THE ROLE OF PLATELETS IN OVARIAN CARCINOMA

Platelets represent one of the largest storage pools of angiogenic and oncogenic growth factors in the human body. The observation that thrombocytosis (platelet count >450,000/uL) occurs in patients with solid malignancies was made over 100 years ago. However, the clinical and biological implications as well as the underlying mechanism of paraneoplastic thrombocytosis associated with ovarian carcinoma remains unknown and were the focus of the current study. Following IRB approval, patient data were collected on 619 patients from 4 U.S. centers and used to test associations between platelet count at initial diagnosis, clinicopathologic factors, and outcome. In vitro effects of plasma-purified platelets on ovarian cancer cell proliferation, docetaxel-induced apoptosis, and migration were evaluated using BrdU-PI flow cytometric and two-chamber chemotaxis assays. In vivo effects of platelet depletion on tumor growth, proliferation, apoptosis, and angiogenesis were examined using an anti-platelet antibody (anti-mouse glycoprotein 1ba, Emfret) to reduce platelets by 50%. Complete blood counts and number of mature megakaryocytes in the spleen and bone marrow were compared between control mice and ovarian cancer-bearing mice. Plasma levels of key megakaryo- and thrombopoietic factors including thrombopoietin (TPO), IL-1a, IL-3, IL-4, IL-6, IL-11, G-CSF, GM-CSF, stem cell factor, and FLT-3 ligand were assayed in a subset of 150 patients at the time of initial diagnosis with advanced stage, high grade epithelial ovarian cancer using immunobead-based cytokine profiling coupled with the Luminex® xMAP platform. Plasma cytokines significantly associated with thrombocytosis in ovarian cancer patients were subsequently evaluated in mouse models of ovarian cancer using ELISA immunoassays. The results of human and mouse plasma cytokine profiling were used to inform subsequent in vivo studies evaluating the effect of siRNA-induced silencing of select megakaryo- and thrombopoietic cytokines on paraneoplastic thrombocytosis. Thirty-one percent of patients had thrombocytosis at initial diagnosis. Compared to patients with normal platelet counts, women with thrombocytosis were significantly more likely to have advanced stage disease (p<0.001) and poor median progression-free (0.94 vs 1.35 years, p<0.001) and overall survival (2.62 vs 4.65 years, p<0.001). On multivariate analysis, thrombocytosis remained an independent predictor of decreased overall survival. Our analysis revealed that thrombocytosis significantly increases the risk of VTE in ovarian cancer patients and that thrombocytosis is an independent predictor of increased mortality in women who do develop a blood clot. Platelets increased ovarian cancer cell proliferation and migration by 4.1- and 2.8-fold (p<0.01), respectively. Platelets reduced docetaxel-induced apoptosis in ovarian cancer cells by 2-fold (p<0.001). In vivo, platelet depletion reduced tumor growth by 50%. Staining of in vivo specimens revealed decreased tumor cell proliferation (p<0.001) and increased tumor and endothelial cell apoptosis (p<0.01). Platelet depletion also significantly decreased microvessel density and pericyte coverage (p<0.001). Platelet counts increase by 31-130% in mice with invasive ovarian cancer compared to controls (p<0.01) and strongly correlate with mean megakaryocyte counts in the spleen and bone marrow (r=0.95, p<0.05). Plasma levels of TPO, IL-6, and G-CSF were significantly increased in ovarian cancer patients with thrombocytosis. Plasma levels of the same cytokines were found to be significantly elevated in orthotopic mouse models of ovarian cancer, which consistently develop paraneoplastic thromocytosis. Silencing TPO, IL-6, and G-CSF significantly abrogated paraneoplastic thrombocytosis in vivo. This study provides new understanding of the clinical and biological significance of paraneoplastic thrombocytosis in ovarian cancer and uncovers key humoral factors driving this process. Blocking the development of paraneoplastic thrombocytosis and interfering with platelet-cancer cell interactions could represent novel therapeutic strategies.

Blind intubation of anaesthetised children with supraglottic airway devices AmbuAura-i and Air-Q cannot be recommended: A randomised controlled trial.

