Predictive Value Of Phase I Trials For Safety In Later Trials And Final Approved Dose: Analysis Of 61 Approved Cancer Drugs.

Phase I trials use a small number of patients to define a maximum tolerated dose (MTD) and the safety of new agents. We compared data from phase I and registration trials to determine whether early trials predicted later safety and final dose. We searched the U.S. Food and Drug Administration (FDA) website for drugs approved in nonpediatric cancers (January 1990-October 2012). The recommended phase II dose (R2PD) and toxicities from phase I were compared with doses and safety in later trials. In 62 of 85 (73%) matched trials, the dose from the later trial was within 20% of the RP2D. In a multivariable analysis, phase I trials of targeted agents were less predictive of the final approved dose (OR, 0.2 for adopting ± 20% of the RP2D for targeted vs. other classes; P = 0.025). Of the 530 clinically relevant toxicities in later trials, 70% (n = 374) were described in phase I. A significant relationship (P = 0.0032) between increasing the number of patients in phase I (up to 60) and the ability to describe future clinically relevant toxicities was observed. Among 28,505 patients in later trials, the death rate that was related to drug was 1.41%. In conclusion, dosing based on phase I trials was associated with a low toxicity-related death rate in later trials. The ability to predict relevant toxicities correlates with the number of patients on the initial phase I trial. The final dose approved was within 20% of the RP2D in 73% of assessed trials.

Impact Of Chemical Changes On The Sensory Characteristics Of Coffee Beans During Storage.

Sensory changes during the storage of coffee beans occur mainly due to lipid oxidation and are responsible for the loss of commercial value. This work aimed to verify how sensory changes of natural coffee and pulped natural coffee are related to the oxidative processes during 15 months of storage. During this period, changes in the content of free fatty acids (1.4-3.8 mg/g oil), TBARS values (8.8-10.2 nmol MDA/g), and carbonyl groups (2.6-3.5 nmol/mg of protein) occurred. The intensity of rested coffee flavour in the coffee brew increased (2.1-6.7) and 5-caffeoylquinic acid concentration decreased (5.2-4.6g/100g). Losses were also observed in seed viability, colour of the beans and cellular structure. All the results of the chemical analyses are coherent with the oxidative process that occurred in the grains during storage. Therefore, oxidation would be also responsible for the loss of cellular structure, seed viability and sensory changes.

Volumetric Capnography For The Evaluation Of Chronic Airways Diseases.

Obstructive lung diseases of different etiologies present with progressive peripheral airway involvement. The peripheral airways, known as the silent lung zone, are not adequately evaluated with conventional function tests. The principle of gas washout has been used to detect pulmonary ventilation inhomogeneity and to estimate the location of the underlying disease process. Volumetric capnography (VC) analyzes the pattern of CO2 elimination as a function of expired volume. To measure normalized phase 3 slopes with VC in patients with non-cystic fibrosis bronchiectasis (NCB) and in bronchitic patients with chronic obstructive pulmonary disease (COPD) in order to compare the slopes obtained for the groups. NCB and severe COPD were enrolled sequentially from an outpatient clinic (Hospital of the State University of Campinas). A control group was established for the NCB group, paired by sex and age. All subjects performed spirometry, VC, and the 6-Minute Walk Test (6MWT). Two comparisons were made: NCB group versus its control group, and NCB group versus COPD group. The project was approved by the ethical committee of the institution. Statistical tests used were Wilcoxon or Student's t-test; P<0.05 was considered to be a statistically significant difference. Concerning the NCB group (N=20) versus the control group (N=20), significant differences were found in body mass index and in several functional variables (spirometric, VC, 6MWT) with worse results observed in the NCB group. In the comparison between the COPD group (N=20) versus the NCB group, although patients with COPD had worse spirometric and 6MWT values, the capnographic variables mean phase 2 slope (Slp2), mean phase 3 slope normalized by the mean expiratory volume, or mean phase 3 slope normalized by the end-tidal CO2 concentration were similar. These findings may indicate that the gas elimination curves are not sensitive enough to monitor the severity of structural abnormalities. The role of normalized phase 3 slope may be worth exploring as a more sensitive index of small airway disease, even though it may not be equally sensitive in discriminating the severity of the alterations.

