Der Lauff grosser Verèanderungen nach Orient auss verschiedener Cometen Bezeichnung Astrologicáe /

Insect damage has caused some loss of legibility throughout text.

STD fact sheet.

"Basic statistics on the sexually transmitted disease problem in the United States."

Hieronymi Osorii Lusitani episcopi algarbiensis De regis institutione et disciplina libri octo : ad serenissimum et inuictissimum Lusitaniae regem Sebastianum primum ; in eosdem lib. praefatio & rerum memorabilium index.

Includes index.

Francisci Lamberti Auenionensis Theologi Commentarii De causis excaecationis multoru[m] saeculorum ...

Old marginalia.

Dn. Henningi Goeden Hauelbergensis iureconsulti clarissimi Iudiciarij ordinis processus : item, domini Odofredi Summa de libellis formandis : cum indice rerum ac verborum notatu dignorum.

Includes index.

Population pharmacokinetics of itraconazole and its active metabolite hydroxy-itraconazole in paediatric cystic fibrosis and bone marrow transplant patients

Objective: The objective of the study was to characterise the population pharmacokinetic properties of itraconazole and its active metabolite hydroxyitraconazole in a representative paediatric population of cystic fibrosis and bone marrow transplant (BMT) patients and to identify patient characteristics influencing the pharmacokinetics of itraconazole. The ultimate goals were to determine the relative bioavailability between the two oral formulations (capsules vs oral solution) and to optimise dosing regimens in these patients. Methods: All paediatric patients with cystic fibrosis or patients undergoing BMT at The Royal Children's Hospital, Brisbane, QLD, Australia, who were prescribed oral itraconazole for the treatment of allergic bronchopulmonary aspergillosis (cystic fibrosis patients) or for prophylaxis of any fungal infection (BMT patients) were eligible for the study. Blood samples were taken from the recruited patients as per an empirical sampling design either during hospitalisation or during outpatient clinic visits. ltraconazole and hydroxy-itraconazole plasma concentrations were determined by a validated high-performance liquid chromatography assay with fluorometric detection. A nonlinear mixed-effect modelling approach using the NONMEM software to simultaneously describe the pharmacokinetics of itraconazole and its metabolite. Results: A one-compartment model with first-order absorption described the itraconazole data, and the metabolism of the parent drug to hydroxy-itraconazole was described by a first-order rate constant. The metabolite data also showed one-compartment characteristics with linear elimination. For itraconazole the apparent clearance (CLitraconazole) was 35.5 L/hour, the apparent volume of distribution (V-d(itraconazole)) was 672L, the absorption rate constant for the capsule formulation was 0.0901 h(-1) and for the oral solution formulation was 0.96 h-1. The lag time was estimated to be 19.1 minutes and the relative bioavailability between capsules and oral solution (F-rel) was 0.55. For the metabolite, volume of distribution, V-m/(F (.) f(m)), and clearance, CL/(F (.) fm), were 10.6L and 5.28 L/h, respectively. The influence of total bodyweight was significant, added as a covariate on CLitraconazoie/F and V-d(itraconazole)/F (standardised to a 70kg person) using allometric three-quarter power scaling on CLitraconazole/F, which therefore reflected adult values. The unexplained between-subject variability (coefficient of variation %) was 68.7%, 75.8%, 73.4% and 61.1% for CLitraconazoie/F, Vd(itraconazole)/F, CLm/(F (.) fm) and F-rel, respectively. The correlation between random effects of CLitraconazole and Vd((itraconazole)) was 0.69. Conclusion: The developed population pharmacokinetic model adequately described the pharmacokinetics of itraconazole and its active metabolite, hydroxy-itraconazole, in paediatric patients with either cystic fibrosis or undergoing BMT. More appropriate dosing schedules have been developed for the oral solution and the capsules to secure a minimum therapeutic trough plasma concentration of 0.5 mg/L for these patients.

