Glucose Control in Acute Myocardial Infarction: A Pilot Randomized Study Controlled by Continuous Glucose Monitoring System Comparing the Use of Insulin Glargine with Standard of Care

Background: This pilot study aimed to verify if glycemic control can be achieved in type 2 diabetes patients after acute myocardial infarction (AMI), using insulin glargine (iGlar) associated with regular insulin (iReg), compared with the standard intensive care unit protocol, which uses continuous insulin intravenous delivery followed by NPH insulin and iReg (St. Care). Patients and Methods: Patients (n = 20) within 24 h of AMI were randomized to iGlar or St. Care. Therapy was guided exclusively by capillary blood glucose (CBG), but glucometric parameters were also analyzed by blinded continuous glucose monitoring system (CGMS). Results: Mean glycemia was 141 +/- 39 mg/dL for St. Care and 132 +/- 42 mg/dL for iGlar by CBG or 138 +/- 35 mg/dL for St. Care and 129 +/- 34 mg/dL for iGlar by CGMS. Percentage of time in range (80-180 mg/dL) by CGMS was 73 +/- 18% for iGlar and 77 +/- 11% for St. Care. No severe hypoglycemia (<= 40 mg/dL) was detected by CBG, but CGMS indicated 11 (St. Care) and seven (iGlar) excursions in four subjects from each group, mostly in sulfonylurea users (six of eight patients). Conclusions: This pilot study suggests that equivalent glycemic control without increase in severe hyperglycemia may be achieved using iGlar with background iReg. Data outputs were controlled by both CBG and CGMS measurements in a real-life setting to ensure reliability. Based on CGMS measurements, there were significant numbers of glycemic excursions outside of the target range. However, this was not detected by CBG. In addition, the data indicate that previous use of sulfonylurea may be a potential major risk factor for severe hypoglycemia irrespective of the type of insulin treatment.

Autoantibodies and High-Risk HLA Susceptibility Markers in First-Degree Relatives of Brazilian Patients with Type 1 Diabetes Mellitus: A Progression to Disease Based Study

The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase(65) (GAD(65)A), insulinoma-associated antigen-2 (IA-2A) and insulin (IAA)-and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ) in first degree relatives of heterogeneous Brazilian patients with type I diabetes(T1DM). A major focus of this study was to determine the influence of age, gender, proband characteristics and ancestry on the prevalence of autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic predisposition to T1DM among the first-degree relatives. IAA, ICA, GAD(65)A, IA-2A and HLA- class II alleles were determined in 546 first-degree-relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients with T1DM. Overall, 8.9% of the relatives were positive for one or more autoantibodies. IAA was the only antibody detected in parents. GAD(65) was the most prevalent antibody in offspring and siblings as compared to parents and it was the sole antibody detected in offspring. Five siblings were positive for the IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or -DR4 alleles) and 1 offspring positive for GAD(65)A progressed to diabetes. The data indicated that the GAD(65) and IA-2 antibodies were the strongest predictors of T1DM in our study population. The high risk HLA haplotypes alone were not predictive of progression to overt diabetes.

Plasma Pro-B-Type Natriuretic Peptide Testing as a Screening Method for Hypertrophic Cardiomyopathy

Background: Clinical multistage risk assessment associated with electrocardiogram (ECG) and NT-proBNP may be a feasible strategy to screen hypertrophic cardiomyopathy (HCM). We investigated the effectiveness of a screening based on ECG and NT-proBNP in first-degree relatives of patients with HCM. Methods and Results: A total of 106 first-degree relatives were included. All individuals were evaluated by echocardiography, ECG, NT-proBNP, and molecular screening (available for 65 individuals). From the 106 individuals, 36 (34%) had diagnosis confirmed by echocardiography. Using echocardiography as the gold standard, ECG criteria had a sensitivity of 0.71, 0.42, and 0.52 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Mean values of NT-ProBNP were higher in affected as compared with nonaffected relatives (26.1 vs. 1290.5, P < .001). The AUC of NT-proBNP was 0.98. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.92 and specificity of 0.96. Using molecular genetics as the gold standard, ECG criteria had a sensitivity of 0.67, 0.37, and 0.42 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.83 and specificity of 0.98. Conclusion: Values of NT-proBNP above 70 pg/mL can be used to effectively select high-risk first-degree relatives for HCM screening. (J Cardiac Fail 2012;18:564-568)

