State-of-the-art treatment of hypertension: established and new drugs.

The treatment of essential hypertension is based essentially on the prescription of four major classes of antihypertensive drugs, i.e. blockers of the renin-angiotensin system, calcium channel blockers, diuretics and beta-blockers. In recent years, very few new drug therapies of hypertension have become available. Therefore, it is crucial for physicians to optimize their antihypertensive therapies with the drugs available on the market. In each of the classes of antihypertensive drugs, questions have recently been raised: are angiotensin-converting enzyme (ACE) inhibitors superior to angiotensin II receptor blockers (ARB)? Is it possible to reduce the incidence of peripheral oedema with calcium antagonists? Is hydrochlorothiazide really the good diuretic to use in combination therapies? The purpose of this review is to discuss these various questions in the light of the most recent clinical studies and meta-analyses. These latter suggest that ACE inhibitors and ARB are equivalent except for a better tolerability profile of ARB. Third generation calcium channel blockers enable to reduce the incidence of peripheral oedema and chlorthalidone is certainly more effective than hydrochlorothiazide in preventing cardiovascular events in hypertension. At last, studies suggest that drug adherence and long-term persistence under therapy is one of the major issues in the actual management of essential hypertension.

Patient adherence and the choice of antihypertensive drugs: focus on lercanidipine.

Despite the development of many effective antihypertensive drugs, target blood pressures are reached in only a minority of patients in clinical practice. Poor adherence to drug therapy and the occurrence of side effects are among the main reasons commonly reported by patients and physicians to explain the poor results of actual antihypertensive therapies. The development of new effective antihypertensive agents with an improved tolerability profile might help to partly overcome these problems. Lercanidipine is an effective dihydropyridine calcium channel blocker of the third generation characterized by a long half-life and its lipophylicity. In contrast to first-generation dihydropyridines, lercanidipine does not induce reflex tachycardia and induces peripheral edema with a lower incidence. Recent data suggest that in addition to lowering blood pressure, lercanidipine might have some renal protective properties. In this review we shall discuss the problems of drug adherence in the management of hypertension with a special emphasis on lercanidipine.

Upgrading of thethird generation of the Remote Diagnostic Systems for ABB Marine Propulsion Systems

Remote diagnostics has become very popular in marine industry. Diagnostic systems are improved all the time and the newest monitoring systems are constantly taken into operation. Most vessels are, however, rigged up by outmoded facilities, which should be updated. In this work the principles of operating of such a remote diagnostic system as the ABB's third generation remote diagnostic system (RDS) and the newest Propulsion Condition Management System (PCMS) are studied. As a result of the thesis the ways of upgrading the old systems of RDS are presented. Specifically, the work focuses on the establishment of the connection between Advant controller AC-110 from the old system and PCMS server, and in other words how to get Modbus data by OPC server.

Collecting Transaction Data in a Fourth Generation Mobile Network

Tässä diplomityössä on oletettu että neljännen sukupolven mobiiliverkko on saumaton yhdistelmä olemassa olevia toisen ja kolmannen sukupolven langattomia verkkoja sekä lyhyen kantaman WLAN- ja Bluetooth-radiotekniikoita. Näiden tekniikoiden on myös oletettu olevan niin yhteensopivia ettei käyttäjä havaitse saanti verkon muuttumista. Työ esittelee neljännen sukupolven mobiiliverkkoihin liittyvien tärkeimpien langattomien tekniikoiden arkkitehtuurin ja perustoiminta-periaatteet. Työ kuvaa eri tekniikoita ja käytäntöjä tiedon mittaamiseen ja keräämiseen. Saatuja transaktiomittauksia voidaan käyttää tarjottaessa erilaistettuja palvelutasoja sekä verkko- ja palvelukapasiteetin optimoimisessa. Lisäksi työssä esitellään Internet Business Information Manager joka on ohjelmistokehys hajautetun tiedon keräämiseen. Sen keräämää mittaustietoa voidaan käyttää palvelun tason seurannassa j a raportoinnissa sekä laskutuksessa. Työn käytännön osuudessa piti kehittää langattoman verkon liikennettä seuraava agentti joka tarkkailisi palvelun laatua. Agentti sijaitsisi matkapuhelimessa mitaten verkon liikennettä. Agenttia ei kuitenkaan voitu toteuttaa koska ohjelmistoympäristö todettiin vajaaksi. Joka tapauksessa työ osoitti että käyttäjän näkökulmasta tietoa kerääville agenteille on todellinen tarve.

