deficient plasmas (n = 20) exhibited ACV ratios which overlapped normal range. ACV ratios of one out of seven patients with antithrombin deficiency, and 10% of patients without identified defect in the PC anticoagulant pathway (n = 30) were < 3.37. An ACV ratio raised to 3.70 could lead to a test identifying all patients with a defect in the PC anticoagulant pathway.

Objectives/Hypothesis To evaluate the efficacy, tolerance, and outcomes of covered stents in the treatment of carotid blowout syndrome (CBS) in head and neck cancer patients. Study Design Individual retrospective cohort study. Methods We retrospectively reviewed the medical and image files of all 20 consecutive head and neck cancer patients treated with covered stent grafts for CBS. Six acute, 12 impending, and two threatened cases of CBS were treated in patients who all had previously received radiation therapy. We evaluated the feasibility, hemostatic efficacy, survival without bleeding, and complications. Results The etiologies of CBS were as follows: group 1, 13 carotid axis (common or internal carotid artery) pseudoaneurysms and one rupture; group 2, six patients with no identifiable source of bleeding on angiography but with a threatened carotid axis on computed tomography (CT). In all patients, a polytetrafluoroethylene-covered nitinol stent graft (Fluency; Bard/Angiomed GmbH & Co, Karlsruhe, Germany) was successfully placed. All of the stents were patent at the end of the procedure. Immediate hemostasis was achieved in the six hemorrhagic cases. Immediate transient ischemic attacks were observed in two patients, and carotid sinus syndrome was observed in one patient. Post-treatment bleeding was observed in five patients in group 2 and no patients in group 1. Survival without bleeding was 251 days in group 1 and 35 days in group 2. During follow-up, three asymptomatic stent thromboses occurred at a mean of 58 days. Conclusions Covered stent placement is highly feasible and proved effective without major complications in CBS due to carotid axis bleeding. Level of Evidence 4. Laryngoscope, 2013

We present the case of a 62-year-old man with colorectal carcinoma with unusual segmental myocardial 18 F-FDG uptake. PET/CT scan was requested for evaluating response to chemotherapy before surgery. Bull’ se ye, short axis (SA) and vertical long axis (VLA) slices of 18 F-FDG showed an inferior segmental FDG hypermetabolism with no significant uptake in other myocardial wall. A rest tetrofosmin myocardial scintigraphy showed inferior myocardial hypoperfusion mismatch congruent with the segmental FDG uptake. Coronary angiography demonstrated a very narrow proximal right coronary artery stenosis treated with percutaneous angioplasty.

We present the case of a 47-year-old man with a previous history of testicular seminoma in 1995 and lymph node metastases in 1997. He had suffered from chronic renal failure since 1998, with severe secondary hyperparathyroidism. Because of an increased βhCG (human chorionic gonadotropin beta-subunit) at 0.4 U/l, an F-FDG PET/CT scan was requested before kidney transplantation. Maximum intensity projection PET images (A) showed multiple areas of increased uptake involving the vertebral plates (which formed a ‘ladder’ pattern), both clavicles, the shoulders and hip joints, the femora and pelvis cortical bone, and a small focus in the right scapula, corresponding to an osteolysis (B, C). Because this bone uptake distribution, especially in the spine, is very close to the ‘rugger jersey spine’ observed on radiographs in patients with hyperparathyroidism [1], this diagnosis was suggested, and the right scapula focus considered as a brown tumour. Eight months after kidney transplantation, the hyperparathyroidism subsided, PET/CT scan displayed no abnormal bony uptake (D, F), the scapula lesion had ossified (E) and the βhCG had returned to normal. Bony FDG uptake in hyperparathyroidism may mimic bone metastases [2]. But, in our patient, the unusual pattern, similar to the radiographic findings in hyperparathyroidism, strongly suggested hyperparathyroidism rather than metastases, which was confirmed by the normalization

International audience; Riluzole has been reported to protect against the deleterious effect of cerebral ischemia by blocking glutamatergic neurotransmission. Here, we investigated whether acoustic trauma-induced cochlear excitotoxicity could be attenuated by riluzole. Cumulative intracochlear perfusion of riluzole completely abolished single-nerve fiber activity in the guinea pig cochlea and the compound action potential of the auditory nerve. Guinea pigs treated with riluzole (100 microM) showed significantly less hearing threshold shift than untreated guinea pigs, and presented no sign of dendritic damage in the cochlea observable by electron microscopy. When coapplied with glutamate, riluzole did not prevent glutamate-induced swelling of auditory nerve dendrites, suggesting that the protective effect of riluzole was mediated principally by inhibition of glutamate release from sensory inner hair cells.

A new scheme for the delineation of raining and non-raining cloud areas applicable to mid-latitudes from daytime and nighttime multispectral satellite data is developed. The technique is based on optical and microphysical cloud properties using an artificial neural network. The tests have been conducted during the rainy season of 2006/2007. The proposed algorithm uses the spectral parameters of SEVIRI (Spinning Enhanced Visible and Infrared): brightness temperature TIR10.8 and brightness temperature differences ΔTIR10.8–IR12.1, ΔTIR8.7–IR10.8, ΔTIR3.9–IR10.8 and ΔTIR3.9–WV7.3 during the nighttime and reflectances RVIS0.6, RNIR1.6, brightness temperature TIR10.8, brightness temperature difference ΔTIR8.7–IR10.8 and ΔTIR10.8–IR12.0 during the daytime. The algorithm is calibrated by instantaneous meteorological radar using multilayer perceptron. Radar provided the ‘‘ground precipitation truth’’ for training and validation. The application shows interesting and encouraging results.