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Introduction: the incidence of Respiratory Syncytial Virus (RSV) infection and their variability in the clinical management, make this disease a candidate for monitoring adequate use of resources. The objective of this study was to evaluate the impact of the updating of clinical guidelines for RSV bronchiolitis on the use of diagnostic testing and medications in tertiary hospitals in Colombia. Methods: we performed a cross-sectional study, evaluating the frequencies of drug prescription and medical tests, before (January-December 2016) and after (January to December 2019) of updating and dissemination of a new protocol for the treatment of RSV bronchiolitis in two tertiary hospitals in Colombia. Results: a total of 108 patients with RSV bronchiolitis were included. The demographic characteristics and clinical manifestations were similar in both groups. The length of hospital stays was similar in both groups. We did not find statistically significant differences in the frequency of medical tests. There was a decrease in the use of salbutamol (67.3% pre-protocol vs 51.8% post-protocol; P < .01). There were also significant reductions in the use of nebulized hypertonic saline solution (91.6% vs 82.6% P = 0.004). Conclusion: our results demonstrate that the updating of clinical guidelines for RSV bronchiolitis was effective, as it achieved decreases in the use of bronchodilators and nebulized hypertonic saline solution. It is necessary to continue developing new strategies targeted to increase adherence to guidelines and evaluate the impact on the use of resources.

Jorge Andres Olave-Rodriguez,1 Francisco Javier Bonilla-Escobar,2– 4 Estephania Candelo,5,6 Lisa Ximena Rodriguez-Rojas1,7 1Universidad Icesi, Faculty of Health Sciences, Cali, Colombia; 2Somos Ciencia al Servicio de la Comunidad, Fundación SCISCO/Science to Serve the Community, SCISCO Foundation, Cali, Colombia; 3Universidad del Valle, Cali, Colombia; 4Institute for Clinical Research Education, University of Pittsburgh, Pittsburgh, PA, USA; 5Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia; 6Centro enfermedades raras y malformaciones congenitas (CIACER), Universidad Icesi, Cali, Colombia; 7Human Genetics Department, Fundación Valle del Lili, Cali, ColombiaCorrespondence: Lisa Ximena Rodriguez-Rojas Cra. 98 ## 18-49, Cali, Valle del Cauca, ColombiaEmail lixiro@gmail.com; lisa.rodriguez@fvl.org.coBackground: Becker’s type myotonia congenita is an autosomal recessive nondystrophic skeletal muscle disorder characterized by muscle stiffness and the inability of muscle relaxation after voluntary contraction. It is caused by mutations in the CLCN1 gene, which encodes for a chloride channel mainly expressed in the striated muscle. Most cases have been reported in the European population, and only mexiletine has demonstrated a randomized placebo-controlled, double-blinded effectiveness.Case Presentation: We present two male siblings from Colombia with Latino ancestry, without parental consanguinity, with myotonia during voluntary movements, muscle hypertrophy of lower extremities, transient weakness, and severe muscle fatigue after exercise from three years of age. A genetic panel for dystrophic muscle disorders and a muscle biopsy were both negative. Genetic testing was performed in their second decade of life. Both patients’ exomic sequencing test reported the mutation c.1129C >T (p.Arg377&ast;) affecting exon 10 of the CLCN1, generating a premature stop codon. This mutation was described as pathogenic and observed in only one other patient in the United Kingdom.Conclusion: To our knowledge, these are the first cases of Becker’s type myotonia congenita reported in Colombia. Increasing awareness of healthcare providers for this type of disease in the region could lead to the identification of undiagnosed patients. Limited availability of medical geneticists as well as genetic testing may be the cause of the lack of previous description of cases, in addition to the delay in the diagnosis of the patients. Further epidemiological studies can reveal underdiagnosed myotonias in the country and in the Latin-American region.Keywords: Becker type myotonia congenita, myotonia congenita, Colombia, muscular diseases, siblings case reports