The Architecture of a Fourth Generation Mobile Network

Neljännen sukupolven mobiiliverkot yhdistävät saumattomasti televerkot, Internetin ja niiden palvelut. Alkuperin Internetiä käytettiin vain paikallaan pysyviltä tietokoneilta perinteisten televerkkojen tarjotessa puhelin- ja datapalveluita. Neljännen sukupolven mobiiliverkkojen käyttäjät voivat käyttää sekä Internetiin perustuvia että perinteisten televerkkojen palveluita liikkuessaankin. Tämä diplomityö esittelee neljännen sukupolven mobiiliverkon yleisen arkkitehtuurin. Arkkitehtuurin perusosat kuvaillaan ja arkkitehtuuria verrataan toisen ja kolmannen sukupolven mobiiliverkkoihin. Aiheeseen liittyvät Internet-standardit esitellään ja niiden soveltuvuutta mobiiliverkkoihin pohditaan. Langattomia, lyhyen kantaman nopeita liitäntäverkkotekniikoita esitellään. Neljännen sukupolven mobiiliverkoissa tarvittavia päätelaitteiden ja käyttäjien liikkuvuuden hallintamenetelmiä esitellään. Esitelty arkkitehtuuri perustuu langattomiin, lyhyen kantaman nopeisiin liitäntäverkkotekniikoihin ja Internet-standardeihin. Arkkitehtuuri mahdollistaa yhteydet toisiin käyttäjiin ilman tietoa heidän senhetkisestä päätelaitteesta tai sijainnista. Internetin palveluitavoidaan käyttää missä tahansa neljännen sukupolven mobiiliverkon alueella. Yleiskäytöistä liikkuvuuden hallintamenetelmää yhden verkon alueelle ehdotetaan. Menetelmää voidaan käyttää yhdessä esitellyn arkkitehtuurin kanssa.

Radiative-dynamical climatology of the first-generation Canadian middle atmosphere model

The Canadian Middle Atmosphere Modelling (MAM) project is a collaboration between thé Atmospheric Environment Service (AES) of Environment Canada and several Canadian universities. Its goal is thé development of a comprehensive General Circulation Model of the troposphere-stratosphere-mesosphere System, starting from the AES/CCCma third-generation atmospheric General Circulation Model. This paper describes the basic features of the first-generation Canadian MAM and some aspects of its radiative-dynamical climatology. Standard first-order mean diagnostics are presented for monthly means and for the annual cycle of zonal-mean winds and temperatures. The mean meridional circulation is examined, and comparison is made between thé steady diabatic, downward controlled, and residual stream functions. It is found that downward control holds quite well in the monthly mean through most of the middle atmosphere, even during equinoctal periods. The relative roles of different drag processes in determining the mean downwelling over the wintertime polar middle stratosphere is examined, and the vertical structure of the drag is quantified.

