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This paper presents a set of tools to compute topological information of simplicial complexes, tools that are applicable to extract topological information from digital pictures. A simplicial complex is encoded in a (non-unique) algebraic-topological format called AM-model. An AM-model for a given object K is determined by a concrete chain homotopy and it provides, in particular, integer (co)homology generators of K and representative (co)cycles of these generators. An algorithm for computing an AM-model and the cohomological invariant HB1 (derived from the rank of the cohomology ring) with integer coefficients for a finite simplicial complex in any dimension is designed here, extending the work done in [R. González-Díaz, P. Real, On the cohomology of 3D digital images, Discrete Appl. Math. 147 (2005) 245–263] in which the ground ring was a field. The concept of generators which are “nicely” representative is also presented. Moreover, we extend the definition of AM-models to 3D binary digital images and we design algorithms to update the AM-model information after voxel set operations (union, intersection, difference and inverse).

Cohomology groups and the cohomology ring of three-dimensional (3D) objects are topological invariants that characterize holes and their relations. Cohomology ring has been traditionally computed on simplicial complexes. Nevertheless, cubical complexes deal directly with the voxels in 3D images, no additional triangulation is necessary. This could facilitate efficient algorithms for the computation of topological invariants in the image context. In this article, we present a constructive process, made up by several algorithms, to compute the cohomology ring of 3D binary-valued digital photographs represented by cubical complexes. Starting from a cubical complex Q that represents such a 3D picture whose foreground has one connected component, we first compute the homological information on the boundary of the object, ∂Q, by an incremental technique; using a face reduction algorithm, we then compute it on the whole object; finally, applying explicit formulas for cubical complexes (without making use of any additional triangulation), the cohomology ring is computed from such information.

To determine the morbidity, mortality and survival of sleeve lobectomy procedures compared to simple broncho-angioplasty procedures.A total of 535 patients diagnosed with bronchogenic cancer between September 2005 and May 2010 who fulfilled the criteria of clinical, oncological and functional operability were treated in our unit. Unresectable central tumours (n=95) using simple lobectomy were scheduled for broncho-angioplasty techniques and a pneumonectomy in those where this was impossible.A total of 58 (11%) were performed, 46 simple broncho-angioplastic lobectomies (SBAL) and 12 extended broncho-angioplastic lobectomies (EBAL). In the SBAL group there were 32 bronchial (70%) and 7 (15%) bronchovascular reconstructions and only vascular (15%). In the EBAL group, 8 (66.7%) were bronchial and 4 (33.3%) were bronchovascular reconstructions. The most common type of resection was the right upper lobe (RUL)+segment 6 in five (41%) cases, followed by RUL+middle lobe. There were 2 (3%) deaths in the SBAL group. There was 34% morbidity in the SBAL and 33% in the EBAL group (P0.05). Fifteen patients received neoadjuvant chemo-radiotherapy treatment, due to histologically confirmed cN2; however, the number of complications was not significantly higher. No risk factors were detected in any variable studied that would affect EBAL compared to the SBAL group (P0.05). The patients in both groups with a higher morbidity were pN1, located in the left upper lobe and associated with vascular reconstruction (P0.05). The overall survival at 5 years was 61.6%, SBAL (61%) and EBAL (68.9%) with no differences between groups (P0.05).EBALs are technically more demanding procedures, but do not increase morbidity or mortality compared to simple broncho-angioplasty techniques, and with a similar survival.

In this paper we present the theoretical and experimental study of a small solar chimney. The dimensions of the solar Chimney channel are 1.95 m high, 1.70 m width and 0.24 m depth. The channel of the solar chimney has in its backside a metallic plate as a solar heat absorber, and it is attached to a concrete wall, which acts as a storage and thermal isolation. On the front part of the chimney there is a glass plate used to decrease the heat losses to the exterior. Because the metallic plate is heated, air circulates from the lower side to the top side of the chimney channel. For the theoretical study, the steady state energy balance equations were solved for each element of the solar chimney following the methodology proposed by Ong in 2003 [8]. A numerical code was developed and reduced to cases of literature in order to validate it (Ong and Chow in 2003 [12]). The results showed the temperature distributions of the glass, the air inside the channel and the metallic plate. Also, the air mass flow rate was determined. For an hourly Irradiance of 400 W/m2 , the efficiency of the solar chimney decreased from 38 to 15% as the height of the chimney increased from 0.25 to 1.95 m.Copyright © 2010 by ASME