How and why did the gospels according to Matthew, Mark, Luke, and John begin to keep exclusive company with one another as the authoritative collection of Jesus books? The present study seeks to answer this question by investigating gospel combinations of the second century. I focus on the textual identities, mode, integrity, interactions, and authority of gospels as they are combined by second-century Christian authors and readers. I examine gospel combinations in interpretive rewriting (the Gospel of Thomas and the Epistula Apostolorum), gospel orchestration (the Diatessaron), pericope interpolation (the Longer Ending of Mark), second-order Christian discourse about gospel books, and artifactual juxtapositions (e.g. P45). My first major conclusion is that the four proto-canonical gospels were keeping congenial company as early as Papias, and consistently throughout the second century. This is seen in the way that the Gospel of Thomas synthesizes material from Matthew and Luke. It is demonstrated in the gospel epitome of the Epistula Apostolorum, which integrates material from all four proto-canonical gospels and situates them in a Johannine-Synoptic sequence. Tatian’s Diatessaron showcases a tapestry of all four proto-canonical gospels, intricately sequenced. The Longer Ending of Mark does the same on a smaller scale. Papias is the first explicitly to mention gospel authors, and throughout the rest of the second century, gospel authors become the literary symbols by which Christians describe the pluriform nature of the one gospel. Multi-gospel codices of the second and third centuries CE corroborate these patterns, combining proto-canonical gospels in ways that manifest their intertextual connectedness. My second major conclusion is that noncanonical traditions were also valued for their contribution to the collective memory of Jesus, but they functioned mainly as ancillary to the fourfold gospel core. Thus, while it may be anachronistic to speak of a fourfold gospel “canon” before Irenaeus, it is certainly accurate to speak of a fourfold gospel “center of gravity” in the first half of the second century.

Simple Summary:& nbsp;This report presents clinically relevant advances in the management of non-muscle-invasive bladder cancer, which have been the focus of discussion of expert members of the Spanish Oncology Genitourinary (SOGUG) Multidisciplinary Working Group in the framework of the Genitourinary Alliance project (12GU), designed as a space for the integration of novel information in the care of bladder cancer patients. The present study is focused on different aspects regarding the evaluation of hematuria, assessment of second (or repeated) transurethral resection of bladder cancer, histopathological diagnosis and problems with tumor grading, importance of histological variants, shortage of drug supply, and the current role and influence of immunotherapy and biological markers on the oncological outcome of patients. All proposals and recommendations have a multidisciplinary practical approach and are intended to help clinicians in shared decision making for patients with non-muscle-invasive urothelial cancer. On the basis of the discussion of the current state of research on relevant topics of non-muscle-invasive bladder cancer (NMIBC) among a group of experts of the Spanish Oncology Genitourinary (SOGUG) Working Group, recommendations were proposed to overcome the challenges posed by the management of NMIBC in clinical practice. A unified definition of the term 'microhematuria' and the profile of the patient at risk are needed. Establishing a 'hematuria clinic' would contribute to a centralized and more efficient evaluation of patients with this clinical sign. Second or repeated transurethral resection (re-TUR) needs to be defined, including the time window after the first procedure within which re-TUR should be performed. Complete tumor resection is mandatory when feasible, with specification of the presence or absence of muscle. Budding should be used as a classification system, and stratification of T1 tumors especially in extensive and deep tumors, is advisable. The percentage of the high-grade component should always be reported, and, in multiple tumors, grades should be reported separately. Luminal and basal subtypes can be identified because of possibly different clinical outcomes. Molecular subtypes and immunotherapy are incorporated in the management of muscle-invasive bladder cancer but data on NMIBC are still preliminary.

In this paper, a resonant system that produces a movement of low amplitude and ultrasonic frequency is used to achieve the vibration assistance in a ball-burnishing process. A full vibration characterization of this process performed in a lathe was done. It is carried out by a new tool designed in the research group of the authors. Its purpose is to demonstrate that the machine and the tool do not have any resonance problem during the process and to prevent possible failures. The analysis of this dynamic behaviour permits to validate the suitability of the tool when it is anchored to a numerical control lathe. This is very important for its future industrial implementation. It is also intended to confirm that the system adequately transmits vibrations through the material. To do this, a methodology to validate the dynamic tool behaviour was developed. Several techniques that combine the usual and ultrasonic vibration ranges through static and dynamic measurements were merged: vibration and acoustic emission measurements. An operational deflection shape (ODS) exercise has been also performed. Results show the suitability of the tool used to transmit the assistance vibrations, and that no damage is produced in the material in any case.