BACKGROUND Paediatric supraglottic airway devices AmbuAura-i and Air-Q were designed as conduits for tracheal intubation. Although fibreoptic-guided intubation has proved successful, blind intubation as a rescue technique has never been evaluated. OBJECTIVE Evaluation of blind intubation through AmbuAura-i and Air-Q. On the basis of fibreoptic view data, we hypothesised that the success rate with the AmbuAura-i would be higher than with the Air-Q. DESIGN A prospective, randomised controlled trial with institutional review board (IRB) approval and written informed consent. SETTING University Childrens' Hospital; September 2012 to July 2014. PATIENTS Eighty children, American Society of Anesthesiologists (ASA) class I to III, weight 5 to 50 kg. INTERVENTIONS Tracheal intubation was performed through the randomised device with the tip of a fibrescope placed inside and proximal to the tip of the tracheal tube. This permitted sight of tube advancement, but without fibreoptic guidance (visualised blind intubation). MAIN OUTCOME MEASURES Primary outcome was successfully visualised blind intubation; secondary outcomes included supraglottic airway device success, insertion times, airway leak pressure, fibreoptic view and adverse events. RESULTS Personal data did not differ between groups. In contrast to our hypothesis, blind intubation was possible in 15% with the Air-Q and in 3% with the AmbuAura-i [95% confidence interval (95% CI) 6 to 31 vs. 0 to 13%; P = 0.057]. First attempt supraglottic airway device insertion success rates were 95% (Air-Q) and 100% (AmbuAura-i; 95% CI 83 to 99 vs. 91 to 100; P = 0.49). Median leak pressures were 18 cmH2O (Air-Q) and 17 cmH2O [AmbuAura-i; interquartile range (IQR) 14 to 18 vs. 14 to 19 cmH2O; P = 0.66]. Air-Q insertion was slower (27 vs. 19 s, P < 0.001). There was no difference in fibreoptic view, or adverse events (P > 0.05). In one child (Air-Q size 1.5, tube size 3.5), the tube dislocated during device removal. CONCLUSION Ventilation with both devices is reliable, but success of blind intubation is unacceptably low and cannot be recommended for elective or rescue purposes. If intubation through a paediatric supraglottic airway device is desired, we suggest that fibreoptic guidance is used. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01692522.

Intravenous Delta-9-Tetrahydrocannabinol to Prevent Postoperative Nausea and Vomiting: A Randomized Controlled Trial.

BACKGROUND Evidence suggests that cannabinoids can prevent chemotherapy-induced nausea and vomiting. The use of tetrahydrocannabinol (THC) has also been suggested for the prevention of postoperative nausea and vomiting (PONV), but evidence is very limited and inconclusive. To evaluate the effectiveness of IV THC in the prevention of PONV, we performed this double-blind, randomized, placebo-controlled trial with patient stratification according to the risk of PONV. Our hypothesis was that THC would reduce the relative risk of PONV by 25% compared with placebo. METHODS With IRB approval and written informed consent, 40 patients at high risk for PONV received either 0.125 mg/kg IV THC or placebo at the end of surgery before emergence from anesthesia. The primary outcome parameter was PONV during the first 24 hours after emergence. Secondary outcome parameters included early and late nausea, emetic episodes and PONV, and side effects such as sedation or psychotropic alterations. RESULTS The relative risk reduction of overall PONV in the THC group was 12% (95% confidence interval, -37% to 43%), potentially less than the clinically significant 25% relative risk reduction demonstrated by other drugs used for PONV prophylaxis. Calculation of the effect of treatment group on overall PONV by logistic regression adjusted for anesthesia time gave an odds ratio of 0.97 (95% confidence interval, 0.21 to 4.43, P = 0.97). Psychotropic THC side effects were clinically relevant and mainly consisted of sedation and confusion that were not tampered by the effects of anesthesia. The study was discontinued after 40 patients because of the inefficacy of THC against PONV and the finding of clinically unacceptable side effects that would impede the use of THC in the studied setting. CONCLUSIONS Because of an unacceptable side effect profile and uncertain antiemetic effects, IV THC administered at the end of surgery before emergence from anesthesia cannot be recommended for the prevention of PONV in high-risk patients.