This study was done of the effects of plasma rich in growth factors (PRGF) on the healing of tongue wounds induced by the CO(2) laser.A prospective blind study was made of 60 Sprague-Dawley rats divided into two groups after the creation of tongue lesions using the CO(2) laser. Nothing was applied to the resulting wounds in the first group, while PRGF was applied to the 30 wounds in the second group. Wound re-epithelialization and inflammation were measured after 7, 14, and 28 d.No significant differences were seen between the two groups in relation to wound re-epithelialization, and the group without PRGF actually showed significantly better resolution of the inflammatory process after 14 d (p = 0.036).After 28 d, the rat tongue wounds produced by the CO(2) laser showed complete healing, independently of PRGF application.

To study the most frequent artifacts of punch biopsies of the healthy oral mucosa, distinguishing between those attributable to the surgical technique and those resulting from sample processing in the laboratory.A total of 186 samples of oral mucosa (dorsal lingual mucosa) were obtained from 186 adult albino rats by the experienced oral surgeons, evaluating the presence of artifacts attributable to the surgical technique (crush, splits, fragmentation, pseudocysts and haemorrhage) and those attributable to sample processing in the laboratory (orientation).The distribution of artifacts attributable to the surgical procedure was as follows: crush 16.67%, splits 0%, fragmentation 0%, pseudocysts 1.08% and hemorrhage 0%. The artifacts corresponding to sample processing in the laboratory (orientation) represented 37.63%.The present study shows use of the punch for obtaining biopsies of the healthy oral mucosa to produce few artifacts. In addition, good or poor orientation of the samples is not attributable to the surgical technique but to processing of the samples in the laboratory.

The authors designed a pressure forceps, called the "B forceps," for use in performing biopsies. They compared biopsy specimens taken with and without the aid of the B forceps from buccal mucosa of 84 patients divided equally into two groups, all of whom satisfied the World Health Organization's diagnostic criteria for oral lichen planus. They analyzed the advantages and disadvantages of using this instrument.The 42 patients in group A underwent a conventional biopsy (29 with a scalpel and 13 with a punch). The 42 patients in group B underwent a biopsy performed with the B forceps and a punch. The authors studied artifacts of fragmentation, pseudocysts, crushing, fissures and hemorrhages histologically in both groups.There were no significant differences within group A between the subjects who had undergone either the scalpel or the punch biopsy. There were, however, significant differences between groups A and B. Group B experienced less fragmentation (P = .021), fewer fissures (P = .001) and fewer hemorrhages (P = .001).The new B forceps was a useful aid in the performance of biopsies. It improved visibility and reduced the time needed for the procedure. Biopsy specimens taken with the B forceps also had histologically fewer artifacts than did those taken without the B forceps.This technique using the B forceps has several advantages, including speed, because the ischemia produced by the clamp stabilizes the tissue and increases visibility, facilitating dissection. The time needed for surgical removal thus is shortened.