Antibacterial dosing in intensive care: Pharmacokinetics, degree of disease and pharmacodynamics of sepsis

Treatment of sepsis remains a significant challenge with persisting high mortality and morbidity. Early and appropriate antibacterial therapy remains an important intervention for such patients. To optimise antibacterial therapy, the clinician must possess knowledge of the pharmacokinetic and pharmacodynamic properties of commonly used antibacterials and how these parameters may be affected by the constellation of pathophysiological changes occurring during sepsis. Sepsis, and the treatment thereof, increases renal preload and, via capillary permeability, leads to 'third-spacing', both resulting in higher antibacterial clearances. Alternatively, sepsis can induce multiple organ dysfunction, including renal and/or hepatic dysfunction, causing a decrease in antibacterial clearance. Aminoglycosides are concentration-dependent antibacterials and they display an increased volume of distribution (V-d) in sepsis, resulting in decreased peak serum concentrations. Reduced clearance from renal dysfunction would increase the likelihood of toxicity. Individualised dosing using extended interval dosing, which maximises the peak serum drug concentration (C-max)/minimum inhibitory concentration ratio is recommended. beta-Lactams and carbapenems are time-dependent antibacterials. An increase in Vd and renal clearance will require increased dosing or administration by continuous infusion. If renal impairment occurs a corresponding dose reduction may be required. Vancomycin displays predominantly time-dependent pharmacodynamic properties and probably requires higher than conventionally recommended doses because of an increased V-d and clearance during sepsis without organ dysfunction. However, optimal dosing regimens remain unresolved. The poor penetration of vancomycin into solid organs may require alternative therapies when sepsis involves solid organs (e.g. lung). Ciprofloxacin displays largely concentration-dependent kill characteristics, but also exerts some time-dependent effects. The V-d of ciprofloxacin is not altered with fluid shifts or over time, and thus no alterations of standard doses are required unless renal dysfunction occurs. In order to optimise antibacterial regimens in patients with sepsis, the pathophysiological effects of systemic inflammatory response syndrome need consideration, in conjunction with knowledge of the different kill characteristics of the various antibacterial classes. In conclusion, certain antibacterials can have a very high V-d, therefore leading to a low C-max and if a high peak is needed, then this would lead to underdosing. The Vd of certain antibacterials, namely aminoglycosides and vancomycin, changes over time, which means dosing may need to be altered over time. Some patients with serum creatinine values within the normal range can have very high drug clearances, thereby producing low serum drug levels and again leading to underdosing. Copyright © 2010 Elsevier Inc. All rights reserved.

Development of a clinical and echocardiographic score for assigning risk of major events after exercise and dobutamine echocardiograms

The prognostic value of exercise (EXE) and dobutamine echocardiograms (DbE) has been well defined in large studies. However, while risk is determined by both clinical and echo features, no simple means of combining these data has been defined. We sought to combine these data into risk scores. Methods. At 3 expert centers, 7650 pts underwent standard EXE (n=5211) and DbE (w2439) for evaluation of known or suspected CAD and were followed for up to 10 years (mean 5-2) for major events (death or myocardial infarction). A subgroup of 2953 EXE and 1025 DbE pts was randomly selected to develop separate multivariate models for prediction of events. After simplication of each model for clinical use, models were validated in the remaining EXE and DbE pts. ResuI1s. The total number of events was 200 in the EXE and 225 in the DbE pts, of which 58 and 99 events occurred in the respective testing groups. The following regression equations gave equivalent results I” the testing and validation groups for both EXE and DbE; DbE = (Age’O.02) + (DM’l .O) + (Low RPP’0.6) + ([CHF+lschemia+Scar]‘O.7) EXE = ([DM+CHF]‘O.S) + O.S(lschemla #) + l.B(Scar#) - (METS0.19) (where each categorical variable scored 1 when present and 0 when absent, Ischemia# = 1 for l-2 VD. 6 for 3 VD; Scar# = 1 for 1-2 VD, 1.7 for 3 VD). The table summarizes the scores and equivalent outcomes for EXE and DbE. Conclusions. Risk scores based on clinical and EXE or DbE results may be used to quantify the risk of events during follow-up.

The interface between Alzheimer's disease, normal aging, and related disorders

Since the earliest descriptions of Alzheimer's disease (AD), the presence of senile plaques (SP) and neurofibrillary tangles (NFT) have been regarded as the typical pathological hallmarks of the disease. Studies over the last twenty years, however, have reported a considerable degree of heterogeneity within the AD phenotype and as a consequence, an overlap between the pathological features of AD not only with normal aging, but also with disorders related to AD. This review discusses: 1) the degree of heterogeneity within AD, 2) the concept of an 'interface' between disorders, 3) the nature and degree of the interface between AD and normal aging, vascular dementia (VD), the tauopathies, synucleinopathies, and prion disease, and 4) whether the original status of AD should be retained or whether AD, normal aging, and the related disorders should be regarded as representing a 'continuum' of neuropathological change.

