Development of a thermodynamics of human cognition and human culture.

Inspired by foundational studies in classical and quantum physics, and by information retrieval studies in quantum information theory, we prove that the notions of 'energy' and 'entropy' can be consistently introduced in human language and, more generally, in human culture. More explicitly, if energy is attributed to words according to their frequency of appearance in a text, then the ensuing energy levels are distributed non-classically, namely, they obey Bose-Einstein, rather than Maxwell-Boltzmann, statistics, as a consequence of the genuinely 'quantum indistinguishability' of the words that appear in the text. Secondly, the 'quantum entanglement' due to the way meaning is carried by a text reduces the (von Neumann) entropy of the words that appear in the text, a behaviour which cannot be explained within classical (thermodynamic or information) entropy. We claim here that this 'quantum-type behaviour is valid in general in human language', namely, any text is conceptually more concrete than the words composing it, which entails that the entropy of the overall text decreases. In addition, we provide examples taken from cognition, where quantization of energy appears in categorical perception, and from culture, where entities collaborate, thus 'entangle', to decrease overall entropy. We use these findings to propose the development of a new 'non-classical thermodynamic theory' for human cognition, which also covers broad parts of human culture and its artefacts and bridges concepts with quantum physics entities. This article is part of the theme issue 'Thermodynamics 2.0: Bridging the natural and social sciences (Part 2)'.

Long-term outcomes of ultra-hypofractionated 2 fractions single day HDR brachytherapy in localized prostate cancer.

INTRODUCTION AND OBJECTIVES: We previously published the toxicity and initial results of a prospective cohort of patients treated with 2 fractions HDR-BRT administered in a single day. In the present analysis we report the long-term cancer control results of our prospective trial and investigate the relationship between PSA nadir and biochemical control. MATERIAL AND METHODS: A total of 120 patients were treated with HDR Brachytherapy monotherapy administered in two fractions in a single day. Between November 2010 and February 2016, 84 patients with low-risk and 36 patients with intermediate-risk prostate cancer in accordance with the NCCN practice guidelines. RESULTS: Median age was 66 years (range 45-84) and median PSA was 7.5 ng/ml (range 0.01-16 ng/ml). Overall, 84.2% had Gleason score 6 and 15.8% Gleason 7. Thirty-one percent of patients received ADT.After a median follow-up of the cohort was 123 months. Actuarial rates of no biochemical evidence of disease (bNED), overall survival, local control and metastasis-free survival for all patients were 93.3%, 86.7%, 95.2% and 96.1%, respectively.The median time to achieve PSA nadir was 80.5 months. Patients who attained a PSA Nadir ≤ 0.20 ng/mL exhibited a 10-year bNED survival rate of 96.9%, whereas thosewho failed to reach this PSA level had a survival rate of only 40%. CONCLUSIONS: In patients with favorable localized prostate cancer, 2 fractions HDR-BT monotherapy is a highly curative radiation technique that attains PSA nadir levels < 0.2 ng/mL in 95% of cases.

Estimating the economic and social impact of conditional cash transfers from the Prospera Program in Mexico.

This research analyses the Prospera program's impact on poverty and income distribution through a computable general equilibrium model. It concludes that transfers to households have a positive impact on the Mexican economy but hide the real problem-the low wage share-that, in the long term, prevents poverty from worsening but does not reduce the population in poverty or inequality. In a scenario without transfers, neither the population in poverty nor the Gini Index decreases significantly. The results obtained lead to an understanding of some of the causes of the high rates of poverty and inequality in Mexico, which in turn have been perpetuated since the economic crisis of 1995. This allows the design of public policies in line with the structural needs of the economy, which combat the problem from the root that generates it, in order to contribute to the reduction of inequality in accordance with the UN Sustainable Development Goal 10.