There is sparse direct experimental evidence that atomic nuclei can exhibit stable pear shapes arising from strong octupole correlations. In order to investigate the nature of octupole collectivity in radium isotopes, electric octupole ($E3$) matrix elements have been determined for transitions in $^{222,228}$Ra nuclei using the method of sub-barrier, multi-step Coulomb excitation. Beams of the radioactive radium isotopes were provided by the HIE-ISOLDE facility at CERN. The observed pattern of $E$3 matrix elements for different nuclear transitions is explained by describing $^{222}$Ra as pear-shaped with stable octupole deformation, while $^{228}$Ra behaves like an octupole vibrator., Comment: to be published in Physical Review Letters

Background Patients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at-risk patients could help to guide the duration of therapy. Methods We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel). Results In December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d-dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19-9.57) events per 100 patient-years in those with raised d-dimer levels and 2.68 (95% CI: 1.45-4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71-10.4) and 3.34 (95% CI: 2.39-4.53), respectively. Patients with major risk factors and raised d-dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio [HR]: 2.14; 95% CI: 0.96-4.79) than those with normal levels. Patients with minor risk factors and raised d-dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51-3.63) than those with normal levels. On multivariate analysis, raised d-dimers (HR: 1.74; 95% CI: 1.09-2.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors. Conclusions Patients with raised d-dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences.

Carlos E Rodríguez-Martínez,1,2 Monica P Sossa-Briceño,3 Jose A Castro-Rodriguez4 1Department of Pediatrics, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia; 2Department of Pediatric Pulmonology and Pediatric Critical Care Medicine, School of Medicine, Universidad El Bosque, Bogota, Colombia; 3Department of Internal Medicine, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia; 4Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Background: For the early identification of persistent asthma symptoms among young children with recurrent wheezing, it would be helpful to identify all available studies that have identified at least one factor for predicting the persistence of early wheezing. The objective of the present study was to perform a systematic review of all studies that have identified factors that predict the persistence of symptoms among young patients with recurring wheezing. Methods: A systematic review of relevant studies was conducted through searching in MEDLINE, EMBASE, CINHAL, and SCOPUS databases up to June 2016. Studies that identified predictors of persistence of wheezing illness among young children with recurrent wheezing were retrieved. Two independent reviewers screened the literature and extracted relevant data. Results: The literature search returned 649 references, 619 of which were excluded due to their irrelevance. Five additional studies were identified from reference lists, and 35 studies were finally included in the review. Among all the identified predictors, the most frequently identified ones were the following: family asthma or atopy; personal history of atopic diseases; allergic sensitization early in life; and frequency, clinical pattern, or severity of wheezing/symptoms. Conclusion: Parental asthma (especially maternal), parental allergy, eczema, allergic rhinitis, persistent wheezing, wheeze without colds, exercise-induced wheeze, severe wheezing episodes, allergic sensitization (especially polysensitization), eosinophils (blood or eosinophil cationic protein in nasal sample), and fraction of exhaled nitric oxide were risk factors predicting persistence of early wheezing through school age. All of them are included in conventional algorithms, for example, Asthma Predictive Index and its modifications, for predicting future asthma. Keywords: birth cohort, infantile asthma, longitudinal studies, persistence, continuance, prognosis

The interaction of water vapor with ZnO/CuOx/Cu(1 1 1) surfaces was investigated using synchrotron-based ambient pressure x-ray photoelectron spectroscopy (AP-XPS) and density-functional theory (DFT) calculations. Cu(1 1 1) does not dissociate the water molecule. Cleavage of O-H bonds was seen with AP-XPS after depositing ZnO or preparing CuOx on the copper substrate. The results of DFT calculations show unique behavior for ZnO/CuOx/Cu(1 1 1), not seen on Cu(1 1 1), CuOx/Cu(1 1 1) or ZnO(0 0 0). The ZnO/CuOx/Cu(1 1 1) system binds water quite well and exhibits the lowest energy barrier for O-H bond cleavage. The presence of unsaturated Zn cations in the islands of ZnO led to high chemical reactivity. In order to remove the OH from ZnO/CuOx/Cu(1 1 1) and ZnO/Cu(1 1 1) surfaces, heating to elevated temperatures was necessary. At 500-600 K, a significant coverage of OH groups was still present on the surfaces and did react with CO during the water-gas shift (WGS) process. The final state of the sample depended strongly on the amount of ZnO present on the catalyst surface. For surfaces with a ZnO coverage below 0.3 ML, the adsorption of water did not change the integrity of the ZnO islands. On the other hand, for surfaces with a ZnO coverage above 0.3 ML, a ZnO → ZnxOH transformation was observed. This transformation led to a decrease in the WGS catalytic activity.

