Integrating ecotoxicity and chemical approaches to compare the effects of ZnO nanoparticles, ZnO bulk, and ZnCl2 on plants and microorganisms in a natural soil.

This work compared the toxicity of ZnO nanoparticles (ZnO-NPs), ZnO bulk, and ZnCl2 on microbial activity (C and N transformations and dehydrogenase and phosphatase activities) and their uptake and toxic effects (emergence, root elongation, and shoot growth) on three plant species namely wheat, radish, and vetch in a natural soil at 1000 mg Zn kg(-1). Additionally, plants were also tested at 250 mg Zn kg(-1). The effects of the chemical species on Zn extractability in soil were studied by performing single and sequential extractions. ZnCl2-1000 presented the highest toxicity for both taxonomic groups. For microorganisms, ZnO-NPs demonstrated adverse effects on all measured parameters, except on N transformations. The effects of both ZnO forms were similar. For plants, ZnO-NPs affected the growth of more plant species than ZnO bulk, although the effects were small in all cases. Regarding accumulation, the total Zn amounts were higher in plants exposed to ZnO-NP than those exposed to ZnO bulk, except for vetch shoots. The soil sequential extraction revealed that the Zn concentration in the most labile forms (water soluble (WS) and exchangeable (EX)) was similar in soil treated with ZnO (NP and bulk) and lower than that of ZnCl2-treated soil, indicating the higher availability of the ionic forms. The strong correlations obtained between WS-Zn fraction and the Zn concentrations in the roots, shoots, and the effects on shoot weight show the suitability of this soil extraction method for predicting bioavailable Zn soil for the three plant species when it was added as ZnO-NPs, ZnO bulk, or ZnCl2. In this work, the hazard associated with the ZnO-NPs was similar to ZnO bulk in most cases.

Toxicity of ZnO nanoparticles, ZnO bulk, and ZnCl2 on earthworms in a spiked natural soil and toxicological effects of leachates on aquatic organisms.

The present study assessed the uptake and toxicity of ZnO nanoparticles (NPs), ZnO bulk, and ZnCl2 salt in earthworms in spiked agricultural soils. In addition, the toxicity of aqueous extracts to Daphnia magna and Chlorella vulgaris was analyzed to determine the risk of these soils to the aquatic compartment. We then investigated the distribution of Zn in soil fractions to interpret the nature of toxicity. Neither mortality nor differences in earthworm body weight were observed compared with the control. The most sensitive end point was reproduction. ZnCl2 was notably toxic in eliminating the production of cocoons. The effects induced by ZnO-NPs and bulk ZnO on fecundity were similar and lower than those of the salt. In contrast to ZnO bulk, ZnO-NPs adversely affected fertility. The internal concentrations of Zn in earthworms in the NP group were greater than those in the salt and bulk groups, although bioconcentration factors were consistently <1. No relationship was found between toxicity and internal Zn amounts in earthworms. The results from the sequential extraction of soil showed that ZnCl2 displayed the highest availability compared with both ZnO. Zn distribution was consistent with the greatest toxicity showed by the salt but not with Zn body concentrations. The soil extracts from both ZnO-NPs and bulk ZnO did not show effects on aquatic organisms (Daphnia and algae) after short-term exposure. However, ZnCl2 extracts (total and 0.45-µm filtered) were toxic to Daphnia.

Volumen de dilución de fármacos intravenosos en pacientes con restricción de fluidos / Dilution volume of intravenous drugs in patients under fluid restriction therapy

