Margin Optimal Classification Trees

In recent years there has been growing attention to interpretable machine learning models which can give explanatory insights on their behavior. Thanks to their interpretability, decision trees have been intensively studied for classification tasks, and due to the remarkable advances in mixed-integer programming (MIP), various approaches have been proposed to formulate the problem of training an Optimal Classification Tree (OCT) as a MIP model. We present a novel mixed-integer quadratic formulation for the OCT problem, which exploits the generalization capabilities of Support Vector Machines for binary classification. Our model, denoted as Margin Optimal Classification Tree (MARGOT), encompasses the use of maximum margin multivariate hyperplanes nested in a binary tree structure. To enhance the interpretability of our approach, we analyse two alternative versions of MARGOT, which include feature selection constraints inducing local sparsity of the hyperplanes. First, MARGOT has been tested on non-linearly separable synthetic datasets in 2-dimensional feature space to provide a graphical representation of the maximum margin approach. Finally, the proposed models have been tested on benchmark datasets from the UCI repository. The MARGOT formulation turns out to be easier to solve than other OCT approaches, and the generated tree better generalizes on new observations. The two interpretable versions are effective in selecting the most relevant features and maintaining good prediction quality

Ageing causes Severe Ultra-Structural Modification of Calcium Release Units and Mitochondria in Cardiomyocytes

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Differential Effect of Calsequestrin Ablation on Structure and Function of Fast and Slow Skeletal Muscle Fibers

We compared structure and function of EDL and Soleus muscles in adult (4–6 m) mice lacking both Calsequestrin (CASQ) isoforms, the main SR Ca2+-binding proteins. Lack of CASQ induced ultrastructural alterations in ~30% of Soleus fibers, but not in EDL. Twitch time parameters were prolonged in both muscles, although tension was not reduced. However, when stimulated for 2 sec at 100 hz, Soleus was able to sustain contraction, while in EDL active tension declined by 70–80%. The results presented in this paper unmask a differential effect of CASQ1&2 ablation in fast versus slow fibers. CASQ is essential in EDL to provide large amount of Ca2+ released from the SR during tetanic stimulation. In contrast, Soleus deals much better with lack of CASQ because slow fibers require lower Ca2+ amounts and slower cycling to function properly. Nevertheless, Soleus suffers more severe structural damage, possibly because SR Ca2+ leak is more pronounced

[Colección de fotografías sobre Labiana (i. e. Laviana)] [Material gráfico]

Contiene fotografías originales, tarjetas postales, algunas de ellas circuladas o con anotaciones manuscritas, e imágenes recortadas de otras publicacionesTít. facticio redactado en base al sobreFecha de publicación tomada por aproximación entre la posible fecha de las postales más antiguas y la fecha de fallecimiento de Fermín Canella y Secades, quien realizó la recopilación de las misma

Exportación de mango Tommy Atkins en el término Incoterm CIF

El objetivo general de la investigación es Dirigir la exportación de Mango Tommy Atkins desde Colombia hacia los Estados Unidos con el término de negociación Incoterm CIF. En este mundo globalizado existe la necesidad de cooperación entre los países en distintos campos posibles, entre los cuales encontramos el comercial en donde se exportan e importan bienes de acuerdo a la demanda y oferta nacional de cada mercado. En la actualidad, están vigentes tratados comerciales los cuales son de gran utilidad al momento de realizar las negociaciones entre naciones, contribuyendo al mejoramiento de la calidad de vida de sus habitantes, promoción y desarrollo social, económico y cultural entre ambas. Colombia posee acuerdo comercial con Estados Unidos, el cual ha sido de gran importancia en cuanto a la ventaja que ofrece en aranceles muy bajos; siendo un gran atractivo para personas naturales y empresas en la iniciativa de exportar mercancía hacia Estados Unidos. Colombia es todavía uno de los pocos países que cuenta con un área cultivable potencial considerable que le permite pensar en expansión de la frontera agrícola para satisfacer sus necesidades de alimento y aun exportar. En el caso particular del mango, que se encuentran a lo largo de dieciséis departamentos principalmente, esta especie originaria de la India, encontró en Colombia una diversidad de pisos térmicos y nichos ecológicos a los cuales se ha adaptado gracias a su rusticidad, de manera tal que produce bien, desde el nivel del mar hasta los 1.650 metros de altitud. La mayor área sembrada se concentra en los departamentos de Cundinamarca 43,41%, Tolima 13,3%, Córdoba 4,19%, Antioquia 12,21%, Magdalena 8,86% y Bolívar 5,54%. En la costa Caribe, el cultivo del mango se extiende por toda su geografía, pero en un alto porcentaje como cultivo de “patio”

Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: the EverExt study

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms

Familial Liability for Eating Disorders and Suicide Attempts: Evidence From a Population Registry in Sweden

IMPORTANCE: Suicide attempts are common in individuals with eating disorders. More precise understanding of the mechanisms underlying their concomitant occurrence is needed. OBJECTIVE: To examine the association between eating disorders and suicide attempts and whether familial risk factors contribute to the association. DESIGN, SETTING, AND PARTICIPANTS: A Swedish birth cohort including individuals born in Sweden between January 1, 1979, and December 31, 2001, was followed up from age 6 years to December 31, 2009 (N = 2,268,786). Information was acquired from Swedish national registers. All individuals were linked to their biological full siblings, maternal half siblings, paternal half siblings, full cousins, and half cousins. Data analysis was conducted from October 5, 2014, to April 28, 2015. MAIN OUTCOMES AND MEASURES: Eating disorders were captured by 3 variables (any eating disorder, anorexia nervosa, and bulimia nervosa) identified by any lifetime diagnoses recorded in the registers. Suicide attempts were defined as any suicide attempts, including death by suicide, recorded in the registers. We examined the association between eating disorders and death by suicide separately, but the study was underpowered to explore familial liability for this association. RESULTS: Of 2,268,786 individuals, 15,457 females (1.40% of all females) and 991 males (0.09% of all males) had any eating disorder, 7680 females (0.70%) and 453 males (0.04%) had anorexia nervosa, and 3349 females (0.30%), and 61 males (0.01%) had bulimia nervosa. Individuals with any eating disorder had an increased risk (reported as odds ratio [95% CI]) of suicide attempts (5.28 [5.04-5.54]) and death by suicide (5.39 [4.00-7.25]). The risks were attenuated but remained significant after adjusting for comorbid major depressive disorder, anxiety disorder, and substance use disorder (suicide attempts: 1.82 [1.72-1.93]; death by suicide: 2.04 [1.49-2.80]). Similar results were found for anorexia nervosa (suicide attempts: crude, 4.42 [4.12-4.74] vs adjusted, 1.70 [1.56-1.85]; death by suicide: crude, 6.46 [4.38-9.54] vs adjusted, 2.67 [1.78-4.01]) and bulimia nervosa (suicide attempts: crude, 6.26 [5.73-6.85] vs adjusted, 1.88 [1.68-2.10]; death by suicide: crude, 4.45 [2.44-8.11] vs adjusted, 1.48 [0.81-2.72]). Individuals (index) who had a full sibling with any eating disorder had an increased risk of suicide attempts (1.41 [1.29-1.53]). The risk was attenuated for any eating disorder in more-distant relatives (maternal half siblings, 1.10 [0.90-1.34]; paternal half siblings, 1.21 [0.98-1.49]; full cousins, 1.11 [1.06-1.18]; half cousins, 0.90 [0.78-1.03]). This familial pattern remained stable after adjusting for the index individuals' eating disorders. Similar patterns were found for anorexia nervosa and bulimia nervosa. CONCLUSIONS AND RELEVANCE: These results suggest an increased risk of suicide attempts in individuals with lifetime eating disorders and their relatives. The pattern of familial coaggregation suggests familial liability for the association between eating disorders and suicide. Psychiatric comorbidities partially explain this association, suggesting particularly high-risk presentations

Variability in genes regulating vitamin D metabolism is associated with vitamin D levels in type 2 diabetes