The first 2^{+} and 3^{-} states of the doubly magic nucleus ^{132}Sn are populated via safe Coulomb excitation employing the recently commissioned HIE-ISOLDE accelerator at CERN in conjunction with the highly efficient MINIBALL array. The ^{132}Sn ions are accelerated to an energy of 5.49 MeV/nucleon and impinged on a ^{206}Pb target. Deexciting γ rays from the low-lying excited states of the target and the projectile are recorded in coincidence with scattered particles. The reduced transition strengths are determined for the transitions 0_{g.s.}^{+}→2_{1}^{+}, 0_{g.s.}^{+}→3_{1}^{-}, and 2_{1}^{+}→3_{1}^{-} in ^{132}Sn. The results on these states provide crucial information on cross-shell configurations which are determined within large-scale shell-model and Monte Carlo shell-model calculations as well as from random-phase approximation and relativistic random-phase approximation. The locally enhanced B(E2;0_{g.s.}^{+}→2_{1}^{+}) strength is consistent with the microscopic description of the structure of the respective states within all theoretical approaches. The presented results of experiment and theory can be considered to be the first direct verification of the sphericity and double magicity of ^{132}Sn. ispartof: PHYSICAL REVIEW LETTERS vol:121 issue:25 ispartof: location:United States status: published

Aggregated tau protein is associated with over 20 neurological disorders, which include Alzheimer's disease. Previous work has shown that tau's sequence segments VQIINK and VQIVYK drive its aggregation, but inhibitors based on the structure of the VQIVYK segment only partially inhibit full-length tau aggregation and are ineffective at inhibiting seeding by full-length fibrils. Here we show that the VQIINK segment is the more powerful driver of tau aggregation. Two structures of this segment determined by the cryo-electron microscopy method micro-electron diffraction explain its dominant influence on tau aggregation. Of practical significance, the structures lead to the design of inhibitors that not only inhibit tau aggregation but also inhibit the ability of exogenous full-length tau fibrils to seed intracellular tau in HEK293 biosensor cells into amyloid. We also raise the possibility that the two VQIINK structures represent amyloid polymorphs of tau that may account for a subset of prion-like strains of tau.

© 2016 American Chemical Society. The role of the interface between a metal and oxide (CeOx-Cu and ZnO-Cu) is critical to the production of methanol through the hydrogenation of CO2(CO2+ 3H2→ CH3OH + H2O). The deposition of nanoparticles of CeOxor ZnO on Cu(111),oxi< 0.3 monolayer, produces highly active catalysts for methanol synthesis. The catalytic activity of these systems increases in the sequence: Cu(111) < ZnO/Cu(111) < CeOx/Cu(111). The apparent activation energy for the CO2→ CH3OH conversion decreases from 25 kcal/mol on Cu(111) to 16 kcal/mol on ZnO/Cu(111) and 13 kcal/mol on CeOx/Cu(111). The surface chemistry of the highly active CeOx-Cu(111) interface was investigated using ambient pressure X-ray photoemission spectroscopy (AP-XPS) and infrared reflection absorption spectroscopy (AP-IRRAS). Both techniques point to the formation of formates (HCOO-) and carboxylates (CO2δ-) during the reaction. Our results show an active state of the catalyst rich in Ce3+sites which stabilize a CO2δ-species that is an essential intermediate for the production of methanol. The inverse oxide/metal configuration favors strong metal-oxide interactions and makes possible reaction channels not seen in conventional metal/oxide catalysts.