Evaluation of the March of Dimes Family Support Program with Focus on Parent to Parent Support

The March of Dimes NICU Family Support Program provides families with support specialists, educational materials, and community resources to aide in the emotional and physical adaptation to a new life with a premature infant. Parent-to-parent support has been shown to more effective than group support because the new NICU parent is able to connect on a more personal level with an experienced NICU parent. The purpose of the research was to develop and implement an evaluation instrument to assess the effectiveness of the March of Dimes NICU Family Support Program (MODFSP) in the NICU at the UConn Health Center, specifically parent-to-parent support. Steps involved in the process included determining areas of focus for the instrument, developing items based on MODFSP materials and literature review, piloting the materials on parents with infants in the NICU (with IRB approval), and utilizing descriptive statistics through SPSS Version 14 to assess the results from the instrument content. Qualitative items were also included in the evaluation, and descriptive qualitative methods, as appropriate, were used to analyze those items. The findings have supported the literature in that all parents that participated in parent to parent support agreed the program was beneficial in assisting them with their transition to life with a premature infant. In addition to evaluating the new NICU parent’s opinions of the program, researchers evaluated the staff and volunteer parents that were involved in the program. The results also revealed that the new NICU parent’s fear, anxiety, and stress decreased after the parent-to-parent interactions. The preliminary results were encouraging that the MODFSP has implemented an effective parent-to-parent support program to support parents through their time of crisis.

Relevant drug to drug interactions between itraconazole and non-nucleoside reverse transcriptase inhibitors in HIV-infected patients on maintenance therapy for disseminated histoplasmosis

Objective. Itraconazole is recommended life-long for preventing relapse of disseminated histoplasmosis in HIV-infected patients. I sought to determine if serum itraconazole levels are affected by the type of Highly Active Anti-Retroviral Therapy (NNRTI or PI) being taken concomitantly to treat HIV. ^ Design. Retrospective cohort. ^ Methods. De-identified data were used from an IRB-approved parent study which identified patients on HAART and maintenance itraconazole for confirmed disseminated histoplasmosis between January 2003 and December 2006. Available itraconazole blood levels were abstracted as well as medications taken by each patient at the time of the blood tests. Mean itraconazole levels were compared using the student's t-test. ^ Results. 11 patients met study criteria. Patient characteristics were: median age 36, 91% men, 18% white, 18% black, 55% Hispanic and 9% Asians, median CD4 cell count 120 cells/mm3. 14 blood levels were available for analysis—8 on PI, 4 on NNRTI and 2 on both. 8/8 itraconazole levels obtained while taking concomitant PI were therapeutic (>0.4 μg/mL) in contrast to 0/4 obtained while taking NNRTI. Two patients switched from NNRTI to PI and reached therapeutic levels. Mean levels on NNRTI (0.05 μg/mL, s.d. 0.0) and on PI (2.45 μg/mL, s.d. 0.21) for these two patients were compared via a paired t-test (t = 16.00, d.f. = 1, P = 0.04). Remaining patient levels were compared using an unpaired t-test. Mean itraconazole on concomitant PI (n = 6) was 1.37 μg/mL (s.d. 0.74), while the mean on concomitant NNRTI was 0.05 μg/mL (s.d. 0.0), t = 2.39, d.f. = 6, P = 0.05. ^ Conclusions. Co-administration of NNRTI and itraconazole results in significant decreases in itraconazole blood levels, likely by inducing the CYP3A4 enzyme system. Itraconazole drug levels should be monitored in patients on concomitant NNRTI. PI-based HAART may be preferred over NNRTI-based HAART when using itraconazole to treat HIV-infected patients with disseminated histoplasmosis. ^

The socioeconomic status of families of hyperglycemic versus non-hyperglycemic children: A descriptive analysis

