4-Second Exercise Test: Reference Values for Ages 18–81 Years

Background: Physiological reflexes modulated primarily by the vagus nerve allow the heart to decelerate and accelerate rapidly after a deep inspiration followed by rapid movement of the limbs. This is the physiological and pharmacologically validated basis for the 4-s exercise test (4sET) used to assess the vagal modulation of cardiac chronotropism. Objective: To present reference data for 4sET in healthy adults. Methods: After applying strict clinical inclusion/exclusion criteria, 1,605 healthy adults (61% men) aged between 18 and 81 years subjected to 4sET were evaluated between 1994 and 2014. Using 4sET, the cardiac vagal index (CVI) was obtained by calculating the ratio between the duration of two RR intervals in the electrocardiogram: 1) after a 4-s rapid and deep breath and immediately before pedaling and 2) at the end of a rapid and resistance-free 4-s pedaling exercise. Results: CVI varied inversely with age (r = -0.33, p < 0.01), and the intercepts and slopes of the linear regressions between CVI and age were similar for men and women (p > 0.05). Considering the heteroscedasticity and the asymmetry of the distribution of the CVI values according to age, we chose to express the reference values in percentiles for eight age groups (years): 18–30, 31–40, 41–45, 46–50, 51–55, 56–60, 61–65, and 66+, obtaining progressively lower median CVI values ranging from 1.63 to 1.24. Conclusion: The availability of CVI percentiles for different age groups should promote the clinical use of 4sET, which is a simple and safe procedure for the evaluation of vagal modulation of cardiac chronotropism.

Los 81 años de vigencia del impuesto sobre incrementos de los terrenos de naturaleza urbana

Siendo este impuesto uno de los más controvertidos en lo que concierne a la jurisprudencia, encontraba interesante el saber el origen y el desarrollo Histórico de este impuesto.Ver la evolución histórica del Impuesto desde un punto de vista tributario o sea si cumple o se adapta a las técnicas tributarias y si esta de acorde con los principios generalmente aceptados, o si ha sido y es un impuesto que sólo cumple con el fin recaudatorio. Hay que tener en cuenta que representa para los entes locales de un 6 ó un 7% de los impuestos directos recaudados, siendo el cuarto en recaudación después del IBI. IAE y del Impuesto sobre Vehículos. Osea que no perdamos de vista que cierto valor recaudatorio lo tiene ahora y antes.

Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

AIM: To confirm the accuracy of sentinel node biopsy (SNB) procedure and its morbidity, and to investigate predictive factors for SN status and prognostic factors for disease-free survival (DFS) and disease-specific survival (DSS). MATERIALS AND METHODS: Between October 1997 and December 2004, 327 consecutive patients in one centre with clinically node-negative primary skin melanoma underwent an SNB by the triple technique, i.e. lymphoscintigraphy, blue-dye and gamma-probe. Multivariate logistic regression analyses as well as the Kaplan-Meier were performed. RESULTS: Twenty-three percent of the patients had at least one metastatic SN, which was significantly associated with Breslow thickness (p<0.001). The success rate of SNB was 99.1% and its morbidity was 7.6%. With a median follow-up of 33 months, the 5-year DFS/DSS were 43%/49% for patients with positive SN and 83.5%/87.4% for patients with negative SN, respectively. The false-negative rate of SNB was 8.6% and sensitivity 91.4%. On multivariate analysis, DFS was significantly worsened by Breslow thickness (RR=5.6, p<0.001), positive SN (RR=5.0, p<0.001) and male sex (RR=2.9, p=0.001). The presence of a metastatic SN (RR=8.4, p<0.001), male sex (RR=6.1, p<0.001), Breslow thickness (RR=3.2, p=0.013) and ulceration (RR=2.6, p=0.015) were significantly associated with a poorer DSS. CONCLUSION: SNB is a reliable procedure with high sensitivity (91.4%) and low morbidity. Breslow thickness was the only statistically significant parameter predictive of SN status. DFS was worsened in decreasing order by Breslow thickness, metastatic SN and male gender. Similarly DSS was significantly worsened by a metastatic SN, male gender, Breslow thickness and ulceration. These data reinforce the SN status as a powerful staging procedure

Isolated office hypertension: a prehypertensive state?

OBJECTIVE AND METHOD: Isolated office hypertension, defined as hypertensive blood pressure values in a medical setting but normal self-measured or ambulatory-recorded blood pressures, is frequently encountered in clinical practice. Yet, whether this condition represents a transient state in the development of a sustained ambulatory hypertension is still unknown as no long-term analysis of the evolution of ambulatory blood pressure has been carried out in patients with isolated office hypertension. To evaluate whether such patients should be considered as truly normotensive or hypertensive, we have studied the long-term changes in office and ambulatory blood pressures in 81 patients in whom isolated office hypertension was observed between 1982 and 1988. RESULTS: After a 5-6 year follow-up, 60 of the 81 patients had a mean 12 h daytime ambulatory blood pressure greater than 140/90 mmHg, suggesting an evolution towards ambulatory hypertension. The development of hypertension could not be predicted on the basis of the follow-up office blood pressures as these tended to decrease during the follow-up period. CONCLUSIONS: The results of this study suggest that patients with isolated office hypertension should not be considered as truly normotensive individuals. Hence, these patients require a careful medical follow-up. Office blood pressure readings alone, however, do not appear to provide a good indicator of the long-term outcome of isolated office hypertension.