The peculiar isolated neutron star in the Carina Nebula Deep XMM-Newton and ESO-VLT observations of 2XMM J104608.7-594306

While fewer in number than the dominant rotation-powered radio pulsar population, peculiar classes of isolated neutron stars (INSs) which include magnetars, the ROSAT-discovered "Magnificent Seven" (M7), rotating radio transients (RRATs), and central compact objects in supernova remnants (CCOs) - represent a key element in understanding the neutron star phenomenology. We report the results of an observational campaign to study the properties of the source 2XMM J104608.7-594306, a newly discovered thermally emitting INS. The evolutionary state of the neutron star is investigated by means of deep dedicated observations obtained with the XMM-Newton Observatory, the ESO Very Large Telescope, as well as publicly available gamma-ray data from the Fermi Space Telescope and the AGILE Mission. The observations confirm previous expectations and reveal a unique type of object. The source, which is likely within the Carina Nebula (N-H = 2.6x10(21) cm(-2)), has a spectrum that is both thermal and soft, with kT(infinity) = 135 eV. Non-thermal (magnetospheric) emission is not detected down to 1% (3 sigma, 0.1-12 keV) of the source luminosity. Significant deviations (absorption features) from a simple blackbody model are identified in the spectrum of the source around energies 0.6 keV and 1.35 keV. While the former deviation is likely related to a local oxygen overabundance in the Carina Nebula, the latter can only be accounted for by an additional spectral component, which is modelled as a Gaussian line in absorption with EW = 91 eV and sigma = 0.14 keV (1 sigma). Furthermore, the optical counterpart is fainter than m(V) = 27 (2 sigma) and no gamma-ray emission is significantly detected by either the Fermi or AGILE missions. Very interestingly, while these characteristics are remarkably similar to those of the M7 or the only RRAT so far detected in X-rays, which all have spin periods of a few seconds, we found intriguing evidence of very rapid rotation, P = 18.6ms, at the 4 sigma confidence level. We interpret these new results in the light of the observed properties of the currently known neutron star population, in particular those of standard rotation-powered pulsars, recycled objects, and CCOs. We find that none of these scenarios can satisfactorily explain the collective properties of 2XMM J104608.7-594306, although it may be related to the still poorly known class of Galactic anti-magnetars. Future XMM-Newton data, granted for the next cycle of observations (AO11), will help us to improve our current observational interpretation of the source, enabling us to significantly constrain the rate of pulsar spin down.

Comparison of venous plasma glycemia and capillary glycemia for the screening of type 2 diabetes mellitus in the Japanese-Brazilian community of Mombuca (Guatapará-SP)

Abstract Background To identify the most appropriate cut-off points of fasting glycemia for the screening of diabetes mellitus type 2 (DM2) with the comparison of the properties of capillary glycemia (CG) and venous blood plasma glycemia (PG) in a population of Japanese origin from the community of Mombuca, Guatapará - SP, Brazil. Methods This was a population-based descriptive cross-sectional study conducted on a sample of 131 individuals of both genders aged 20 years or more (66.8% of the target population). CG was measured with a glucometer in a blood sample obtained from the fingertip and PG was determined by an enzymatic method (hexokinase) in venous blood plasma, after a 10-14 hour fast in both cases. Data were analyzed by the receiver operating characteristic (ROC) curve in order to identify the best cut-off point for fasting glycemia (CG and PG) for the diagnosis of DM, using the 2-hour plasma glycemia > 200 mg/dl as gold - standard. Results The ROC curve revealed that the best cut-off point for the screening of DM was 110 mg/dl for CG and 105 mg/dl for PG, values that would optimize the relation between individuals with positive and false-positive results. The area under the ROC curve was 0.814 for CG (p < 0.01) and 0.836 for PG (p < 0.01). Conclusions The cut-off points of 105 mg/dl(5.8 mmol/l) for PG and of 110 mg/dl(6.1 mmol/l) for CG appear to be the most appropriate for the screening of DM2 in the population under study, with emphasis on the fact that the value recommended for CG is 5 mg/dl higher than that for PG, in contrast to WHO recommendations.