The proportion of children and adolescents living with type 2 diabetes mellitus (DM) is rising at an alarming rate. Studies have shown that poor dietary choices and sedentary behaviors account for progression of some of the most prevalent diseases in America, including obesity, heart disease and diabetes. Other studies have shown that genetics plays a role in the diabetic determination of an individual, although not very common. What are some of the differentiating factors between elevated and non-elevated fasting capillary glucose (FCG) levels in children of similar ages, knowing they spend a majority of their lives at home or at school? Why are some children acquiring diabetes while others are not? This study utilized an IRB-approved Family Demographic Survey to determine gender, family income, parent education levels, sedentary practices, and household size. Only those families who gave consent to take part in the study received a questionnaire. The statistical results were used to test the hypothesis that children living with elevated FCG levels are more likely to descend from families with lower incomes, and lower levels of education.^ With regard to household income and FCG status of non-hyperglycemic and hyperglycemic children (Table 4b), there are 10.4% more hyperglycemic children in the lower income bracket than non-hyperglycemic children in the same income bracket.^ With regard to maternal education and FCG status (Table 5b), there are 7.0% more hyperglycemic children in the high school or less maternal educational attainment level than non-hyperglycemic children in the same maternal educational level. The Pearson correlation of maternal education and FCG status showed a negative correlation value of -.035 (Table 5d). The higher the occurrence of hyperglycemia in a child, the lower the maternal educational status is. Household size ranges and averages are nearly identical in families of both hyperglycemic and non-hyperglycemic children. ^

Association of left ventricular hypertrophy and stage of hypertension by ambulatory blood pressure monitor

Hypertension in adults is defined by risk for cardiovascular morbidity and mortality, but in children, hypertension is defined using population norms. The diagnosis of hypertension in children and adolescents requires only casual blood pressure measurements, but the use of ambulatory blood pressure monitoring to further evaluate patients with elevated blood pressure has been recommended in the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. The aim of this study is to assess the association between stage of hypertension (using both casual and 24 hour ambulatory blood pressure measurements) and target organ damage defined by left ventricular hypertrophy (LVH) in a sample of children and adolescents in Houston, TX. A retrospective analysis was performed on the primary de-identified data from the combination of participants in two, IRB approved, cross-sectional studies. The studies collected basic demographic data, height, weight, casual blood pressures, ambulatory blood pressures, and left ventricular measurements by echocardiography on children age 8 to 18 years old. Hypertension was defined and staged using the criteria for ambulatory blood pressure reported by Lurbe et al. [1] with some modification. Left ventricular hypertrophy was defined using left ventricular mass index (LVMI) criteria specific for children and adults. The pediatric criterion was LVMI2.7 > 95th percentile for gender and the adult criterion was LVMI2.7 > 51g/m2.7. Participants from the original studies were included in this analysis if they had complete demographic information, anthropometric measures, casual blood pressures, ambulatory blood pressures, and echocardiography data. There were 241 children and adolescents included: 19.1% were normotensive, 17.0% had white coat hypertension, 11.6% had masked hypertension, and 52.4% had confirmed hypertension. Of those with hypertension, 22.4% had stage 1 hypertension, 5.8% had stage 2 hypertension, and 24.1% had stage 3 hypertension. Participants with confirmed hypertension were more likely to have LVH by pediatric criterion than those who were normotensive [OR 2.19, 95% CI (1.04–4.63)]; LVH defined by adult criterion did not differ significantly in normotensives compared with hypertensives [OR 2.08, 95% CI (0.58–7.52)]. However, there was a significant trend in the increased prevalence of LVH across the six blood pressure categories for LVH defined by both pediatric and adult criteria (p < 0.001 and p = 0.02, respectively). Additionally, the mean LVM indexed by height 2.7 had a significantly increased trend across blood pressure stages from normal to stage 3 hypertension (p < 0.02). Pediatric hypertension is defined using population norms, and although children with mild hypertension are not at increased odds of having target organ damage defined by LVH, those with severe hypertension are more likely to have LVH. Staging hypertension by ambulatory blood pressure further describes an individual's risk for LVH target organ damage. ^