Fluctuaciones del estado emocional en adolescentes embarazadas de zonas rurales en el norte de Colombia. Un estudio cualitativo / Emotional fluctuations in pregnant adolescents from rural areas in the north of Colombia

Esta investigación analiza las fluctuaciones del estado emocional en adolescentes embarazadas de zonas rurales del departamento de Sucre (Colombia). Se halló que la mayoría de las adolescentes ha experimentado cambios bruscos de humor, fluctuando de emociones positivas a negativas y de negativas a positivas, variaciones asociadas principalmente al apoyo sociofamiliar percibido, a la vivencia de acontecimientos vitales estresantes y, al parecer, a cambios hormo-nales. Es positivo para aquellas que consideran que el embarazo les ha dado un motivo para vivir y cambiar su vida. Es negativo para aquellas que tienen problemas en su proceso de gestación (patologías asociadas, problemas con la salud del bebé) o para aquellas cuya familia o esposo no apoyan la nueva situación de la adolescente (AU)

The current study analyses the fluctuations of the emotional state in pregnant adolescents from rural areas of the north of Colombia. Most adolescent girls have experienced sudden positive and / or negative mood swings. The mood fluctuations occurred from positive to negative emotions and from negative to positive, this fluctuation depended mainly on perceived social and family support, the experience of stressful life events and, apparently, hormonal changes. It was positive for those who considered that pregnancy has given them a reason to live and change their life. It was negative for those who have problems in their gestation process (associated pathologies, problems with the baby’s health, among others) or for those whose family or husband did not support the new situation of the adolescent (AU)

The effect of weight loss and exercise on Health-Related Quality of Life (HRQOL) following Endoscopic Bariatric Therapies (EBT) for obesity.

INTRODUCTION: Endoscopic bariatric therapies (EBT) have demonstrated to induce weight loss and improve comorbidities in obese patients. However, little is known about its impact on health-related quality of life (HRQOL) outcomes and physical activity status. This study aimed to evaluate the change in HRQOL and physical activity following EBT induced weight loss in obese patients. METHODS: We approached 181 patients who underwent EBT in a standardized multidisciplinary follow-up program to participate in the study. We provided them two questionnaires-a) Short Form-36 health survey with the physical (PSC) and mental (MSC) summary component scores to capture generic HRQOL, and b) international physical activity questionnaire (IPAQ) for physical activity (PA). We administered the survey at baseline and at 9 months post-procedure. We expressed the procedure outcome as percentage total body weight loss (%TBWL). We expressed continuous variables as mean (SD) or median and categorical variables as percentages. We used non-parametric tests for comparison and performed multivariable linear regression analysis to identify factors associated with improvement in HRQOL. RESULTS: The mean age was 42.2 (11.3) years, and the mean BMI was 38 (5.9)kg/m2. A majority of them were female (n-132, 73%). The EBT included intragastric balloons (n-136, 75%) and endoscopic sleeve gastroplasty (n-24, 25%). The mean %TBWL achieved after the intervention was 16.9 (9.7)%. We noticed a significant improvement in the median PSC (77.8 vs. 90.4, p < 0.001) and MSC (67 vs. 80.2, p < 0.001) scores after EBT. Similarly, we observed a significant positive change in physical activity compared to baseline (1606.2 vs. 2749 MET-minutes/week, p = < 0.001). Linear regression analysis showed an increase in %TBWL was associated with significant improvement in PSC (ß = 0.193, p = 0.003) and MSC (ß = 0.166, p = 0.02) scores of HRQOL, and likewise, increase in PA was independently associated with improvement in MSC (ß = 0.192, p = 0.01). We did not find any difference in outcome based on gender or the type of intervention. CONCLUSION: EBT improves HRQOL in obese patients regardless of the type of intervention. The weight loss induced by EBT and the improvement in PA positively influence the health outcomes and quality of life.

Tau immunotherapies: Lessons learned, current status and future considerations.

The majority of clinical trials targeting the tau protein in Alzheimer's disease and other tauopathies are tau immunotherapies. Because tau pathology correlates better with the degree of dementia than amyloid-ß lesions, targeting tau is likely to be more effective in improving cognition than clearing amyloid-ß in Alzheimer's disease. However, the development of tau therapies is in many ways more complex than for amyloid-ß therapies as briefly outlined in this review. Most of the trials are on humanized antibodies, which may have very different properties than the original mouse antibodies. The impact of these differences are to a large extent unknown, can be difficult to decipher, and may not always be properly considered. Furthermore, the ideal antibody properties for efficacy are not well established and can depend on several factors. However, considering the varied approaches in clinical trials, there is a general optimism that at least some of these trials may provide functional benefits to patients suffering of various tauopathies. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.