Development of an enantiomer selective microsampling assay for the quantification of ketorolac suitable for paediatric pharmacokinetic studies

Background: Ketorolac, a potent nonsteroidal anti-inflammatory drug used for pain control in children, exists as a racemate of inactive R (+) and active S (-) enantiomers. Aim: To develop a microsampling assay for the enantioselective analysis of ketorolac in children. Methods: Ketorolac enantiomers were extracted from 50 µl of plasma by liquid–liquid extraction and separated on a ChiralPak AD-RH. Detection was by a TSQ quantum triple quadrupole mass spectrometer with an electrospray ionisation source operating in a positive ion mode. Five children (age 13.8 (1.6) years, weight 52.7 (7.2) kg), were administered intravenous ketorolac 0.5 mg/kg (maximum 10 mg) and blood samples were taken at 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h post administration. CL, VD and t1/2 were calculated based on non-compartmental methods. Results: The standard curves for R (+) and S (-) ketorolac were linear in the range 0–2000 ng/ml. The LLOQs of the method were 0.15 ng on column and 0.31 ng on column for R (+) and S (-) ketorolac, respectively. The median (range) VD and CL of R (+) and S (-) ketorolac were 0.12 l/kg (0.07–0.17), 0.017 l/h/kg (0.12–0.29) and 0.17 (0.09–0.31) l/kg, 0.049 (0.02–0.1) l/h/kg, p = 0.043), respectively. The median (range) elimination half-life (t1/2) of the R (+) and S (-) ketorolac was 5.0 h (2.5–5.8) and 3.1 h (1.8–4.4), p = 0.043), respectively. Conclusion: The development of a simple, rapid and reliable ketorolac assay suitable for paediatric PK studies is reported. Copyright © 2013 John Wiley & Sons, Ltd.

Linked knowledge sources for topic classification of microposts:a semantic graph-based approach

Short text messages a.k.a Microposts (e.g. Tweets) have proven to be an effective channel for revealing information about trends and events, ranging from those related to Disaster (e.g. hurricane Sandy) to those related to Violence (e.g. Egyptian revolution). Being informed about such events as they occur could be extremely important to authorities and emergency professionals by allowing such parties to immediately respond. In this work we study the problem of topic classification (TC) of Microposts, which aims to automatically classify short messages based on the subject(s) discussed in them. The accurate TC of Microposts however is a challenging task since the limited number of tokens in a post often implies a lack of sufficient contextual information. In order to provide contextual information to Microposts, we present and evaluate several graph structures surrounding concepts present in linked knowledge sources (KSs). Traditional TC techniques enrich the content of Microposts with features extracted only from the Microposts content. In contrast our approach relies on the generation of different weighted semantic meta-graphs extracted from linked KSs. We introduce a new semantic graph, called category meta-graph. This novel meta-graph provides a more fine grained categorisation of concepts providing a set of novel semantic features. Our findings show that such category meta-graph features effectively improve the performance of a topic classifier of Microposts. Furthermore our goal is also to understand which semantic feature contributes to the performance of a topic classifier. For this reason we propose an approach for automatic estimation of accuracy loss of a topic classifier on new, unseen Microposts. We introduce and evaluate novel topic similarity measures, which capture the similarity between the KS documents and Microposts at a conceptual level, considering the enriched representation of these documents. Extensive evaluation in the context of Emergency Response (ER) and Violence Detection (VD) revealed that our approach outperforms previous approaches using single KS without linked data and Twitter data only up to 31.4% in terms of F1 measure. Our main findings indicate that the new category graph contains useful information for TC and achieves comparable results to previously used semantic graphs. Furthermore our results also indicate that the accuracy of a topic classifier can be accurately predicted using the enhanced text representation, outperforming previous approaches considering content-based similarity measures. © 2014 Elsevier B.V. All rights reserved.