Mortality rate is increased in type 2 diabetes (T2D). Low vitamin D levels are associated with increased mortality risk in T2D. In the general population, genetic variants affecting vitamin D metabolism (DHCR7 rs12785878, CYP2R1 rs10741657, GC rs4588) have been associated with serum vitamin D. We studied the association of these variants with serum vitamin D in 2163 patients with T2D from the "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes". Measurements of serum vitamin D were centralised. Genotypes were obtained by Eco™ Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 x 10-4) and GC rs4588 (p = 1 x 10-6) but not CYP2R1 rs10741657 (p = 0.31) were significantly associated with vitamin D levels. One unit of a weighted genotype risk score (GRS) was strongly associated with vitamin D levels (p = 1.1 x 10-11) and insufficiency (<30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, p = 1.1 x 10-7). In conclusion, DHCR7 rs12785878 and GC rs4588, but not CYP2R1 rs10741657, are significantly associated with vitamin D levels. When the 3 variants were considered together as GRS, a strong association with vitamin D levels and vitamin D insufficiency was observed, thus providing robust evidence that genes involved in vitamin D metabolism modulate serum vitamin D in T2D

Integrated Bayesian Approaches Shed Light on the Dissemination Routes of the Eurasian Grapevine Germplasm

The domestication and spreading of grapevine as well as the gene flow history had been described in many studies. We used a high-quality 7k SNP dataset of 1,038 Eurasian grape varieties with unique profiles to assess the population genetic diversity, structure, and relatedness, and to infer the most likely migration events. Comparisons of putative scenarios of gene flow throughout Europe from Caucasus helped to fit the more reliable migration routes around the Mediterranean Basin. Approximate Bayesian computation (ABC) approach made possible to provide a response to several questions so far remaining unsolved. Firstly, the assessment of genetic diversity and population structure within a well-covered dataset of ancient Italian varieties suggested the different histories between the Northern and Southern Italian grapevines. Moreover, Italian genotypes were shown to be distinguishable from all the other Eurasian populations for the first time. The entire Eurasian panel confirmed the east-to-west gene flow, highlighting the Greek role as a “bridge” between the Western and Eastern Eurasia. Portuguese germplasm showed a greater proximity to French varieties than the Spanish ones, thus being the main route for gene flow from Iberian Peninsula to Central Europe. Our findings reconciled genetic and archaeological data for one of the most cultivated and fascinating crops in the world

Acute shock efficacy of the subcutaneous implantable cardioverter-defibrillator according to the implantation technique

Background: The traditional technique for subcutaneous implantable cardioverter defibrillator (S-ICD) implantation involves three incisions and a subcutaneous (SC) pocket. An intermuscular (IM) 2-incision technique has been recently adopted. Aims: We assessed acute defibrillation efficacy (DE) of S-ICD (DE ≤65 J) according to the implantation technique. Methods: We analyzed consecutive patients who underwent S-ICD implantation and DE testing at 53 Italian centers. Regression analysis was used to determine the association between DFT and implantation technique. Results: A total of 805 patients were enrolled. Four groups were assessed: IM + 2 incisions (n = 546), SC + 2 incisions (n = 133), SC + 3 incisions (n = 111), and IM + 3 incisions (n = 15). DE was ≤65 J in 782 (97.1%) patients. Patients with DE ≤65 J showed a trend towards lower body mass index (25.1 vs. 26.5; p = .12), were less frequently on antiarrhythmic drugs (13% vs. 26%; p = .06) and more commonly underwent implantation with the 2-incision technique (85% vs. 70%; p = .04). The IM + 2-incision technique showed the lowest defibrillation failure rate (2.2%) and shock impedance (66 Ohm, interquartile range: 57-77). On multivariate analysis, the 2-incision technique was associated with a lower incidence of shock failure (hazard ratio: 0.305; 95% confidence interval: 0.102-0.907; p = .033). Shock impedance was lower with the IM than with the SC approach (66 vs. 70 Ohm p = .002) and with the 2-incision than the 3-incision technique (67 vs. 72 Ohm; p = .006). Conclusions: In a large population of S-ICD patients, we observed a high defibrillation success rate. The IM + 2-incision technique provides lower shock impedance and a higher likelihood of successful defibrillation