Clinical ultrasonography in cardiovascular risk. / Ecografía clínica en el riesgo cardiovascular.

In the prevention of cardiovascular disease, determining the cardiovascular risk is the cornerstone of preventive interventions. In this risk estimation, detecting subclinical cardiovascular damage represents a complementary tool to classic stratification based on risk factors. The versatility, availability, speed, low cost and safety of ultrasonography place it ahead of other techniques employed in detecting subclinical cardiovascular damage. The clinical practice guidelines for cardiovascular risk prevention recommend the use of ultrasonography for assessing atheromatous plaques and left ventricular hypertrophy as modulators of cardiovascular risk. Ultrasonography also has other relevant applications in cardiovascular risk, including the diagnosis of abdominal aortic aneurysms, kidney assessments for patients with chronic kidney disease or suspected secondary arterial hypertension and the detection of steatosis when nonalcoholic fatty liver disease is suspected.

PIMA: A population informative multiplex for the Americas.

We describe an ancestry-informative autosomal SNP multiplex designed to be a small-scale, flexible panel that can complement uniparental markers in assessing the American variability (i.e. pre-Colombian) found in contemporary indigenous American populations. This study centered on choosing SNPs with the specific characteristics of: 1) extreme allele frequency differences between indigenous Americans and the African, European and East Asian population groups that contribute to present-day population variation in the Americas; 2) high informativeness-for-assignment In values; and 3) well-spaced genomic distribution and chromosomal separation from existing small-scale forensic ancestry marker sets. The resulting capillary electrophoresis SNaPshot single base extension test was named: PIMA (Population Informative Multiplex for the Americas), comprising 26 autosomal SNPs, a single X-chromosome SNP plus the amelogenin sex marker adapted for SNaPshot. PIMA complements the established 34plex forensic ancestry panel to provide a powerful and simple tool for the analysis of American populations, including those with admixed histories, commonly encountered in America. Comparing the results obtained with the combined marker panels of PIMA and 34plex to SNP data from a much larger ancestry panel allowed us to gauge their relative efficiency. PIMA+34plex gives equivalent power to the 314-SNP 'LACE' genomic ancestry control panel, while requiring a much smaller genotyping effort. The ancestry profiles and genetic structure of 22 populations spread across the American continent were estimated using PIMA+34plex data, and those estimates were contrasted with information provided by uniparental markers (mtDNA and Y-chromosome loci) for a small set of admixed individuals from Venezuela. Our results indicate that an American genetic component is efficiently detected in contemporary American populations using a small set of ancestry informative SNPs, and these co-ancestry estimates are consistent with the known history and demography of the Americas. The small scale and high population differentiation power of PIMA, particularly when combined with 34plex, provides a practical and powerful tool for genetic studies of American populations as well as forensic DNA analyses.

Efecto de una actividad grupal educativa en la calidad de vida de la persona con EPOC / Effect of an educational group activity on the quality of life of persons with COPD / Efeito de uma atividade grupal educativa na qualidade de vida da pessoa com DPOC

Resumen Introducción: La enfermedad pulmonar obstructiva crónica (EPOC), es un importante problema de salud pública que repercute sobre la calidad de vida. Se requieren intervenciones que reduzcan su impacto. Objetivo: Determinar el efecto de una actividad educativa grupal sobre la calidad de vida de personas con EPOC, que asisten a una institución de cuarto nivel durante septiembre-2017 y junio-2018, en Bogotá, Colombia. Métodos: Diseño cuasi-experimental. La variable independiente fue la actividad educativa grupal y la variable dependiente la calidad de vida, medida con el Cuestionario Respiratorio de Saint George (SGRQ). Los pacientes se aleatorizaron con una tabla generada por computador. El grupo control (n=30) recibió la intervención usual y el grupo experimental (n=30) una actividad educativa grupal diseñada bajo recomendaciones internacionales, impartida por el personal de enfermería. Se excluyeron pacientes con asistencia a actividades grupales durante los últimos dos meses. Resultados: La media de la calidad de vida pos-intervención fue 41% y 32% para el grupo control y experimental, respectivamente, se redujeron dos puntos con respecto a la medición inicial. La dimensión de actividad fue la más comprometida. No se encontraron diferencias estadísticamente significativas en el análisis intragrupal ni intergrupal. Discusión: La leve mejoría pos-intervención en las dimensiones de actividad e impacto, así como las variables sociodemográficas son congruentes con otros estudios. Los resultados pueden guardar relación con la cantidad de actividades desarrolladas. Conclusiones: La actividad grupal no genera mejoría estadísticamente significativa en la calidad de vida de las personas con EPOC. Se identificó una mejoría clínica en las dimensiones de actividad e impacto, así como en la puntuación global.

