Twist grain boundaries in three-dimensional lamellar Turing structures

Steady spatial self-organization of three-dimensional chemical reaction-diffusion systems is discussed with the emphasis put on the possible defects that may alter the Turing patterns. It is shown that one of the stable defects of a three-dimensional lamellar Turing structure is a twist grain boundary embedding a Scherk minimal surface.

Cystoid Macular Edema: Causes, Diagnosis and Treatment

The purpose of this paper is to conduct a review of studies on cystoid macular edema published in the last seven years. Cystoid macular edema is a major cause of loss of visual acuity. It is the final common pathway of many diseases and can be caused by numerous processes including inflammatory, vascular, adverse drug reactions, retinal dystrophy or intraocular tumors. These processes disrupt the blood-retinal barrier, with fluid extravasation to the macular parenchyma. Imaging tests are essential for both detection and monitoring of this pathology. Fluorescein angiography and autofluorescence show the leakage of liquid from perifoveal vessels into the tissue where it forms cystic spaces. Optical coherence tomography is currently the gold standard technique for diagnosis and monitoring. This allows objective measurement of retinal thickness, which correlates with visual acuity and provides more complete morphological information. Based on the underlying etiology, the therapeutic approach can be either surgical or medical with anti-inflammatory drugs. We found that disruption of the blood-retinal barrier for various reasons is the key point in the pathogenesis of cystoid macular edema, therefore we believe that studies on its treatment should proceed on this path.

TrendMiner: Large-scale Cross-lingual Trend Mining Summarization of Real-time Media Streams

El reciente crecimiento masivo de medios on-line y el incremento de los contenidos generados por los usuarios (por ejemplo, weblogs, Twitter, Facebook) plantea retos en el acceso e interpretación de datos multilingües de manera eficiente, rápida y asequible. El objetivo del proyecto TredMiner es desarrollar métodos innovadores, portables, de código abierto y que funcionen en tiempo real para generación de resúmenes y minería cross-lingüe de medios sociales a gran escala. Los resultados se están validando en tres casos de uso: soporte a la decisión en el dominio financiero (con analistas, empresarios, reguladores y economistas), monitorización y análisis político (con periodistas, economistas y políticos) y monitorización de medios sociales sobre salud con el fin de detectar información sobre efectos adversos a medicamentos.

ADRSpanishTool: una herramienta para la detección de efectos adversos e indicaciones

Presentamos una herramienta basada en coocurrencias de fármaco-efecto para la detección de reacciones adversas e indicaciones en comentarios de usuarios procedentes de un foro médico en español. Además, se describe la construcción automática de la primera base de datos en español sobre indicaciones y efectos adversos de fármacos.

Notificação de incidentes e segurança do doente : perceção dos enfermeiros

Enquadramento: A segurança do doente é um problema internacional e uma prioridade das políticas de saúde de múltiplos organismos/instituições nacionais de saúde. Neste âmbito, surgem os sistemas de notificação de incidentes. Objetivo: Conhecer a perceção dos enfermeiros sobre a notificação de incidentes e sobre a segurança do doente. Métodos: Recorremos a uma triangulação metodológica constituída por um estudo quantitativo (estudo A) e outro qualitativo (estudo B). O estudo A é analítico, transversal, realizado com 182 enfermeiros. Os dados foram recolhidos por questionário, constituído por variáveis sociodemográficas e profissionais e escalas para avaliar doze dimensões da notificação e segurança do doente. O estudo B é exploratório, realizado com 18 enfermeiros, através de entrevista semiestruturada. Resultados: Para os enfermeiros todos os incidentes devem ser notificados, mas a frequência de notificação é baixa e diminui com a gravidade do dano, 65,0% não registou qualquer ocorrência no último ano e 82,3% desconhece o sistema de notificação. Os principais obstáculos à notificação são o receio de punição e os principais fatores facilitadores são os benefícios que advêm da notificação para o doente, a ausência de retaliações no trabalho, uma relação positiva com os superiores hierárquicos, o anonimato e a perceção de resultados da notificação. Aproximadamente 60,0% dos enfermeiros tem uma perceção geral da segurança do doente positiva. Conclusão: A perceção dos enfermeiros sobre a notificação de incidentes reflete desconhecimento da temática, elevado receio de punição, originando baixa frequência de notificação. A perceção sobre a segurança do doente é positiva. É necessário melhorar a cultura de segurança da organização e o conhecimento dos enfermeiros sobre o papel da notificação. Palavras-Chave: segurança do doente, notificação de incidentes, enfermeiros.

Trends in the prevalence of birth defects in Illinois and Chicago.

Description based on: 1989-1994.

