Search

Next-generation sequencing (NGS) of tumor biopsies of both solid tumors, as well as hematological malignancies, using commercially available platforms has broadly entered routine clinical practice in medical oncology. This molecular diagnostic approach is now used mainly to test for predictive biomarkers for patients with no available further standard therapies, as diagnostics rely on genomic testing of molecular alterations to enable effective cancer treatment. However, the high cost of large multigenic panels and especially the sequencing of the entire tumor exome is a concern, especially in a developing country such as Brazil. Here we report the clinical application of a panel of 57 genes that we call ONCOTARGET (ONCOALVO) which is based on the Thermo Fisher Oncomine Focus Assay, an integrated, commercially available NGS assay for the rapid and simultaneous detection of single nucleotide variants, short insertions and deletions, copy number variations, and gene rearrangements in 52 cancer genes with therapeutic relevance, but with 5 additional genes: the homologous recombination repair (HRR) genes BRCA1, BRCA2, ATM and CHEK2 that determine tumor sensitivity to inhibitors of the PARP enzyme and also KDR, which determines sensitivity to regorafenib. Twenty-five diagnostic samples of formalin-fixed, paraffin-embedded material submitted for molecular testing over a 8-month time period were analyzed so far. All patients had advanced solid tumors already refractory to conventional systemic therapy. Libraries were prepared from isolated nucleic acids and sequenced on the Ion Torrent S5 sequencer. Sequencing datasets were analyzed using the Ion Reporter software. From the samples of the 39 patients tested, we found 30 potential therapy target pathogenic gene aberrations in 22 (56.4%) patients: KRAS - 7 (23.3%), BRCA1 - 6 (20%), BRCA2 - 5 (16.6%), PIK3CA - 3 (10%), MAP2K1 - 2 (6.6%), BRAF-V600E - 2 (6.6%) mutations; and also one of each: ERBB2 (3.3%), mTOR (3.3%), KIT (3.3%), ALK (3.3%) mutations and one (3,3%) CCND1 amplification. In 3 (7,69%) patients there were double mutations: BRCA1 and BRCA2 in 2 cases and BRCA2 and KRAS and one case. The Oncotarget workflow enabled a turnaround of 18 frac12 days. Taken together, ONCOTARGET was found to be a convenient tool for fast, reliable, broadly applicable and cost-effective targeted NGS of tumor samples in routine diagnostics and therapeutic decisions with a potential to become an important assay for precision oncology in Brazil. Citation Format: Andre M. Murad, Jose Claudio Casali-da-Rocha, Juliana G. Carneiro, Ana L. Godard. ONCOTARGET (ONCOALVO): A custom NGS panel for therapeutic decision in solid tumors refractory to conventional therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3991.

Purpose To study the value and efficacy of botulinum toxin for treatment of cases of non-neurogenic detrusor overactivity (NNDO) that are refractory to anticholinergic drugs. Materials and methods A systematic review of the literature, based on a keyword search of the Medline database. Selection of articles in French and English (meta-analyses, reviews, case studies and randomized, controlled clinical trials) on intradetrusor botulinum toxin injection in the management of refractory NNDO. Results Nineteen publications (including three randomized, controlled trials) were selected. Intradetrusor injection of botulinum toxin in patients with refractory NNDO has produced promising results, with a significant improvement in physical symptoms, urodynamic parameters and quality of life. The rare side effects consist primarily of dose-dependent urine retention. Conclusion On the basis of preliminary data, botulinum toxin appears to be a valuable therapeutic option and fills the gap between anticholinergics and surgery in the treatment of NNDO that is refractory to anticholinergic agents. Botulinum toxin has a promising future in urology but requires further scientific evaluation.

La clonidine injectee par voie intrathecale a ete testee chez des patients blesses medullaires intolerants ou resistants au traitement parasympathicolytique. Si l’effet precoce de la clonidine sur les parametres urodynamiques etait satisfaisant, les effets secondaires cardiovasculaires et la survenue d’une tolerance precoce en ont limite l’utilisation en infusion chronique. Le baclofene intrathecal a, quant a` lui, un effet sur le reflexe mictionnel sur le plan theorique, mais peu d’effets en pratique clinique sur l’hyperactivite vesicale de patients souffrant d’une spasticite d’origine spinale. Il peut provoquer par ailleurs une modification de la qualite des erections et une incapacite a l’obtention d’ejaculations par stimulation vibratoire penienne. L’evaluation de nouvelles cibles pharmacologiques medullaires telles que les recepteurs serotoninergiques ou dopaminergiques pourraient avoir un interet a l’avenir.