The role of the interface between a metal and oxide (CeOx-Cu and ZnO-Cu) is critical to the production of methanol through the hydrogenation of CO2 (CO2 + 3H2 → CH3OH + H2O). The deposition of nanoparticles of CeOx or ZnO on Cu(111),oxi < 0.3 monolayer, produces highly active catalysts for methanol synthesis. The catalytic activity of these systems increases in the sequence: Cu(111) < ZnO/Cu(111) < CeOx/Cu(111). The apparent activation energy for the CO2 → CH3OH conversion decreases from 25 kcal/mol on Cu(111) to 16 kcal/mol on ZnO/Cu(111) and 13 kcal/mol on CeOx/Cu(111). The surface chemistry of the highly active CeOx-Cu(111) interface was investigated using ambient pressure X-ray photoemission spectroscopy (AP-XPS) and infrared reflection absorption spectroscopy (AP-IRRAS). Both techniques point to the formation of formates (HCOO-) and carboxylates (CO2δ-) during the reaction. Our results show an active state of the catalyst rich in Ce3+ sites which stabilize a CO2δ- species that is an essential intermediate for the production of methanol. The inverse oxide/metal configuration favors strong metal-oxide interactions and makes possible reaction channels not seen in conventional metal/oxide catalysts.

© the Owner Societies 2016. Ambient-Pressure X-ray Photoelectron Spectroscopy (AP-XPS) and Infrared Reflection Absorption Spectroscopy (AP-IRRAS) have been used to elucidate the active sites and mechanistic steps associated with the ethanol steam reforming reaction (ESR) over Ni-CeO2(111) model catalysts. Our results reveal that surface layers of the ceria substrate are both highly reduced and hydroxylated under reaction conditions while the small supported Ni nanoparticles are present as Ni0/NixC. A multifunctional, synergistic role is highlighted in which Ni, CeOxand the interface provide an ensemble effect in the active chemistry that leads to H2. Ni0is the active phase leading to both C-C and C-H bond cleavage in ethanol and it is also responsible for carbon accumulation. On the other hand, CeOxis important for the deprotonation of ethanol/water to ethoxy and OH intermediates. The active state of CeOxis a Ce3+(OH)xcompound that results from extensive reduction by ethanol and the efficient dissociation of water. Additionally, we gain an important insight into the stability and selectivity of the catalyst by its effective water dissociation, where the accumulation of surface carbon can be mitigated by the increased presence of surface OH groups. The co-existence and cooperative interplay of Ni0and Ce3+(OH)xthrough a metal-support interaction facilitate oxygen transfer, activation of ethanol/water as well as the removal of coke.

None of the definitions of severity used in acute pancreatitis (AP) is ideal. Many of the scoring systems used to predict and measure its severity are complex, cumbersome and inaccurate. to evaluate the usefulness of the most commonly used early markers for predicting severity, necrosis and mortality in patients with AP, and the need for surgery or Intensive Care Unit (ICU) admission. Prospective study was performed from March 2009 to August 2010 based on patients diagnosed with AP seen consecutively at a secondary hospital. The early prognostic markers used were Apache II score a parts per thousand yen8 and Ranson's score a parts per thousand yen3, RCP > 120mg/l and Ht > 44% in the first 24 hours. 131 patients were prospectively enrolled. Median age was 63 years, 60% were men. The most frequent etiology of AP was biliary (68%). Fifteen patients were admitted to the ICU (11.6%) and five (3.9%) required surgery. Twelve patients (9.2%) had necrosis on CT. Four patients (3%) died, all of them in the Severe AP group. Only hematocrit > 44 was predictor of mortality in univariate analysis. hematocrit a parts per thousand yen 44% was a significant predictor of mortality. The other indicators present limitations for predicting severity, necrosis and mortality, especially in the first 24 hours.