Abstract Introduction: Chronic obstructive pulmonary disease (COPD) is an important public health problem which affects the quality of life. Consequently, interventions aimed at reducing these impacts are necessary. Objective: To determine the effect of an educational group activity on the quality of life of persons with COPD being attended in a fourth level institution in Bogota, Colombia, in september, 2017 and june, 2018. Methods: The study design was quasi-experimental. The independent variable was the educational group activity, and the dependent variable was the quality of life measured by the St George's Respiratory Questionnaire (SGRQ). Patients were randomized using a computer generated table. The control group (n=30) received the usual intervention while the experimental group (n=30) had an educational group activity designed under international recommendations and given by the nursing staff. Patients who had had other group activities during the last two months were excluded. Results: The post intervention quality of life mean was 41% and 32% for the control and experimental groups respectively. The most compromised dimension was activity. No statistically significant differences were found in the within-group and between-group analyzes. Discussion: The slight post intervention improvement in the dimensions of activity and impact is consistent with other similar studies, but results might vary in relation to the activities performed. Conclusions: This group activity did not induce a statistically significant improvement in the overall quality of life of persons living with COPD, nevertheless, slight improvements were found in the dimensions of activity, impact, and total score.

Resumo Introdução: A doença pulmonar obstrutiva crónica (DPOC), é um importante problema de saúde pública que tem influência sobre a qualidade de vida. Requerem-se intervenções que reduzam seu impacto. Objetivo: Determinar o efeito de uma atividade educativa grupal sobre a qualidade de vida de pessoas com DPOC, que assistem a uma instituição de quarto nível durante setembro-2017 e junho-2018, em Bogotá, Colômbia. Métodos: Desenho quase-experimental. A variável independente foi a atividade educativa grupal e a variável dependente, a qualidade de vida, medida com o Questionário Respiratório de Saint George (SGRQ). Os pacientes foram aleatorizados com uma tabela gerada por computador. O grupo controle (n=30) recebeu a intervenção usual e o grupo experimental (n=30) uma atividade educativa grupal desenhada sob recomendações internacionais, ministrada pelo pessoal de enfermagem. Excluíram-se pacientes com assistência a atividades grupais durante os últimos dois meses. Resultados: A média da qualidade de vida pós- intervenção foi 41% e 32% para o grupo controle e experimental, respetivamente, reduziram-se dois pontos ao respeito da medição inicial. A dimensão de atividade foi a mais comprometida. Não se encontraram diferenças estatisticamente significativas na análise intragrupal nem na intergrupal. Discussão: A leve melhora pós-intervenção nas dimensões de atividade e impacto, assim como as variáveis sociodemográficas são congruentes com outros estudos. Os resultados podem guardar relação com a quantidade de atividades desenvolvidas. Conclusões: A atividade grupal não gera melhora estatisticamente significativa na qualidade de vida das pessoas com DPOC. Encontrou-se uma melhora clínica nas dimensões de atividade e impacto, assim como na pontuação global.

Réplica a «Tratamiento de la hiperuricemia asintomática» / Reply to «Treatment of asymptomatic hyperuricaemia»

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Ultrasonography in the diagnosis of asymptomatic hyperuricemia and gout.

Sonography has detected urate deposits in 34%-42% of the patients with asymptomatic hyperuricemia. This may prompt reclassification of asymptomatic hyperuricemia into "asymptomatic gout" and consideration of urate lowering therapy (ULT) to resolve urate deposits. In patients with gout and no visible tophi, sonography has detected urate deposits in half of the patients. This may allow diagnosing "tophaceous gout" and influencing the serum urate target level, prophylaxis to avoid acute gout flares during ULT, and clinical follow-up. Current accessibility to sonography may better classify patients with hyperuricemia and gout and contribute to delineate therapeutic objectives and clinical guidance.