Wireless systems for the fourth generation

Today, third generation networks are consolidated realities, and user expectations on new applications and services are becoming higher and higher. Therefore, new systems and technologies are necessary to move towards the market needs and the user requirements. This has driven the development of fourth generation networks. ”Wireless network for the fourth generation” is the expression used to describe the next step in wireless communications. There is no formal definition for what these fourth generation networks are; however, we can say that the next generation networks will be based on the coexistence of heterogeneous networks, on the integration with the existing radio access network (e.g. GPRS, UMTS, WIFI, ...) and, in particular, on new emerging architectures that are obtaining more and more relevance, as Wireless Ad Hoc and Sensor Networks (WASN). Thanks to their characteristics, fourth generation wireless systems will be able to offer custom-made solutions and applications personalized according to the user requirements; they will offer all types of services at an affordable cost, and solutions characterized by flexibility, scalability and reconfigurability. This PhD’s work has been focused on WASNs, autoconfiguring networks which are not based on a fixed infrastructure, but are characterized by being infrastructure less, where devices have to automatically generate the network in the initial phase, and maintain it through reconfiguration procedures (if nodes’ mobility, or energy drain, etc..., cause disconnections). The main part of the PhD activity has been focused on an analytical study on connectivity models for wireless ad hoc and sensor networks, nevertheless a small part of my work was experimental. Anyway, both the theoretical and experimental activities have had a common aim, related to the performance evaluation of WASNs. Concerning the theoretical analysis, the objective of the connectivity studies has been the evaluation of models for the interference estimation. This is due to the fact that interference is the most important performance degradation cause in WASNs. As a consequence, is very important to find an accurate model that allows its investigation, and I’ve tried to obtain a model the most realistic and general as possible, in particular for the evaluation of the interference coming from bounded interfering areas (i.e. a WiFi hot spot, a wireless covered research laboratory, ...). On the other hand, the experimental activity has led to Throughput and Packet Error Rare measurements on a real IEEE802.15.4 Wireless Sensor Network.

Estrogen receptor modulators and down regulators: optimal use in postmenopausal women with breast cancer

Endocrine treatments have been used in breast cancer since 1896, when Beatson reported on the results of oophorectomy for advanced breast cancer. In the second half of the last century, different endocrine-based compounds were developed and, in this review, the role of the selective estrogen receptor modulators (SERMs) and selective estrogen receptor down regulators (SERDs) in the postmenopausal setting are discussed. Tamoxifen is the most investigated and most widely used representative of these agents, and has been introduced in the advanced disease, in the neoadjuvant and adjuvant setting, and for the prevention of the disease. Its role has been challenged in recent years by the introduction of third-generation aromatase inhibitors that have proven higher activities than tamoxifen with different toxicity patterns. Several other SERMs have been investigated, but none have been clearly superior to tamoxifen. SERDs act as pure estrogen antagonists and should compare favourably to tamoxifen. For the time being, they have been used in the treatment of advanced breast cancers and their role in other settings still needs investigation. The increased use of aromatase inhibitors as first-line endocrine therapy has resulted in new discussions regarding the role that tamoxifen and other SERMs or SERDs may play in breast cancer. The sequencing of endocrine therapies in hormone-sensitive breast cancer remains a very important research issue.

Clínica de cães com cardiomiopatia dilatada idiopática, tratados ou não com carvedilol

O tratamento convencionalmente preconizado para cães acometidos pela CMD consiste na prescrição de vasodilatadores, agentes inotrópicos positivos (digitálico), diuréticos, dieta hipossódica e, quando necessário, antiarrítmicos. O carvedilol é um β-bloqueador de 3ª geração, não seletivo, que bloqueia igualmente e competitivamente os receptores (β1, β2 e α1). Produz uma evidente vasodilatação periférica, exerce efeitos anti-oxidantes, removendo radicais livres de oxigênio e prevenindo a peroxidação lipídica nas membranas cardíacas, prevenindo a perda de miócitos e a ocorrência de arritmias e reduzindo a taxa de mortalidade em pacientes humanos. O objetivo do presente estudo foi avaliar clínica, eletrocardiográfica, radiográfica e ecocardiograficamente a evolução de cães com cardiomiopatia dilatada (CMD) tratatos com terapia convencional associada ao carvedilol. Para tal foram avaliados 49 cães com CMD divididos em: grupo NT, tratado com terapia convencional, e grupo T, tratado com terapia convencional associada ao carvedilol. Os animais foram submetidos à avaliação clínica e a exames complementares durante o período de um ano. Os resultados demonstraram que a terapia com carvedilol apresentou boa tolerabilidade na dose de 0,3mg kg-1 12-12horas, aumentou a sobrevida dos cães em 30,9%, não alterou as pressões sistólica e diastólica, reduziu a frequência cardíaca após três semanas de terapia, melhorou significantemente as frações de encurtamento e ejeção após seis meses de tratamento, não promoveu alterações radiográficas e da distância E-septo, diminuiu o índice de letalidade da doença, fato demonstrado pela melhora no escore clínico e na classe funcional dos animais, obtida após três semanas de terapia com carvedilol.

