Les maladies rares affectent 30 millions de personnes en Europe

En Europe, une maladie est dite rare lorsqu'elle affecte moins d'une personne sur 2000. C'est une affection invalidante pouvant mettre en jeu le pronostic vital et qui nécessite des efforts combinés spéciaux pour sa prise en charge. Plus de 7000 maladies rares ont été identifiées à ce jour. Prises dans leur ensemble, elles affectent 30 millions de personnes en Europe et constituent un problème majeur de santé publique. L'Union européenne et de nombreux Etats membres ont déjà pris des mesures spécifiques de grande ampleur pour lutter contre les maladies rares, mais cette problématique est encore largement méconnue en Suisse. La première Journée européenne des maladies rares invite les autorités politiques suisses, les professionnels de santé, les scientifiques et l'industrie pharmaceutique à soutenir les efforts déjà initiés et progresser dans la lutte contre les maladies rares dans notre pays.

Relatório de Jogos de Marketing - Evolutec-Computer

A Evolutec-Computer é uma empresa especializada em engenharia eletrônica, que recebeu um financiamento de uma firma internacional de acionistas, que decidiu entrar no mercado de produção de microcomputador. Por conseguinte, foi criada uma nova divisão de PC Marketing para prosseguir nesta oportunidade de negócio. A fim de iniciar essa divisão, a Cooporate Headquarters forneceu o capital inicial (dinheiro do investimento). O montante concedido seria usado para abrir escritórios de vendas, design das marcas e realizar atividades de pesquisas R&D para as novas tecnologias. A nossa empresa recebeu 500.000 USD nos primeiros quatro semestres e 5.000.000 USD no quinto semestre, somando um total de 7.000.000 USD. A Evolutec-Computer terá o controlo da divisão de PC para os próximos dois anos (8 semestres/períodos de decisão). Dentro desse prazo, a Coorporate Headquarters espera ver a criação de uma divisão autossuficiente. A equipa criada pela Evolutec terá que ser capaz de gerar proveito das operações e contribuir para o lucro da corporação como um todo. Dentro dos 8 semestres, espera-se obter lucro suficiente para cobrir os investimentos iniciais...The Evolutec-Computer is a company specialized in electronic engineering, which has received funding from an international firm shareholder, who decided to enter the PC production market. Therefore, a new PC Marketing Division was created to pursue this business opportunity. In order to start this division, the Corporate Headquarters provided the initial capital (investment money). The sum would be used to open sales offices, design brands and carry out R & D research activities for new technologies. Our company received $ 500,000 in the first four semesters and $ 5,000,000 in the fifth semester, for a total of $ 7,000,000. The Evolutec-Computer will control the PC division for the next two years (eight semesters/decision periods). Within that period, the Coorporate Headquarters hopes to see the creation of a selfsufficient division. The team set up by Evolutec will have to be able to generate profit from operations and contribute to the profit of the corporation as a whole. Within 8 semesters, is expected to make enough profit to cover the initial investment. The performance of our company will be measured by Headquarter through the Balanced Scorecard, which will be based on financial performance, effectiveness of the marketing plan, market performance, investments in the company's future and wealth creation.

Relatório Final Jogos-Simulação De Marketing – Power Computer

This school in the course of Marketing Business Management and specifically Entrepr This school in the course of Marketing Business Management and specifically Entrepreneurship in the discipline of Simulation - Games Marketing year was accordingly for the creation of a company in the computer business in business online simulator called Marketplace, in order to put into practice all the theoretical knowledge acquired during all previous semesters. This platform we were confronted with decisions in eight quarters corresponding 4 every year , in order to encourage learning in a practical way, a virtual and dynamic environment. Every quarter acareados with well organized tasks taking as a reference point defined strategies such as market research analysis, branding , store management after its creation , development of the policy of the 4Ps , identifying opportunities , monitoring of finances and invest heavily . All quarters were subjected decisions and are then given the results , such as: market performance , financial performance, investments in the future , the "health" of the company 's marketing efficiency then analyzed by our company , teaching and also by competition Balanced Scorecard ie , semi-annual and cumulative . For the start of activities it was awarded the 1st year a total of 2,000,000, corresponding to 500,000 out of 4 first quarter , and 5,000,000 in the fifth quarter in a total of 7,000,000 . The capital invested was used to buy market research, opening sales offices , create brands , contract sales force , advertise products created and perform activity R & D in order to make a profit and become self- sufficient to guarantee the payment of principal invested to headquarters ( Corporate Headquarters ) .