INTRODUCTION Anemia is the most frequent cytopenia in lower-risk MDS. Erythropoietic-stimulating agents (ESAs) are commonly used in these patients. The use of ÒclassicalÓ parameters (EPO and ferritin levels) and the revised IPSS (IPSS-R) has been proposed1 (SantiniÕs score) to predict response to ESAs and overall survival (OS) among patients with lower risk MDS by IPSS and a favorable Nordic group score2. OBJECTIVES The main objective of the study was to evaluate overall response rate (ORR) to ESAs and OS according to the proposed SantiniÕs score in an independent and large cohort of anemic lower risk MDS patients receiving treatment with ESAs. METHODS Data from 530 anemic patients with low/int1 risk IPSS de novo MDS (according to FAB and WHO criteria) and sufficient follow-up data available were recorded in Spresas3 (SPanish Registry of Erythropoietic Stimulating Agents Study from GESMD). Two hundred and twenty six patients (42.6% of the patients) were selected according to specific criteria regarding the published SantiniÕs score1: Hb level 200mU/mL(=1), serum ferritin (SF) >350 ng/mL(=1) and IPSS-R very low=0, low=1, intermediate=2 and high=3) yielded a score ranging from 0 to 5. ESAs response rate and overall survival were analysed according to these score. Response to treatment was evaluated according to IWG 2006 response criteria and a multivariate logistic regression analysis was used to identify independent predictors of erythroid response (ER). OS were defined as the time between diagnosis and the corresponding event or last follow up (Feb 2015) and were analyzed using univariable and multivariable Cox proportional hazards regression methods. RESULTS Median age was 77 years (interquartile range [IQR] 25%-75%: 71-83 y), median Hb level at start of treatment was 10 g/dL (IQR25-75: 9-10), median EPO level was 90 (IQR25-75: 27,25-108) and median ferritin level was 338,5 (IQR25-75: 146,5-568,75). Among 139 patients with this data available, 85 patients (61,1%) were RBC transfusion dependent before ESAs treatment. Median time from diagnosis to ESAs treatment was 82 (IQR25-75: 27-353) days. According to the IPSS, 68.6% (N=155) and 31.4% (N=71) were in low and Int-1 risk groups, respectively. Regarding IPSS-R, 23% (N=52), 66.8% (N=151), 9.7% (N=22) and 0.4% (N=1) were in very low, low, intermediate and high risk, respectively. ORR to ESA treatment was 71.2% (N=161), with a median duration of response of 2.06 years. Prognosis factors of ER showed a trend toward to a higher ER among patients in the lower IPSS-R (P>0.05), low IPSS (p=0.039) and lower EPO levels (p According to SantiniÕs score, 11.5%(N=26), 42.9%(N=97), 25.8%(N=81), 8%(N=18) and 1.8%(N=4) of the patients were in the 0, 1, 2 3 and 4 score. Erythroid response was better for patients in the lower scores, with response rates of 73.1%, 82.5%, 65.4%, 50% and 0%, for patients in 0, 1, 2, 3 and 4 score, respectively (p CONCLUSIONS The present study confirms that SantiniÕs score is useful to identify patients with a higher probability of response to ESAs and better OS among lower risk MDS patients with an expected favorable response to ESA according to Nordic group score. Spresas study was partly supported by Janssen 1.-Santini et al, Blood 122(13), 2013. 2.-Hellstršm-Lindberg, Br J Haematol 120(6), 2003. 3.-D'ez Campelo, EHA 2015 meeting, P244. Disclosures Díez Campelo: Novartis: Research Funding, Speakers Bureau; Janssen: Research Funding; Celgene: Research Funding, Speakers Bureau. Off Label Use: Use of erythropoietic stimulating agents for anemia in patients with myelodysplastic syndromes. Ramos:JANSSEN: Honoraria, Membership on an entity's Board of Directors or advisory committees; AMGEN: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Falantes:Celgene: Honoraria. Garcia:Celgene: Research Funding. Sanz:JANSSEN CILAG: Honoraria, Research Funding, Speakers Bureau.

In Mustard/Senning-repaired (MSR) patients, the right and left ventricles (RV, LV) act as the systemic and pulmonary ventricle, respectively. The purpose of the study was to compare non-invasively, at rest, pulmonary ventricle systolic function and hemodynamics in MSR patients with those of healthy volunteers. Velocity-encoded MR imaging was performed at the level of the main pulmonary artery (MPA) in ten male patients late after a Mustard/Senning correction performed early in infancy and in ten male volunteers. Both blood flow and MPA cross-sectional area variations were recorded over a complete cardiac cycle. MPA distensibility, body surface area (BSA)-normalized pulmonary ventricle systolic power and work were significantly lower in the MSR patients compared to volunteers. In particular, BSA-normalized LV systolic power and work in MSR patients were equal to 82 and 77% on average of those of the RV in volunteers (0.32 vs. 0.39 W/m2 and 0.10 vs. 0.13 J/m2), respectively. We conclude that in MSR patients at rest two unrelated findings were observed: (1) a reduced MPA distensibility and (2) a significantly lower systolic mechanical performance of the pulmonary LV compared to that of the RV in healthy volunteers. The latter quantification indirectly confirms the lowest systemic RV systolic mechanical performance previously published.

