CD10 is inversely associated with nuclear factor-kappa B and predicts biochemical recurrence after radical prostatectomy.

INTRODUCTION: The cell surface endopeptidase CD10 (neutral endopeptidase) and nuclear factor-κB (NF-κB) have been independently associated with prostate cancer (PC) progression. We investigated the correlations between these two factors and their prognostic relevance in terms of biochemical (prostate-specific antigen, PSA) relapse after radical prostatectomy (RP) for localized PC. PATIENTS AND METHODS: The immunohistochemical expression of CD10 and NF-κB in samples from 70 patients who underwent RP for localized PC was correlated with the preoperative PSA level, Gleason score, pathological stage and time to PSA failure. RESULTS: CD10 expression was inversely associated with NF-κB expression (p < 0.001), stage (p = 0.03) and grade (p = 0.003), whereas NF-κB was directly related with stage (p = 0.006) and grade (p = 0.002). The median time to PSA failure was 56 months. CD10 and NF-κB were directly (p < 0.001) and inversely (p < 0.001) correlated with biochemical recurrence-free survival, respectively. CD10 expression (p = 0.022) and stage (p = 0.018) were independently associated with time to biochemical recurrence. CONCLUSION: Low CD10 expression is an adverse prognostic factor for biochemical relapse after RP in localized PC, which is also associated with high NF-κB expression. Decreased CD10 expression which would lead to increased neuropeptide signaling and NF-κB activity may be present in a subset of early PCs.

Applications of the bootstrap to survival analysis

En este trabajo se revisan algunas de las aplicaciones clásicas del bootstrap al análisis de la supervivencia. Se consideran en primer lugar el estimador bootstrap de la varianza y el estimador de la mediana corregido para el sesgo del estimador de Kaplan-Meier de la función de supervivencia. A continuación se consideran algunos aspectos mas recientes, tales como métodos para construir bandas de confianza para el estimador de la funcidn de supervivencia y contrastes aproximados para la comparación de funciones de supervivencia. En ambas situaciones el bootstrap resulta de gran utilidad para la aproximación de 10s valores críticos necesarios.

Indicadores de qualidade de solos de área de mineração e metalurgia de chumbo: II - Mesofauna e plantas

A influência do manejo ou a adição de contaminante ao solo, normalmente, induz uma resposta mais rápida sobre a mesofauna do solo do que em outros atributos pedológicos, o que torna esses organismos bons indicadores de qualidade ambiental. Os objetivos deste trabalho foram identificar e quantificar os grupos de organismos da mesofauna dos solos e determinar os teores de Pb e Zn de plantas da área de mineração e metalurgia de Pb, no município de Adrianópolis (PR), de modo que fossem gerados indicadores biológicos da qualidade desses solos. Os solos selecionados apresentaram as seguintes características em relação às formas de contaminação: solo 1 - referência (mata nativa); solo 2 - resíduos incorporados ao perfil; solos 3 e 6 - próximos às chaminés da fábrica, com potencial de aporte de material particulado; e solo 5 - grande volume de rejeitos sobre o solo. Foram utilizados funis de Berlese, coletando-se amostras na profundidade de 0 a 5 cm (20 funis x 5 solos x 1 profundidade x 4 épocas = 400 amostras). Após separação da mesofauna, procedeu-se à triagem e identificação dos organismos com o auxílio de lupa. Amostras de formiga foram digeridas com HNO3 concentrado em sistema fechado de micro-ondas, e os teores de Pb e Zn foram determinados por espectroscopia de emissão atômica com plasma indutivamente acoplado (ICP-AES). Plantas da família Poaceae foram coletadas em todos os solos e, após digestão das amostras da parte aérea e da raiz pelo método nítrico-perclórico, determinaram-se os teores de Pb e Zn por ICP-AES. O número total de organismos dos 21 grupos identificados e o Índice de Qualidade Ambiental da Mesofauna não foram bons indicadores do nível de contaminação dos solos por metais pesados. A ocorrência e distribuição de espécies isoladas mostraram-se mais eficientes nesse propósito. A melhor qualidade ambiental do solo 1 (teores naturais de Pb - solo de referência) foi atestada pela maior riqueza de grupos de organismos e ocorrência de representantes dos grupos Pseudoscorpiones, Mollusca e Isopoda apenas nesse solo. Os grupos Aracnídeos e Psocoptera também foram considerados bons indicadores ambientais, com incremento de suas populações nos solos com maiores teores de metais pesados (solos 2, 3 e 5), possivelmente devido à menor ocorrência de organismos competidores/predadores desses grupos. Os teores de metais pesados nos indivíduos do grupo Formicidae tiveram relação direta com os teores de Pb extraídos com HNO3 0,5 mol L-1 no solo. Quanto ao acúmulo de metais pesados nas plantas coletadas na área, com exceção do solo 1, todas as espécies encontravam-se sob efeito fitotóxico para Pb e Zn, o que sugere a proibição de pastejo na área.

Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging.

AIMS: We studied the respective added value of the quantitative myocardial blood flow (MBF) and the myocardial flow reserve (MFR) as assessed with (82)Rb positron emission tomography (PET)/CT in predicting major adverse cardiovascular events (MACEs) in patients with suspected myocardial ischaemia. METHODS AND RESULTS: Myocardial perfusion images were analysed semi-quantitatively (SDS, summed difference score) and quantitatively (MBF, MFR) in 351 patients. Follow-up was completed in 335 patients and annualized MACE (cardiac death, myocardial infarction, revascularization, or hospitalization for congestive heart failure or de novo stable angor) rates were analysed with the Kaplan-Meier method in 318 patients after excluding 17 patients with early revascularizations (<60 days). Independent predictors of MACEs were identified by multivariate analysis. During a median follow-up of 624 days (inter-quartile range 540-697), 35 MACEs occurred. An annualized MACE rate was higher in patients with ischaemia (SDS >2) (n = 105) than those without [14% (95% CI = 9.1-22%) vs. 4.5% (2.7-7.4%), P < 0.0001]. The lowest MFR tertile group (MFR <1.8) had the highest MACE rate [16% (11-25%) vs. 2.9% (1.2-7.0%) and 4.3% (2.1-9.0%), P < 0.0001]. Similarly, the lowest stress MBF tertile group (MBF <1.8 mL/min/g) had the highest MACE rate [14% (9.2-22%) vs. 7.3% (4.2-13%) and 1.8% (0.6-5.5%), P = 0.0005]. Quantitation with stress MBF or MFR had a significant independent prognostic power in addition to semi-quantitative findings. The largest added value was conferred by combining stress MBF to SDS. This holds true even for patients without ischaemia. CONCLUSION: Perfusion findings in (82)Rb PET/CT are strong MACE outcome predictors. MBF quantification has an added value allowing further risk stratification in patients with normal and abnormal perfusion images.

Genomics and the origin of species.

Speciation is a fundamental evolutionary process, the knowledge of which is crucial for understanding the origins of biodiversity. Genomic approaches are an increasingly important aspect of this research field. We review current understanding of genome-wide effects of accumulating reproductive isolation and of genomic properties that influence the process of speciation. Building on this work, we identify emergent trends and gaps in our understanding, propose new approaches to more fully integrate genomics into speciation research, translate speciation theory into hypotheses that are testable using genomic tools and provide an integrative definition of the field of speciation genomics.

Characteristics and outcome of 27 elbow periprosthetic joint infections: results from a 14-year cohort study of 358 elbow prostheses.

Elbow arthroplasty is increasingly performed in patients with rheumatic and post-traumatic arthritis. Data on elbow periprosthetic joint infection (PJI) are limited. We investigated the characteristics and outcome of elbow PJI in a 14-year cohort of total elbow arthroplasties in a single centre. Elbow prosthesis, which were implanted between 1994 and 2007 at Schulthess Clinic in Zurich, were retrospectively screened for infection. PJI was defined as periprosthetic purulence, the presence of sinus tract or microbial growth. A Kaplan-Meier survival method and Cox proportional hazard analysis were performed. Of 358 elbow prostheses, PJI was identified in 27 (7.5%). The median patient age (range) was 61 (39-82) years; 63% were females. Seventeen patients (63%) had a rheumatic disorder and ten (37%) had osteoarthritis. Debridement and implant retention was performed in 78%, followed by exchange or removal of the prosthesis (15%) or no surgery (7%).The relapse-free survival (95% CI) was 79% (63-95%) after 1 year and 65% (45-85%) after 2 years. The outcome after 2 years was significantly better when patients were treated according to the algorithm compared to patients who were not (100% vs. 33%, p &lt;0.05). In 21 patients treated with debridement and retention, the cure rate was also higher when the algorithm was followed (100% vs. 11%, p &lt;0.05). The findings of the present study suggest that the treatment algorithm developed for hip and knee PJI can be applied to elbow PJI. With proper patient selection and antimicrobial therapy, debridement and retention of the elbow prosthesis is associated with good treatment outcome.

