Combined radiohormonotherapy in node positive lymph node prostate cancer

Purpose: Pelvic radiation therapy (RT) represents a therapeutic option in the treatment of node-positive prostate cancer but it remains controversial, because of its high rate toxicities. New radiation technique such as IMRT may reduce these complications. In this study, we aimed to assess the rate of toxicities according to CTC-NCI.v3 in such patients treated with either 3DCRT or IMRT (Tomotherapy).Methods and Materials: From January 2008 to December 2010, data were analyzed from 30 consecutive patients including 29 node-positive prostate cancer undergoing definitive or adjuvant RT (IMRT and/or 3DCRT) after radical prostatectomy and lymphadenectomy combined to hormonal therapy. Median age was 66 years (range : 52-83). Median preoperative PSA value was 12 ng/ml (range: 2.72-165). According to the pT-classification, there were 4 pT2, 7 pT3a, 10 pT3b, and 1 pT4 patients. Pathologic positive lymph nodes were found in 23 patients. Radiologic positive lymph nodes were found in 5 patients. Two patients were node negative. Gleason score was ranging between 7 to 10. Twelve patients were treated by Tomotherapy including 4 with simultaneous integrated boost (SIB). Eighteen patients were treated by Tomotherapy including 2 with SIB to the whole pelvis and 3DCRT boost to the prostate. V50% for bladder and rectum were recorded. Acute and late toxicities were assessed according to CTC-NCI.v3 classification.Results: With a median follow-up of 17 months, only one patient presented nodal and metastatic failure. Urinary incontinence was graded 1 after surgery for 6 patients and grade 2 in two. Sexual impuissance was noted in 3 patients. Acute toxicities during RT were proctitis grade 0 in 23 patients (76.5%), grade 1 in 7 (23.5%). Nocturia grade 1 in 9 patients. Interruption of treatment was seen in only case because of grade 3 urinary incontinence. Late effects included erectile dysfunction in 5 patients (83%) and one patient had grade 3proctitis requiring colostomy 3 months after RT. Median Dose-Volume Histogram according to radiation techniques V50% bladder V50% rectum Tomotherapy (IMRT) 36.25 Gy 39 Gy Tomotherapy + 3DCRT 41.26 Gy 39.18 GyConclusion: Based on our above-mentioned findings, there is no a significant difference in morbidity in patients treated with Tomotherapy or Tomotherapy with 3DCRT boost.

NCoR1 is a conserved physiological modulator of muscle mass and oxidative function.

Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARβ/δ, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function.

Vaccine and immunotherapeutic interventions.

PURPOSE OF REVIEW: As we enter the fourth decade in HIV epidemic, advances in understanding HIV pathogenesis and development of potent and safer antiretroviral drugs have been spectacular. More than 30 antiviral drugs have been registered and the impact of combination antiviral therapy on morbidity and mortality has been dramatic. However, despite long-term virus suppression, HIV invariably rebounds after interruption of therapy. Long-term antiviral therapy does not cure HIV infection nor does it induce restoration/development of virus-specific immune responses capable of controlling HIV replication. Therefore, development of immune-based interventions is needed to restore effective defenses that can lead to HIV functional cure and ultimately eradication. RECENT FINDINGS: Therapeutic vaccination and immune interventions that generate de-novo or that boost preexisting HIV-specific T-cell responses are being investigated as a potential means to achieve a 'functional HIV cure'. One major hurdle in the quest of an HIV cure is control and elimination of the HIV latent reservoir. Several immune interventions that target the latent reservoir have been tried in recent years. In parallel, several therapeutic vaccination strategies have been developed and tested in early clinical studies. Recent encouraging studies show for the first time that vaccination can have an impact on HIV load. SUMMARY: This review summarizes the main immune interventions evaluated over the last years. Ways to improve them, as well as challenges in monitoring/evaluating effects of such strategies, are being discussed. In addition, clinical efficacy and potential clinical benefits of immunotherapeutic interventions are particularly difficult to measure. This review highlights current assays used and their shortcoming.

The Outlook for Asian Dairy Markets: The Role of Demographics, Income, and Prices, June 2005

The paper first presents a 10-year outlook for major Asian dairy markets (China, India, Indonesia, Japan, South Korea, Malaysia, the Philippines, Thailand, and Vietnam) based on a world dairy model. Then, using Heien and Wessells’s technique, dairy product consumption growth is decomposed into contributions generated by income growth, population growth, price change, and urbanization and these contributions are quantified. Using the world dairy model, the paper also analyzes the impacts of alternative assumptions of higher income levels and technology development in Asia on Asian dairy consumptions and world dairy prices. The outlook projects that Asian dairy consumption will continue to grow strongly in the next decade. The consumption decomposition suggests that the growth would be mostly driven by income and population growth and, as a result, would raise world dairy prices. The simulation results show that technology improvement in Asian countries would dampen world dairy prices and meanwhile boost domestic dairy consumption.