El clima social i emocional en els mòduls de participació i convivència dels centres penitenciaris catalans

Aquest estudi es proposa valorar indicadors descriptius de la població penitenciària estudiada, analitzar les diferències entre programes d’organització (mòduls de participació i convivència versus ordinaris), i avaluar els indicadors de clima (social i emocional), per tal d’establir hipòtesi explicatives de la comparació dels resultats entre els mòduls de participació i convivència i altres mòduls de la mateixa àrea especialitzada (violència, drogodependències o preparació per a la vida en llibertat). Per això, s’han recollit dades de 14 indicadors descriptius de població i de 18 indicadors d’organització i participació de 1124 interns, dels 10 mòduls residencials estudiats de 3 de les presons catalanes. A més, s’han recollit 327 inventaris d’interns i 57 de professionals de clima emocional, i 331 escales d’interns i 92 de professionals de clima social per a Institucions Penitenciàries (Moos). Els resultats de les respostes als dos instruments de clima emocional i clima social emprats, ofereixen un índex de consistència interna o fiabilitat molt elevada, considerant que tenen una validesa predictiva molt potent. D’aquests resultats, s’analitzen les diferències en el clima emocional i social en relació al tipus d’organització de la unitat (participació i convivència o ordinària), al col·lectiu d’interns i al de professionals, i en relació a les variables descriptives de la població de cada unitat residencial d’estudi. Finalment s’estableixen unes hipòtesi explicatives d’aquests resultats, per tal de plantejar propostes de millora per al funcionament dels mòduls estudiats i per a l’avaluació futura, alhora que es valoren les possibilitats de generalització dels mòduls de participació i convivència als centres penitenciaris catalans en general i s’efectuen recomanacions per a l’adequada implantació dels mateixos (condicions mínimes d’execució): establiment d’un programa marc per part del centre directiu, que comprometi els centres al compliment d’uns estàndards de qualitat.

[Horace] Van Ruith (81 ans) travaillant au tableau de Miss Cavell : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 56988

Archives parlementaires de 1787 à 1860 ; 52-61, 63-82. Convention nationale. Série 1 / Tome 81 / impr. par ordre du Sénat et de la Chambre des députés ; fondé par MM. Mavidal et E. Laurent ; continué́ par M. L. Lataste,... M. Louis Claveau,... M. Constant Pionnier,... [et al.]

Collection : Les archives de la Révolution française ; 3.1

Evaluación de bancos naturales de “palabritas” (Donax spp.) en el litoral de Lambayeque, 2010.

En marzo y junio 2010, se efectuaron evaluaciones poblacionales del recurso Donax spp., entre El Palo y playa La Punta del litoral de Lambayeque. La talla fluctuó entre 5 y 32 mm (marzo) y 7 a 33 mm (junio). La madurez gonadal en hembras en marzo, mostró el predominio de madurez total (24,35%), y en junio predominaron en estadio de evacuación parcial (22,2%) y evacuación total (18,9%). La densidad media en marzo varió entre 5,00 y 243,74 ind.m-2, encontrándose mayor concentración en El María y mayor dispersión en Playa Monsefú; en junio fluctuó entre 9,19 y 80,48 ind.m-2 con mayor concentración en El María. En marzo la población estimada fue 329,22 millones de individuos ± 27,96% y biomasa 702,24 t ± 27,94%; en junio fue 229,20 millones de individuos ± 32,69% y biomasa 577,27 t ± 31,91%. En marzo una mayor abundancia se registró en El María (110,90 millones de individuos) y Bodegones (81,28 millones de individuos), en junio El Gigante (50,83 millones de ejemplares) y El María (46,28 millones de ejemplares).

Friday Facts, December 3, 2010, Vol. 81

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

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.

CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation.

Previously we determined that S81 is the highest stoichiometric phosphorylation on the androgen receptor (AR) in response to hormone. To explore the role of this phosphorylation on growth, we stably expressed wild-type and S81A mutant AR in LHS and LAPC4 cells. The cells with increased wild-type AR expression grow faster compared with parental cells and S81A mutant-expressing cells, indicating that loss of S81 phosphorylation limits cell growth. To explore how S81 regulates cell growth, we tested whether S81 phosphorylation regulates AR transcriptional activity. LHS cells stably expressing wild-type and S81A mutant AR showed differences in the regulation of endogenous AR target genes, suggesting that S81 phosphorylation regulates promoter selectivity. We next sought to identify the S81 kinase using ion trap mass spectrometry to analyze AR-associated proteins in immunoprecipitates from cells. We observed cyclin-dependent kinase (CDK)9 association with the AR. CDK9 phosphorylates the AR on S81 in vitro. Phosphorylation is specific to S81 because CDK9 did not phosphorylate the AR on other serine phosphorylation sites. Overexpression of CDK9 with its cognate cyclin, Cyclin T, increased S81 phosphorylation levels in cells. Small interfering RNA knockdown of CDK9 protein levels decreased hormone-induced S81 phosphorylation. Additionally, treatment of LNCaP cells with the CDK9 inhibitors, 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole and Flavopiridol, reduced S81 phosphorylation further, suggesting that CDK9 regulates S81 phosphorylation. Pharmacological inhibition of CDK9 also resulted in decreased AR transcription in LNCaP cells. Collectively these results suggest that CDK9 phosphorylation of AR S81 is an important step in regulating AR transcriptional activity and prostate cancer cell growth.