Acyl glucuronide reactivity in perspective: biological consequences

The metabolic conjugation of exogenous and endogenous carboxylic acid substrates with endogenous glucuronic acid, mediated by the uridine diphosphoglucuronosyl transferase (UGT) superfamily of enzymes, leads to the formation of acyl glucuronide metabolites. Since the late 1970s, acyl glucuronides have been increasingly identified as reactive electrophilic metabolites, capable of undergoing three reactions: intramolecular rearrangement, hydrolysis, and intermolecular reactions with proteins leading to covalent drug-protein adducts. This essential dogma has been accepted for over a decade. The key question proposed by researchers, and now the pharmaceutical industry, is: does or can the covalent modification of endogenous proteins, mediated by reactive acyl glucuronide metabolites, lead to adverse drug reactions, perhaps idiosyncratic in nature? This review evaluates the evidence for acyl glucuronide-derived perturbation of homeostasis, particularly that which might result from the covalent modification of endogenous proteins and other macromolecules. Because of the availability of acyl glucuronides for test tube/in vitro experiments, there is now a substantial literature documenting their rearrangement, hydrolysis and covalent modification of proteins in vitro. It is certain from in vitro experiments that serum albumin, dipeptidyl peptidase IV, tubulin and UGTs are covalently modified by acyl glucuronides. However, these in vitro experiments have been specifically designed to amplify any interference with a biological process in order to find biological effects. The in vivo situation is not at all clear. Certainly it must be concluded that all humans taking carboxylate drugs that form reactive acyl glucuronides will form covalent drug-protein adducts, and it must also be concluded that this in itself is normally benign. However, there is enough in vivo evidence implicating acyl glucuronides, which, when backed up by in vivo circumstantial and documented in vitro evidence, supports the view that reactive acyl glucuronides may initiate toxicity/immune responses. In summary, though acyl glucuronide-derived covalent modification of endogenous macromolecules is well-defined, the work ahead needs to provide detailed links between such modification and its possible biological consequences. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Using pharmacogenetics and pharmacogenomics in the treatment of psychiatric disorders: some ethical and economic considerations"

Current pharmacotherapies for psychiatric disorders are generally incompletely effective. Many patients do not respond well or suffer adverse reactions to these drugs, which can result in poor patient compliance and poor treatment outcome. Adverse drug reactions and non-response are likely to be influenced by genetic polymorphisms. Pharmacogenetics holds some promise for improving the treatment of mood disorders by utilising information about genetic polymorphisms to match patients to the drug therapy that is the most effective with the fewest side effects. Pharmacogenomics promises to facilitate the development of new drugs for treatment. However, these technologies raise many ethical, economic and regulatory issues that need to be addressed before they can be integrated into psychiatry, and medicine more generally. We discuss ethical and policy issues arising from pharmacogenetic testing and pharmacogenomics research, such as informed consent, privacy and confidentiality, research on vulnerable persons and discrimination; and economic viability of pharmacogenetics and pharmacogenomics. We conclude with recommendations for the regulation and distribution of pharmacogenetic testing services and pharmacogenomic drugs.

Options for guaranteeing the effective management of the world's protected areas

A rapid increase in the number and size of protected areas has prompted interest in their effectiveness and calls for guarantees that they are providing a good return on investment by maintaining their values. Research reviewed here suggests that many remain under threat and a significant number are already suffering deterioration. One suggestion for encouraging good management is to develop a protected-area certification system: however this idea remains controversial and has created intense debate. We list a typology of options for guaranteeing good protected-area management, and give examples, including: danger lists; self-reporting systems against individual or standardised criteria; and independent assessment including standardised third-party reporting, use of existing certification systems such as those for forestry and farming and certification tailored specifically to protected areas. We review the arguments for and against certification and identify some options, such as: development of an accreditation scheme to ensure that assessment systems meet minimum standards; building up experience from projects that are experimenting with certification in protected areas; and initiating certification schemes for specific users such as private protected areas or institutions like the World Heritage Convention.

Medication management at home: medication-related risk factors associated with poor health outcomes

Background: some patients may have medication-related risk factors only identified by home visits, but the extent to which those risk factors are associated with poor health outcomes remains unclear. Objective: to determine the association between medication-related risk factors and poor patient health outcomes from observations in the patients' homes. Design: cross-sectional study. Setting: patients' homes. Subjects: 204 general practice patients living in their own homes and at risk of medication-related poor health outcomes. Methods: medications and medication-related risk factors were identified in the patients' homes by community pharmacists and general practitioners (GPs). The medication-related risk factors were examined as determinants of patients' self-reported health related quality of life (SF-36) and their medication use, as well as physicians' impression of patient adverse drug events and health status. Results: key medication-related risk factors associated with poor health outcomes included: Lack of any medication administration routine, therapeutic duplication, hoarding, confusion between generic and trade names, multiple prescribers, discontinued medication repeats retained and multiple storage locations. Older age and female gender were associated with some poorer health outcomes. In addition, expired medication and poor adherence were also associated with poor health outcomes, however, not independently. Conclusion: the findings support the theory that polypharmacy and medication-related risk factors as a result of polypharmacy are correlated to poor health outcomes.