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Abstract Background An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Results Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Conclusions Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

Finite element methods for the Stokes system based on a Zienkiewicz type N-simplex

Hermite interpolation is increasingly showing to be a powerful numerical solution tool, as applied to different kinds of second order boundary value problems. In this work we present two Hermite finite element methods to solve viscous incompressible flows problems, in both two- and three-dimension space. In the two-dimensional case we use the Zienkiewicz triangle to represent the velocity field, and in the three-dimensional case an extension of this element to tetrahedra, still called a Zienkiewicz element. Taking as a model the Stokes system, the pressure is approximated with continuous functions, either piecewise linear or piecewise quadratic, according to the version of the Zienkiewicz element in use, that is, with either incomplete or complete cubics. The methods employ both the standard Galerkin or the Petrov–Galerkin formulation first proposed in Hughes et al. (1986) [18], based on the addition of a balance of force term. A priori error analyses point to optimal convergence rates for the PG approach, and for the Galerkin formulation too, at least in some particular cases. From the point of view of both accuracy and the global number of degrees of freedom, the new methods are shown to have a favorable cost-benefit ratio, as compared to velocity Lagrange finite elements of the same order, especially if the Galerkin approach is employed.

Perturbative and non perturbative effects in the Standard Model and orbifolded ADS/CFT based theories

We study some perturbative and nonperturbative effects in the framework of the Standard Model of particle physics. In particular we consider the time dependence of the Higgs vacuum expectation value given by the dynamics of the StandardModel and study the non-adiabatic production of both bosons and fermions, which is intrinsically non-perturbative. In theHartree approximation, we analyze the general expressions that describe the dissipative dynamics due to the backreaction of the produced particles. Then, we solve numerically some relevant cases for the Standard Model phenomenology in the regime of relatively small oscillations of the Higgs vacuum expectation value (vev). As perturbative effects, we consider the leading logarithmic resummation in small Bjorken x QCD, concentrating ourselves on the Nc dependence of the Green functions associated to reggeized gluons. Here the eigenvalues of the BKP kernel for states of more than three reggeized gluons are unknown in general, contrary to the large Nc limit (planar limit) case where the problem becomes integrable. In this contest we consider a 4-gluon kernel for a finite number of colors and define some simple toy models for the configuration space dynamics, which are directly solvable with group theoretical methods. In particular we study the depencence of the spectrum of thesemodelswith respect to the number of colors andmake comparisons with the planar limit case. In the final part we move on the study of theories beyond the Standard Model, considering models built on AdS5 S5/Γ orbifold compactifications of the type IIB superstring, where Γ is the abelian group Zn. We present an appealing three family N = 0 SUSY model with n = 7 for the order of the orbifolding group. This result in a modified Pati–Salam Model which reduced to the StandardModel after symmetry breaking and has interesting phenomenological consequences for LHC.

First Ramsey-type mass measurements with ISOLTRAP and design studies of the new PENTATRAP project

Der Einsatz von Penningfallen in der Massenspektrometrie hat zu einem einmaligen Genauigkeitssprung geführt. Dadurch wurden Massenwerte verschiedenster Atome zu wichtigen Eingangsparametern bei immer mehr physikalischen Fragestellungen. Die Massenspektrometrie mit Hilfe von Penningfallen basiert auf der Bestimmung der freien Zyklotronfrequenz eines Ions in einem homogenen Magnetfeld νc=qB/(2πm). Sie wird mit Flugzeitmethode (TOF-ICR) bestimmt, wobei eine relative Massenungenauigkeit δm/m von wenigen 10^-9 bei Nukliden mit Lebensdauern von <500 ms erreicht wird. Dies wurde durch die im Rahmen dieser Arbeit erstmals in der Penningfallen-Massenspektrometrie eingesetzten Ramsey-Methode möglich. Dabei werden zeitlich separierte, oszillierenden Feldern zur resonanten Ionenanregung genutzt, um die Frequenzmessung durch die Flugzeitmethode zu verbessern. Damit wurden am Penningfallenmassenspektrometer ISOLTRAP an ISOLDE/CERN die Massen der Nuklide 26,27Al und 38,39Ca bestimmt. Alle Massen wurden in die „Atomic Mass Evaluation“ eingebettet. Die Massenwerte von 26Al und 38Ca dienten insbesondere zu Tests des Standardmodells. Um mit Massenwerten fundamentale Symmetrien oder die Quantenelektrodynamik (QED) in extremen Feldern zu testen wurde ein neues Penningfallenprojekt (PENTATRAP) für hochpräzise Massenmessungen an hochgeladenen Ionen konzipiert. In dieser Doktorarbeit wurde vornehmlich die Entwicklung der Penningfallen betrieben. Eine Neuerung bei Penningfallenexperimenten ist dabei die permanente Beobachtung des Magnetfeldes B und seiner zeitlichen Fluktuationen durch so genannte „Monitorfallen“.