The purpose of the present study was to non-invasively compare ascending aortic blood flow and cross-sectional area (CSA) variations vs time in Mustard or Senning repaired (MSR) patients against those of healthy volunteers at rest. Velocity-encoded MR imaging was performed in 10 male patients (age range 18–24 years, median age 20.5 years) late after a Mustard or Senning correction, and in 10 male healthy volunteers (age range 21–25 years, median age 22.5 years), at the upper part of the ascending aorta. Both aortic cross-sectional area (CSA) and blood-flow variations were recorded over a complete cardiac cycle, with a 30-ms time of resolution. The body-surface area (BSA), the mean CSA over the systolic phase, and the BSA-normalized systemic ventricle power and work were significantly lower in the patient series compared with those of the volunteer series. The BSA-normalized right ventricle (RV) power and work of MSR patients were equal to 87 and 83% on average of those of the left ventricle (LV) of healthy volunteers. We conclude that, at rest, the mechanical performance of the systemic RV in MSR patients is significantly lower than that of the LV in healthy volunteers. Furthermore, the significantly lower aortic CSA found in MSR patients than in healthy volunteers may reveal an increase in the vasomotor tone.

Background: Clinical, morphological and genetic characteristics of chronic myelomonocytic leukemia (CMML) are heterogeneous and vary from a myelodysplastic predominant profile to a myeloproliferative one. CMML has a highly variable course, with a median overall survival (OS) of 20 months and 15-30% of progression to acute myeloid leukemia (AML). Cytogenetic abnormalities are present in only 20-40% of cases. CMML-specific cytogenetic risk classification stratifies karyotypes into three groups: low risk (normal karyotype and isolated loss of Y chromosome, -Y), poor risk (trisomy 8, monosomy 7, 7q deletion and complex karyotype) and intermediate risk (all other chromosomal abnormalities). According to this model, 65-85% of patients fall into the low risk cytogenetic category. The aim of this study was to characterize type, frequency and prognostic impact of cytogenetic alterations detected by SNP arrays (SNP-A) in a series of 128 patients with CMML and low risk cytogenetic features or no metaphases. Methods: A retrospective study was performed on 128 patients with CMML. Cases with normal karyotype (n=120), isolated -Y (n=4) and no metaphases (n=4) were selected. Median age at diagnosis was 73 years (range 39-98), there was a 2.4:1 male predominance and 22.4% (28/125) of cases progressed to AML. Median follow up of patients was 26 months (range 1-115). Morphological WHO subtypes were CMML-1 in 104 (81%) cases and CMML-2 in 24 (19%). According to the FAB criteria 82 (64%) cases were included in the myelodysplastic variant (CMML-MD) and 46 (36%) in the myeloproliferative one (CMML-MP). High density SNP-A (Cytoscan HD, Affymetrix) were performed using DNA extracted from bone marrow (n=124) or peripheral blood (n=4) samples at diagnosis. The statistical analysis was performed with SPSS. Kaplan-Meier method was used for OS and progression-free survival (PFS) analysis and log-rank test was used for comparisons between groups. Results: SNP-A revealed novel chromosomal alterations (copy number alterations, CNA, and loss of heterozygosity, LOH) in 66% (85/128) of cases. Among the abnormal cases (CNA plus LOH), 1 alteration was detected in 65% (55/85) of cases, 2 in 20% (17/85) and ≥3 in 15% (13/85). The median size of the affected genome for CNA and LOH was 759 Kb (range 0-142Mb). CNA were detected in 38% (48/128) of cases, most of them being gains and losses smaller than 10Mb. Only 7 CNA were larger than 10Mb, four of them corresponded to patients with isolated -Y and three were novel alterations that had not been detected by conventional G-banding cytogenetics. Most affected regions (detected in 5 cases) were gains in chromosomes 3q, 8p and 21q as well as losses in chromosomes 10q and 12p. LOH were detected in 39% (50/128) of patients. Interstitial LOH larger than >25Mb were detected in 30% (39/128) of cases. Recurrent interstitial LOH were detected in: 4q24-4q35 region (12 cases), involving TET2 gene, which is mutated in 40-50% of CMML; and in chromosome 11 (9 cases), 7 of which included 11q13.3-11q25 region, involving CBLgene, mutated in 5-20% of CMML. Although the number of total alterations (1, 2 or ≥3) do not have a survival impact, we found a significant correlation between the size of the affected genome (≥30 Mb, including CNA and LOH) and a poorer OS (OS at 3 years 26% vs. 46%, P=0.039). Regarding type of alterations, cases with interstitial LOH had lower OS than cases without LOH (OS at 3 years 19% vs. 45%, P=0.049). Cases with high risk alterations as defined by CMML-specific cytogenetic risk classification (losses in 7q, gains in 8q and ≥3 CNA) had lower PFS than patients with other aberrations (PFS at 1 year 76% vs. 93%, P=0.036), although statistical significance was not reached for OS (OS at 3 years, 27% vs.49%, P=0.096). Conclusions: SNP-A in CMML patients with low risk cytogenetic features or no metaphases has led to the detection of chromosomal alterations in 66% of cases. Using this technique the prognosis can be better defined, and we can detect a group of patients with worse outcome who could be considered for more intensive treatment. Acknowledgments: Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain (PI 11/02519; PI 11/02010); RTICC, FEDER (RD12/0036/0044; RD12/0036/0014); 2014 SGR225 (GRE) Generalitat de Catalunya; Fundació Internacional Josep Carreras, Obra Social “La Caixa” and Celgene Spain; NHRI-EX103-10003NI, Taiwan. Footnote: Francesc Solé and Lurdes Zamora contributed equally Disclosures Xicoy: Celgene: Honoraria. Sole:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