Global Genomic Diversity of Human Papillomavirus 6 Based on 724 Isolates and 190 Complete Genome Sequences.

Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution. IMPORTANCE: This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new, complete HPV6 genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease, and/or gender. We additionally identified several HPV6 lineage- and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within the L2 gene that is suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination, and molecular assay development studies.

Otorgamiento de la Asignación por Concepto de Racionamiento

Establecer las normas y procedimientos administrativos para regular el otorgamiento de la asignación por concepto de racionamiento, como un estímulo a la producción intelectual de los directivos, profesionales, técnicos y auxiliares, bajo el Régimen Laboral de la Actividad Privada del Decreto legislativo Nº728 de las áreas científica y administrativa del IMARPE, que laboran dentro de la jurisdicción de manera efectiva y fuera del horario normal de trabajo.

The role of migration and domestic transmission in the spread of HIV-1 non-B subtypes in Switzerland.

BACKGROUND: By analyzing human immunodeficiency virus type 1 (HIV-1) pol sequences from the Swiss HIV Cohort Study (SHCS), we explored whether the prevalence of non-B subtypes reflects domestic transmission or migration patterns. METHODS: Swiss non-B sequences and sequences collected abroad were pooled to construct maximum likelihood trees, which were analyzed for Swiss-specific subepidemics, (subtrees including ≥80% Swiss sequences, bootstrap >70%; macroscale analysis) or evidence for domestic transmission (sequence pairs with genetic distance <1.5%, bootstrap ≥98%; microscale analysis). RESULTS: Of 8287 SHCS participants, 1732 (21%) were infected with non-B subtypes, of which A (n = 328), C (n = 272), CRF01_AE (n = 258), and CRF02_AG (n = 285) were studied further. The macroscale analysis revealed that 21% (A), 16% (C), 24% (CRF01_AE), and 28% (CRF02_AG) belonged to Swiss-specific subepidemics. The microscale analysis identified 26 possible transmission pairs: 3 (12%) including only homosexual Swiss men of white ethnicity; 3 (12%) including homosexual white men from Switzerland and partners from foreign countries; and 10 (38%) involving heterosexual white Swiss men and females of different nationality and predominantly nonwhite ethnicity. CONCLUSIONS: Of all non-B infections diagnosed in Switzerland, <25% could be prevented by domestic interventions. Awareness should be raised among immigrants and Swiss individuals with partners from high prevalence countries to contain the spread of non-B subtypes.

Sedation and analgesia for colonoscopy: patient tolerance, pain, and cardiorespiratory parameters.

BACKGROUND: Colonoscopy is generally performed with the patient sedated and receiving analgesics. However, the benefit of the most often used combination of intravenous midazolam and pethidine on patient tolerance and pain and its cardiorespiratory risk have not been fully defined. METHODS: In this double-blind prospective study, 150 outpatients undergoing routine colonoscopy were randomly assigned to receive either (1) low-dose midazolam (35 micrograms/kg) and pethidine (700 micrograms/kg in 48 patients, 500 micrograms/kg in 102 patients), (2) midazolam and placebo pethidine, or (3) pethidine and placebo midazolam. RESULTS: Tolerance (visual analog scale, 0 to 100 points: 0 = excellent; 100 = unbearable) did not improve significantly more in group 1 compared with group 2 (7 points; 95% confidence interval [-2-17]) and group 3 (2 points; 95% confidence interval [-7-12]). Similarly, pain was not significantly improved in group 1 as compared with the other groups. Male gender (p < 0.001) and shorter duration of the procedure (p = 0.004), but not amnesia, were associated with better patient tolerance and less pain. Patient satisfaction was similar in all groups. Oxygen desaturation and hypotension occurred in 33% and 11%, respectively, with a similar frequency in all three groups. CONCLUSIONS: In this study, the combination of low-dose midazolam and pethidine does not improve patient tolerance and lessen pain during colonoscopy as compared with either drug given alone. When applying low-dose midazolam, oxygen desaturation and hypotension do not occur more often after combined use of both drugs. For the individual patient, sedation and analgesia should be based on the endoscopist's clinical judgement.