La toxicologie forensique, une discipline scientifique en plein essor [Forensic toxicology, a growing scientific discipline]

La recherche de substances ayant pu jouer un rôle direct ou indirect dans la cause de la mort ou ayant pu modifier le comportement d'un individu constitue la mission première de la toxicologie forensique. L'augmentation de la consommation de substances illégales et de médicaments dans les sociétés modernes a fait connaître à la toxicologie forensique un essor très important ces dernières décennies. D'autre part, les développements technologiques analytiques ont permis d'obtenir des outils très sensibles et spécifiques pour la recherche et le dosage d'une multitude de substances dans une grande variété d'échantillons biologiques, parfois présentes à des concentrations très faibles, conséquence d'une dose équivalente à la prise d'une seule unité galénique. Forensic toxicology has to bring evidence of substances that could have been involved directly or indirectly in the cause of death or that could influence the behaviour of somebody. The increase of the consumption of illegal and legal drugs in modern societies during last decades gave a boost to forensic toxicology. Moreover, improvement with analytical technology gave tools with high degrees of sensitivity and specificity for the screening and quantification of a large amount of substances in various biological specimens, even with very low concentration resulting of a single dose of medication.

Improved immunogenicity against HIV-1 clade C antigens by using NYVAC-C with restored replication competence.

In order to improve the immunogenicity of currently available non-replicating pox virus HIV vaccine vectors, NYVAC was genetically modified through re-insertion of two host range genes (K1L and C7L), resulting in restored replicative capacity in human cells. In the present study these vectors, expressing either a combination of the HIV-1 clade C antigens Env, Gag, Pol, Nef, or a combination of Gal, Pol, Nef were evaluated for safety and immunogenicity in rhesus macaques, which were immunized at weeks 0, 4 and 12 either by scarification (conventional poxvirus route of immunization), intradermal or by intramuscular injection (route used in previous vaccine studies).Replication competent NYVAC-C-KC vectors induced higher HIV-specific responses, as measured by IFN- ELISpot assay, than the replication defective NYVAC-C vectors. Application through scarification only required one immunization to induce maximum HIV-specific immune responses. This method simultaneously induced relatively lower anti-vector responses. In contrast, two to three immunizations were required when the NYVAC-C-KC vectors were given by intradermal or intramuscular injection and this method tended to generate slightly lower responses. Responses were predominantly directed against Env in the animals that received NYVAC-C-KC vectors expressing HIV-1 Env, Gag, Pol, Nef, while Gag responses were dominant in the NYVAC-C-KC HIV-1 Gag, Pol, Nef immunized animals.The current study demonstrates that NYVAC replication competent vectors were well tolerated and showed increased immunogenicity as compared to replication defective vectors. Further studies are needed to evaluate the most efficient route of immunization and to explore the use of these replication competent NYVAC vectors in prime/boost combination with gp120 protein-based vaccine candidates. This studies was performed within the Poxvirus T-cell Vaccine Discovery Consortium (PTVDC) which is part of the CAVD program.

Relatório dos Progressos Realizados para Atingir os ODM

Com o virar do século a Organização das Nações Unidas (ONU) decidiu que era propício e muito simbólico dar um novo impulso à própria Organização e comprometeu-se a combater a pobreza e as doenças que vitimam milhões de crianças em todo o mundo, a maioria das quais com menos de cinco anos, devido a causas totalmente evitáveis como a malária, a diarreia e a pneumonia. Assim, a 8 de Setembro de 2000, 189 Estados membros das ONU adoptaram os “Objectivos de Desenvolvimento do Milénio” (ODM) surgidos da Declaração do Milénio. Foram definidos oito objectivos — cada um deles, um compromisso específico para inverter a propagação da pobreza e das doenças — que são suportados por um Plano de Acção com 18 metas quantificáveis para combater a pobreza, a fome, a doença, o analfabetismo, a discriminação contra a mulher e a degradação ambiental. Muitas das metas dos ODM reflectem um nível de ambição modesto em termos de desenvolvimento humano que os países da ONU se comprometeram a atingir até 2015. Os Objectivos representam igualmente uma parceria entre países desenvolvidos e em desenvolvimento tendo em vista criar um clima a nível nacional e mundial conducente ao desenvolvimento e à eliminação da pobreza. Essa parceria atribui responsabilidades muito claras aos países ricos em termos de prestação de mais ajuda; estabelecimento de regras comerciais mais justas; e alívio significativo da dívida dos países em desenvolvimento. Por seu turno os países em desenvolvimento comprometem-se a vencer o desafio que os ODM colocam. Cabo Verde aceitou o desafio lançado pela ONU para implementar um conjunto de acções estratégicas para que até o ano 2015 um conjunto de objectivos e metas seja realizado. Essa assumpção impõe a integração das metas e indicadores ODM nas políticas públicas nacionais.