Harnessing linked knowledge sources for topic classification in social media

Topic classification (TC) of short text messages offers an effective and fast way to reveal events happening around the world ranging from those related to Disaster (e.g. Sandy hurricane) to those related to Violence (e.g. Egypt revolution). Previous approaches to TC have mostly focused on exploiting individual knowledge sources (KS) (e.g. DBpedia or Freebase) without considering the graph structures that surround concepts present in KSs when detecting the topics of Tweets. In this paper we introduce a novel approach for harnessing such graph structures from multiple linked KSs, by: (i) building a conceptual representation of the KSs, (ii) leveraging contextual information about concepts by exploiting semantic concept graphs, and (iii) providing a principled way for the combination of KSs. Experiments evaluating our TC classifier in the context of Violence detection (VD) and Emergency Responses (ER) show promising results that significantly outperform various baseline models including an approach using a single KS without linked data and an approach using only Tweets. Copyright 2013 ACM.

A magyarországi közművállalatok tehernövekedését eredményező állami intézkedések hatása. Három magyarországi víziközmű-vállalkozás GDP-megoszlásának tanulságai

A közmű-szolgáltatások fogyasztói árának általános hatósági csökkentése, a gazdasági és pénzügyi válság sújtotta magyar lakosságot "védő" kormányzati intézkedéssorozat részeként, mára szervesen betagozódott az európai közvéleményt egyaránt foglalkoztató kérdések sorába. A tagországok által eleddig szakpolitikai szinten kezelt témakör az általános politika szintjére emelkedett. Az árcsökkentéssel együtt járó, a közműcégeket az eddigieknél nagyobb mértékű tehervállalásra kényszerítő intézkedések következményei azonban egyelőre még nem ismertek. Az elemzés három magyarországi víziközmű-vállalkozás által előállított GDP megoszlását vizsgálja, az elmúlt években állandósult adóterhek következtében kialakult, valamint azok esetleges további növelése esetén bekövetkező szolgáltatói magatartás modellezésére tesz kísérletet. Az eredmények elemzése során pedig arra a következtetésre jut, hogy a vállalatokat eddigiekben terhelő elvonási arányok negatív irányba történő megváltoztatása, a jövőben fenntarthatatlan működésre kényszerítheti ezeket a vállalkozásokat.

Prevalência e fatores associados à alteração vocal em idosos institucionalizados com capacidade cognitiva preservada

Voice disorders (VD) in the elderly can interfere negatively in communication, emotional well-being and quality of life, conditions that correspond to greater exposure to illness and social isolation bringing consequent economic impact for the health system. It is assumed that institutionalized confinement, weakness and morbidity associated to nursing home (NH) contribute to transform VD an especially prevalent condition in institutionalized elderly, including those without cognitive impairment. Thus, the aim of this study was to determine the prevalence and associated factors of VD in NH elderly residents without cognitive impairment. There is no epidemiological diagnostic instruments of VD for elderly populations, so the first step of this study was dedicated to prepare and analyze the psychometric properties of a short, inexpensive and easy to use questionnaire named Screening for Voice Disorders in Older Adults (Rastreamento de Alterações Vocais em Idosos—RAVI). The methodological procedures of this step followed the guidelines of the Standards for Educational and Psychological Testing and contemplated validity evidence based on test content, based on response processes, based on internal structure and based on relations with other variables, as well as reliability analysis and clinical consistency. The result of the validation process showed that the RAVI final score generate valid and reliable interpretations for the epidemiological diagnosis of VD in the elderly, which endorsed the use of the questionnaire in the second stage of the study, performed in ten NH located in the city of Natal, Rio Grande do Norte. At this stage, data from socioeconomic and demographic variables, lifestyle, general health conditions and characterization of the institution were collected. It was performed a bivariate analysis and it was calculated the prevalence ratio as a magnitude association measure, with a confidence interval of 95%. The variables with p-value less than 0.20 were included in the multiple logistic regression model that followed the Forward selection method. The odds ratio found in the multivariate model was converted into prevalence ratio and the level of significance was 5%. The sample consisted of 117 subjects with predominance of females and average of 79.68 (± 7.92) years old. The prevalence of VD was 39.3% (95% CI: 30.4-48.1%). The multivariate model showed statistically significant association between VD and depressive symptoms, smoking for a year or more and selfreported hearing loss. In conclusion, VD is a prevalent health condition in NH elderly residents without cognitive impairment and is associated with factors involving psychosocial, lifestyle and communicative disability that require attention of managers and professionals involved with NH environment. Strategies to encourage communication and social integration, actions to combat smoking and minimizing the effects of hearing loss could stimulate the physical well-being, emotional and mental health of institutionalized elderly population, contributing to the vocal and communicative maintenance, a more effective social inclusion and better overall health condition.