Predictors of Contralateral Breast Cancer in BRCA Negative Women

Breast cancer is the most common cancer diagnosis and second leading cause of death in women. Risk factors associated with breast cancer include: increased age, alcohol consumption, cigarette smoking, white race, physical inactivity, benign breast conditions, reproductive and hormonal factors, dietary factors, and family history. Hereditary breast and ovarian cancer syndrome (HBOC) is caused by mutations in the BRCA1 and BRCA2 genes. Women carrying a mutation in these genes are at an increased risk to develop a second breast cancer. Contralateral breast cancer is the most common second primary cancer in patients treated for a first breast cancer. Other risk factors for developing contralateral breast cancer include a strong family history of breast cancer, age of onset of first primary breast cancer, and if the first primary was a lobular carcinoma, which has an increased risk of being bilateral. A retrospective chart review was performed on a select cohort of women in an IRB approved database at MD Anderson Cancer Center. The final cohort contained 572 women who tested negative for a BRCA1 or BRCA2 mutation, had their primary invasive breast cancer diagnosed under the age of 50, and had a BRCAPro risk assessment number over 10%. Of the 572 women, 97 women developed contralateral breast cancer. A number of predictors of contralateral breast cancer were looked at between the two groups. Using univariable Cox Proportional Hazard model, thirteen statistically interesting risk factors were found, defined as having a p-value under 0.2. Multivariable stepwise Cox Proportional Hazard model found four statistically significant variables out of the thirteen found in the univariable analysis. In our study population, the incidence of contralateral breast cancer was 17%. Four statistically significant variables were identified. Undergoing a prophylactic mastectomy was found to reduce the risk of developing contralateral breast cancer, while not having a prophylactic mastecomy, a young age at primary diagnosis, having a positive estrogen receptor status of the primary tumor, and having a family history of breast cancer increased a woman’s risk to develop contralateral breast cancer.

Platelets and Anti-Angiogenic Resistance in Ovarian Carcinoma

Background: Resistance to targeted anti-angiogenic therapy is a growing clinical concern given the disappointing clinical impact of anti-angiogenic. Platelets represent a component of the tumor microenvironment that are implicated in metastasis and represent a significant reservoir of angiogenic regulators. Thrombocytosis has been shown to be caused by malignancy and associated with adverse clinical outcomes, however the causal connections between these associations remain to be identified. Materials and Methods: Following IRB approval, patient data were collected on patients from four U.S. centers and platelet levels through and after therapy were considered as indicators of recurrence of disease. In vitro effects of platelets on cancer cell proliferation, apoptosis, and migration were examined. RNA interference was used to query signaling pathways mediating these effects. The necessity of platelet activation for in vitro effect was analyzed. In vivo orthotopic models were used to query the impact of thrombocytosis and thrombocytopenia on the efficacy of cytotoxic chemotherapy, the effect of aspirin on thrombocytosis and cancer, and platelet effect on anti-angiogenic therapy. Results: Platelets were found to increase at the time of diagnosis of ovarian cancer recurrence in a pattern comparable to CA-125. Platelet co-culture increased proliferation, increased migration, and decreased apoptosis in all cell lines tested. RNA interference implicated platelet derived growth factor alpha (PDGFRA) and transforming growth factor beta-receptor 1 (TGFBR1) signaling. Biodistribution studies suggested minimal platelet sequestration of taxanes. Blockade of platelet activation blocked in vitro effects. In vivo, thrombocytosis blocked chemotherapeutic efficacy, thrombocytopenia increased chemotherapeutic efficacy, and aspirin therapy partially blocked the effects of thrombocytosis. In vivo, withdrawal of anti-angiogenic therapy caused loss of therapeutic benefit with evidence of accelerated disease growth. This effect was blocked by use of a small-molecule inhibitor of Focal Adhesion Kinase. Anti-angiogenic therapy was also associated with increased platelet infiltration into tumor that was not seen to the same degree in the control or FAK-inhibitor-treated mice. Conclusions: Platelets are active participants in the growth and metastasis of tumor, both directly and via facilitation of angiogenesis. Blocking platelets, blocking platelet activation, and blocking platelet trafficking into tumor are novel therapeutic avenues supported by this data. Copyright © 2012 Justin Neal Bottsford-Miller, all rights reserved.