La ecografía en el diagnóstico de la hiperuricemia asintomática y la gota / Ultrasound in the diagnosis of asymptomatic hyperuricaemia and gout

El aumento de la concentración sérica de uratos (hiperuricemia, mayor o igual a 7,0mg/dL) ocasiona cristales que promueven inflamación y lesión articular. La ecografía puede poner de manifiesto estos depósitos de urato. Su presencia obliga a considerar que un paciente con hiperuricemia en realidad padece gota asintomática, y que un enfermo con gota sin tofos subcutáneos puede tener gota tofácea. La información que ofrece la ecografía (signo del «doble contorno» y de concreciones hiperecogénicas simulando nubes) posibilita una clasificación de la hiperuricemia y de la gota más precisas. Además, esta información puede dar lugar a modificaciones relevantes en cuanto al proceder diagnóstico y terapéutico en los enfermos con hiperuricemia y gota (AU)

The increase in serum urate concentrations (hyperuricaemia, ≥7.0mg/dL) creates crystals, which promote inflammation and joint lesions. Ultrasonography can reveal these urate deposits. The presence of crystals suggests that a patient with hyperuricaemia is actually experiencing asymptomatic gout, and that a patient with gout without subcutaneous tophi could experience tophaceous gout. The information offered by ultrasound (double contour sign and hyperechoic concretions mimicking clouds) enables a more specific classification of hyperuricaemia and gout. Additionally, this information can lead to relevant changes in terms of the diagnosis and therapeutic approach for patients with hyperuricaemia and gout (AU)

Ultrasound in the diagnosis of asymptomatic hyperuricaemia and gout. / La ecografía en el diagnóstico de la hiperuricemia asintomática y la gota.

The increase in serum urate concentrations (hyperuricaemia, ≥7.0mg/dL) creates crystals, which promote inflammation and joint lesions. Ultrasonography can reveal these urate deposits. The presence of crystals suggests that a patient with hyperuricaemia is actually experiencing asymptomatic gout, and that a patient with gout without subcutaneous tophi could experience tophaceous gout. The information offered by ultrasound (double contour sign and hyperechoic concretions mimicking clouds) enables a more specific classification of hyperuricaemia and gout. Additionally, this information can lead to relevant changes in terms of the diagnosis and therapeutic approach for patients with hyperuricaemia and gout.

Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension.

BACKGROUND AND PURPOSE: Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension. EXPERIMENTAL APPROACH: Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mg · kg(-1) · day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mg · kg(-1) · day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mg · kg(-1) · day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used. KEY RESULTS: Celecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR-infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE2 production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF-α expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment. CONCLUSIONS AND IMPLICATIONS: COX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE2 receptors might have benefits in hypertension-associated vascular damage.

A randomized, double-blind phase II study evaluating cediranib versus cediranib and saracatinib in patients with relapsed metastatic clear-cell renal cancer (COSAK).