Meccanismi di produzione di energia in astrofisica

Prima di fornire una formulazione esaustiva dell'onda d'urto, è d'uopo definire il gas come oggetto fisico e le sue principali caratteristiche. Quanto si farà nei paragrafi seguenti quindi, sarà tentare di formalizzare il sistema gassoso dal punto di vista fisico e matematico. Sarà necessario introdurre un modello del sistema (par. 1.1) che ci permetta di lavorare a livello statistico sull'insieme di particelle che lo compongono per caratterizzare le funzioni termodinamiche classiche come medie temporali. Tramite queste considerazioni si stabilirà quali sono le quantità che si conservano nel moto di un fluido e si vedrà che tali leggi di conservazione formano un sistema di 5 equazioni differenziali parziali in 6 incognite. Tramite la linearizzazione di questo sistema si individueranno delle soluzioni chiamate onde sonore che danno un'indicazione sul modo in cui si propagano delle perturbazioni all'interno di un fluido; in particolar modo saranno utili per la determinazione del numero di Mach che rende possibile la distinzione tra due regimi: subsonico e supersonico (par. 1.2). Sarà possibile, a questo punto, indagare il fenomeno dell'onda d'urto (par. 2.1) e, nel dettaglio, due casi particolarmente utili in contesto astrofisico quali: l'onda d'urto per un gas politropico (par. 2.2), un'onda d'urto sferica che avanza verso il suo centro (2.2). Lo scopo di questa trattazione è indagare, o se non altro tentare, quanto avviene in un'esplosione di Supernova (par. 3). Relativamente a questo fenomeno, ne viene data una classificazione sommaria (par. 3.1), mentre particolare attenzione sarà rivolta alle Supernovae di tipo Ia (par. 3.2) che grazie alla loro luminosità standard costituiscono un punto di riferimento nell'Universo visibile.

Type Systems for Distributed Programs: Components and Sessions

Modern software systems, in particular distributed ones, are everywhere around us and are at the basis of our everyday activities. Hence, guaranteeing their cor- rectness, consistency and safety is of paramount importance. Their complexity makes the verification of such properties a very challenging task. It is natural to expect that these systems are reliable and above all usable. i) In order to be reliable, compositional models of software systems need to account for consistent dynamic reconfiguration, i.e., changing at runtime the communication patterns of a program. ii) In order to be useful, compositional models of software systems need to account for interaction, which can be seen as communication patterns among components which collaborate together to achieve a common task. The aim of the Ph.D. was to develop powerful techniques based on formal methods for the verification of correctness, consistency and safety properties related to dynamic reconfiguration and communication in complex distributed systems. In particular, static analysis techniques based on types and type systems appeared to be an adequate methodology, considering their success in guaranteeing not only basic safety properties, but also more sophisticated ones like, deadlock or livelock freedom in a concurrent setting. The main contributions of this dissertation are twofold. i) On the components side: we design types and a type system for a concurrent object-oriented calculus to statically ensure consistency of dynamic reconfigurations related to modifications of communication patterns in a program during execution time. ii) On the communication side: we study advanced safety properties related to communication in complex distributed systems like deadlock-freedom, livelock- freedom and progress. Most importantly, we exploit an encoding of types and terms of a typical distributed language, session π-calculus, into the standard typed π- calculus, in order to understand their expressive power.