Introducción: El mantenimiento del equilibrio hidroelectrolítico es esencial para el buen funcionamiento del organismo. Existen situaciones en las que se producen desequilibrios en los líquidos corporales, originando sobrecargas de fluidos, y sus consecuentes problemas asociados. Los pacientes con esta problemática, pueden beneficiarse de la administración de fármacos parenterales en el menor volumen posible. Los pacientes en estado crí- tico suelen requerir un gran número de fármacos por vía intravenosa, y altas dosis de éstos a diluir en grandes cantidades de suero. Por todo ello, parece útil buscar una estrategia de optimización de la administración de los fármacos parenterales. Objetivo: Revisar y recopilar datos referentes a volúmenes mí- nimos de dilución. Además de las vías de administración, reconstitución, diluyentes compatibles, tiempos de infusión. Método: Se incluyeron en el estudio aquellos principios activos utilizados con más frecuencia en pacientes críticos. Se realizó una búsqueda en varias fuentes de información: fichas técnicas de las especialidades farmacéuticas, Handbook on Injectable Drugs, Trissel L., American Society Healh-System Pharmacists, 15thEd., 2009, Thomson Micromedex® Healthcare series, o vía telefónica con el laboratorio fabricante del producto. Resultados: Los resultados se muestran en forma de tabla. Se revisaron 65 especialidades farmacéuticas. Conclusiones: Consideramos útil la recopilación de estos datos para optimizar la administración parenteral en pacientes críticos o que requieran una terapia restrictiva en fluidos ya que la información ha tenido que ser recopilada de distintas fuentes no encontrándose siempre en la ficha técnica. (AU)

Introduction: A fluid and electrolyte balance is essential for human health. There are some situations in which fluid imbalance occurs, causing fluid overload and consequent associated problems. Patients with these problems, may benefit from the administration of parenteral drugs in the smallest possible volume. Patients in critical condition typically require a large number of drugs intravenously, and high doses of these diluted in large quantities of serum. Therefore, it seems useful to seek an optimization strategy of parenteral drug administration. Objective: To review and collect data on minimum dilution volumes. Besides administration s routes, recons - titution, compatible diluents, infusion times. Methods: The study included those drug substances frequently used in critically ill patients. A search through multiple sources of information has been made: technical data for Propietary medicinal products, Handbook on Injectable Drugs, Trissel L., American Society Healh-System Pharmacists, 15thEd., 2009, Thomson Micromedex® Healthcare Series, or by phone calls to the manufacturers of the product. Results: Results are shown in a table. 65 drugs were revised. Conclusions: It is considered useful the collection of these data to optimize parenteral administration in critically ill patients, or in those who require restrictive fluid therapy, because information has been collected from different sources, not always found it in the technical data of the drugs (AU)

[Dilution volume of intravenous drugs in patients under fluid restriction therapy]. / Volumen de dilución de fármacos intravenosos en pacientes con restricción de fluidos.

INTRODUCTION: A fluid and electrolyte balance is essential for human health. There are some situations in which fluid imbalance occurs, causing fluid overload and consequent associated problems. Patients with these problems, may benefit from the administration of parenteral drugs in the smallest possible volume. Patients in critical condition typically require a large number of drugs intravenously, and high doses of these diluted in large quantities of serum. Therefore, it seems useful to seek an optimization strategy of parenteral drug admi - nistration. OBJECTIVE: To review and collect data on minimum dilution volumes. Besides administration s routes, reconstitution, compatible diluents, infusion times. METHODS: The study included those drug substances frequently used in critically ill patients. A search through multiple sources of information has been made: technical data for Propietary medicinal products, Handbook on Injectable Drugs, Trissel L., American Society Healh-System Pharmacists, 15thEd., 2009, Thomson Micromedex® Healthcare Series, or by phone calls to the manufacturers of the product. RESULTS: RESULTS are shown in a table. 65 drugs were revised. CONCLUSIONS: It is considered useful the collection of these data to optimize parenteral administration in critically ill patients, or in those who require restrictive fluid therapy, because information has been collected from different sources, not always found it in the technical data of the drugs.

Impact of antiplatelet therapy in the development of severe ischemic complications and in the outcome of patients with giant cell arteritis.

OBJECTIVE: To evaluate whether concomitant treatment with low-dose aspirin or other antiplatelet agents have an impact on the risk of severe ischemic complications and in the outcome of patients with giant cell arteritis (GCA). METHODS: A retrospective follow-up study of an unselected population of 121 patients with GCA. RESULTS: Thirty-seven patients (30.5%) received antiplatelet therapy before the onset of GCA symptoms and continued taking it during the corticosteroid treatment (30 received aspirin and 7 other antiplatelet agents). No statistically significant reduction in the incidence of ischemic manifestations (including jaw claudication, visual manifestations, cerebrovascular accidents, ischemic heart disease, and limb claudication due to large artery stenosis) was observed in this group compared with the remaining patients. When we analyzed follow-up data, we found no significant differences between groups in terms of frequency of relapses and percentage of patients recovered from GCA. Corticosteroid requirements among patients in long-lasting remission were lower in those under antiplatelet therapy, but this reduction was fairly modest, statistically non significant and thus of uncertain clinical significance. Similar results were found when only aspirin exposed patients (n=30) were compared to non-exposed patients. Logistic regression analysis showed that antiplatelet therapy (p=0.54, OR 1.31; 95% CI: 0.54-3.19) had not an independent protective effect against ischemic events when adjusted for age, sex, and the presence of atherosclerotic risk factors. CONCLUSION: We did not observe a significant benefit derived from the use of antiplatelet therapy in either the incidence of severe ischemic events or the disease outcome. Although our results do not discard a potential therapeutic effect of high-dose aspirin, they do not confirm its suggested protective effect in preventing ischemic complications when used at antiplatelet doses.