[meanings Of The Sickening Process For Patients With Systemic Lupus Erythematosus: A Review Of The Literature.]

Systemic lupus erythematosus is an autoimmune disease that causes many psychological repercussions that have been studied through qualitative research. These are considered relevant, since they reveal the amplitude experienced by patients. Given this importance, this study aims to map the qualitative production in this theme, derived from studies of experiences of adult patients of both genders and that had used as a tool a semi-structured interview and/or field observations, and had made use of a sampling by a saturation criterion to determine the number of participants in each study. The survey was conducted in Pubmed, Lilacs, Psycinfo e Cochrane databases, searching productions in English and Portuguese idioms published between January 2005 and June 2012. The 19 revised papers that have dealt with patients in the acute phase of the disease showed themes that were categorized into eight topics that contemplated the experienced process at various stages, from the onset of the disease, extending through the knowledge of the diagnosis and the understanding of the manifestations of the disease, drug treatment and general care, evolution and prognosis. The collected papers also point to the difficulty of understanding, of the patients, on what consists the remission phase, revealing also that this is a clinical stage underexplored by psychological studies.

Value Of Sentinel Lymph Node Biopsy In Papillary Thyroid Cancer: Initial Results Of A Prospective Trial.

The objectives of the study were to evaluate the performance of sentinel lymph node biopsy (SLNB) in detecting occult metastases in papillary thyroid carcinoma (PTC) and to correlate their presence to tumor and patient characteristics. Twenty-three clinically node-negative PTC patients (21 females, mean age 48.4 years) were prospectively enrolled. Patients were submitted to sentinel lymph node (SLN) lymphoscintigraphy prior to total thyroidectomy. Ultrasound-guided peritumoral injections of (99m)Tc-phytate (7.4 MBq) were performed. Cervical single-photon emission computed tomography and computed tomography (SPECT/CT) images were acquired 15 min after radiotracer injection and 2 h prior to surgery. Intra-operatively, SLNs were located with a gamma probe and removed along with non-SLNs located in the same neck compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted to histopathology analysis. Sentinel lymph nodes were located in levels: II in 34.7 % of patients; III in 26 %; IV in 30.4 %; V in 4.3 %; VI in 82.6 % and VII in 4.3 %. Metastases in the SLN were noted in seven patients (30.4 %), in non-SLN in three patients (13.1 %), and in the lateral compartments in 20 % of patients. There were significant associations between lymph node (LN) metastases and the presence of angio-lymphatic invasion (p = 0.04), extra-thyroid extension (p = 0.03) and tumor size (p = 0.003). No correlations were noted among LN metastases and patient age, gender, stimulated thyroglobulin levels, positive surgical margins, aggressive histology and multifocal lesions. Sentinel lymph node biopsy can detect occult metastases in PTC. The risk of a metastatic SLN was associated with extra-thyroid extension, larger tumors and angio-lymphatic invasion. This may help guide future neck dissection, patient surveillance and radioiodine therapy doses.

The Value Of Audiovisual Archives.

