Serum HER-2 concentration is associated with insulin resistance and decreases after weight loss.

HER2/neu is a member of the epidermal growth factor receptor family easily detectable in the serum of cancer patients. We aimed to evaluate circulating HER-2 concentrations in association with insulin resistance in healthy and obese subjects. METHODS: Insulin sensitivity (minimal model) and serum HER-2 concentrations were evaluated in a cross sectional study in men (cohort 1, n = 167) and longitudinally after weight loss in obese subjects (cohort 2, n = 30). RESULTS: Serum HER-2 concentrations were positively associated with BMI and waist circumference (both r = 0.18, p = 0.02), post-load glucose (r = 0.28, p = 0.001) and fasting triglycerides (r = 0.26, p = 0.001); and negatively associated with insulin sensitivity (r = -0.29, p = 0.002, n = 109). Subjects with type 2 diabetes showed significantly increased soluble serum HER-2 concentrations. In different multivariate regression models, fasting triglycerides emerged as the factor that independently contributed to 10-11% of serum HER-2 variance.Serum HER-2 concentrations correlated significantly with fasting triglycerides and insulin sensitivity index in subjects from cohort 2. Weight loss led to a significant decrease of serum HER-2 concentrations. The change in serum HER-2 concentrations were significantly associated with the change in percent body fat and fasting triglycerides in young (below the median age of the cohort) subjects. CONCLUSIONS: Serum HER-2 concentrations might be implicated in the pathophysiology of insulin resistance and associated comorbidities

Circulating omentin concentration increases after weight loss

Omentin-1 is a novel adipokine expressed in visceral adipose tissue and negatively associated with insulin resistance and obesity. We aimed to study the effects of weight loss-induced improved insulin sensitivity on circulating omentin concentrations. METHODS: Circulating omentin-1 (ELISA) concentration in association with metabolic variables was measured in 35 obese subjects (18 men, 17 women) before and after hypocaloric weight loss. RESULTS: Baseline circulating omentin-1 concentrations correlated negatively with BMI (r = -0.58, p < 0.001), body weight (r = -0.35, p = 0.045), fat mass (r = -0.67, p < 0.001), circulating leptin (r = -0.7, p < 0.001) and fasting insulin (r = -0.37, p = 0.03). Circulating omentin-1 concentration increased significantly after weight loss (from 44.9 +/- 9.02 to 53.41 +/- 8.8 ng/ml, p < 0.001). This increase in circulating omentin after weight loss was associated with improved insulin sensitivity (negatively associated with HOMA value and fasting insulin, r = -0.42, p = 0.02 and r = -0.45, p = 0.01, respectively) and decreased BMI (r = -0.54, p = 0.001). CONCLUSION: As previously described with adiponectin, circulating omentin-1 concentrations increase after weight loss-induced improvement of insulin sensitivity

A New Microlensing Event in the Doubly-Imaged Quasar Q0957+561

We present evidence for ultraviolet/optical microlensing in the gravitationally lensed quasar Q0957+561. We combine new measurements from our optical monitoring campaign at the United States Naval Observatory, Flagstaff (USNO) with measurements from the literature and find that the time-delay-corrected r-band flux ratio m_A - m_B has increased by ~0.1 magnitudes over a period of five years beginning in the fall of 2005. We apply our Monte Carlo microlensing analysis procedure to the composite light curves, obtaining a measurement of the optical accretion disk size, log {(r_s/cm)[cos(i)/0.5]^{1/2}} = 16.2^{+0.5}_{-0.6}, that is consistent with the quasar accretion disk size - black hole mass relation.Comment: Replaced with accepted version. Minor adjustments to text but conclusions unchanged. Data in Table 2 have been updated and table now includes additional observation

The INT Search for Metal-Poor Stars. Spectroscopic Observations and Classification via Artificial Neural Networks

With the dual aims of enlarging the list of extremely metal-poor stars identified in the Galaxy, and boosting the numbers of moderately metal-deficient stars in directions that sample the rotational properties of the thick disk, we have used the 2.5m Isaac Newton Telescope and the Intermediate Dispersion Spectrograph to carry out a survey of brighter (primarily northern hemisphere) metal-poor candidates selected from the HK objective-prism/interference-filter survey of Beers and collaborators. Over the course of only three observing runs (15 nights) we have obtained medium-resolution (resolving power ~ 2000) spectra for 1203 objects (V ~ 11-15). Spectral absorption-line indices and radial velocities have been measured for all of the candidates. Metallicities, quantified by [Fe/H], and intrinsic (B-V)o colors have been estimated for 731 stars with effective temperatures cooler than roughly 6500 K, making use of artificial neural networks (ANNs), trained with spectral indices. We show that this method performs as well as a previously explored Ca II K calibration technique, yet it presents some practical advantages. Among the candidates in our sample, we identify 195 stars with [Fe/H] <= -1.0, 67 stars with [Fe/H] <= -2.0, and 12 new stars with [Fe/H] <= -3.0. Although the EFECTIVE YIELD of metal-poor stars in our sample is not as large as previous HK survey follow-up programs, the rate of discovery per unit of telescope time is quite high.Comment: 27 pages (including 13 figures) + 6 tables (20 pages); uses aastex, lscape and graphicx; to appear in A