We use homological perturbation machinery specific for the algebra category [P. Real. Homological Perturbation Theory and Associativity. Homology, Homotopy and Applications vol. 2, n. 5 (2000) 51-88] to give an algorithm for computing the differential structure of a small 1--homological model for commutative differential graded algebras (briefly, CDGAs). The complexity of the procedure is studied and a computer package in Mathematica is described for determining such models., 17 pages

In [3] “small” 1-homological model H of a commutative differential graded algebra is described. Homological Perturbation Theory (HPT) [7-9] provides an explicit description of an A∞-coalgebra structure (Δ1,Δ2,Δ3,...) of H. In this paper, we are mainly interested in the determination of the map Δ2 : H - H H ⊗ H as a first step in the study of this structure. Developing the techniques given in [20] (inversion theory), we get an important improvement in the computation of Δ2 with regard to the first formula given by HPT. In the case of purely quadratic algebras, we sketch a procedure for giving the complete Hopf algebra structure of its 1-homology. Ministerio de Educación y Ciencia PB98-1621-C02-02 Junta de Andalucía FQM-296

Background There is scarce information about the efficacy of ESA in CMML although their use is common in clinical practice. The objective of this study was to analyze the response and OS in a series of 99 pts with CMML treated with ESA and to evaluate the feasibility of the predictive model of response to ESA used in MDS (Hellström-Lindberg, et al. Br J Haematol. 1997; 99: 344-51). Method Between January 1997 and March 2013 99 pts with CMML from the Spanish Registry of MDS and the Düsseldorf-MDS registry were studied. Clinical characteristics, response and OS were analyzed. Predictive model of response to ESA (0 good, 1 intermediate, and 2 poor) based on erythropoetin (EPO) level (< or ≥ 500 U/L) and red blood cell (RBC) transfusion need (< 2 or ≥ 2 RBC/month) was applied. Results 66 (67%) pts were males. Median age (range) was 75 (52-93) years. CMML subtype: myelodysplastic 58 (59%), myeloproliferative 41 (41%), CMML-I 84/98 (86%), CMML-II 14/98 (14%). CPSS score: Low/Int-1 65/90 (72%), Int-2/High 25/90 (28%). Transfusion dependence on initiation of ESA 24/86 (28%). Score based on predicted model of response to ESA: 0 43/62 (69%), 1 15/62 (24%), 2 4/62 (7%). ESA type: EPO alfa 22/94 (24%), EPO beta 16/94 (17%), EPO theta 3/94 (3%) darbepoetin 53/94 (56%). Concomitant medication: hydroxyurea 19 (39%), iron 18 (37%), steroids 4 (8%), azacitidine 3 (6%), etoposide 2 (4%), G-CSF 1 (2%), romiplostim 1 (2%) and oral chelation 1 (2%). Four pts were excluded for response analysis because they received azacitidine (3) and oral chelation (1). Response: Erythroid response (ER) 55/86 (64%), transfusion independence 5/22 (23%). ER according to CPSS (Low/Int-1 vs. Int-2/High): 71% vs. 43%, p=0,032. Median (min,max) time of ER was 4 months (0,88). Pts with 0 score according to predictive model of response to ESA presented significantly higher ER than pts with 1-2 score (77% vs. 24%, p Conclusions A high frequency of ER was observed in this series of pts with CMML, the majority belonging to Low-risk CPSS. Predictive model of response to ESA from MDS was feasible, with a similar ER than that of MDS pts. Pts with low-risk CPSS with ER to ESA had a better OS than non-ER patients Supported by RD12/0036/0029 from RTICC-Instituto Carlos III, Spain Disclosures: Germing: Celgene: Honoraria, Research Funding; Jansen-Cilag: Honoraria; Novartis: Research Funding; GSK: Research Funding; Amgen: Research Funding.