Magnetic-field dependence of hole levels in self-assembled InGaAs quantum dots

Recent magnetotransport experiments of holes in InGaAs quantum dots [D. Reuter, P. Kailuweit, A. D. Wieck, U. Zeitler, O. Wibbelhoff, C. Meier, A. Lorke, and J. C. Maan, Phys. Rev. Lett. 94, 026808 (2005)] are interpreted by employing a multiband k¿p Hamiltonian, which considers the interaction between heavy hole and light hole subbands explicitly. No need of invoking an incomplete energy shell filling is required within this model. The crucial role we ascribe to the heavy hole-light hole interaction is further supported by one-band local-spin-density functional calculations, which show that Coulomb interactions do not induce any incomplete hole shell filling and therefore cannot account for the experimental magnetic field dispersion.

Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.

BACKGROUND: Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. METHODS: BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years. Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere. Follow-up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at clinicaltrials.govNCT00004205. FINDINGS: 8010 patients were included in the trial, with a median follow-up of 8·1 years (range 0-12·4). 2459 were randomly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years. In the four-arm option of the trial, 1546 were randomly assigned to letrozole for 5 years, 1548 to tamoxifen for 5 years, 1540 to letrozole for 2 years followed by tamoxifen for 3 years, and 1548 to tamoxifen for 2 years followed by letrozole for 3 years. At a median follow-up of 8·7 years from randomisation (range 0-12·4), letrozole monotherapy was significantly better than tamoxifen, whether by IPCW or intention-to-treat analysis (IPCW disease-free survival HR 0·82 [95% CI 0·74-0·92], overall survival HR 0·79 [0·69-0·90], DRFI HR 0·79 [0·68-0·92], BCFI HR 0·80 [0·70-0·92]; intention-to-treat disease-free survival HR 0·86 [0·78-0·96], overall survival HR 0·87 [0·77-0·999], DRFI HR 0·86 [0·74-0·998], BCFI HR 0·86 [0·76-0·98]). At a median follow-up of 8·0 years from randomisation (range 0-11·2) for the comparison of the sequential groups with letrozole monotherapy, there were no statistically significant differences in any of the four endpoints for either sequence. 8-year intention-to-treat estimates (each with SE ≤1·1%) for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78·6%, 77·8%, 77·3% for disease-free survival; 87·5%, 87·7%, 85·9% for overall survival; 89·9%, 88·7%, 88·1% for DRFI; and 86·1%, 85·3%, 84·3% for BCFI. INTERPRETATION: For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability. FUNDING: Novartis, United States National Cancer Institute, International Breast Cancer Study Group.

Recommendation of soil fertility levels for willow in the southern highlands of Santa Catarina

The species Salix x rubens is being grown on the Southern Plateau of Santa Catarina since the 1940s, but so far the soil fertility requirements of the crop have not been assessed. This study is the first to evaluate the production profile of willow plantations in this region, based on the modified method of Summer & Farina (1986), for the recommendation of fertility levels for willow. By this method, based on the law of Minimum and of Maximum for willow production for the conditions on the Southern Plateau of Santa Catarina, the following ranges could be recommended: pH: 5.0-6.5; P: 12-89 mg dm-3; Mg: 3.2-7.5 mg; Zn: 5.0-8.3 mg dm-3; Cu: 0.8-4.6 mg dm-3; and Mn; 20-164 mg dm-3. The Ca/Mg ratio should be between 1.2 and 2.9. For K and Ca only the lower (sufficiency level), but not the upper threshold (excess) was established, with respectively 114 mg dm-3 and 5.3 cmol c dm-3. It was also possible to determine the upper threshold for Al and the Al/Ca ratio, i.e., 1.7 cmol c dm-3 and 0.28, respectively. For maximum yields, the clay in the soil surface layer should be below 320 g dm-3.