Tractor cabin ergonomics analyses by means of Kinect motion capture technology

Kinect is the de facto standard for real-time depth sensing and motion capture cameras. The sensor is here proposed for exploiting body tracking during driving operations. The motion capture system was developed taking advantage of the Microsoft software development kit (SDK), and implemented for real-time monitoring of body movements of a beginner and an expert tractor drivers, on different tracks (straight and with curves) and with different driving conditions (manual and assisted steering). Tests show how analyses can be done not only in terms of absolute movements, but also in terms of relative shifts, allowing for quantification of angular displacements or rotations

Targeted therapy in lymphoma

Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR) pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor) and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma

Effect of carbamide peroxide-based bleaching agents containing fluoride or calcium on tensile strength of human enamel

OBJECTIVE: The aim of this study was to evaluate the effects of carbamide peroxide-based bleaching agents (CPG) containing fluoride (CF) or calcium (CCa) on the ultimate tensile strength of enamel (UTS). METHOD: A "cube-like" resin composite structure was built-up on the occlusal surface of twenty-two sound third molars to facilitate specimen preparation for the micro-tensile test. The restored teeth were serially sectioned in buccal-lingual direction in slices with approximate 0.7 mm thickness. Each slice was trimmed with a fine diamond bur to reduce the buccal, internal slope enamel of the cusps to a dumb-bell shape with a cross-sectional area at the "neck" of less than 0.5 mm². The samples were randomly divided into 12 groups (n=11). The control groups were not submitted to the bleaching regimen. Specimens were treated with 10% CPG gel or with 10% CPG formulations containing CF (0.2% and 0.5%) or CCa (0.05% and 0.2%). Bleached groups received the application of the 10% CPGs for 6 hours/day at 37º C, during 14 consecutive days and were stored in artificial saliva (AS) or 100% relative humidity (RH) among each application. After bleaching, specimens were tested with the microtensile method at 0.5 mm/min. Data were analyzed by two-way ANOVA and Tukey test (5%). RESULTS: No significant difference was observed between groups stored in AS or RH. Specimens treated with CF or CCa presented similar UTS as unbleached control groups. CONCLUSION: Either 10% CPG formulations containing CF or CCa can preserve the UTS after bleaching regimen.OBJETIVO: O propósito deste estudo foi avaliar os efeitos de agents clareadores à base de peróxido de carbamida (CPG) contendo fluoreto (CF) e cálcio (CCa) na resistência à tração do esmalte (UTS). MÉTODO: Um bloco de resina composta foi confeccionada na superfície oclusal de vinte e dois terceiros molars hígidos para facilitar a preparação dos espécimes para o teste de micro-tração. Os dentes restaurados foram seccionados com disco diamantado no sentido vestíbulo-lingual em fatias de aproximadamente 0,7 mm de espessura. Com uma ponta diamantada, foi realizada uma constrição na região de esmalte da vertente oclusal interna. Os espécimes apresentaram aproximadamente 0,5 mm² de área na secção transversal da região de constrição e foram divididos em 12 grupos (n=11). Os grupos controles não foram submetidos ao regime clareador e os experimentais foram tratados com gel de CPG 10% ou com formulações de CPG 10% contendo CF (0,2% e 0,5%) ou CCa (0,05% e 0,2%). Os grupos clareadores receberam a aplicação dos CPGs por 6 horas/dia a 37ºC, durante 14 dias consecutivos e foram armazenados em saliva artificial (AS) ou em umidade relativa 100% (RH), entre as aplicações do gel clareador. Após o clareamento, os espécimes foram testados através do método de micro-tração (0,5 mm/min). Os dados foram analisados pela ANOVA (2 fatores) e teste Tukey (5%). RESULTADOS: Nenhuma diferença foi observada entre os grupos armazenados em AS ou RH. Os espécimes tratados com CPG com CF ou Cca apresentaram similar UTS aos grupos controles não clareados. CONCLUSÃO: Ambos CPGs 10% CF or CCa não alteraram a UTS após o tratamento clareador

Análise dos genes CYP1A1, CYP2D6 e GSTP1 em portadores de câncer de mama esporádico

Orientadora: Enilze Maria de Souza Fonseca RibeiroCoorientador: Iglenir João CavalliMonografia (Bacharelado) - Universidade Federal do Paraná. Setor de Ciencias Biológicas. Curso de Graduaçao em Ciencias BiológicasResumo : O câncer de mama é o segundo tipo de câncer mais freqüente no mundo, sendo o mais comum entre as mulheres (INCA/MS, 2006). Admite-se que a exposição prolongada a níveis aumentados de estrogênio seja o fator central na etiologia do câncer de mama (BERNSTEIN, 2002). O objetivo deste trabalho foi investigar a associação entre o câncer de mama e polimorfismos em três genes atuantes na via metabólica do estrogênio (CYP1A1, CYP2D6 e GSTP1). A amostra foi composta de 85 pacientes e 85 controles do sexo feminino, pareadas por idade (±5 anos) e etnia. Foram coletadas amostras de sangue periférico para extração de DNA pelo método de salting out, e em seguida realizou-se a análise molecular por PCR-RFLP, seguida de visualização em gel de agarose 3,0%. Nossos resultados não demonstraram associação entre a ocorrência de câncer de mama e os genótipos considerados de risco: OR= 1,57 (IC 95%= 0,77 - 3,20) para o polimorfismo CYP1A1 – Msp1, OR= 1,30 (IC 95%= 0,69 - 2,47) para o polimorfismo CYP2D6*4 e OR= 1,69 (IC 95%=0,92 – 3,11) para o polimorfismo GSTP1 – BsmA1. Ao combinar os genótipos considerados de risco dos três genes, não observamos associações com um genótipo de risco (OR= 1,28; IC 95%=0,61 – 2,70), mas encontramos associação com dois ou três genótipos (OR= 2,94; IC 95%=1,21 – 7,16). Na análise dos parâmetros clínicos (idade da menarca, idade da menopausa, tempo entre menarca e menopausa, tempo de uso de pílulas anticoncepcionais, número de filhos e idade da primeira gravidez), encontramos diferenças entre pacientes e controles quanto à idade média da menarca (t= 6,43; P0,01 para o gene GSTP1) e média do tempo entre menarca e menopausa (t= 2,18; P>0,02 para o gene CYP1A1 e t= 2,16; P>0,02 para o gene GSTP1). A análise dos parâmetros histopatológicos (grau histológico do tumor, envolvimento de linfonodos e tamanho do tumor) não apresentou diferenças estatisticamente significantes entre os subgrupos considerados de risco e as pacientes homozigotas selvagens para cada um dos genes estudados. Portanto, uma interação entre os genes em estudo pode estar influenciando o risco ao câncer de mama, assim como alguns dos parâmetros clínicos analisados. Para corroborar estes e os outros resultados do trabalho, torna-se importante a ampliação da amostra utilizada