Background: Guidelines recommend the use of inhaled long-acting bronchodilators, inhaled corticosteroids (ICS) and their combinations for maintenance treatment of moderate to severe COPD. However, there are limited data supporting combination therapy. Methods: This systematic review assessed the efficacy of three therapeutic approaches: tiotropium plus long-acting beta2-agonist (LABA) ("dual" therapy), LABA/ICS ("combined" therapy), and tiotropium plus LABAJICS ("triple" therapy), all compared with tiotropium monotherapy. Randomized controlled trials were identified after a search of different databases of published and unpublished trials. Results: Twenty trials (6803 participants) were included. "Dual" therapy showed significant improvements in forced volume in the first second (FEV1), health-related quality of life (HRQoL), and dyspnea. However, it failed to reduce the risk of COPD exacerbations. Compared with tiotropium, "combined" therapy presented modest but significant effects on FEV1, HRQoL, and dyspnea. Again, there was no significant difference in exacerbations, but it was associated with a significant increase of serious adverse effects (SAE) (number need to treat for harm [NNTH] = 20; 95% CI: 11-119). Finally, "triple therapy" increased FEV1, improved HRQoL (both benefits exceeded minimal important differences) and decrease COPD exacerbations in anon-significant way. (Odds ratio [OR] = 0.57; 95% CI: 0.24 to 1.37, p = 0.21). Conclusions: "Dual" and "triple" therapy seem like the most promising for patients with moderate to very severe COPD. However, data are still scarce and studies too short to generate a strong recommendation. Future studies should examine long-term efficacy and safety. (C) 2011 Elsevier Ltd. All rights reserved.

Background: Safety of long-acting beta agonists (LABA) has been questioned and recent evidence suggested a detrimental effect on asthma control as well as an increased risk of death. Objective: To evaluate the safety of regular use of LABA compared with placebo or LABA added to inhaled corticosteroids (ICS) compared with ICS in persistent asthma. Methods: Randomized studies from MEDLINE, EMBASE, and Cochrane Controlled Trials Register were identified. Additionally, AstraZeneca, GlaxoSmithKline, Novartis and FDA clinical trials databases were searched. Primary outcomes were asthma exacerbations (AE) requiring systemic corticosteroids or hospitalization, life-threatening exacerbations and asthma-related deaths. Results: We identified 92 randomized clinical trials with 74,092 subjects. LABA (as monotherapy) reduced exacerbations requiring corticostereids (Relative Risk [RR] - 0.80; 95% CI, 0.73-0.88), without detrimental effects on hospitalizations or life-threatening episodes. Contrarily, LABA showed a significant increase in asthma-related deaths (Relative Risk - 3.83; 95% CI, 1.21-12.14). Subgroup analysis suggests that children, patients receiving salmeterol, and a duration of treatment >12 weeks are associated with a higher risk of serious adverse effects; also there was a protective effect of concomitant use of ICS. On the other hand, combination of LABA/ICS reduced exacerbations (RR=0.73; 95% CI, 0.67-0.79), and hospitalizations (RR = 0.58, 95% CI, 0.45-0.74). Combined therapy was also equivalent to ICS in terms of life-threatening episodes and asthma-related deaths. Again, children and use of salmeterol were associated with an increased risk of some severe outcomes as compared with adults and formoterol users, respectively. Conclusions: This review reinforced the international recommendations in terms or the use of LABA remains the preferred acid-on therapy to ICS for patients whose disease cannot adequately controlled with ICS, and that LABA cannot be prescribed as a monotherapy. Nevertheless, in spite of the protective effect of the ICS, children and salmeterol use still show an increased risk of non-fatal serious adverse events. (c) 2008 Elsevier Ltd. All rights reserved.