EVIDENCE OF HUMAN ENDOGENOUS RETROVIRUS K INVOLVEMENT IN HUMAN CANCER

Many lines of clinical and experimental evidence indicate a viral role in carcinogenesis (1-6). Our access to patient plasma, serum, and tissue samples from invasive breast cancer (N=19), ductal carcinoma in situ (N=13), malignant ovarian cancer (N=12), and benign ovarian tumors (N=9), via IRB-approved and informed consent protocols through M.D. Anderson Cancer Center, as well as normal donor plasmas purchased from Gulf Coast Regional Blood Center (N=6), has allowed us to survey primary patient blood and tissue samples, healthy donor blood from the general population, as well as commercially available human cell lines for the presence of human endogenous retrovirus K (HERV-K) Env viral RNA (vRNA), protein, and viral particles. We hypothesize that HERV-K proteins are tumor-associated antigens and as such can be profiled and targeted in patients for diagnostic and therapeutic purposes. To test this hypothesis, we employed isopycnic ultracentrifugation, a microplate-based reverse transcriptase enzyme activity assay, reverse transcription – polymerase chain reaction (RT-PCR), cDNA sequencing, SDS-PAGE and western blotting, immunofluorescent staining, confocal microscopy, and transmission electron microscopy to evaluate v HERV-K activation in cancer. Data from large numbers of patients tested by reverse transcriptase activity assay were analyzed statistically by t-test to determine the potential use of this assay as a diagnostic tool for cancer. Significant reverse transcriptase enzyme activity was detected in 75% of ovarian cancer patients, 53.8% of ductal carcinoma in situ patient, and 42.1% of invasive breast cancer patient samples. Only 11.1% of benign ovarian patient and 16.7% of normal donor samples tested positive. HERV-K Env vRNA, or Env SU were detected in the majority of cancer types screened, as demonstrated by the results shown herein, and were largely absent in normal controls. These findings support our hypothesis that the presence of HERV-K in patient blood circulation is an indicator of cancer or pre-malignancy in vivo, that the presence of HERV-K Env on tumor cell surfaces is indicative of malignant phenotype, and that HERV-K Env is a tumor-associated antigen useful not only as a diagnostic screening tool to predict patient disease status, but also as an exploitable therapeutic target for various novel antibody-based immunotherapies.

Cataract surgery in cancer patients and its impact on quality of life as measured by the National Eye Institute Visual Functioning Questionnaire - 25 (NEI-VFQ-25)

Purpose. The measurement of quality of life has become an important topic in healthcare and in the allocation of limited healthcare resources. Improving the quality of life (QOL) in cancer patients is paramount. Cataract removal and lens implantation appears to improve patient well-being of cancer patients, though a formal measurement has never been published in the US literature. In this current study, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), a validated vision quality of life metric, was used to study the change in vision-related quality of life in cancer patients who underwent cataract extraction with intraocular lens implantation. ^ Methods. Under an IRB approved protocol, cancer patients who underwent cataract surgery with intraocular lens implantation (by a single surgeon) from December 2008 to March 2011, and who had completed a pre- and postoperative NEI-VFQ-25 were retrospectively reviewed. Post-operative data was collected at their routine 4-6 week post-op visit. Patients' demographics, cancer history, their pre and postoperative ocular examinations, visual acuities, and NEI-VFQ-25 with twelve components were included in the evaluation. The responses were evaluated using the Student t test, Spearman correlation and Wilcoxon signed rank test. ^ Results. 63 cases of cataract surgery (from 54 patients) from the MD Anderson Cancer Center were included in the study. Cancer patients had a significant improvement in the visual acuity (P<0.0001) postoperatively, along with a significant increase in vision-related quality of life (P<0.0001). Patients also had a statistically significant improvement in ten of the twelve subcategories which are addressed in the NEI-VFQ-25. ^ Conclusions. In our study, cataract extraction and intraocular implantation showed a significant impact on the vision-related quality of life in cancer patients. Although this study includes a small sample size, it serves as a positive pilot study to evaluate and quantify the impact of a surgical intervention on QOL in cancer patients and may help to design a larger study to measure vision related QOL per dollar spent for health care cost in cancer patients.^