Antimicrobial drug administration errors identified in Brazilian multicentric study

Medication administration errors (MAE) are the most frequent kind of medication errors. Errors with antimicrobial drugs (AD) are relevant because they may interfere inpatient safety and in the development of microbial resistance. The aim of this study is to analyze the AD errors detected in a Brazilian multicentric study of MAE. It was a devcriptive and explorotory study carried out in clinical units in five Brazilian teaching hospitals. The hospitals were investigated during 30 days. MAE were detected by observation technique. MAE were classified in categories: wrong route(WR), wrong patient(WP), wrong dose(WD) wrong time (WT) and unordered drug (UD). AD with MA E were classified by Anatomical-Therapeutical-Chemical Classification System. AD with narrow therapeutic index (NTI) wet-e identified A descriptive statistical analysis was performed using SPSS version 11.5 software. A total of 1500 errors were observed, 277 (18.5%) of them were error with AD. The hopes of AD error were: WT87.7%, QD 6.9%, WR 1.5%, UD 3.2% and WP 0.7%. The number of AD found was 36. The mostly ATC class were fluoroquinolones 13.9%, combinations of penicillin 13.9%, macrolides 8.3% and third-generation cephalosporines 5.6%. The parenteral drug dosage form was associated with 55.6% of AD. 16.7% of AD were NTI. 47.4% of WD and 21.8% WT were with NTI drugs. This study shows that these errors should be considered potential areas for improvement in the medication process and patient safety plus there is requirement to develop rational drug use of AD.

Jointly multi-user detection and channel estimation with genetic algorithm

This work aims at proposing the use of the evolutionary computation methodology in order to jointly solve the multiuser channel estimation (MuChE) and detection problems at its maximum-likelihood, both related to the direct sequence code division multiple access (DS/CDMA). The effectiveness of the proposed heuristic approach is proven by comparing performance and complexity merit figures with that obtained by traditional methods found in literature. Simulation results considering genetic algorithm (GA) applied to multipath, DS/CDMA and MuChE and multi-user detection (MuD) show that the proposed genetic algorithm multi-user channel estimation (GAMuChE) yields a normalized mean square error estimation (nMSE) inferior to 11%, under slowly varying multipath fading channels, large range of Doppler frequencies and medium system load, it exhibits lower complexity when compared to both maximum likelihood multi-user channel estimation (MLMuChE) and gradient descent method (GrdDsc). A near-optimum multi-user detector (MuD) based on the genetic algorithm (GAMuD), also proposed in this work, provides a significant reduction in the computational complexity when compared to the optimum multi-user detector (OMuD). In addition, the complexity of the GAMuChE and GAMuD algorithms were (jointly) analyzed in terms of number of operations necessary to reach the convergence, and compared to other jointly MuChE and MuD strategies. The joint GAMuChE-GAMuD scheme can be regarded as a promising alternative for implementing third-generation (3G) and fourth-generation (4G) wireless systems in the near future. Copyright (C) 2010 John Wiley & Sons, Ltd.

Analysis of long-term light-trap data for Helicoverpa spp. (Lepidoptera : Noctuidae) in Australia: the effect of climate and crop host plants

Regression analyses of a long series of light-trap catches at Narrabri, Australia, were used to describe the seasonal dynamics of Helicoverpa armigera (Hubner). The size of the second generation was significantly related to the size of the first generation, to winter rainfall, which had a positive effect, and to spring rainfall which had a negative effect. These variables accounted for up to 96% of the variation in size of the second generation from year to year. Rainfall and crop hosts were also important for the size of the third generation. The area and tonnage of many potential host crops were significantly correlated with winter rain. When winter rain was omitted from the analysis, the sizes of both the second and third generations could be expressed as a function of the size of the previous generation and of the areas planted to lucerne, sorghum and maize. Lucerne and maize always had positive coefficients and sorghum a negative one. We extended our analysis to catches of H. punctigera (Wallengren), which declines in abundance after the second generation. Winter rain had a positive effect on the sizes of the second and third generations, and rain in spring or early summer had a negative effect. Only the area grown to lucerne had a positive effect on abundance. Forecasts of pest levels from a few months to a few weeks in advance are discussed, along with the improved understanding of the seasonal dynamics of both species and the significance of crops in the management of insecticide resistance for H. armigera.