Design options for sample-based mortality surveillance

Background Reliable information on causes of death is a fundamental component of health development strategies, yet globally only about one-third of countries have access to such information. For countries currently without adequate mortality reporting systems there are useful models other than resource-intensive population-wide medical certification. Sample-based mortality surveillance is one such approach. This paper provides methods for addressing appropriate sample size considerations in relation to mortality surveillance, with particular reference to situations in which prior information on mortality is lacking. Methods The feasibility of model-based approaches for predicting the expected mortality structure and cause composition is demonstrated for populations in which only limited empirical data is available. An algorithm approach is then provided to derive the minimum person-years of observation needed to generate robust estimates for the rarest cause of interest in three hypothetical populations, each representing different levels of health development. Results Modelled life expectancies at birth and cause of death structures were within expected ranges based on published estimates for countries at comparable levels of health development. Total person-years of observation required in each population could be more than halved by limiting the set of age, sex, and cause groups regarded as 'of interest'. Discussion The methods proposed are consistent with the philosophy of establishing priorities across broad clusters of causes for which the public health response implications are similar. The examples provided illustrate the options available when considering the design of mortality surveillance for population health monitoring purposes.

Using different structure types of microemulsions for the preparation of poly(alkylcyanoacrylate) nanoparticles by interfacial polymerization

A phase diagram of the pseudoternary system ethyloleate, polyoxyethylene 20 sorbitan mono-oleate/sorbitan monolaurate and water with butanol as a cosurfactant was prepared. Areas containing optically isotropic, low viscosity one-phase systems were identified and systems therein designated as w/o droplet-, bicontinuous- or solution-type microemulsions using conductivity, viscosity, cryo-field emission scanning electron microscopy and self-diffusion NMR. Nanoparticles were prepared by interfacial polymerization of selected w/o droplet, bicontinuous- or solution-type microemulsions with ethyl-2-cyanoacrylate. Morphology of the particles and entrapment of the water-soluble model protein ovalbumin were investigated. Addition of monomer to the different types of microemulsions (w/o droplet, bicontinuous, solution) led to the formation of nanoparticles, which were similar in size (similar to 250 nm), polydispersity index (similar to 0.13), zeta-potential (similar to-17 mV) and morphology. The entrapment of the protein within these particles was up to 95%, depending on the amount of monomer used for polymerization and the type of microemulsion used as a polymerization template. The formation of particles with similar characteristics from templates having different microstructure is surprising, particularly considering that polymerization is expected to occur at the water-oil interface by base-catalysed polymerization. Dynamics within the template (stirring, viscosity) or indeed interfacial phenomena relating to the solid-liquid interface appear to be more important for the determination of nanoparticle morphology and characteristics than the microstructure of the template system. (c) 2005 Elsevier B.V. All rights reserved.

Factors predictive of intravenous fluid administration errors in Australian surgical care wards

Background: Intravenous (IV) fluid administration is an integral component of clinical care. Errors in administration can cause detrimental patient outcomes and increase healthcare costs, although little is known about medication administration errors associated with continuous IV infusions. Objectives: ( 1) To ascertain the prevalence of medication administration errors for continuous IV infusions and identify the variables that caused them. ( 2) To quantify the probability of errors by fitting a logistic regression model to the data. Methods: A prospective study was conducted on three surgical wards at a teaching hospital in Australia. All study participants received continuous infusions of IV fluids. Parenteral nutrition and non-electrolyte containing intermittent drug infusions ( such as antibiotics) were excluded. Medication administration errors and contributing variables were documented using a direct observational approach. Results: Six hundred and eighty seven observations were made, with 124 (18.0%) having at least one medication administration error. The most common error observed was wrong administration rate. The median deviation from the prescribed rate was 247 ml/h (interquartile range 275 to + 33.8 ml/ h). Errors were more likely to occur if an IV infusion control device was not used and as the duration of the infusion increased. Conclusions: Administration errors involving continuous IV infusions occur frequently. They could be reduced by more common use of IV infusion control devices and regular checking of administration rates.