Is obesity a possible risk factor for Clostridium difficile infection

Aims: Obesity is a state of chronic inflammation characterized by depressed Th2 immune response. Animal studies have shown decreased IgA levels in obese rats and Leptin an adipose cell origin cytokine have been shown to enhance the activity of Clostridium difficile Toxin A. Hence we hypothesized that obesity is a risk factor for C. difficile infection (CDI) ^ Methods: 33 cases of CDI and 131 controls matched by age and HORNS index were identified from an IRB approved observational study at St. Luke's Episcopal Hospital in Houston. Variables like age, gender, height, weight, chronic antibiotic use, proton pump inhibitor use, diabetes mellitus, myocardial infarction, inflammatory bowel disease, diverticulitis, transfer from nursing home, hospital or home, nasogastric tube use and use of hemodialysis were provided in the dataset. Height and weight of the patient were used to calculate the BMI, based on which the study subjects were classified as obese and non-obese. Using STATA these variables were analyzed using test, chi square test followed by conditional logistic regression. ^ Results: On univariate analysis and conditional logistic regression, no significant increase in risk was associated with obesity (OR: 1.24; 95% CI: 0.46 - 3.36; p = 0.67) or BMI (OR: 0.98; CI: 0.92 - 1.04; p = 0.92). Hence, we cannot reject our hypothesis and conclude that "obesity is a risk factor associated with higher incidence of CDI in hospitalized patients. On univariate analysis using hemodialysis, nursing home transfer, home transfer, PPI and chronic antibiotics were found to be significantly different (p<0.05) in the cases and controls. On conditional logistic regression home (OR: 3.4; 95% CI: 1.15 - 9.61) and hemodialysis (OR: 4.1; 95% CI: 1.14 - 15.57) were found to be significantly different (p<0.05) between the case and control groups. ^ Conclusion: Our results show that obesity is not a significant risk factor for CDI. Our sample size was small and hence this may need conformation with a larger study. Patients transferred from home to the hospital and patients on hemodialysis had significantly higher incidence of CDI.^

Construction cost and energy consumption resulting from energy retrofitting in an apartment building in Madrid (Spain).

This theoretical study analyzes the relation between the measures necessesary for the energy retrofitting of a residential building constructed in Madrid, their cost and the improvement of the energy rating of the dwellings. The aim of this work is to establish an evaluation methodology that allows developers and architects to obtain conclusions and orientates therm in the decisioin-making process. It will allow finding the most suitable cost-effective solutions in each case. This paper describes the methodology and the findings obtained. Energy retrofitting and the improvement of the energy behaviour of the building depend on the selection of the retrofitting solutions and also on the investment. In this case study to achieve the best energy rates it is necessary to improve the thermal performance of the envelope as well as the energy systems. Energy retrofitting means an increase in property value but it can't only be considered in economic terms. It is necessary to take into account unquantifiable aspects as increased comfort, improved sound insulation, livability, health, or the elimination of energy poverty situations.

Retos y carencias de la regulación financiera internacional.

En 2004 Basilea II introdujo el modelo basado en calificaciones internas (IRB) para el cómputo del capital mínimo regulatorio por riesgo de crédito. Para los defensores de esta metodología, ello supuso una gran innovación con respecto al Acuerdo de 1988, pero a pesar de su extendida implementación, el modelo regulatorio se enfrenta una serie de problemas insuperables que hacen que la estimación y contraste de sus principales parámetros no sea posible en los términos planteados por la misma regulación. En este artículo se analizará la fuente de las debilidades en la estimación y la dificultad de validación de las probabilidades de incumplimiento y las pérdidas en caso de incumplimiento. Esta metodología permanece inalterada después de la reforma que después de la crisis se concreta en Basilea III.

Avaliação do impacto do horizonte temporal nas estimativas de EAD de linhas de crédito com limites explícitos a PME

Tese de mestrado em Matemática Aplicada à Economia e Gestão, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016