Identification of RAD51-BRCA2 Inhibitors Using N-Acylhydrazone-Based Dynamic Combinatorial Chemistry

RAD51 is an ATP-dependent recombinase, recruited by BRCA2 to mediate DNA double-strand breaks repair through homologous recombination and represents an attractive cancer drug target. Herein, we applied for the first-time protein-templated dynamic combinatorial chemistry on RAD51 as a hit identification strategy. Upon design of N-acylhydrazone-based dynamic combinatorial libraries, RAD51 showed a clear templating effect, amplifying 19 N-acylhydrazones. Screening against the RAD51-BRCA2 protein-protein interaction via ELISA assay afforded 10 inhibitors in the micromolar range. Further 19F NMR experiments revealed that 7 could bind RAD51 and be displaced by BRC4, suggesting an interaction in the same binding pocket of BRCA2. These results proved not only that ptDCC could be successfully applied on full-length oligomeric RAD51, but also that it could address the need of alternative strategies toward the identification of small-molecule PPI inhibitors

Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study

In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met.LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II-IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1:1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and bortezomib 1·3 mg/m2, plus oral prednisone 100 mg/m2) or R-CHOP (intravenous vincristine 1·4 mg/m2 [2 mg maximum], rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2, plus oral prednisone 100 mg/m2). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed.Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82·0 months (IQR 74·1-94·2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51-0·85]; p=0·001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease.Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma.Janssen Research & Development

FANCD2 and BRCA1 have differential expression among the FA-BRCA genes in primary breast cancer/ Expressão diferencial de FANCD2 e BRCA1 no câncer de mama primário

The molecular pathways of DNA repair in tumors may play a role in tailoring patient therapy. The Fanconi anemia DNA repair pathway operates in the repair of DNA interstrand crosslink induced by several chemotherapeutic drugs. In this study we evaluated the expression of Fanconi anemia DNA repair genes (FANCA, C, D2, F, BRCA1 and PALB2) in 46 primary breast tumors and ten non-compromised breast samples, by Real-Time Quantitative Reverse Transcription PCR, and to correlated gene expression with breast cancer subtypes and clinico-pathological parameters. Tumor samples were classified in subtypes based on immunohistochemistry markers, and clinico-pathological parameters were obtained from the medical reports. FANCD2 was twice more expressed in tumors than in the non-compromised group (p= 0.02). BRCA1 showed a differential expression in the luminal group, three times less expressed in Luminal-B than in Luminal-A group (p= 0.01). In conclusion, the higher level of expression of FANCD2 in tumors may indicate activation of the Fanconi anemia DNA repair pathway, which has been implicated in breast carcinogenesis and in chemotherapeutic resistance. The loss of BRCA1 expression in the Luminal-B group may indicate that the use of cisplatin-based neo/adjuvant therapies is preferable, and that the use of taxol-based therapies should be avoided due to the risk of drug resistance

Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma

The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of (18)F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin- and rituximab-based regimens; 93 had consolidation radiotherapy. Cutoff values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P = .001) and PFS (P < .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P = .0001), whereas PFS was 99% vs 64%, respectively (P < .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567

Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma

Background: the proteasome inhibitor bortezomib was initially approved for the treatment of relapsed mantle-cell lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed mantle-cell lymphoma. Methods: in this phase 3 trial, we randomly assigned 487 adults with newly diagnosed mantle-cell lymphoma who were ineligible or not considered for stem-cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival. Results: after a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-CHOP group versus 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; P<0.001), a relative improvement of 59%. On the basis of investigator assessment, the median durations of progression-free survival were 16.1 months and 30.7 months, respectively (hazard ratio, 0.51; P<0.001), a relative improvement of 96%. Secondary end points were consistently improved in the VR-CAP group, including the complete response rate (42% vs. 53%), the median duration of complete response (18.0 months vs. 42.1 months), the median treatment-free interval (20.5 months vs. 40.6 months), and the 4-year overall survival rate (54% vs. 64%). Rates of neutropenia and thrombocytopenia were higher in the VR-CAP group. Conclusions: VR-CAP was more effective than R-CHOP in patients with newly diagnosed mantle-cell lymphoma but at the cost of increased hematologic toxicity. (Funded by Janssen Research and Development and Millennium Pharmaceuticals; LYM-3002 ClinicalTrials.gov number, NCT00722137)