4809 Introduction: Chronic myelomonocytic leukemia (CMML) is a clonal haematopoietic malignancy characterized by features from both myelodisplastic syndromes and myeloproloferative neoplasms. CMML median overall survival is 20 months and 15–30% of cases progress to acute myeloid leukemia (AML). Molecular biology of CMML is poorly understood. Clonal cytogenetic abnormalities are found in 20–30% of cases. Recently, some recurrent gene mutations have been reported. The most frequent mutated genes are TET2 (30–50%), ASXL1 (35–56%), SRSF2 (28–47%), RUNX1 (8–37%), CBL (10–22%) and K/NRAS (2–22%). We sought to characterize type, frequency and prognostic implication of cytogenetic alterations and genetic mutations ( ASXL1 , CBL , JAK2 and SRSF2 ) in a cohort of 20 patients with CMML. Methods: A retrospective study was performed on 20 CMML cases (11 CMML-1, 9 CMML-2) for whom clinical and biological data were available. Median age at diagnosis was 66 years (range: 49 – 84 years), with a male predominance of 1.9:1 and 42% frequency of progression to AML. Conventional cytogenetic analysis was performed in bone marrow (BM) samples obtained at diagnosis (n=19) and at progression to AML (n=8). For mutation analysis, DNA was extracted from BM samples at diagnosis (n= 20). Sanger sequencing was performed to study mutations in ASXL1 (exon 12), SRSF2 (exon 1) and CBL (exons 8 and 9) genes, while JAK2 V617F mutation was analyzed by endpoint genotyping. Survival analysis was performed using Kaplan-Meier estimate and log-rank tests were used for comparisons. The χ2 and Fisher's exact tests were used to analyze differences in the distribution of variables among patient subsets. Results: Aberrant karyotypes were seen in 5/19 (26%) cases at diagnosis and 6/8 (83%) cases at progression to AML. Alterations observed at diagnosis were typical from CMML (trisomy 8, 7q deletions and 12p structural alterations), while those observed at progression were more common in AML ([Table 1][1]). Heterozygous somatic ASXL1 mutations were detected in 8/19 (42%) cases. A total of 6 different mutations were seen in these 8 cases, being the recurrent mutation p.G646WfsX12 (g.76303dupG) the only one seen in more than one patient (4/8, 50%). In addition, 4 cases harboured two point mutations located at 3' of exon 12 (g.79017A>G and g.78128C>T). Somatic SRSF2 mutations were detected in 4/20 (20%) cases. All of them were heterozygous, missense mutations located at hotspot P95. In 3 cases P95 changed to P95H (g.535 C>A), while in 1 case it changed to P95L (g.535 C>T). In addition, 1 silence mutation was detected in 1 patient at the beginning of exon 1 (g.395 C>T) of SRSF2 . No mutations were seen in CBL and JAK2 genes. ASXL1 and SRSF2 mutations did not correlate with either CMML-1/CMML-2 subtypes or myelodysplastic/myeloproliferative variants. Survival analysis revealed that the only adverse prognostic factor was CMML-2 subtype. Compared to CMML-1, patients with CMML-2 had worse overall survival (median OS at 2 years: 18% vs 21%, p=0.05) and progression-free survival (median PFS at 2 years: 21% vs 57%, p=0.002). Mutations in ASXL1 had no prognostic impact, while a trend towards higher PFS was seen in cases with SRSF2 mutations, although it was not statistically significant. Conclusions: Cytogenetic analysis revealed that the percentage of aberrant karyotypes in CMML increases considerably at progression to AML. Mutational analysis showed that ASXL1 and SRSF2 are frequently mutated in CMML. There are multiple ASXL1 mutations throughout the exon 12, while missense SRSF2 mutations located at the hotspot P95. CMML-2 is still the only prognostic factor associated to worse OS and PFS. | CMML (n=19) | AML (n=8) | |:-------------------------------------:| ------------------------------------------------------------------------------------------------------------------ | | Patients that did not progress (n=10) | | | 46,XY \[20\] (n=4) | | | 46,XX \[20\] (n=5) | | | 46,XY,del(11)(q23) [18]/46,XY [2] | | | 47,XY,+8,del(12)(p13) [20] | | | Patients that progressed to AML (n=8) | | | 46,XX [20] | No data | | 46,XY [20] | No data | | 46,XY [20] | 46,XY [20] | | 46,XX,t(9;11)(p22;q23) [13]/46,XX [7] | 46, XX, t(9;11)(p22;q23) [16]/46,XX [4] | | 46,XY [20] | 44,XY,del(3)(p21),del(5)(q22q23,del(7)(q11.2),-9,-13,-14,+mar1,+mar2 ![Formula][2] /46,XY ![Formula][3] | | 46,XY [20] | 46,XY,t(8;16)(p11;p13) [18]/46,XY [2] | | 46,XX,t(1;3)(p36;q21) [20] | 46,XX,t(1;3)(p36;q21)[19]/46,XX,t(1;3)(p36;q21),der(1)[1] | | 46,XY,del(7q) [3]/46,XY [17] | 46,XY,t(2;3)(p23;q26.2) [30] | Table 1. Cytogenetic alterations of CMML at diagnosis (n=19) and at progression to AML (n=8) Disclosures: No relevant conflicts of interest to declare. [1]: #T1 [2]: T1/embed/tex-math-1.gif [3]: T1/embed/tex-math-2.gif