Data Mining and Machine Learning in Astronomy

We review the current state of data mining and machine learning in astronomy. 'Data Mining' can have a somewhat mixed connotation from the point of view of a researcher in this field. If used correctly, it can be a powerful approach, holding the potential to fully exploit the exponentially increasing amount of available data, promising great scientific advance. However, if misused, it can be little more than the black-box application of complex computing algorithms that may give little physical insight, and provide questionable results. Here, we give an overview of the entire data mining process, from data collection through to the interpretation of results. We cover common machine learning algorithms, such as artificial neural networks and support vector machines, applications from a broad range of astronomy, emphasizing those where data mining techniques directly resulted in improved science, and important current and future directions, including probability density functions, parallel algorithms, petascale computing, and the time domain. We conclude that, so long as one carefully selects an appropriate algorithm, and is guided by the astronomical problem at hand, data mining can be very much the powerful tool, and not the questionable black box.Comment: Published in IJMPD. 61 pages, uses ws-ijmpd.cls. Several extra figures, some minor additions to the tex

Study of caveolin-1 gene expression in whole adipose tissue and its subfractions and during differentiation of human adipocytes

Caveolins are 21-24 kDa integral membrane proteins that serve as scaffolds to recruit numerous signaling molecules. Specific subclasses of caveolae carry out specific functions in cell metabolism. In particular, triglycerides are synthesized at the site of fatty acid entry in one of these caveolae classes. OBJECTIVE AND METHODS: We studied the expression of caveolin-1 (CAV-1) gene in association with metabolic variables in 90 visceral and 55 subcutaneous adipose tissue samples from subjects with a wide range of fat mass, in the stromovascular fraction (SVC) and isolated adipocytes, and during differentiation of human adipocytes. RESULTS: CAV-1 gene expression was significantly decreased in visceral adipose tissue (v-CAV-1) of obese subjects. v-CAV-1 was positively associated with several lipogenic genes such as acetyl-coA carboxylase (ACACA, r = 0.34, p = 0.004) and spot-14 (r = 0.33, p = 0.004). In non-obese subjects v-CAV-1 also correlated with fatty acid synthase (FAS, r = 0.60, p < 0.0001). Subcutaneous (sc) adipose tissue (sc-CAV-1) gene expression was not associated with these lipogenic factors when obese and non-obese subjects were studied together. In obese subjects, however, sc-CAV-1 was associated with fatty acid synthase (FAS, r = 0.36, p = 0.02), sterol regulatory element binding protein-1c (SREBP-1c (r = 0.58, p < 0.0001), ACACA (r = 0.33, p = 0.03), spot-14 (r = 0.36, p = 0.02), PPAR-gamma co-activator-1 (PGC-1, r = 0.88, n = 19). In these obese subjects, sc-CAV-1 was also associated with fasting triglycerides (r = -0.50, p < 0.0001).CAV-1 expression in mature adipocytes was significantly higher than in stromal vascular cells. CAV-1 gene expression in adipocytes from subcutaneous adipose tissue (but not in adipocytes from visceral adipose tissue) was significatively associated with fasting triglycerides. CAV-1 gene expression did not change significantly during differentiation of human preadipocytes from lean or obese subjects despite significant increase of FAS gene expression. CONCLUSION: Decreased CAV-1 gene expression was simultaneously linked to increased triglycerides and decreased lipogenic gene expression among obese subjects, paralleling the observations of hypertriglyceridemia in CAV-1 knockout mice. However, the regulation of CAV-1 gene expression seems independent of the adipogenic program

Prevalencia de la obesidad en la población atendida en asistencia primaria de Girona, 1995–1999