High HDL-cholesterol in women with rheumatoid arthritis on low-dose glucocorticoid therapy.

BACKGROUND: Dyslipidaemia has been described in non-treated rheumatoid arthritis (RA), and improves after therapy with disease modifying anti-rheumatic drugs or glucocorticoids; however, it has generally been perceived that glucocorticoids adversely affect lipid metabolism. The association of low dose glucocorticoid therapy with plasma lipid levels was evaluated in female RA patients. MATERIALS AND METHODS: A cross-sectional study was conducted in 78 female RA patients [mean age: 60 (12) years; mean disease duration: 13 (9) years]. Sixty-five (83%) were on glucocorticoid therapy [total equivalent mean prednisone dose: 5.1 (1.7) mg d(-1)]. Each patient was assessed through a self-reported questionnaire, structured interview and physical examination. Blood samples were obtained for routine biochemistry, lipid profile and haematological tests. Lipid profiles of RA patients who were and were not on glucocorticoid therapy were compared. RESULTS: Clinical and laboratory features of the two groups of patients were similar, except for the Health Assessment Questionnaire and body mass index, which were significantly higher in the patients on glucocorticoid therapy. These patients had 14.7% higher serum high-density lipoprotein cholesterol (HDL-c) levels than untreated patients (P = 0.043), mainly at the expense of HDL2 subfraction, which was 24.4% higher (P < 0.039), whereas HDL3-c was only 7.4% higher (P = 0.219). Serum levels of glucose and total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL -c), very low-density lipoprotein cholesterol, apolipoproteins A-I and B were not increased in patients on glucocorticoid therapy. CONCLUSIONS: Low dose glucocorticoid therapy in RA patients is associated with an increase in HDL-c, without increasing LDL-c or triglyceride. These lipid changes may overall be considered favourable.

Réplica. Comentarios sobre la automatización / Author´s responseComments about the automated-procedure

No disponible

[Computer-aided electronic prescribing in Spanish hospitals]. / Características de la prescripción electrónica asistida en hospitales españoles.

OBJECTIVE: To describe electronic prescribing in a sample of Spanish hospitals and activities derived from its implementation in Hospital Pharmacy Departments, software features and acceptance. METHOD: A survey that included data related to program implantation and performance in hospitals with diverse characteristics was designed. It was posted at the Sociedad Española de Farmacia Hospitalaria website for a 6-month period and completed by phone. RESULTS: A total of 47 hospitals answered the survey. 13 (27.7%) had electronic prescribing systems, and of these, 8 of them had more than 75% of beds included in the system. In 15 (31.9%) hospitals that did not have it, its implementation was in project in the near future. Software applications used in this new health technology were not homogeneous, while integration of applications that facilitate Pharmaceutical Care tasks was infrequent. In 61.5% of the hospitals with electronic prescribing, transcription used to be the pharmacist s task. In 92.3% of these hospitals, order validation is currently carried out by pharmacists. The degree of satisfaction with the system was rated as good or very good by 92.3% of pharmacists. CONCLUSIONS: Computer-aided electronic prescribing appears to be a helpful tool for restructuring Department organization and investing time in new activities. A more ambitious and effective approach to clinical activities will therefore be possible. System optimization requires taking into account factors such as worker time investment, since new activities will be developed, along with the need for training courses.