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Levantamento fitossociológico e caráter sucessional de um trecho de floresta secundária ciliar em Juquitiba, SP, Brasil

The objective of this study was to evaluate the horizontal and vertical structures of tree community in regeneration in a fragment of a secondary riparian forest at approximately 30 years of age and to identify the most abundant species in each fragment of the forest to determine the sucessional stage. An area of 800 m² was subdivided into 16 samples of 10 x 5 m and all individuals with DBH ≥ 1 cm were sampled and identified for the following analyzes: horizontal parameters (DR, FR, DoR, IVC and IVI), vertical parameters (PSR and RNR) and mixed parameters, from of value of increased importance index (IVIa). The survey measured 689 individuals, belonging to 38 families, 74 genus and 109 species. The total density was 8,614 individuals/ha. The index of Shannon´s diversity was 3.99 and the index of Pielou´s equability was 0.85. Tibouchina pulchra, Psychotria suterella and Endlicheria paniculata obtained high values of IVIa. Guarea macrophylla, Gomidesia anacardiaefolia, Xylopia langsdorffiana and Endlicheria paniculata achieved high values of RNT, indicating adequate natural regeneration in the plot. The initial secondary and umbrophylous species showed the highest ecological importance in this fragment of the forest, with the highest values of sociologic position and importance index. Furthermore, the presence of late secondary species in all layers suggest that the studied fragment is in intermediate succession degree.

Projeto de um cortador de base para colhedora de cana-de-açúcar utilizando otimização matemática

A base-cutter represented for a mechanism of four bars, was developed using the Autocad program. The normal force of reaction of the profile in the contact point was determined through the dynamic analysis. The equations of dynamic balance were based on the laws of Newton-Euler. The linkage was subject to an optimization technique that considered the peak value of soil reaction force as the objective function to be minimized while the link lengths and the spring constant varied through a specified range. The Algorithm of Sequential Quadratic Programming-SQP was implemented of the program computational Matlab. Results were very encouraging; the maximum value of the normal reaction force was reduced from 4,250.33 to 237.13 N, making the floating process much less disturbing to the soil and the sugarcane rate. Later, others variables had been incorporated the mechanism optimized and new otimization process was implemented .

Modelo de programação quadrática para análise da movimentação logística e comercialização da soja brasileira

The purpose of this work was to analyze the logistical distribution of Brazilian soybean by applying a quadratic programming to a spatial equilibrium model. The soybean transportation system is an important part of the soybean complex in Brazil, since the major part of the costs of this commodity derives from the transportation costs. Therefore, the optimization of this part of the process is essential to a better competitiveness of the Brazilian soybean in the international market. The Brazilian soybean complex have been increasing its agricultural share in the total of the exportation value in the last ten years, but due to other countries' investments the Brazilian exportations cannot be only focused on increasing its production but it still have to be more efficient. This way, a model was reached which can project new frames by switching the transportation costs and conduce the policy makers to new investments in the sector.

Proposta metodológica utilizando ferramentas de qualidade na avaliação do processo de pulverização

The present work aimed to create a methodology to evaluate the pulverization process with the use of quality tools. It was listed the primary factors, secondary factors, tertiary factors and, with the check list tool support, the list was elaborated. It was evaluated the factors labor, agriculture machine, material and method of 32 pulverization process before pesticide application, in that each factor received a punctuation, having as total sum of 750 points. The medium punctuation to the factors labor, agriculture machine, material and method was 78; 211; 49; 20 and 94 points, respectively. The sum of the factors points for the 32 processes, the minimum value found was 230 and maximum was 620 points. With the proposed methodology, can be identify which common causes of the processes can affect its result.

Taxonomic value of foliar characters in Dahlstedtia Malme: Leguminosae, Papilionoideae, Millettieae