Background: Current guidelines recommend the use of inhaled corticosteroids (ICSs) added to long-acting beta-agonists (LABAs) for treatment of symptomatic patients with severe and very severe COPD. However, the evidence has been inconclusive. The aim of this review was to assess the safety and efficacy of LABAs/ICSs compared with LA-BA monotherapy for patients with moderate-to-very severe COPD. Methods: Systematic searches were conducted on MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and the trial registers of manufacturers, without language restriction. Primary outcomes were COPD exacerbations and mortality. Secondary outcomes included lung function, health-related quality of life, and adverse effects. Results: Eighteen randomized controlled trials (12,446 participants) were selected. Therapy with LABAs/ICSs did not decrease the number of severe exacerbations (relative risk [RR], 0.91; 95% CI, 0.82 to 1.01; I-2 = 1%), or all-cause mortality (RR, 0.90; 95% CI, 0.76 to 1.06; I-2 = 0%), respiratory mortality (RR, 0.80; 95% CI, 0.61 to 1.05; I-2 = 0%), and cardiovascular mortality (RR, 1.22; 95% CI, 0.88 to 1.71; I-2 = 0%). To the contrary, the number of moderate exacerbations (RR, 0.84; 95% CI, 0.74 to 0.96; I-2 = 50%) and the St. George respiratory questionnaire total score (weighted mean difference, -1.88; 95% CI, -2.44 to -1.33; I-2 = 29%) were significantly reduced with LABA/ICS therapy. Although therapy with LABAs/ICSs increases FEV1 significantly (0.06 and 0.04 L, respectively), they were associated with an increased risk of pneumonia (RR, 1.63; 95% CI, 1.35 to 1.98; I-2 = 20%). Conclusions: Compared with LABA monotherapy, the magnitude of the benefits of LABA/ICS therapy did not reach that of the criteria for predefined clinically important effects and were associated with serious adverse effects. (CHEST 2009; 136:1 029-1038)

Chromosomal deletions at segment 11q23-q24 have been identified in a variety of human epithelial tumors, including cervical carcinoma (CC), indicating the presence in this region of at least a tumor suppressor gene (TSG) involved in the development of these neoplasms. To localize the 11q deletion target more precisely, 54 primary cervical carcinomas were examined for loss of heterozygosity (LOH) using a panel of microsatellite DNA markers mapping to 11 p. 15 and spanning region 11q23-qter. Nineteen tumors were found to have LOH at chromosome 11q. The highest frequency of LOH was observed at locus APOC-3, located in 11q23.1-q23.2, which was deleted in 42% of the informative cases. In contrast, LOH was infrequent at distal 11q in current series of CC. The smallest common region of loss included APOC-3 and was defined distally by marker D11S925 in region 11q23. The present data strongly suggest that the 11q suppressor gene(s) involved in cervical tumorigenesis is likely to be located at chromosome region 11q22-q23.

Alterations in microsatellite sequences have been reported in a variety of human cancers. Microsatellite instability is thought to reflect the inactivation of genes involved in DNA mismatch repair (MMR), which could predispose to the accumulation of further genetic errors in affected cells. Genomic instability in human cancers might also result from the inactivation of cell cycle controls such as the p53-dependent G1 checkpoint that prevents cell replication in response to DNA damage. High-risk human papillomavirus (HPV) is thought to contribute to the development of HPV-associated cancers, including cervical carcinoma, through the interaction of the E6 and E7 viral oncoproteins with two major cell cycle regulatory proteins, namely p53 and the retinoblastoma gene product (pRb). Although the high-risk HPV is prevalent in cervical carcinomas, viral DNA is not detected in a minor proportion of the cases. The HPV infection is insufficient for the development of cervical cancer, which indicates that additional genetic events are involved in the process. This study reports the potential role of MMR gene defects (in addition to or independent of HPV infection) in patients with cervical carcinogenesis. Microsatellite instability and HPV status were analyzed in a series of 54 patients with cervical carcinomas and in two associated cell lines. Microsatellite alterations were examined at 10 loci located in different chromosomes by using semiautomated fluorescent DNA technology and polymerase chain reaction. The HPV types were detected by a general primer polymerase chain reaction method. The results indicate that microsatellite instability is very infrequent in cervical carcinoma and occurs independently of HPV status.