This paper reports the study of different aspects of data based modelling, focusing on physical issues and considering a simplified case study. Different analysis approaches have been applied to several data series recorded in different test conditions. The results have been compared. The effect of solar radiation, and the relevance of non- constant surface effects have been evaluated through an exploratory mono-dimensional analysis. Afterwards tri- dimensional analysis has been applied, to estimate the overall UA and gA value of the simplified building. The robustness of the results is studied comparing results from data set recorded under different test conditions.

This document describes guidelines for using time series analysis methods and tools for estimating the thermal performance of buildings and building components. This is integrated in a more comprehensive work. This first part is mainly dealing with physical aspects. A second part focused on statistical aspects has been also elaborated. Both documents must be considered as complementary. Minimum steps to carry out data analysis are reported and different alternative analysis approaches are outlined. This document is mainly focused on the most critical aspects particularly regarding energy performance assessment of buildings and building components. More general techniques also required to carry out data analysis are briefly presented in this document including references for more comprehensive information. Case studies that help to understand the different aspects discussed are included along this text and references are given for further information.

We provide the explicit solution of a general second order linear difference equation via the computation of its associated Green function. This Green function is completely characterized and we obtain a closed expression for it using functions of two–variables, that we have called Chebyshev functions due to its intimate relation with the usual one–variable Chebyshev polynomials. In fact, we show that Chebyshev functions become Chebyshev polynomials if constant coefficients are considered.