Metodologia de Análise de Investimentos em Sistemas e Tecnologias da Informação, pelas empresas caboverdeanas

O aumento da competitividade das empresas caboverdeanas impõe-se sobretudo por causa do momento histórico que particularmente o país atravessa. A graduação para país de rendimento médio, a adesão à Organização Mundial de Comércio e o estatuto de parceria especial com a União Europeia constituem razões de grande vulto para as empresas nacionais e outras que empreendem no mercado caboverdeano, definirem eficazmente e eficientemente os seus processos organizacionais de forma a atingirem patamares de produtividade e performance aos níveis internacionais. A envolvente externa às empresas caboverdeanas tem sido alvo de alterações profundas com a globalização dos mercados e o novo paradigma de economia baseada no conhecimento. Para que as empresas mantenham posições competitivas são muitos os desafios que terão que superar. Inexoravelmente, terão que reorganizar e redefinir os seus processos de negócio e suas estratégias de forma coerente. Os SI/TI constituem o factor potencial de reorganização e modernização, a alavanca de diferenciação competitiva e da concretização de negócios e resultados adicionais. O objectivo deste trabalho é o desenvolvimento e a validação de uma metodologia de enquadramento, análise e avaliação de investimentos em SI/TI. O procedimento proposto é fundamentado pela literatura e nas práticas das empresas cabo-verdianas e visa apoiar as empresas a atingirem estágios de performance e produtividade elevados, decorrentes da utilização optimizada dos recursos oferecidos pelos SI/TI. Porque elevadas somas de recursos financeiros são investidos em Sistemas e Tecnologias de Informação e nem todos os benefícios associados são quantificáveis e dado que os riscos associados são elevados, propõe-se com este trabalho um procedimento metodológico de apoio às empresas. Esta metodologia simplificada de análise de investimentos em Sistemas e Tecnologias da Informação propõe uma abordagem científica, sólida e objectiva de avaliação de investimentos em SI/TI, visando propiciar incremento do valor acrescentado dos produtos e/ou serviços das empresas. Os resultados obtidos a partir das análises quantitativas e qualitativas elaboradas permitem retratar a prática das empresas caboverdeanas no domínio de análise e avaliação de investimentos em SI/TI e gerar inferências importantes sobre o comportamento dos responsáveis empresariais e de SI/TI. The increase in competition by the Capeverdean companies is taking place mainly because of the historic moment the country is going through. The recent nomination of Cape Verde as a medium development country, the adhesion to the WCO (World Commerce Organization) and the special partnership with the European Union are relevant reasons for the national companies and others that operate in the Capeverdean market to define efficiently their organizational processes in order to reach levels of productivity and performance comparable to the international ones. The external component of the Capeverdean companies has been undergoing deep changes with market globalization and with the new economic paradigma based on kowledge. In order to maintain their competitive position there are many challenges to overcome. Surely and steadily, they will have to reorganize and redefine their business processes and strategies in a coherent way. The IS/IT (information systems / information technologies) constitute the potential factor of reorganization and modernization, the boost-lever that will produce competitive diferentiation and concretization of businesses and additional results. The main goal of this work is development and validation of a methology of insertion, analysis and evaluation of investments in the IS/IT. The proposed procedure is fundamented by the literature and practice of the Capeverdian companies, and aims at supporting these companies so that they can reach high stages of performance and productivity due to the correct use of the resources offered by the IS/IT. As high amounts of financial resources are invested in Information Systems and Tehnologies, and because of the fact that not all associated benefits may be quantified, and since the associated risks are high, with this work we propose a methodological procedure to support these companies. This simplified analysis methodology in Information and Technologies Systems proposes a sound and objective scientific approach to evaluate investments in IS/IT aiming at providing an increase of the added value of the products and/or services supplied by these companies. The incoming results from the quantitative and qualitative analyses made will allow portraying the practice of the capeverdean companies in the domain of analysis and evaluation of investments in IS/IT and generating important inferences on the behaviour of the executives and IS/IT.

Paisagens Naturais” como Recursos Turísticos: o caso do Parque Natural de Serra da Malagueta na Ilha de Santiago, Cabo Verde

Esta dissertação coloca em evidência o valor das “Paisagens Naturais” como recursos turísticos, sendo o estudo de caso é o parque natural de Serra da Malagueta, em Cabo Verde, ilha de Santiago. A consciencialização da necessidade de preservar os valores naturais (assumida na actividade turística a partir de 1993, com elaboração da Agenda 21), necessidades psicológicas de encontrar alternativas para lazer e recreio diferentes das dos centros urbanos, necessidade de contacto com formas simples de viver e a busca de uma maior interacção com a Natureza, são factores que influenciaram o surgimento do turismo sustentável, o que valorizou a “Paisagem Natural” que pode ser encontrado nos parques naturais. Os componentes dos parques naturais constituem ofertas potenciais para actividades alternativas de lazer e recreio, daí utilizadas para diversas actividades turísticas de Natureza. A sua concretização implica a intervenção humana para ordenar os usos relativamente às componentes naturais, o que implica a criação de serviços básicos (informação, alojamento, restauração, animação cultural, ambiental). Tal tem conduzido a que alguns parques naturais tenham evoluído de simples recurso natural para destinos turísticos. A sua gestão como destinos turísticos deve complementar a gestão dos processos naturais que ali têm origem, por isso no seu planeamento devem ser incluídas acções de formação dos intervenientes. Este procedimento aumentará a eficácia das actividades turísticas e minimizar-se-á os aspectos negativos, que poderão advir do uso público dos parques naturais, de modo a serem pólos de desenvolvimento local pela sua diferenciação como produtos turísticos, relativamente aos convencionais. Esta deve ser uma das vias a ser seguida em Cabo Verde, pois predomina o turismo de sol e praia. O turismo cultural e de Natureza aparecem como “produtos secundários”, o que não tem favorecido a integração dos diversos parques naturais. Contudo, é frequente encontrar alguns operadores turísticos nacionais a enviarem os turistas aos parques naturais para visitas, mas alguns são usados só como pontos de passagem. Tal deve-se à inexistência de ofertas de alojamento, restauração e animação, o que não tem trazido nenhum benefício para as comunidades locais, situação verificada no parque natural de Serra da Malagueta, objecto deste estudo. Para inverter esta tendência as intervenções devem passar pela instalação dos serviços em falta, regulamentar as actividades do turismo de Natureza, envolver a população local e promover o conhecimento do parque natural junto dos consumidores turísticos.

Cost of nursing turnover in a Teaching Hospital

Abstract OBJECTIVE To map the sub processes related to turnover of nursing staff and to investigate and measure the nursing turnover cost. METHOD This is a descriptive-exploratory study, classified as case study, conducted in a teaching hospital in the southeastern, Brazil, in the period from May to November 2013. The population was composed by the nursing staff, using Nursing Turnover Cost Calculation Methodology. RESULTS The total cost of turnover was R$314.605,62, and ranged from R$2.221,42 to R$3.073,23 per employee. The costs of pre-hire totaled R$101.004,60 (32,1%), and the hiring process consumed R$92.743,60 (91.8%) The costs of post-hire totaled R$213.601,02 (67,9%), for the sub process decreased productivity, R$199.982,40 (93.6%). CONCLUSION The study identified the importance of managing the cost of staff turnover and the financial impact of the cost of the employee termination, which represented three times the average salary of the nursing staff.

As comunidades imigrantes em Cabo Verde: os chineses em São Vicente e a sua participação no desenvolvimento do comércio

Esta investigação insere-se na temática do Empreendedorismo Imigrante e do Comércio Étnico. Trata-se de uma pesquisa que se debruça sobre a imigração para Cabo Verde, com destaque para a análise da imigração chinesa, sobretudo dedicada ao comércio na ilha de São Vicente. O objectivo geral deste trabalho prende-se com a identificação do contributo da comunidade imigrante supracitada no processo de desenvolvimento de São Vicente, através da instalação e da prática de actividades comerciais. Para concretização deste objectivo foi desenvolvido, durante 5 meses, um trabalho de terreno em Cabo Verde (Santiago e São Vicente). O trabalho empírico socorreu-se de entrevistas formais à presidente da Câmara Municipal de São Vicente e a personalidades da Embaixada de China em Cabo Verde , e informais efectuadas aos comerciantes chineses e seus funcionários, bem como aos comerciantes locais. Foram ainda aplicados inquéritos a todos os comerciantes chineses na ilha de São Vicente, processo que permitiu obter a informação necessária para a caracterização da comunidade chinesa e das actividades comerciais por ela aqui desenvolvidas. Os resultados destes questionários foram armazenados numa base de dados informática, com recurso ao SPSS- Statistical Package for Social Sciences, também utilizado como instrumento de tratamento da informação, assim como a folha de cálculo Excel. Dos resultados da nossa investigação, ressalta que o comércio chinês tem dinamizado muito o tecido comercial sãovicentino, contribuindo para a criação de novos postos de trabalho, diversificando as ofertas e estabilizando ou levando mesmo à redução do preço dos produtos, o que vem generalizar as possibilidades de consumo a segmentos da população menos solventes, que até então tinham muita dificuldade em comprar bens como brinquedos ou certos artigos para o lar. De realçar também que, entre o comércio chinês e o comércio local, existe para além da concorrência como é óbvio, uma certa complementaridade. Esta relação recíproca é estabelecida através de aquisição e revenda de produtos diversificados adquiridos aos comerciantes locas, permitindo assim oferecer assim mais produtos e de melhor qualidade aos seus clientes. Todavia, conclui-se que o comércio chinês, com todas as implicações que trás, ainda não constitui um vector central do desenvolvimento da ilha, designadamente se entendermos o desenvolvimento numa perspectiva abrangente e integral, que incorpora dimensões culturais, sociais e ecológicas que ultrapassam a esfera económica. Contudo, pode-se dizer que a presença do comércio chinês na ilha tem sido bastante positiva, uma vez que coloca no mercado uma diversidade de produtos a preços razoavelmente acessíveis, contribuindo para melhorar a qualidade de vida dos São Vicentinos.

Bonds between fibronectin and fibronectin-binding proteins on Staphylococcus aureus and Lactococcus lactis.

Bacterial cell-wall-associated fibronectin binding proteins A and B (FnBPA and FnBPB) form bonds with host fibronectin. This binding reaction is often the initial step in prosthetic device infections. Atomic force microscopy was used to evaluate binding interactions between a fibronectin-coated probe and laboratory-derived Staphylococcus aureus that are (i) defective in both FnBPA and FnBPB (fnbA fnbB double mutant, DU5883), (ii) capable of expressing only FnBPA (fnbA fnbB double mutant complemented with pFNBA4), or (iii) capable of expressing only FnBPB (fnbA fnbB double mutant complemented with pFNBB4). These experiments were repeated using Lactococcus lactis constructs expressing fnbA and fnbB genes from S. aureus. A distinct force signature was observed for those bacteria that expressed FnBPA or FnBPB. Analysis of this force signature with the biomechanical wormlike chain model suggests that parallel bonds form between fibronectin and FnBPs on a bacterium. The strength and covalence of bonds were evaluated via nonlinear regression of force profiles. Binding events were more frequent (p < 0.01) for S. aureus expressing FnBPA or FnBPB than for the S. aureus double mutant. The binding force, frequency, and profile were similar between the FnBPA and FnBPB expressing strains of S. aureus. The absence of both FnBPs from the surface of S. aureus removed its ability to form a detectable bond with fibronectin. By contrast, ectopic expression of FnBPA or FnBPB on the surface of L. lactis conferred fibronectin binding characteristics similar to those of S. aureus. These measurements demonstrate that fibronectin-binding adhesins FnBPA and FnBPB are necessary and sufficient for the binding of S. aureus to prosthetic devices that are coated with host fibronectin.

Relatório dos Processos Realizados para Atingir os - ODM - Foco Monicipal - Relatório 2007 - 2009 - Cabo Verde

Com o virar do século a Organização das Nações Unidas (ONU) decidiu que era propício e muito simbólico dar um novo impulso à própria Organização e comprometeu-se a combater a pobreza e as doenças que vitimam milhões de crianças em todo o mundo, a maioria das quais com menos de cinco anos, devido a causas totalmente evitáveis como a malária, a diarreia e a pneumonia. Assim, a 8 de Setembro de 2000, 189 Estados membros das ONU adoptaram os “Objectivos de Desenvolvimento do Milénio” (ODM) surgidos da Declaração do Milénio. Foram definidos oito objectivos — cada um deles, um compromisso específico para inverter a propagação da pobreza e das doenças — que são suportados por um Plano de Acção com 18 metas quantificáveis para combater a pobreza, a fome, a doença, o analfabetismo, a discriminação contra a mulher e a degradação ambiental. Muitas das metas dos ODM reflectem um nível de ambição modesto em termos de desenvolvimento humano que os países da ONU se comprometeram a atingir até 2015. Os Objectivos representam igualmente uma parceria entre países desenvolvidos e em desenvolvimento tendo em vista criar um clima a nível nacional e mundial conducente ao desenvolvimento e à eliminação da pobreza. Essa parceria atribui responsabilidades muito claras aos países ricos em termos de prestação de mais ajuda; estabelecimento de regras comerciais mais justas; e alívio significativo da dívida dos países em desenvolvimento. Por seu turno os países em desenvolvimento comprometem-se a vencer o desafio que os ODM colocam. Cabo Verde aceitou o desafio lançado pela ONU para implementar um conjunto de acções estratégicas para que até o ano 2015 um conjunto de objectivos e metas seja realizado. Essa assumpção impõe a integração das metas e indicadores ODM nas políticas públicas nacionais.

Radiothérapie externe accélérée postopératoire des carcinomes épidermoïdes localement évolués de la sphère ORL: étude prospective de phase II [Prospective study of accelerated postoperative radiation therapy in patients with squamous-cell carcinoma of the head and neck]

PURPOSE: To assess the feasibility and efficacy of accelerated postoperative radiation therapy (RT) in patients with squamous-cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Between December 1997 and July 2001, 68 patients (male to female ratio: 52/16; median age: 60-years (range: 43-81) with pT1-pT4 and/or pN0-pN3 SCCHN (24 oropharynx, 19 oral cavity, 13 hypopharynx, 5 larynx, 3 unknown primary, 2 maxillary sinus, and 2 salivary gland) were included in this prospective study. Postoperative RT was indicated because extracapsular infiltration (ECI) was observed in 20 (29%), positive surgical margins (PSM) in 20 (29%) or both in 23 patients (34%). Treatment consisted of external beam RT 66 Gy in 5 weeks and 3 days. Median follow-up was 15 months. RESULTS: According to CTC 2.0, acute morbidity was acceptable: grade 3 mucositis was observed in 15 (22%) patients, grade 3 dysphagia in 19 (28%) patients, grade 3 skin erythema in 21 (31%) patients with a median weight loss of 3.1 kg (range: 0-16). No grade 4 toxicity was observed. Median time to relapse was 13 months; we observed only three (4%) local and four (6%) regional relapses, whereas eight (12%) patients developed distant metastases without any evidence of locoregional recurrence. The 2 years overall-, disease-free survival, and actuarial locoregional control rates were 85, 73 and 83% respectively. CONCLUSION: The reduction of the overall treatment time using postoperative accelerated RT with weekly concomitant boost (six fractions per week) is feasible with local control rates comparable to that of published data. Acute RT-related morbidity is acceptable.

De Novo Assembly of the Pneumocystis jirovecii Genome from a Single Bronchoalveolar Lavage Fluid Specimen from a Patient.

ABSTRACT Pneumocystis jirovecii is a fungus that causes severe pneumonia in immunocompromised patients. However, its study is hindered by the lack of an in vitro culture method. We report here the genome of P. jirovecii that was obtained from a single bronchoalveolar lavage fluid specimen from a patient. The major challenge was the in silico sorting of the reads from a mixture representing the different organisms of the lung microbiome. This genome lacks virulence factors and most amino acid biosynthesis enzymes and presents reduced GC content and size. Together with epidemiological observations, these features suggest that P. jirovecii is an obligate parasite specialized in the colonization of human lungs, which causes disease only in immune-deficient individuals. This genome sequence will boost research on this deadly pathogen. IMPORTANCE Pneumocystis pneumonia is a major cause of mortality in patients with impaired immune systems. The availability of the P. jirovecii genome sequence allows new analyses to be performed which open avenues to solve critical issues for this deadly human disease. The most important ones are (i) identification of nutritional supplements for development of culture in vitro, which is still lacking 100 years after discovery of the pathogen; (ii) identification of new targets for development of new drugs, given the paucity of present treatments and emerging resistance; and (iii) identification of targets for development of vaccines.