The Marketing and Reception of Women Writers in the Twenty-First Century Spanish Nation-State By Jennifer Anne Rodriguez This thesis is a comparative study of the marketing and reception of women writers in the twenty-first century Spanish nation-state; more specifically, Galicia, Catalonia, the Basque Country and central Spain. This study analyses and discusses the strategies women writers in the Spanish nation-state use to achieve success and visibility within their respective literary fields, and also takes into account the complex situation that surrounds these women writers. As such, this thesis also discusses issues including language choice and national identity, as well as how women writers negotiate their position with their respective literary fields. Taking a cultural studies approach, this thesis takes eight women writers as case studies: María Xosé Queizán and María Reimóndez (Galicia); Mariasun Landa and Laura Mintegi (the Basque Country); Carme Riera and Maria de la Pau Janer (Catalonia); and Almudena Grandes and Lucía Etxebarria (central Spain) and examines the individual strategies they use to market their work and achieve success, associating themselves with canonical authors and careful use of paratexts such as prologues and epilogues. In addition, the reception of their mediated identities and their work is discussed through analysis of reviews and interviews in the press. This thesis shows that that women writers in the Spanish nation-state are engaged constantly in a complex negotiation of various inter-dependent factors. Achieving success – both economic and symbolic – is a complex process, and there may often be cases where economic success can be detrimental to symbolic success, or vice versa. However, if women writers in the Spanish nation-state are able to negotiate these complex inter-dependent factors, success – both economic and symbolic -, prestige and even canonisation are achievable.

Membro di una famiglia aristocratica siciliana e appartenente all’ordine benedettino, Giovanni Paternò ottenne la nomina ad arcivescovo di Palermo nel luglio del 1489, dopo una lunga permanenza alla guida della diocesi maltese. “Dottissimo” secondo il canonico Antonino Mongitore, che ne offre un sintetico profilo biografico, si interessò anche di questioni architettoniche, mostrando preferenze che spaziano dalle soluzioni più aggiornate del tardogotico mediterraneo e del mondo della costruzione in pietra da taglio, al linguaggio all’antica veicolato dagli scultori del marmo bianco (marmorari). Il contributo mette a fuoco la figura di questo committente e il contesto culturale nel quale si svolse la sua attività come promotore di imprese architettoniche, attraverso lo studio delle fonti coeve rintracciate, l’analisi diretta delle opere dallo stesso patrocinate ancora esistenti, ipotesi ricostruttive relative alle opere scomparse e il confronto con altre opere esistenti in possibili contesti di riferimento del committente e dei suoi artefici di fiducia. Member of an aristocratic Sicilian family and belonging to the Benedictine order, Giovanni Paternò obtained the appointment as archbishop of Palermo in July 1489, after a long stay at the head of the Maltese diocese. "Very learned" according to Antonino Mongitore, who wrote a synthetic biography, he was also interested in architecture, showing preferences ranging from the most up-to-date solutions of the late Mediterranean Gothic and the world of stone construction, to the “all’antica” language conveyed by the sculptors of white marble (marmorari). This contribution focuses on the figure of this client and the cultural context in which his activity as promoter of architectural works took place, through the study of coeval sources, the direct analysis of the still existing works promoted by the same, reconstructive hypotheses for the missing works and the comparison with other existing works in possible reference contexts of the client and his trusted architects.

Aim To analyze the outcomes of component separation techniques (CST) to treat incisional hernias (IH) in a large multicenter cohort of patients. Methods All IH repair using CST, registered in EVEREG from July 2012 to December 2019, were included. Data on the pre-operative patient characteristics and comorbidities, IH characteristics, surgical technique, complications, and recurrence were collected. Outcomes between anterior (ACS) and posterior component separation (PCS) techniques were compared. Risk factors for complications and recurrences were analyzed. Results During the study period, 1536 patients underwent CST (45.5% females) with a median age of 64.0 years and median body mass index (BMI) of 29.7 kg/m2. ACS was the most common technique (77.7%). Overall complications were frequent in both ACS and PCS techniques (36.5%), with a higher frequency of wound infection (10.6% vs. 7.0%; P = 0.05) and skin necrosis (4.4% vs. 0.1%; P P = 0.001), previous repair (OR 0.75; P = 0.038), morbid obesity (OR 0.67; P = 0.015), ASA grade (OR 0.62; P P P = 0.001). After a minimum follow-up of 6 months (median 15 months; N = 590), 59 (10.0%) recurrences were diagnosed. Operations performed in a non-specialized unit were significantly associated with recurrences (HR 4.903, CI 1.64–14.65; P = 0.004). Conclusion CST is a complex procedure with a high rate of complications. Both ACS and PCS techniques have similar complication and recurrence rates. Operations performed in a specialized unit have better outcomes.