Características de la prescripción electrónica asistida en hospitales españoles / Computer-aided electronic prescribing in spanish hospitals

Objetivo: Conocer las características de la prescripción electrónicaen una muestra de hospitales españoles, describir las actividadesderivadas de su implantación en los Servicios de Farmacia,características de los programas utilizados y su aceptación.Método: Se diseñó una encuesta que recogía datos de implantacióny funcionamiento del programa en hospitales con distintascaracterísticas. Se publicó en la web de la SEFH durante 6 mesesy se completó telefónicamente.Resultados: De 47 hospitales encuestados, 13 (27,7%) disponende prescripción electrónica asistida, en 8 de ellos estáimplantada en más del 75% de sus camas. En 15 (31,9%) de loscentros donde no disponen de ella, la implantación es un proyectoa corto-medio plazo. Existe dispersión en los programas utilizadosy son de instauración reciente. La integración de aplicacionescruzadas para desarrollar atención farmacéutica está poco explotada.En el 61,5% de los centros con prescripción electrónica asistida,la transcripción tradicionalmente era función del farmacéutico.En un 92,3% valida los tratamientos. Su satisfacción es buena omuy buena en un 92,3%.Conclusiones: Las capacidades de la prescripción electrónicaasistida y los cambios graduales en las funciones que desarrolla elfarmacéutico a raíz de su implantación podrían potenciar el desarrollode programas más amplios de atención farmacéutica.Para la optimización del uso del sistema es importante considerarfactores como la inversión en tiempo del personal, teniendoen cuenta que se asumen nuevas actividades, y la necesidad deformación de los usuarios

Objective: To describe electronic prescribing in a sample of Spanish hospitals and activities derived from its implementation in Hospital Pharmacy Departments, software features and acceptance. Method: A survey that included data related to program implantation and performance in hospitals with diverse characteristics was designed. It was posted at the Sociedad Española de Farmacia Hospitalaria website for a 6-month period and completed by phone. Results: A total of 47 hospitals answered the survey. 13 (27.7%) had electronic prescribing systems, and of these, 8 of them had more than 75% of beds included in the system. In 15 (31.9%) hospitals that did not have it, its implementation was in project in the near future. Software applications used in this new health technology were not homogeneous, while integration of applications that facilitate Pharmaceutical Care tasks was infrequent. In 61.5% of the hospitals with electronic prescribing, transcription used to be the pharmacist’s task. In 92.3% of these hospitals, order validation is currently carried out by pharmacists. The degree of satisfaction with the system was rated as good or very good by 92.3% of pharmacists. Conclusions: Computer-aided electronic prescribing appears to be a helpful tool for restructuring Department organization and investing time in new activities. A more ambitious and effective approach to clinical activities will therefore be possible. System optimization requires taking into account factors such as worker time investment, since new activities will be developed, along with the need for training courses

[Analyzing the evolution of a Pharmacy Department using a relative value unit system]. / Análisis de la evolución de un Servicio de Farmacia a través del sitema de unidades relativas de valor.

INTRODUCTION: This study proposes the use of relative value units (RVU) as a clinical management tool to evaluate departmental services. OBJECTIVES: To measure productivity from 2000 to 2002 by estimating RVU. To determine RVU cost in constant Euros and evaluate system efficiency during this period of time. METHODS: Retrospective, observational study of a pharmacy department s production. RVU assigned to each activity have been obtained from a standardized document drawn up by the Sociedad Española de Farmacia Hospitalaria. Cost of each RVU was determined based on total cost assigned to the pharmacy department and the total number of RVUs produced. RESULTS: Drug dispensation activities account for 76% of the total production, followed by elaboration activities (21%). CONCLUSIONS: Productivity in our department has increased 46.48% in this period of time, while efficiency has increased by 23.8%.

[Cost-benefit analysis of a semi-automated process in the preparation of unit-doses by the Pharmacy Department]. / Análisis coste-beneficio del proceso de semiautomatización en la preparación de dosis unitarias por el Servicio de Farmacia.

OBJECTIVE: To determine in monetary terms the effect of implementing a semi-automated procedure for preparation of drugs for unit dose distribution. METHODS: The current net value was estimated for three different flows involved in the evaluation of semi-automated drug storage and retrieval systems used in the unit dose distribution area in a hospital: capital investment, staff costs and structural costs related to physical space occupied. RESULTS: Implantation of the new work procedure produced an annual saving of 32,390 euro in staff costs and 5,645 euro in structural costs. Global cash flow has been estimated in -96,565 euro for a five year amortization period, with a benefit/cost ratio of 2.19. CONCLUSION: Replacement of traditional unit dose cart filling systems by a semi automated procedure presents a positive benefit/cost ratio and initial investment is paid off in 44 months.