The training, recruitment, and retention of staff for public mental health systems continue to be problematic at the state and local levels. Academic training programs offer a valuable resource to address these workforce requirements. One model of maintaining a publicacademic collaboration is the “linchpin” person who works in both academic and service or administrative institutions and can assist in finding solutions to these problems.

In a joint effort ONERA and DLR have assessed the interference effects of a generic twin-engine transport aircraft configuration equipped with throughflow nacelles. Both experimental and theoretical investigations were performed. The results showed that the installation of the nacelles had substantial effects on total forces at cruise Mach number. With respect to the clean configuration, total lift decreased at constant incidence, and total drag increased at constant lift. A detailed analysis of the flowfield revealed that for transonic flows the installation of the nacelle influenced the complete upper wing surface. On the lower wing surface the flow was considerably accelerated due to the propulsion system, and a supersonic region terminated by a shock wave appeared. The nacelle pressure distribution was also substantially influenced by interference effects. Comparison of experimental and numerical results showed that the solution of the Euler equations is well capable of simulating the interference effects.

State hospitals provide essential services to many of society's most ill and needy individuals. As the next century approaches, state hospitals can best fulfil their missions by developing as high-quality neuropsychiatric/rehabilitation institutes, as opposed to custodial care centers. Highly skilled professionals whose education has included the special knowledge and skill pertinent to state hospitals are central to this development. Although “training units” in state hospitals have existed in many locales, a specific curriculum is often lacking. This article describes the curriculum for psychiatric residents who rotate through the Professional Education Unit at Dammasch State Hospital, as part of the Oregon Public Psychiatry Training Program. The curriculum is described by exploration of the individual learning contract, known as the “Educational Plan,” which guides each resident's work.

Training has been a longstanding and fruitful area of collaboration between the public and academic sectors. Graduate medical education for psychiatry residents is one example. This paper reviews the history of Oregon's public psychiatry training program and highlights factors contributing to its success.

This paper proposes a new method for multi-scale localization. This method employs fractals to create pilot signals for localization. The localization process can be configured in function of the desired resolution (or scale). In this paper we propose also an adaptive localization receiver. The first part of the paper introduces the fractal theory, while the second part is focalized on fractal signal definition used in localization. Finally, simulation results are shown compared to CDMA pilots. The obtained performances of the new method open a real perspectives in localization.

International audience; This paper proposes a functional management architecture for Cognitive Radio systems. It relies on a previously defined configuration management architecture for multi-standard SDR systems, and complement it to support cognitive radio features. This paper explains the requirements of Cognitive Radio systems in terms of reconfiguration, smartness and sensing capabilities. A configuration management architecture capable of dealing with the hardware heterogeneity and a wide range of reconfiguration scenarios expected with SDR systems is presented. The management is distributed over the system and a hierarchical dependency is set on 3 layers, each having a different level of knowledge of the system and the associated hardware constraints of the elements it supervises. Then a cognitive management functional architecture is derived from the previous one, copying the 3 layers of hierarchy. The roles of the elements of each layer are discussed, as well as their respective interactions and their relationships with the elements of the configuration management architecture.

La prise en charge des hypertonies neurologiques chez les personnes tres âgees n’a qu’exceptionnellement ete etudiee dans la litterature. La toxine botulique A est le traitement de premiere intention mais a des limites de cout liees a la mise en place effective des filieres de soins et aux troubles comportementaux des patients durant les injections. La phenolisation nerveuse a une place de choix lorsque les nerfs a contingent moteur sont en cause: faible cout, realisation en ambulatoire, geste parfois unique. La phenolisation intramusculaire doit etre evaluee et precisee, car elle est actuellement peu realisee et ne fait l’objet d’aucun consensus.

The “linchpin” model of collaboration between state mental health agencies and university training programs has been developed in two states. This paper describes the model, pointing out both strengths and weaknesses. Recommendations for institutions seeking this type of collaboration and persons who are in the collaborative role are provided.