Molecular Characterization, Distribution, and Dynamics of Hepatitis C Virus Genotypes in Blood Donors in Colombia

Hepatitis C virus (HCV) is a frequent cause of acute and chronic hepatitis and a leading cause for cirrhosis of the liver and hepatocellular carcinoma. HCV is classified in six major genotypes and more than 70 subtypes. In Colombian blood banks, serum samples were tested for anti-HCV antibodies using a third-generation ELISA. The aim of this study was to characterize the viral sequences in plasma of 184 volunteer blood donors who attended the ""Banco Nacional de Sangre de la Cruz Roja Colombiana,`` Bogota, Colombia. Three different HCV genomic regions were amplified by nested PCR. The first of these was a segment of 180 bp of the 5`UTR region to confirm the previous diagnosis by ELISA. From those that were positive to the 5`UTR region, two further segments were amplified for genotyping and subtyping by phylogenetic analysis: a segment of 380 bp from the NS5B region; and a segment of 391 bp from the E1 region. The distribution of HCV subtypes was: 1b (82.8%), 1a (5.7%), 2a (5.7%), 2b (2.8%), and 3a (2.8%). By applying Bayesian Markov chain Monte Carlo simulation, it was estimated that HCV-1b was introduced into Bogota around 1950. Also, this subtype spread at an exponential rate between about 1970 to about 1990, after which transmission of HCV was reduced by anti-HCV testing of this population. Among Colombian blood donors, HCV genotype 1b is the most frequent genotype, especially in large urban conglomerates such as Bogota, as is the case in other South American countries. J. Med. Virol. 82: 1889-1898, 2010. (C) 2010 Wiley-Liss, Inc.

OCT findings in macular hole formation in eyes with complete vitreofoveal separation

The current study describes the morphologic macular features in two eyes that developed full-thickness macular holes in the setting of documented vitreofoveal separation. Using third-generation optical coherence tomography, complete vitreofoveal separation associated with the disruption of the inner foveal retina was documented in both cases. Five months after presentation, decreased vision and epiretinal membrane formation associated with development of a full-thickness macular hole were observed in the first patient. In the second patient, a full-thickness macular hole was demonstrated by optical coherence tomography 6 weeks after presentation. These findings suggest that full-thickness macular holes may develop in eyes with vitreofoveal separation. Evidence of the disturbance of the inner foveal architecture on optical coherence tomography indicates the potential role of factors other than anteroposterior or oblique vitreoretinal tractional forces in the genesis of some full-thickness macular holes.

Thermostable variants of the recombinant xylanase A from Bacillus subtilis produced by directed evolution show reduced heat capacity changes

Directed evolution techniques have been used to improve the thermal stability of the xylanase A from Bacillus subtilis (XylA). Two generations of random mutant libraries generated by error prone PCR coupled with a single generation of DNA shuffling produced a series of mutant proteins with increasing thermostability. The most Thermostable XylA variant from the third generation contained four mutations Q7H, G13R, S22P, and S179C that showed an increase in melting temperature of 20 degrees C. The thermodynamic properties Of a representative subset of nine XylA variants showing a range of thermostabilities were measured by thermal denaturation as monitored by the change in the far ultraviolet circular dichroism signal. Analysis of the data from these thermostable variants demonstrated a correlation between the decrease in the heat capacity change (Delta C(p)) with an increase in the midpoint of the transition temperature (T(m)) on transition from the native to the unfolded state. This result could not be interpreted within the context of the changes in accessible surface area of the protein on transition from the native to unfolded states. Since all the mutations are located at the surface of the protein, these results suggest that an explanation of the decrease in Delta C(p) on should include effects arising from the prot inlsolvent interface.