Análisis coste-beneficio del proceso de semiautomatización en la preparación de dosis unitarias por el Servicio de Farmacia / Cost-benefit analysis of a semi-automated process in the preparation of unit-doses by the Pharmacy Department

Objetivo: Determinar en términos monetarios los efectos de la implantación de un proceso de semiautomatización en la preparación de medicamentos por el sistema de distribución mediante Dosis Unitarias. Material y método: Se ha determinado el valor actual neto de los 3 flujos implicados en la valoración de los sistemas semiautomáticos de preparación de medicamentos para su distribución por dosis unitarias (SSPDU) en un hospital, esto es: inversiones de capital, coste del personal implicado, costes del espacio físico utilizado. Resultados: La implantación produce en términos monetarios un ahorro anual de 32.390 € en tiempos de personal y de 5.645 € en gastos estructurales. Globalmente, el movimiento de fondos o flujos de caja es de -96.565 €, estimados para un periodo de amortización de cinco años, siendo el ratio beneficio/coste de 2,19. Conclusión: La sustitución del proceso tradicional de llenado de carros de dosis unitarias por un proceso semiautomático presenta una favorable relación beneficio/coste y su inversión es amortizable en 44 meses (AU)

Modelling the absorption and desorption of cadmium on paper pulp using kinetic approaches.

The presence of toxic metals on paper pulp and the migration of these metals to food from the food package is receiving significant attention. The final exposure levels for consumers depend on two main processes. First the potential of metals to bind paper pulp during manufacture. Second, the metal potential to migrate from paper to food during storage and use. Binding and unbinding processes are modelled for cadmium kinetics through kinetic approaches. The cadmium concentration in paper pulp is estimated from the cadmium concentration in the water-pulp liquor during manufacture, the temperature, and contact time. Two food simulants have been employed for desorption studies, water and acetic solution (3%, w/w). As expected, under acidic conditions desorption is total and rapid (close to 100% desorption reached in a few minutes). However, the desorption of cadmium into the neutral food simulant depends on the initial cadmium concentration in the paper pulp, temperature and contact time. Surface response curves for each combination are presented. Temperature did not affect cadmium binding, but played a significant role for the desorption processes into the neutral food simulant. The proposed equations offer a good fitting of the experimental values, with p < 0.001 and residuals within a factor of 3 for over 99% of the measured data. These models allow estimations of the expected exposure levels in consumers, on the basis of manufacture and use conditions. Linking the expected exposure with toxicity thresholds, such as the admissible daily intake (ADI), would allow a scientific assessment of the maximum acceptable cadmium levels in water-pulp liquors during manufacture and in the final paper pulp on the basic of the use patterns of each food packaging material.

[Cost-benefit analysis of the implementation of automated drug-dispensing systems in Critical Care and Emergency Units]. / Análisis coste-beneficio de la implantación de los sistemas automáticos de dispensación de medicamentos en las Unidades de Críticos y Urgencias.

OBJECTIVE: To determine monetary impact when traditional drug floor stocks are replaced by Automated Drug Dispensing Systems (ADDS) in the Medical Intensive Care Unit, Surgical Intensive Care Unit and the Emergency Room. METHODS: We analysed four different flows considered to be determinant when implementing ADDS in a hospital environment: capital investment, staff costs, inventory costs and costs related to drug use policies. RESULTS: Costs were estimated by calculation of the current net value. Its analysis shows that those expenses derived from initial investment are compensated by the three remaining flows, with costs related to drug use policies showing the most substantial savings. Five years after initial investment, global cash-flows have been estimated at 300.525 euros. CONCLUSION: Replacement of traditional floor stocks by ADDS in the Medical Intensive Care Unit, Surgery Intensive Care Unit and the Emergency Room produces a positive benefit/cost ratio (1.95).