The right to refuse treatment seems well established for psychiatric patients. Individual states, however, have very different procedures for managing this right and for overriding the refusal. Oregon's administrative procedure for override depends on an evaluation by an independent examining psychiatrist. This article empirically examines the 432 refusals leading to override requests in three Oregon psychiatric institutions in 1983 and 1984. Treatment refusal was found to be a common occurrence in all age groups. Those who refused treatment were seriously ill, unemployed, single individuals with previous psychiatric hospitalizations. Most refused treatment because of denial of their illness or delusional thinking about medication. Most refusals were overridden following the independent psychiatrist's examination. Because of the significant cost of the override procedure to the patient and the mental health system, the authors propose a new procedure which combines parts of the current procedure with a requirement that, at the time of the civil commitment hearing, the judge makes a separate decision as to the patient's competency to make treatment decisions. Language: en

Un gradient thermique important cree entre une aiguille creuse chaude et une plaque de verre froide permet la capture des particules de l'air qui est insuffle dans l'aiguille.

Objective By proposing a new terminology (acquired deforming hypertonia or ADH) and a new definition for contractures, the main objective of this study was to establish their prevalence among institutionalized elderly patients. Secondary objectives were to analyze the negative impact of ADH and collect the opinions of clinicians on the possible treatments available. Methodology A multicenter cross-sectional study was conducted among residents of 39 geriatric institutions (29 EHPAD and 10 USLD). All subjects presenting at least one ADH were surveyed over a one-week period. Results Among 3145 observed patients (mean age 88.9 ± 9.7 years) 22% ( n = 692) presented at least one ADH. In average, each patient presented 4.4 ± 3.2 ADHs. Negative consequences on self-care, nursing and difficulties in getting dressed were most frequently observed. Only 25.4% of clinicians considered the ADH to be potentially reversible. Physical therapy was the therapeutic option most frequently chosen over medication and surgery. Conclusion This study confirms the important prevalence of ADH among elderly institutionalized patients. Consequences on the level of dependence were significant. It seems relevant to elaborate hierarchical therapeutic strategies in order to counter these disorders and the fatalism that ensues.

The unplanned extension of the right to refuse treatment to the precommitment period is described in this paper. This extension of the right to refuse treatment has important public policy implications for the civil commitment process. These implications, as well as the pros and cons of the extension of the right to refuse treatment, are discussed.

Public psychiatry training in Oregon traces its roots to the community mental health movement of the 1960s and now includes a focus on training in the community and in state hospitals.

The Public Psychiatry Training Program offers an education in the unique knowledge, attitudes, and skills essential for working with persons with severe and chronic illness in both hospital and community settings.

This technical article discusses design and integration associated with distributed propulsion as a means of providing motive power with significantly reduced emissions and external noise for future aircraft concepts. The technical work reflects activities performed within a European Commission funded Framework 7 project entitled Distributed Propulsion and Ultra-high By-Pass Rotor Study at Aircraft Level, or, DisPURSAL. In this instance, the approach of distributed propulsion includes a Distributed Multiple-Fans Concept driven by a limited number of engine cores as well as one unique solution that integrates the fuselage with a single propulsor (dubbed Propulsive-Fuselage Concept) – both targeting entry-in-service year 2035+. Compared to a state-of-the-art, year 2000 reference aircraft, designs with tighter coupling between airframe aerodynamics and motive power system performance for medium-to-long-range operations indicated potentially a 40-45% reduction in CO2-emissions. An evolutionary, year 2035, conventional morphology gas-turbine aircraft was predicted to be –33% in CO2-emissions.

Attention to our patients’ lives reveals that often it is the most mundane difficulties that are the most disabling or distressing. In this issue and the next issue of the Journal, we will explore the effect of neuro psychiatric disease on the ability to drive. In the current issue, a group of investigators led by Jeffrey Metzner, M.D., from the University of Colorado, describes the impairment of driving by psychiatric illness and its drug treatment. In the next issue, Charles Poser, M.D., from the Beth Israel Hospital, Boston, describes the effect of neurological disease on the capacity to drive. Both contributions are specific as to doctors’ responsibilities under the law, and both should be helpful to practitioners addressing this issue with patients.