ResumenObjetivosEstimar y comparar la prevalencia de la obesidad y el sobrepeso en la población de Girona, entre 1995 y 1999, estratificando geográficamente por sexo y edad.MétodosMedidas directas de talla y peso correspondientes a 24.554 usuarios mayores de 14 años (10.595 varones y 13.959 mujeres) atendidos en cuatro áreas básicas de salud (ABS): Girona 1, Girona 4, Salt y Camprodon, así como en un centro de atención primaria (CAP) de la provincia de Girona. Se calculó el índice de masa corporal (IMC) como el cociente entre el peso y la talla al cuadrado. La obesidad se define como los grados II y III del índice de Garrow (IMC ≥ 30 kg/m2) y el sobrepeso como el grado I (25 kg/m2 ≤ IMC < 30 kg/m2). Al no utilizarse una muestra aleatoria de sujetos, el cálculo de prevalencias y de sus errores estándar se corrigió mediante el uso de ponderaciones adecuadas. La comparación de las prevalencias entre dos ABS distintas para cada sexo se realizó utilizando un contraste paramétrico de diferencia de proporciones. La comparación entre las prevalencias de un determinado grado del índice de Garrow, controlando por sexo y edad, se llevó a cabo utilizando una regresión logística jerárquica.ResultadosLa prevalencia de la obesidad se estimó en 15,6% entre los varones de 20 a 74 años (desde el 14,0% en Girona 1 hasta el 22,4% en Camprodon) y en un 17,5% entre las mujeres (un 15,6% en Girona 1 y un 22,7% en Camprodon), un 16,7% de promedio ponderado. La prevalencia del sobrepeso se sitúa en el 44% en varones y en un 33% en mujeres, un 37,8% de promedio ponderado. Existe una gradación en las prevalencias de la obesidad, con diferencias estadísticamente significativas: Girona 1, Salt, Girona 4, Camprodon y Sils.ConclusionesLas estimaciones de la prevalencia de la obesidad y sobrepeso obtenidas en este trabajo no están tan alejadas como se creía de las estimadas en poblaciones de nuestro entorno. De hecho, podrían ser muy similares a las estimadas en la Unión Europea y, para algunos grupos de edad, incluso a las de Estados Unidos.AbstractObjectivesTo estimate the prevalence of obesity and overweight in the population of Girona (Spain) between 1995 and 1999 and to divide the prevalences in geographical areas according to age and sex.MethodsHeight and weight were directly measures in 24,554 health care consumers older than 14 years (10,595 men and 13,959 women) treated in four primary health care areas: Girona 1, Girona 4, Salt and Camprodon and in one primary health care center in the province of Girona. Body mas index (BMI) was calcuted by dividing weight in kilograms bye height in meters squared. Obesity was defined as grades II and III of Garrow's index (BMI ≥ 30 kg/m2) and overweight as degree I (25 kg/m2 ≥ BMI < 30 kg/m2). Because the sample was not randomized, the prevalences were adequately weighted. The comparison between prevalences in two different primary health care areas for each sex (in the same Garrow's index and age group) was carried out using a parametric test of differences in proportions (Student's t-test). A hierarchical logistic regression was used to compare prevalences in the same grade Garrow's index, controlling for age and sex.ResultsThe prevalence of obesity was estimated as 15.6% in men aged from 20-74 years (from 14.0% in Girona 1 to 22.4% in Camprodon) and 17.5% for women (15.6% in Girona 1, 22.7% in Camprodon). The weighted mean was 16.7%. The prevalence of overweight was 44% in men and 33% in women and the weighted mean was 37.8%. The prevalence of obesity was graduated with statistically significant differences between Girona 1, Salt, Girona 4, Camprodon and Sils.ConclusionsThe estimates of the prevalences of obesity and overweight obtained in this study were closer to those of other studies in similar populations than previously believed. Inde-ed, the prevalences may be similar to those of the European Union and, in some age groups, to those of the United States

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin

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Erlotinib dosing-to-rash: A phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer

Background: To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacokinetics (PK) and pharmacodynamics (PD) of higher doses of erlotinib. Methods: Patients initially received erlotinib 150 mg per day. The dose was successively increased in each patient to that associated with a TR. Anticancer activity was evaluated. Plasma, skin, and hair were sampled for PK and PD studies. Results: Erlotinib dose escalation to 200-475 mg per day was feasible in 38 (90%) of 42 patients. Twenty-four (57%) patients developed a TR, but 19 (79%) did so at 150 mg per day. Five (12%) patients, all of whom developed a TR, had a partial response. Median progression-free survival (PFS) was 2.3 months (95% CI: 1.61, 4.14); median PFS was 3.5 months and 1.9 months, respectively, for patients who did and did not experience a TR (hazard ratio, 0.51; P0.051). Neither rash severity nor response correlated with erlotinib exposure. Conclusion: Intrapatient dose escalation of erlotinib does not appreciably increase the propensity to experience a maximal level of tolerable skin toxicity, or appear to increase the anticancer activity of erlotinib in NSCLC