Vincoli cosmologici da supernovae ad alto redshift

Le SNe Ia vengono utilizzate in cosmologia come indicatori di distanza. Nel 1998 due team di ricerca, il Supernova Cosmology Project e l'High-z Supernova Search Team compirono degli studi su un campione di SNe in galassie lontane a z=0.2-0.9. Da questi lavori emerse che le luminosità apparenti erano tipicamente inferiori del 25% rispetto ai valori attesi. Questo indica che tali oggetti si trovano ad una distanza di luminosità superiore a quella prevista da modelli d'Universo dominati da materia. Venne quindi determinata per la prima volta l'evidenza di un Universo in condizione di espansione accelerata. Lo scopo del presente lavoro di tesi è quello di analizzare i vincoli cosmologici imposti da SNe Ia ad alto redshift. È stato compiuto uno studio sui moduli di distanza osservativi di un campione di 580 SNe Ia al fine di trovare i parametri cosmologici che meglio descrivono il loro andamento in funzione del redshift nell'ambito dei modelli cosmologici standard con costante cosmologica positiva. Nella prima parte si illustreranno i modelli d’Universo di Friedmann, introducendo i concetti di redshift, di fattore di scala e i vari tipi di distanza. Nella seconda parte si descriverà cosa sono le Supernovae, e in particolare, le SNe di tipo Ia, le proprietà che le rendono candele standard e l'importanza che hanno assunto in cosmologia. Nella terza parte verranno presentanti i risultati prodotti per i due modelli studiati, verrà inoltre discussa la compatibilità con i parametri prodotti nei lavori compiuti dai due team di ricerca.

Long-term follow-up of patients with Bartter syndrome type I and II

BACKGROUND: Little information is available on a long-term follow-up in Bartter syndrome type I and II. METHODS: Clinical presentation, treatment and long-term follow-up (5.0-21, median 11 years) were evaluated in 15 Italian patients with homozygous (n = 7) or compound heterozygous (n = 8) mutations in the SLC12A1 (n = 10) or KCNJ1 (n = 5) genes. RESULTS: Thirteen new mutations were identified. The 15 children were born pre-term with a normal for gestational age body weight. Medical treatment at the last follow-up control included supplementation with potassium in 13, non-steroidal anti-inflammatory agents in 12 and gastroprotective drugs in five patients. At last follow-up, body weight and height were within normal ranges in the patients. Glomerular filtration rate was <90 mL/min/1.73 m(2) in four patients (one of them with a pathologically increased urinary protein excretion). In three patients, abdominal ultrasound detected gallstones. The group of patients with antenatal Bartter syndrome had a lower renin ratio (P < 0.05) and a higher standard deviation score (SDS) for height (P < 0.05) than a previously studied group of patients with classical Bartter syndrome. CONCLUSIONS: Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years. Gallstones might represent a new complication of antenatal Bartter syndrome.

Growth hormone (GH) deficiency type II: a novel GH-1 gene mutation (GH-R178H) affecting secretion and action

Context and Objective: Main features of the autosomal dominant form of GH deficiency (IGHD II) include markedly reduced secretion of GH combined with low concentrations of IGF-I leading to short stature. Design, Setting, and Patients: A female patient presented with short stature (height -6.0 sd score) and a delayed bone age of 2 yr at the chronological age of 5 yr. Later, at the age of 9 yr, GHD was confirmed by standard GH provocation test, which revealed subnormal concentrations of GH and a very low IGF-I. Genetic analysis of the GH-1 gene revealed the presence of a heterozygous R178H mutation. Interventions and Results: AtT-20 cells coexpressing both wt-GH and GH-R178H showed a reduced GH secretion after forskolin stimulation compared with the cells expressing only wt-GH, supporting the diagnosis of IGHD II. Because reduced GH concentrations found in the circulation of our untreated patient could not totally explain her severe short stature, functional characterization of the GH-R178H performed by studies of GH receptor binding and activation of the Janus kinase-2/signal transducer and activator of transcription-5 pathway revealed a reduced binding affinity of GH-R178H for GH receptor and signaling compared with the wt-GH. Conclusion: This is the first report of a patient suffering from short stature caused by a GH-1 gene alteration affecting not only GH secretion (IGHD II) but also GH binding and signaling, highlighting the necessity of functional analysis of any GH variant, even in the alleged situation of IGHD II.

Quality of life after acute type B dissection in the era of thoracic endovascular aortic repair

Conservative management of acute type B aortic dissection is currently being challenged by primary thoracic endovascular aortic repair. Aim was to assess outcome and quality of life after these different approaches using an adjusted standard population as benchmark.