Alternativa agronômica para o biossólido produzido no Distrito Federal: I - efeito na produção de milho e na adição de metais pesados em Latossolo no cerrado

O crescimento urbano em Brasília aumentou o volume de esgoto doméstico coletado, gerando maior volume de biossólido - resíduo final do tratamento do esgoto - depositado nos pátios da Companhia de Água e Esgoto de Brasília (CAESB). Embora ainda haja carência de informações técnicas que possam garantir segurança ambiental, viabilidade econômica e satisfação social de seu uso, a maior parte do biossólido tem sido utilizada como condicionador de solos e fertilizante pelos agricultores nas áreas agrícolas vizinhas. Neste trabalho, o biossólido, que continha 90 dag kg-1 de água (10 dag kg-1 de matéria seca), foi aplicado a um Latossolo Vermelho distrófico, em doses únicas de 54, 108 e 216 t ha-1. Na menor dose e sem qualquer adição de outros fertilizantes, o material forneceu nutrientes para o milho por três anos, resultando em uma produtividade média de grãos de 4.700 kg ha-1. O modelo de ajuste aos dados, definido pela equação quadrática Y = 2349,3** + 41,579** X - 0,1097** X ², R² = 0,9824**, em que Y representa a produtividade de milho (kg ha-1) e X, a dose de biossólido úmido aplicado (t ha-1), estima que a aplicação de 189,51 t ha-1 produziria o rendimento máximo de milho. Usando-se o fósforo (P2O5) como referência, o biossólido foi mais eficiente do que a adubação mineral com superfosfato triplo, apresentando um valor fertilizante médio de 125 % nos três anos de cultivo. Na dose de 54 t ha-1, o biossólido da CAESB incorpora ao solo 240 kg de P2O5, 320 kg de N, 160 kg de Ca, 13 kg de K2O. As concentrações dos metais pesados (Cd, Pb e Hg) presentes no biossólido são muito inferiores aos limites críticos para aplicação do material, e a aplicação de 54 t ha-1 de biossólido úmido incorpora ao solo pequenas quantidades daqueles metais, indicando que a contaminação do solo por aqueles poluentes não constituirá problema, desde que o esgoto urbano não receba contaminação por resíduos industriais.

Alternativa agronômica para o biossólido produzido no Distrito Federal: II - aspectos qualitativos, econômicos e práticos de seu uso

A utilização agronômica do biossólido tem sido vista como a forma mais viável para sua disposição; entretanto, além do conhecimento técnico de suas propriedades como fertilizante, aspectos qualitativos, econômicos e práticos de seu uso são importantes para o produtor. O biossólido produzido pela Companhia de Saneamento de Brasília (CAESB) apresentou uma grande variabilidade entre as concentrações dos nutrientes a cada amostra coletada mensalmente no período entre agosto/1995 e julho/1996 e entre as estações de tratamento de origem do material. A variabilidade, maior para os macronutrientes (Ca, N, P, K, Mg e S) e menor para os micronutrientes e metais pesados, determina a necessidade de ajuste no cálculo das quantidades do material a cada aplicação. Apesar de fornecido gratuitamente, os usuários pagam pelo transporte do biossólido, o qual, pelo seu elevado conteúdo de água, só é viável até determinada distância. Nas condições deste trabalho, a distância máxima foi de 122 km. A simulação de secagem do produto mostrou que, reduzindo o conteúdo de água da pasta de 90 dag kg-1 para 70 dag kg-1, a distância de transporte aumenta de 122 para 365 km, ampliando a área de abrangência de seu uso. A aplicação de 54 t ha-1 de biossólido úmido (90 dag kg-1) apresentou a melhor relação benefício/custo (retorno de R$ 1,12 para cada R$ 1,00 investido no material), comparada às demais aplicações e às adubações com fertilizantes minerais (todas com retornos abaixo de R$ 1,00 para cada R$ 1,00 investido; a maior dose de biossólido teve retorno negativo). Embora tenha apresentado melhor desempenho comparativo, o que pode qualificá-la, preliminarmente, como dose para recomendação, a aplicação de 54 t ha-1 de biossólido úmido requer a movimentação e manipulação de um grande volume de material, o que pode ser um fator de limitação de seu uso.