Prevalência, fatores associados e efeitos da violência doméstica na mobilidade em idosos: evidências do estudo imias (international mobility in aging study) sob a perspectiva epidemiológica do curso da vida

A capacidade de mover-se com independência e segurança é fundamental para a execução das atividades de vida diária e manutenção da qualidade de vida do indivíduo. Diversos fatores, dentre eles o envelhecimento podem contribuir para seu declínio. Estudos têm demonstrado associação entre experiências de violência doméstica (VD) e diversos problemas de saúde física e mental. Até o momento, não há estudos que tenham avaliado a associação entre experiências de VD no curso de vida e limitações de mobilidade na senescência. OBJETIVOS: estimar a prevalência da VD (física e psicológica) em idosos, e avaliar o impacto da VD no curso de vida na limitação de mobilidade. MATERIAIS E MÉTODO: Estudo observacional analítico a partir da primeira coleta de dados do estudo longitudinal International Mobility in Aging Study (IMIAS). Idosos (n = 1995) de ambos os sexos entre 65 e 74 anos de cinco localidades distintas (Kingston e Saint-Hyacinthe, Canadá; Tirana, Albânia; Maniazales, Colômbia; e Natal, Brasil) participaram do estudo. Dados sobre variáveis sociodemográficas, econômicas, condições de saúde e experiências de VD (física e psicológica) durante o curso de vida foram coletados. A limitação de mobilidade na senescência foi avaliada pelo Short Physical Performance Battery (SPPB) e pela dificuldade de andar 400 metros e/ou subir um lance de escadas. As prevalências foram avaliadas mediante frequências absolutas e relativas das exposições à VD, limitação de mobilidade e co-variáveis. Diferenças de gênero, bem como entre cidades foram analisadas utilizando o teste de qui-quadrado. Associação entre exposição à VD e limitação de mobilidade foi avaliada utilizando a regressão logística binária multivariada, ajustando pelas co-variáveis. Análise de mediação foram utilizadas, para avaliar possíveis caminhos entre a exposição à VD no curso de vida e a limitação de mobilidade. RESULTADOS: A violência física foi rara, com valores entre 0,63 e 0,85%. Relatos de violência psicológica variaram entre 3,2% e 23,5% (homens) e de 9% para 26% (mulheres). Mulheres experimentaram mais violência do que os homens em Saint-Hyacinthe (homens: 3,2% vs mulheres: 14%, p <0,001), Tirana (homens: 4,3% vs mulheres: 10,3%, p = 0,017), em Manizales (homens: 8,3 % vs mulheres: 18,3%, p = 0,004) e Natal (homens: 11,1% vs mulheres: 26%, p = 0,002). Em geral, o baixo suporte social pelo parceiro foi associado com a VD. Estar trabalhando foi associado a vitimização entre os homens, enquanto o oposto foi verdade para as mulheres. Arranjos de vida Multi-familiares e baixo suporte pelos parceiros, filhos e família foram associados com a VD. Baixo suporte social foi da maior importância para as mulheres do que os homens. A VD física foi associada tanto com o SPPB < 8 (OR 1,623 95%IC 1,161-2,269) como com a dificuldade para andar 400 metros e/ou subir um lance de escadas (OR 1,394 95%IC 1,063-1,829). A limitação de mobilidade decorrente da violência física no curso de vida pelo parceiro íntimo foi mediada pelas condições crônicas (efeito 25,56% 95%IC 0,036-0,277) e depressão (efeito 33,05% 95%IC 0,087-0,333). No caso da violência física por outros familiares, a limitação de mobilidade foi mediada pelas condições crônicas (efeito 20,85% 95%IC 0,022-0,202), não adesão à prática de atividades físicas (efeito 34,14% 95%IC 0,076-0,351) e depressão (efeito 44,40% 95%IC 0,144-0,315). CONCLUSÕES: A violência doméstica no curso de vida é uma realidade, que pode acarretar consequências que favorecem a limitação de mobilidade em idosos. São necessárias políticas públicas que combatam efetivamente a violência doméstica, garantindo um envelhecimento mais digno e independente funcionalmente.