BACKGROUND: Preclinical work suggests SRC proteins have a role in the development of resistance to vascular endothelial growth factor (VEGF) targeted therapy in metastatic clear-cell renal cancer (mRCC). This hypothesis was tested in this trial using the SRC inhibitor saracatinib and the VEGF inhibitor cediranib. PATIENTS AND METHODS: Patients with disease progression after ≥1 VEGF-targeted therapy were eligible to participate in this double-blind, randomized (1:1) phase II study. The study compared the combination cediranib 30 mg once daily (o.d.) and saracatinib 175 mg o.d. (CS) (n = 69) or cediranib 45 mg o.d. and placebo o.d. (C) (n = 69). Archived tissue was used for biomarker analysis [SRC, focal adhesion kinase (FAK), von Hippel-Lindau, protein tyrosine phosphatase 1b and hypoxia-inducible factor 2α : n = 86]. The primary end point was progression-free survival (PFS) by RECIST v1.1. RESULTS: Between 2010 and 2012, 138 patients were randomized across 16 UK sites. The characteristics of the two groups were well balanced. Partial responses were seen in 13.0% for C and 14.5% for CS (P > 0.05). There was no significant difference in PFS [5.4 months (3.6-7.3 months) for C and 3.9 (2.4-5.3 months) for CS; hazard ratio (HR) 1.18 (0.94-1.48)] or overall survival (OS) [14.2 months (11.2-16.8 months) for C and 10.0 (6.7-13.2 months) for CS; HR 1.28 (1.00-1.63)]. There was no significant difference in the frequency of key adverse events, dose reductions or drug discontinuations. None of the biomarkers were prognostic for PFS or OS. FAK overexpression correlated with an OS benefit [HR 2.29 (1.09-4.82), P > 0.05], but not PFS, for CS. CONCLUSIONS: Saracatinib did not increase the efficacy of a VEGF-targeted therapy (cediranib) in this setting. Biomarker analysis did not identify consistent predictive biomarkers. CLINICALTRIALSGOV: NCT00942877.

A common molecular signature in ASD gene expression: following Root 66 to autism.

Several gene expression experiments on autism spectrum disorders have been conducted using both blood and brain tissue. Individually, these studies have advanced our understanding of the molecular systems involved in the molecular pathology of autism and have formed the bases of ongoing work to build autism biomarkers. In this study, we conducted an integrated systems biology analysis of 9 independent gene expression experiments covering 657 autism, 9 mental retardation and developmental delay and 566 control samples to determine if a common signature exists and to test whether regulatory patterns in the brain relevant to autism can also be detected in blood. We constructed a matrix of differentially expressed genes from these experiments and used a Jaccard coefficient to create a gene-based phylogeny, validated by bootstrap. As expected, experiments and tissue types clustered together with high statistical confidence. However, we discovered a statistically significant subgrouping of 3 blood and 2 brain data sets from 3 different experiments rooted by a highly correlated regulatory pattern of 66 genes. This Root 66 appeared to be non-random and of potential etiologic relevance to autism, given their enriched roles in neurological processes key for normal brain growth and function, learning and memory, neurodegeneration, social behavior and cognition. Our results suggest that there is a detectable autism signature in the blood that may be a molecular echo of autism-related dysregulation in the brain.

Dermatitis de contacto inducida por henna: Reporte de un caso / Contact dermatitis induced by henna: A case report

La henna es un colorante vegetal ampliamente utilizado para crear tatuajes temporales. Su coloración negra se debe a la adición de parafenilendiamina, potente sensibilizador, conocido como agente causal de dermatitis de contacto por reacciones de hipersensibilidad tipo IV. La frecuencia de dermatitis de contacto secundarias a este compuesto parece ir en aumento, siendo necesario educar a la población en relación a los efectos secundarios a su uso, que en algunos casos pueden ser severos y permanentes.

Henna is a vegetal colorant widely used to create temporary tattoos. Its black color is created by the addition of paraphenylenediamine that is a potent sensitizer agent, known as a cause of type-IV allergic contact dermatitis. The frequency of contact dermatitis secondary to this compound appears to be increasing, being necessary to educate people regarding the secondary effects of its use, which in some cases can be severe and permanent.

Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.

BACKGROUND: The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score. METHODS: Paraffin sections from 761 men with clinically localized prostate cancer diagnosed by needle biopsy and managed conservatively in the United Kingdom, mostly between 2000 and 2003. The primary end point was prostate cancer death. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA level, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Full data were available for 585 men who formed a fully independent validation cohort. RESULTS: In univariate analysis, the CCP score hazard ratio was 2.08 (95% CI (1.76, 2.46), P<10(-13)) for one unit change of the score. In multivariate analysis including CAPRA, the CCP score hazard ratio was 1.76 (95% CI (1.44, 2.14), P<10(-6)). The predefined CCR score was highly predictive, hazard ratio 2.17 (95% CI (1.83, 2.57), χ(2)=89.0, P<10(-20)) and captured virtually all available prognostic information. CONCLUSIONS: The CCP score provides significant pretreatment prognostic information that cannot be provided by clinical variables and is useful for determining which patients can be safely managed conservatively, avoiding radical treatment.