Seltene Erkrankungen: 30 Millionen Menschen in Europa sind betroffen

Gemäss der in Europa geltenden Definition werden Krankheiten als selten bezeichnet, an denen weniger als einer von 2000 Menschen leidet. Die Erkrankungen sind mit schweren Beeinträchtigungen und zum Teil auch einer verkürzten Lebenserwartung verbunden und erfordern eine komplexe und hochspezialisierte Behandlung. Über 7000 seltene Erkrankungen sind bis heute bekannt, an denen insgesamt 30 Millionen Menschen in Europa leiden. Die seltenen Erkrankungen in ihrer Gesamtheit stellen somit ein schwerwiegendes Problem für das Gesundheitswesen dar. Die Europäische Union und zahlreiche Mitgliedsstaaten haben im Kampf gegen die seltenen Erkrankungen bereits umfassende spezifische Massnahmen ergriffen, während in der Schweiz der Problematik noch zuwenig Gewicht beigemessen wird. Mit dem ersten Europäischen Tag der seltenen Erkrankungen werden alle Verantwortlichen in Politik, Gesundheitswesen, Wissenschaft und pharmazeutischer Industrie in der Schweiz aufgerufen, in ihren bisherigen Bemühungen nicht nachzulassen und im Kampf gegen die seltenen Krankheiten in unserem Land weitere Fortschritte zu erzielen.

Benchmarking for routines and organizational knowledge

We use best practice benchmarking rationales to propose a dynamic research design that accounts for the endogenous components of across-firms heterogeneous routines to study changes in performance and their link to organizational knowledge investments. We thus contribute to the operationalization of management theoretical frameworks based on resources and routines. The research design employs frontier measures that provide industry-level benchmarking in organizational settings, and proposes some new indicators for firm-level strategic benchmarking. A profit-oriented analysis of the U.S. technology industry during 2000-2011 illustrates the usefulness of our design. Findings reveal that industry revival following economic distress comes along with wider gaps between best and worst performers. Second stage analyses show that increasing intangibles stocks is positively associated with fixed target benchmarking, while enhancing R&D spending is linked to local frontier progress. The discussion develops managerial interpretations of the benchmarking measures that are suitable for control mechanisms and reward systems.

Further characterisation of the 91500 zircon crystal

This paper reports the results from a second characterisation of the 91500 zircon, including data from electron probe microanalysis, laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS), secondary ion mass spectrometry (SIMS) and laser fluorination analyses. The focus of this initiative was to establish the suitability of this large single zircon crystal for calibrating in situ analyses of the rare earth elements and oxygen isotopes, as well as to provide working values for key geochemical systems. In addition to extensive testing of the chemical and structural homogeneity of this sample, the occurrence of banding in 91500 in both backscattered electron and cathodoluminescence images is described in detail. Blind intercomparison data reported by both LA-ICP-MS and SIMS laboratories indicate that only small systematic differences exist between the data sets provided by these two techniques. Furthermore, the use of NIST SRM 610 glass as the calibrant for SIMS analyses was found to introduce little or no systematic error into the results for zircon. Based on both laser fluorination and SIMS data, zircon 91500 seems to be very well suited for calibrating in situ oxygen isotopic analyses.

Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93.

To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.

Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism.

RATIONALE: Concomitant deep vein thrombosis (DVT) in patients with acute pulmonary embolism (PE) has an uncertain prognostic significance. OBJECTIVES: In a cohort of patients with PE, this study compared the risk of death in those with and those without concomitant DVT. METHODS: We conducted a prospective cohort study of outpatients diagnosed with a first episode of acute symptomatic PE. Patients underwent bilateral lower extremity venous compression ultrasonography to assess for concomitant DVT. MEASUREMENTS AND MAIN RESULTS: The primary study outcome, all-cause mortality, and the secondary outcome of PE-specific mortality were assessed during the 3 months of follow-up after PE diagnosis. Multivariate Cox proportional hazards regression was done to adjust for significant covariates. Of 707 patients diagnosed with PE, 51.2% (362 of 707) had concomitant DVT and 10.9% (77 of 707) died during follow-up. Patients with concomitant DVT had an increased all-cause mortality (adjusted hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.24 to 3.38; P = 0.005) and PE-specific mortality (adjusted HR, 4.25; 95% CI, 1.61 to 11.25; P = 0.04) compared with those without concomitant DVT. In an external validation cohort of 4,476 patients with acute PE enrolled in the international multicenter RIETE Registry, concomitant DVT remained a significant predictor of all-cause (adjusted HR, 1.66; 95% CI, 1.28 to 2.15; P < 0.001) and PE-specific mortality (adjusted HR, 2.01; 95% CI, 1.18 to 3.44; P = 0.01). CONCLUSIONS: In patients with a first episode of acute symptomatic PE, the presence of concomitant DVT is an independent predictor of death in the ensuing 3 months after diagnosis. Assessment of the thrombotic burden should assist with risk stratification of patients with acute PE.

The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain.

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes. METHODS: The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks. RESULTS: The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician. CONCLUSIONS: The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly.