Ultra-High Field (7 Tesla) MRI for Gamma Knife Surgery Targeting of the Ventro-Intermediate Nucleus: A Pilot in Vivo Study

Aim: Gamma Knife surgery (GKS) is a non-invasive neurosurgical stereotactic procedure, increasingly used as an alternative to open functional procedures. This includes the targeting of the ventro-intermediate (Vim) nucleus of the thalamus for tremor. We currently perform an indirect targeting, using the "quadrilatere of Guyot," as the Vim nucleus is not visible on current 3 Tesla (T) MRI acquisitions. The primary objective of the current study was to enhance anatomic imaging for Vim GKS using high-field (7 T) MRI, with the aim of refining the visualization and precision of anatomical targeting. Method: Five young healthy subjects (mean age 23 years) were scanned both on 3 and 7 T MRI in Lausanne University Hospital (CHUV) and Center for Biomedical Imaging (CIBM). Classical T1-weighted MPRAGE, T2 CISS sequences (replacing former ventriculography) and diffusion tensor imaging were acquired at 3T. We obtained high-resolution susceptibility weighted images (SWI) at 7T for the visualization of thalamic subparts. SWI was further integrated for the first time into Leksell Gamma Plan® (LGP) software and co-registered with the 3T images. A simulation of targeting of the Vim was done using the "quadrilatere of Guyot" methodology on the 3T images. Furthermore, a correlation with the position of the found target on SWI was performed. The atlas of Morel et al. was used to confirm the findings on a detailed computer analysis outside LGP. Also, 3T and 7T MRI of one patient undergoing GKS Vim thalamotomy, were obtained before and 2 years after the procedure, and studied similarly. Results: The use of SWI provided a superior resolution and improved image contrast within the central gray matter. This allowed visualization and direct delineation of groups of thalamic nuclei in vivo, including the Vim. The position of the target, as assessed with the "quadrilatere of Guyot" method on 3 T, perfectly matched with the supposed one of the Vim on the SWI. Furthermore, a 3-dimensional model of the Vim target area was created on the basis of 3T and 7T images. Conclusion: This is the first report of the integration of SWI high-field MRI into the LGP in healthy subjects and in one patient treated GKS Vim thalamotomy. This approach aims at the improvement of targeting validation and further direct targeting of the Vim in tremor. The anatomical correlation between the direct visualization on 7T and the current targeting methods on 3T seems to show a very good anatomical matching.

Melhoria da estrutura de um latossolo por sistemas de culturas em plantio direto nos Campos Gerais do Paraná

O plantio direto de qualidade depende de um manejo adequado do solo que promova melhorias em sua estrutura. Isso está associado ao sistema de culturas adotado. O objetivo deste trabalho foi avaliar a contribuição de sistemas de culturas de longo prazo (18 anos) na qualidade estrutural de um Latossolo Vermelho mesoférrico argiloso sob plantio direto nos Campos Gerais do Paraná. Foram avaliados cinco sistemas de culturas: trigo-soja [Tr-So]; aveia-milho-trigo-soja [Av-Mi-Tr-So]; ervilhaca-milho-trigo-soja [Er-Mi-Tr-So]; azevém-milho-azevém-soja [Az-Mi-Az-So]; e alfafa-milho [Alf-Mi]. Amostras de solo foram coletadas nas camadas de 0-5, 5-10 e 10-20 cm, em anéis volumétricos e em blocos com estrutura preservada. Na camada de 0-5 cm, as menores densidades de solo tenderam a ocorrer nos sistemas Av-Mi-Tr-So (0,96 Mg m-3) e Er-Mi-Tr-So (0,93 Mg m-3). Nas camadas de 5-10 e 10-20 cm, as menores densidades de solo ocorreram no sistema Alf-Mi (1,14 e 1,17 Mg m-3, respectivamente). Tendência coerente foi observada para a macroporosidade, que na camada superficial foi maior nos sistemas Av-Mi-Tr-So (0,29 m³ m-3) e Er-Mi-Tr-So (0,30 m³ m-3) e, nas camadas de 5-10 e 10-20 cm, tendeu a ser maior no sistema Alf-Mi (0,19 m³ m-3). A microporosidade não apresentou tendência clara entre os sistemas. A condutividade hidráulica saturada teve relação direta com a macroporosidade, com Er-Mi-Tr-So apresentando o maior valor na camada de 0-5 cm (224 mm h-1) e Alf-Mi nas camadas de 5-10 (170 mm h-1) e 10-20 cm (147 mm h-1). O sistema Er-Mi-Tr-So apresentou o menor diâmetro médio ponderado úmido de agregados na camada de 0-5 cm (2,39 mm), e o Tr-So, o maior (3,04 mm). Os maiores valores de resistência mecânica do solo à penetração foram observados no sistema Tr-So, superando 1,5 MPa na camada de 7,5 a 22,5 cm de profundidade. O sistema Alf-Mi apresentou o menor grau de compactação (0,2 MPa cm). Os resultados são atribuídos, principalmente, à ação das raízes das espécies que constituem os sistemas de culturas e à intensidade de tráfego de máquinas em cada sistema. Considerando a camada de 0-20 cm como um todo, o sistema semiperene Alf-Mi possui maior capacidade de promover melhorias na qualidade estrutural do solo, em comparação aos sistemas baseados em cultivos de espécies anuais. Sistemas bianuais de rotação, baseados em plantas de cobertura como aveia-preta ou ervilhaca, promovem melhorias na qualidade estrutural do solo em relação à sucessão trigo-soja.

Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: study design and baseline characteristics.

OBJECTIVE: Intervention during the pre-psychotic period of illness holds the potential of delaying or even preventing the onset of a full-threshold disorder, or at least of reducing the impact of such a disorder if it does develop. The first step in realizing this aim was achieved more than 10 years ago with the development and validation of criteria for the identification of young people at ultra-high risk (UHR) of psychosis. Results of three clinical trials have been published that provide mixed support for the effectiveness of psychological and pharmacological interventions in preventing the onset of psychotic disorder. METHOD: The present paper describes a fourth study that has now been undertaken in which young people who met UHR criteria were randomized to one of three treatment groups: cognitive therapy plus risperidone (CogTher + Risp: n = 43); cognitive therapy plus placebo (CogTher + Placebo: n = 44); and supportive counselling + placebo (Supp + Placebo; n = 28). A fourth group of young people who did not agree to randomization were also followed up (monitoring: n = 78). Baseline characteristics of participants are provided. RESULTS AND CONCLUSION: The present study improves on the previous studies because treatment was provided for 12 months and the independent contributions of psychological and pharmacological treatments in preventing transition to psychosis in the UHR cohort and on levels of psychopathology and functioning can be directly compared. Issues associated with recruitment and randomization are discussed.

An ultra-sensitive impedimetric immunosensor for detection of the serum oncomarker CA-125 in ovarian cancer patients.

Effective treatment of ovarian cancer depends upon the early detection of the malignancy. Here, we report on the development of a new nanostructured immunosensor for early detection of cancer antigen 125 (CA-125). A gold electrode was modified with mercaptopropionic acid (MPA), and then consecutively conjugated with silica coated gold nanoparticles (AuNP@SiO2), CdSe quantum dots (QDs) and anti-CA-125 monoclonal antibody (mAb). The engineered MPA|AuNP@SiO2|QD|mAb immunosensor was characterised using transmission electron microscopy (TEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Successive conjugation of AuNP@SiO2, CdSe QD and anti-CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U mL(-1) and a linear detection range (LDR) of 0-0.1 U mL(-1). Based on the high sensitivity and specificity of the immunosensor, we propose this highly stable and reproducible biosensor for the early detection of CA-125.

Estrutura e armazenamento de água em um Argissolo sob pastagem cultivada, floresta nativa e povoamento de eucalipto no Rio Grande do Sul

Práticas pouco adequadas de manejo têm ocasionado a compactação e a degradação da estrutura do solo. Identificar atributos que melhor representem essas alterações são relevantes na recuperação e na indicação de práticas para evitar danos na estrutura do solo. Objetivou-se avaliar o impacto de diferentes usos em atributos estruturais e hídricos de um Argissolo Vermelho. O estudo foi realizado no município de Butiá, na região fisiográfica da Serra do Sudeste do Estado do Rio Grande do Sul, em um Argissolo Vermelho distrófico. As áreas analisadas corresponderam a: floresta antropizada constituída por espécies arbóreas e arbustivas (Floresta); pastagem com cinco anos de idade, com braquiária brizanta (Brachiaria brizantha) consorciada com pensacola (Paspalum lourai) e trevo (Trifolium sp.) (Pastagem); povoamento de Eucalyptus saligna com 20 anos de idade (Eucalipto 20); e plantio clonal de Eucalyptus saligna conduzido em segunda rotação, com 4,5 anos de idade (Eucalipto 4,5). Avaliaram-se nessas áreas a textura, a condutividade hidráulica, a porosidade, a densidade, o diâmetro médio ponderado de agregados (DMP), a curva de retenção de água, a distribuição do tamanho de poros e o parâmetro S, obtendo-se as seguintes conclusões: até a camada de 0,10 m na Pastagem, e 0,40 m no Eucalipto 4,5, os agregados foram formados pela ação da textura e matéria orgânica e pelo efeito compressivo, decorrente do pisoteio dos bovinos e da colheita do eucalipto. Conforme a profundidade aumentou, ocorreu redução do DMP de agregados, em razão da diminuição da matéria orgânica, e aumento do cascalho, especialmente para as áreas de Pastagem e Eucalipto 4,5, e ao menor efeito da compressão do solo. A textura e a matéria orgânica evidenciaram influência na agregação do solo e, mesmo em pequena proporção, o cascalho reduziu o DMP de agregados, pois sua baixa reatividade e seu maior diâmetro dificultaram a formação de agregados estáveis. Em relação aos atributos hídricos do solo, as áreas de Floresta e a Pastagem apresentaram maior disponibilidade de água, enquanto o maior parâmetro S está relacionado ao maior armazenamento de água.

ESTRUTURA DO SOLO SOB FEIJÃO IRRIGADO E DIFERENTES MANEJO DO SOLO

O manejo agrícola influencia a estrutura do solo, modificando os atributos físicos e o comportamento hídrico do solo. O objetivo deste trabalho foi avaliar os efeitos da semeadura direta (SD) e do preparo convencional (PC) sobre a estrutura do solo, por meio de atributos físicos e da distribuição dos poros, utilizando imagens digitais 2-D. O estudo foi realizado em um Latossolo Vermelho distroférrico com delineamento de blocos casualizados. A densidade do solo, macroporosidade, diâmetro médio ponderado (DMP), condutividade hidráulica do solo saturado (Kfs) e análise de imagens digitais 2-D (resolução de 156,25 μm2) foram avaliadas nas profundidades de 0-0,20 e 0,20-0,40 m. Os manejos não diferiram para a densidade e macroporosidade do solo. A SD revelou maior DMP e Kfs em relação ao PC. O PC apresentou maior área total de poros na profundidade de 0-0,20 m em relação ao SD, ocorrendo o inverso na profundidade de 0,20-0,40 m. A SD apresentou maior quantidade de poros complexos de tamanho grande (>0,156 mm2) na camada de 0,20-0,40 m em relação ao PC, que evidenciou predomínio de poros arredondados. A SD demonstrou melhorias na estrutura do solo em relação ao PC, com maior estabilidade dos agregados, condutividade hidráulica e área total de poros, contribuindo para a conservação do solo e da água em sistemas produtivos.

Le sevrage ultra-rapide sous anesthésie générale: l'expérience de l'Hôpital de St-Loup [Ultrafast opiate detoxification under general anesthesia: the St. Loup Hospital experience]

Rapid antagonist induction under anesthesia is a method that has been increasingly used to detoxify opiate addicts. These procedures are useful to reduce the duration and the discomfort of withdrawal. However, the high risk and the cost of these methods require randomized clinical trial to evaluate safety and clinical effectiveness. The University Substance Abuse Division of Lausanne and the Intensive Care Unit of the St-Loup Hospital work on a randomized clinical trial comparing anesthesia-assisted versus traditional clonidine detoxification combined with an additional psychosocial week. This paper describes the technique of anesthesia used in our study. Our clinical experience suggests that, integrating this technique in a multidisciplinary network, with a strong emphasis on post-anesthetic follow-up, is a viable and safe option in the treatment of opiate dependence.

Design and Performance Verifcation of Ultra-High Performance Concrete Piles for Deep Foundations Final Report, November 2008

The strategic plan for bridge engineering issued by AASHTO in 2005 identified extending the service life and optimizing structural systems of bridges in the United States as two grand challenges in bridge engineering, with the objective of producing safer bridges that have a minimum service life of 75 years and reduced maintenance cost. Material deterioration was identified as one of the primary challenges to achieving the objective of extended life. In substructural applications (e.g., deep foundations), construction materials such as timber, steel, and concrete are subjected to deterioration due to environmental impacts. Using innovative and new materials for foundation applications makes the AASHTO objective of 75 years service life achievable. Ultra High Performance Concrete (UHPC) with compressive strength of 180 MPa (26,000 psi) and excellent durability has been used in superstructure applications but not in geotechnical and foundation applications. This study explores the use of precast, prestressed UHPC piles in future foundations of bridges and other structures. An H-shaped UHPC section, which is 10-in. (250-mm) deep with weight similar to that of an HP10×57 steel pile, was designed to improve constructability and reduce cost. In this project, instrumented UHPC piles were cast and laboratory and field tests were conducted. Laboratory tests were used to verify the moment-curvature response of UHPC pile section. In the field, two UHPC piles have been successfully driven in glacial till clay soil and load tested under vertical and lateral loads. This report provides a complete set of results for the field investigation conducted on UHPC H-shaped piles. Test results, durability, drivability, and other material advantages over normal concrete and steel indicate that UHPC piles are a viable alternative to achieve the goals of AASHTO strategic plan.

Alterations of Neuromuscular Function after the World's Most Challenging Mountain Ultra-Marathon

We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time = 122.43 hours +/-17.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean +/- SD maximal voluntary contraction force declined significantly at Mid- (-13+/-17% and -10+/-16%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- (-24+/-13% and -26+/-19%, P<0.01) with alteration of the central activation ratio (-24+/-24% and -28+/-34% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: -18+/-18% and PF: -20+/-15%, P<0.01) and peak twitch (KE: -33+/-12%, P<0.001 and PF: -19+/-14%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719+/-3045 Ul.1), lactate dehydrogenase (1145+/-511 UI.L-1), C-Reactive Protein (13.1+/-7.5 mg.L-1) and myoglobin (449.3+/-338.2 microg.L-1) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half.

Single-step extraction of fluconazole from plasma by ultra-filtration for the measurement of its free concentration by high performance liquid chromatography.

High performance liquid chromatography (HPLC) is the reference method for measuring concentrations of antimicrobials in blood. This technique requires careful sample preparation. Protocols using organic solvents and/or solid extraction phases are time consuming and entail several manipulations, which can lead to partial loss of the determined compound and increased analytical variability. Moreover, to obtain sufficient material for analysis, at least 1 ml of plasma is required. This constraint makes it difficult to determine drug levels when blood sample volumes are limited. However, drugs with low plasma-protein binding can be reliably extracted from plasma by ultra-filtration with a minimal loss due to the protein-bound fraction. This study validated a single-step ultra-filtration method for extracting fluconazole (FLC), a first-line antifungal agent with a weak plasma-protein binding, from plasma to determine its concentration by HPLC. Spiked FLC standards and unknowns were prepared in human and rat plasma. Samples (240 microl) were transferred into disposable microtube filtration units containing cellulose or polysulfone filters with a 5 kDa cut-off. After centrifugation for 60 min at 15000g, FLC concentrations were measured by direct injection of the filtrate into the HPLC. Using cellulose filters, low molecular weight proteins were eluted early in the chromatogram and well separated from FLC that eluted at 8.40 min as a sharp single peak. In contrast, with polysulfone filters several additional peaks interfering with the FLC peak were observed. Moreover, the FLC recovery using cellulose filters compared to polysulfone filters was higher and had a better reproducibility. Cellulose filters were therefore used for the subsequent validation procedure. The quantification limit was 0.195 mgl(-1). Standard curves with a quadratic regression coefficient &gt; or = 0.9999 were obtained in the concentration range of 0.195-100 mgl(-1). The inter and intra-run accuracies and precisions over the clinically relevant concentration range, 1.875-60 mgl(-1), fell well within the +/-15% variation recommended by the current guidelines for the validation of analytical methods. Furthermore, no analytical interference was observed with commonly used antibiotics, antifungals, antivirals and immunosuppressive agents. Ultra-filtration of plasma with cellulose filters permits the extraction of FLC from small volumes (240 microl). The determination of FLC concentrations by HPLC after this single-step procedure is selective, precise and accurate.

Capacitação no uso das bases Medline e Lilacs: avaliação de conteúdo, estrutura e metodologia

Avaliação dos resultados da capacitação de usuários de buscas informatizadas do Curso de Acesso às Bases em cd-rom Medline e Lilacs, modalidade do Programa Educativo da Biblioteca/CIR da Faculdade de Saúde Pública da USP, oferecido a docentes e alunos da pós-graduação em saúde pública. O universo de estudo foi constituído de 92 participantes entre 1993 e 1995. Os egressos do curso opinaram sobre o seu conteúdo, estrutura, metodologia, material didático e demais aspectos específicos à organização de capacitação desse nível. Concluiu-se que o Curso Medline e Lilacs está atendendo às necessidades dos usuários das buscas informatizadas, precisando de algumas adequações, as quais são apontadas neste artigo.

Ultra high throughput sequencing excludes MDH1 as candidate gene for RP28-linked retinitis pigmentosa.

PURPOSE: Mutations in IDH3B, an enzyme participating in the Krebs cycle, have recently been found to cause autosomal recessive retinitis pigmentosa (arRP). The MDH1 gene maps within the RP28 arRP linkage interval and encodes cytoplasmic malate dehydrogenase, an enzyme functionally related to IDH3B. As a proof of concept for candidate gene screening to be routinely performed by ultra high throughput sequencing (UHTs), we analyzed MDH1 in a patient from each of the two families described so far to show linkage between arRP and RP28. METHODS: With genomic long-range PCR, we amplified all introns and exons of the MDH1 gene (23.4 kb). PCR products were then sequenced by short-read UHTs with no further processing. Computer-based mapping of the reads and mutation detection were performed by three independent software packages. RESULTS: Despite the intrinsic complexity of human genome sequences, reads were easily mapped and analyzed, and all algorithms used provided the same results. The two patients were homozygous for all DNA variants identified in the region, which confirms previous linkage and homozygosity mapping results, but had different haplotypes, indicating genetic or allelic heterogeneity. None of the DNA changes detected could be associated with the disease. CONCLUSIONS: The MDH1 gene is not the cause of RP28-linked arRP. Our experimental strategy shows that long-range genomic PCR followed by UHTs provides an excellent system to perform a thorough screening of candidate genes for hereditary retinal degeneration.

Alterations in Postural Control during the World's Most Challenging Mountain Ultra-Marathon

We investigated postural control (PC) effects of a mountain ultra-marathon (MUM): a 330-km trail run with 24000 m of positive and negative change in elevation. PC was assessed prior to (PRE), during (MID) and after (POST) the MUM in experienced ultra-marathon runners (n = 18; finish time = 126+/-16 h) and in a control group (n = 8) with a similar level of sleep deprivation. Subjects were instructed to stand upright on a posturographic platform over a period of 51.2 seconds using a double-leg stance under two test conditions: eyes open (EO) and eyes closed (EC). Traditional measures of postural stability (center of pressure trajectory analysis) and stabilogram-diffusion analysis (SDA) parameters were analysed. For the SDA, a significantly greater short-term effective diffusion was found at POST compared with PRE in the medio-lateral (ML; Dxs) and antero-posterior (AP) directions (Dys) in runners (p<0.05) The critical time interval (Ctx) in the ML direction was significantly higher at MID (p<0.001) and POST (p<0.05) than at PRE in runners. At MID (p<0.001) and POST (p<0.05), there was a significant difference between the two groups. The critical displacement (Cdx) in the ML was significantly higher at MID and at POST (p<0.001) compared with PRE for runners. A significant difference in Cdx was observed between groups in EO at MID (p<0.05) and POST (p<0.005) in the ML direction and in EC at POST in the ML and AP directions (p<0.05). Our findings revealed significant effects of fatigue on PC in runners, including, a significant increase in Ctx (critical time in ML plan) in EO and EC conditions. Thus, runners take longer to stabilise their body at POST than at MID. It is likely that the mountainous characteristics of MUM (unstable ground, primarily uphill/downhill running, and altitude) increase this fatigue, leading to difficulty in maintaining balance.

Comunidades científicas e infra-estrutura tecnológica no Brasil para uso de recursos eletrônicos de comunicação e informação na pesquisa

Estudo do uso de recursos eletrônicos de comunicação e informação por pesquisadores brasileiros, na geração de novos conhecimentos. A análise abrange a freqüência de participação na rede, fatores intervenientes, finalidades de uso e o grau de relevância dessa tecnologia. No acesso e uso da informação científica e técnica, são comparados os recursos eletrônicos/digitais e os impressos/ tradicionais. A partir dos resultados, são identificadas percepções e perspectivas, entre as quais a aproximação entre comunicação científica e divulgação científica, a confluência dos processos de comunicação e informação e o crescente interesse pela temática da pesquisa, inclusive no Brasil. Pela importância dos recursos eletrônicos para pesquisa, há necessidade de sua expansão e atualização constantes, com investimento das instituições e sua inserção nas políticas públicas nacionais.