An analysis of returned medicines in primary care

Objective: The number of pharmaceutical items issued on prescription is continually rising and contributing to spiralling healthcare costs. Although there is some data highlighting the quantity, in terms of weight of medicines returned specifically to community pharmacies, little is known about the specific details of such returns or other destinations for wasted medications. This pilot study has been designed to investigate the types and amounts of medicines returned to both general practices (GPs) and associated local community pharmacies determining the reasons why these medicines have been returned. Method: The study was conducted in eight community pharmacies and five GP surgeries within East Birmingham over a 4-week period. Main outcome Measure: Reason for return and details of returned medication. Results: A total of 114 returns were made during the study: 24 (21.1) to GP surgeries and 90 (78.9) to community pharmacies. The total returns comprised 340 items, of which 42 (12.4) were returned to GPs and 298 (87.6) to pharmacies, with the mean number of items per return being 1.8 and 3.3, respectively. Half of the returns in the study were attributed to the doctor changing or stopping the medicine; 23.7 of returns were recorded as excess supplies or clearout often associated with patients' death and 3.5 of returns were related to adverse drug reactions. Cardiovascular drugs were most commonly returned, amounting to 28.5 of the total drugs returned during the study. Conclusions: The results from this pilot study indicate that unused medicines impose a significant financial burden on the National Health Service as well as a social burden on the United Kingdom population. Further studies are examining the precise nature of returned medicines and possible solutions to these issues. © Springer 2005.

Soft [beta]-adrenoceptor agonists for topical use in psoriasis

Psoriasis is characterised by epidermal proliferation and inflammation resulting in the appearance of elevated erythematous plaques. The ratio of c~AMP/c~GMP is decreased in psoriatic skin and when the epidermal cell surface receptors are stimulated by β-adrenergic agonists, intracellular ATP is transformed into c-AMP, thus restoring the c~AMP/c~GMP levels. This thesis describes a series of β-adrenoceptor agonists for topical delivery based upon the soft-drug approach. Soft drugs are defined as biologically active, therapeutically useful chemical compounds (drugs) characterised by a predictable and controllable In vivo destruction (metabolism) to non-toxic moieties. after they achieve their therapeutic role, The N-substituent can accommodate a broad range of structures and here the alkoxycarbonylethyl group has been used to provide metabolic susceptability. The increased polarity of the dihydroxy acid, expected after metabolic conversion of the soft~drug, ethyl N-[2'-(3',4'-dihydroxyphenyl)-2'-hydroxyethyl]-3- aminopropionate, should eliminate agonist activity. Further. to prevent oxidation and enhance topical delivery, the catechol hydroxyl groups have been esterified to produce a pro-soft-drug which generates the soft-drug in enzymic systems. The chemical hydrolysis of the pro-soft-drug proceeded via the formation of the dlpivaloyloxy acid and it failed to generate the active dihydroxy ester soft-drug. In contrast, in the presence of porcine liver carboxyesterase, the hydrolysis of the pro-soft drug proceeded via the formation of the required active soft-drug. This compound, thus, has the appropnate kinetic features to enable it to be evaluated further as a drug for the treatment of psoriasis. The pH rate-profile for the hydrolysis of soft-drug indicated a maximum stability at pH ∼ 4.0. The individual rate constants for the degradation and the pKa were analysed by nonlinear regression. The pKa of 7.40 is in excellent agreement with that determined by direct titration (7.43) and indicates that satisfactory convergence was achieved. The soft-drug was poorly transported across a silicone membrane; it was also air-sensitive due to oxidation of the catechol group. The transport of the pro-soft-drug was more efficient and, over the donor pH range 3-8, increased with pH. At lower values, the largely protonated species was not transported. However, above pH 7. chemical degradation was rapid so that a donor pH of 5-6 was optimum. The β-adrenergic agonist activity of these compounds was tested in vitro by measuring chronotropic and inotropic responses in the guinea pig atria and relaxation of guinea pig trachea precontracted with acetylcholine (10-3 M). The soft~drug was a full agonist on the tracheal preparation but was less potent than isoprenaline. Responses of the soft~drug were competitively antagonised by propranolol (10-6 M). The soft~drug produced an increase in force and rate of the isolated atrial preparatIon. The propyl analogue was equally potent with ED50 of 6.52 x 10-7 M. In contrast, at equivalent doses, the dihydroxy acid showed no activity; only a marginal effect was observed on the tracheal preparation. For the pro~soft-drug, responses were of slow onset, in both preparations, with a slowly developing relaxatlon of the tracheal preparatlon at high concentrations (10-5 M). This is consistent with in vitro results where the dipivaloyl groups are hydrolysed more readily than the ethyl ester to gIve the active soft-drug. These results confirm the validity tif the pro-soft-drug approach to the deUvery of β-adrenoceptor agonists.