Background: Chronic myelomonocytic leukemia (CMML) is a heterogeneous disease that can vary from a myelodysplastic (MD) predominant profile to a myeloproliferative (MP) one. CMML has a variable course, with a median overall survival of 20 months and 15-30% of progression to acute myeloid leukemia (AML). Cytogenetic abnormalities are present in 20-40% of cases and recurrent gene mutations have been reported in several genes. Patients with low risk cytogenetic features (normal karyotype and isolated -Y) account for approximately 80% of CMML patients and often fall into the low risk categories of CMML prognostic scores. Our hypothesis is that mutational study can contribute to diagnosis and prognostic stratification in this subset of patients. Methods: A retrospective study was performed on 57 patients with CMML. Cases with normal karyotype (n=53), isolated -Y (n=2) and no metaphases (n=2) were selected. DNA was extracted from BM (n=52) and PB (n=5) samples at diagnosis. Targeted deep-sequencing was performed in a panel of 83 myeloid-related genes. Libraries were prepared with 1μg of genomic DNA using the KAPA Library Preparation Kit (Kapa Biosystems) and then enriched using the SeqCap EZ capture chemistry (Nimblegen, Roche). Libraries were sequenced with 150 bp paired-end reads on an Illumina MiSeq. Herein we present the results of 43 cases which were preliminarily analyzed using the Illumina MiSeq Reporter and Variant Studio softwares. High-probability oncogenic mutations were called by eliminating sequencing and mapping errors and known SNPs based on the available databases. An in-house bioinformatics pipeline will be designed to analyze the whole series of patients. A preliminar statistical analysis was performed with SPSS. Fisher's exact test was used to compare variables between patient subsets. Complete study, including the correlation of the sequencing findings with the clinical data, will be presented in the meeting. Results: Median age at diagnosis was 70 years (range 48-87) and there was a 2:1 male predominance. Median follow up of patients was 23 months (range 1-116) during which 23% (11/43) of cases progressed to AML. Morphological WHO subtypes were CMML-1 in 36 (84%) cases and CMML-2 in 7 (16%). According to the FAB criteria 34 (79%) cases were classified as CMML-MD and 9 (21%) as CMML-MP. According to the CMML-specific scoring system (CPSS) 28/43 (65%) patients belonged to the low-risk category, 10/43 (23%) to the intermediate-1 and 4/43 (12%) to the intermediate-2. The mean depth of the targeted resequencing per base per sample was 810-fold. After excluding sequencing and mapping errors a mean of 293 single nucleotide variants (snv) and insertions/deletions (indels) were called per sample. After filtering non-silent variants and excluding known polymorphisms a mean of 6 variants per sample were called as high-probability somatic changes. Distribution of detected variants across the patients can be seen in Figure 1. Most frequently affected genes were TET2 (70%), ASXL1 (47%) and SRSF2 (35%); followed by RUNX1 (23%), NRAS (16%), CBL (12%), EZH2 (12%), SETBP1 (12%) and ZRSR2 (12%). Variants detected in 5-10% of patients included IDH2, CRBBP, SH2B3, UMODL1, DNMT3A, JAK2, PTPN11, SF3B1 and U2AF1 genes. Statistical analysis revealed that some variants correlated with CMML subtypes: SH2B3 (P=0.010) and STEBP1 (P=0.024) associated with CMML-2; JAK2 (0.007), NRAS (P=0.026) and EZH2 (P=0.05) associated with CMML-MP. Variants in NRAS also correlated with progression to AML (P=0.04) and patients in intermediate groups of CPSS associated with JAK2 (P=0.008) and EZH2 (P=0.011) variants. Conclusions: Genetic profiling using targeted deep-sequencing is a highly promising approach for CMML diagnosis and varies according to the cytological subtypes. With the correlation of the results with the clinical data of patients, we expect to determine if targeted molecular profiling can contribute to prognostic stratification of patients with CMML and low risk cytogenetic features. For the moment, we have already found a correlation with progression to AML. Acknowledgments: Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain (PI 11/02519; PI 11/02010); RTICC, FEDER (RD12/0036/0044); 2014 SGR225 (GRE) Generalitat de Catalunya; Fundació Josep Carreras, Obra Social "La Caixa" and Celgene Spain. Figure 1. Distribution of the affected genes across the 43 studied patients with CMML Figure 1. Distribution of the affected genes across the 43 studied patients with CMML Disclosures Sole: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.