Dahlstedtia Malme (Leguminosae) is a neotropical genus, native to the Brazilian Atlantic Forest, and comprises two species, D. pinnata (Benth.) Malme and D. pentaphylla (Taub.) Burk., although it has been considered a monotypic genus by some authors. Leaf anatomy was compared to verify the presence of anatomical characters to help delimit species. Foliar primordium, leaflet, petiolule, petiole and pulvinus were collected from cultivated plants (Campinas, SP, Brazil) and from natural populations (Picinguaba, Ubatuba and Caraguatatuba, SP, Brazil - D. pinnata; Antonina, PR, Brazil - D. pentaphylla). Studies on leaflet surface assessment (Scanning Electron Microscopy), as well as histology and venation analyses were carried out of dehydrated, fresh and fixed material from two species. Leaflet material was macerated for stomatal counts. Histological sections, obtained by free-hand cut or microtome, were stained with Toluidine Blue, Safranin/Alcian Blue, Ferric Chloride, Acid Phloroglucin. Secretory cavities are present in the lamina, petiolule, petiole, pulvinus and leaf primordium in D. pentaphylla, but not in D. pinnata, and can be considered an important character for species diagnosis. Other leaf characters were uninformative in delimiting Dahlstedtia species. There is cambial activity in the petiolule, petiole and pulvinus. This study, associated with other available data, supports the recognition of two species in Dahlstedtia.

Folhas verdes, folhas secas, fibra do colmo e a clarificação do caldo de cana-de-açúcar

The presence of vegetal impurities in sugarcane delivered to sugarmills as green and dry leaves is a problem not only because they are non-value materials to be processed along with sugarcane stalks, but also because they can rise the color of the clarified juice and, consequently, the color of the sugar produced, with a reduction of its quality for the market. Another problem is the mud volume sedimented in the clarifiers, which also can result in a larger recirculation and greater volume of filtrate juice, with higher losses of sucrose and utilization of the vacuum rotary filters. The objective of this work was to observe the effect of the presence of green and dry leaves on sugarcane juice clarification, related to a control treatment with the addition of fiber extracted from the stalks. The experiments were planned based on the addition of quantities of fibrous sources in order to formulate samples with absolute increase of 0.25 , 0.50 and 0.75 percentual points over the fiber content of the sugarcane stalks (control treatment). The juice clarification was conducted with a laboratory clarifier. The clarified juice color and the mud volume were evaluated. The presence of green leaves caused higher color and mud volume due to the extraction of non-sucrose components of the leaves. Soluble compounds of dry leaves were also extracted, though not detected by juice analysis. The addition of the fiber extracted from the stalks did not induce alterations in the clarification process.

Avaliação do amaciamento de carne bovina de dianteiro (Triceps brachii) pelos métodos de maturação, estimulação elétrica, injeção de ácidos e tenderização mecânica

Twenty-two Triceps brachii muscle obtained from 11 cows aged 3 and 4 years , killed in an experimental slaughter plant, were submitted to mechanical tenderization, injection with acetic acid 0,1M and lactic acid 0,2M, ageing for 9 and 14 days and electrical stimulation (250v - 60Hz - 90s), some of them were reserved as a control group, without treatment. The 14 days ageing time presented 21% of increase in subjective tenderness and 12% of reduction in shear force, these values were similar to the electrical stimulated meat. However the injection with acids and the ageing time 9 days did not present significant effect in the texture. Although the shear force values of mechanical tenderized meat was the shortest among all treatments, suspect of superestimation because of the fractures plan created by this process. Another analyses were carried out: pH reduction curve, R value; colour analysis; weight losses by cooking and by treatment; and microbiological analysis.

Ocorrência de fungos filamentosos termo-resistentes em polpa de tomate envasada assepticamente

This work aimed at determining the occurrence of heat resistant molds during the aseptic processing of tomato pulp (8° BRIX). During tomato harvest, 9 lots were sampled (3 at the beginning, 3 at the apex and 3 at the end of harvest) and other 5 lots were sampled between harvest. For each lot, the enumeration of heat resistant molds was carried out in samples collected during the aseptic process. The mean count of heat resistant molds was relatively low, ranging from <1 to 8CFU/100mL of sample. The higher counts were observed in the raw material and the pre-wash and transportation water. Fifty strains of heat resistant molds detected in the enumeration procedure were isolated, codified and stocked. One-month-old spores of each isolate were submitted to different heat shocks to select the most heat resistant mold. The most heat resistant isolated strain (survived 100° C/25 minutes) was identified as Neosartorya fischeri.