Análisis coste-beneficio de la implantación de los sistemas automáticos de dispensación de medicamentos en las unidades de críticos y urgencias / Cost-benefit analysis of the implementation of automated drug-dispensing systems in Critical Care Emenrgency Units

Objetivo: Determinar en términos económicos las consecuencias de la sustitución de botiquines de planta por la implantación de sistemas automáticos de dispensación de medicamentos (SADME) en las Unidades de Unidad de Cuidados Intensivos (UCI), Reanimación (Rea) y Urgencias. Material y método: Para nuestro estudio, se han considerado cuatro flujos, determinantes a la hora de implantar los SADME en un hospital, y éstos han sido: inversiones de capital, coste del personal implicado, costes del inventariado de medicamentos y costes en política de consumo. Resultados: Los resultados han sido estimados mediante el cálculo del valor actualizado neto. Tras su análisis, comprobamos cómo el gasto realizado por la inversión inicial se ve compensado por el beneficio generado por los otros tres flujos, siendo el referido a la política de consumos de medicamentos, aquél que genera un mayor beneficio. Globalmente el movimiento de fondos o flujos de caja es de -300.525 ¤, estimados para un periodo de amortización de cinco años. Conclusión: La sustitución de botiquines de planta por sistemas automáticos de dispensación de medicamentos en las Unidades de UCI, Rea y Urgencias, presenta una favorable relación beneficio/coste (1,95) (AU)

Binding of cadmium on raw paper pulp. Relationship between temperature and sorption kinetics.

Several assays have been carried out in order to study in detail the cadmium mobility from water to virgin pulp as previous step of cadmium mobility description from paper into food. Virgin pulp has been immersed in different concentration aqueous solutions at several temperatures and during short and long time. The absorbed cadmium amounts have been measured by atomic absorption spectroscopy. For a long time, the temperature of storage is not an important factor except during the first 3 h. In general, percentage of migrated cadmium into pulp is between 30% and 90% of initial charge. Kinetic equation of cadmium mobility has been described employing statistics methods with a very good correlation.

Encuesta sobre el estado de la docencia a farmacéuticos internos residentes de farmacia hospitalaria / Survey on the status of teaching to In-Hospital Pharmacy internal residents pharmacists

Objetivo: El presente trabajo expone los resultados de una encuesta realizada en colaboración con la Sociedad Española de Farmacia Hospitalaria (SEFH) para conocer la percepción que los farmacéuticos tenemos de la formación y docencia que desarrollamos en los Servicios de Farmacia, así como conocer la opinión de los farmacéuticos de aquellos Servicios con programa acreditado para la formación de especialistas en Farmacia Hospitalaria, sobre las posibilidades de implantar con éxito los contenidos que el cuarto año de la especialidad demanda. Métodos: Se diseñaron tres modelos de encuesta destinados a FIR, tutores y resto de personal facultativo que fueron enviadas a 83 hospitales españoles con docencia acreditada. Resultados: En su mayoría los tutores (71 per cent) han sido designados por el Jefe de Servicio y disponen (92 per cent) de menos de 3 horas semanales para realizar dicha tarea. Un 33 per cent de los mismos dejaría la tutoría y a un 54 per cent le gustaría que esta labor fuera recompensada con el pago de cursos o congresos. Los resultados reflejan que más del 80 per cent de los farmacéuticos opina que la formación que se da a los residentes es buena. Es casi unánime la creencia entre los farmacéuticos internos residentes (94 per cent), tutores (92 per cent) y facultativos de plantilla (90 per cent) de que es positiva la ampliación del periodo de residencia a cuatro años. El 54 per cent de los tutores cree que, actualmente, estamos capacitados para formar en las áreas clínicas en el cuarto año y el 30 per cent opina que, aunque no lo estamos ahora, lo estaremos dentro de dos años. Conclusión: La opinión mayoritaria de los farmacéuticos encuestados sobre la formación que se imparte a los FIR es positiva, al igual que lo es la consideración sobre la posibilidad de adaptación de los Servicios de Farmacia a los requerimientos del nuevo Programa de la Especialidad (AU)

Heterocyclic structures useful in medicinal chemistry: the case of pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide.

Different aspects of a particular kind of heterocycle, namely pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide are discussed. These include synthesis, reactivity, tautomerism and acid-base properties, results of x-ray analysis and molecular orbital calcultations. Besides, some of the derivatives have shown interesting biological effects, among which are the diuretic properties which are also presented.