A Data Based Perspective on the Environmental Risk Assesssment of Human Pharmaceuticals

The EU Medicinal Products Directive (65/65/EEC) has been amended to require an environmental risk assessment (ERA) for human pharmaceuticals effective January 1995. At present, official ERA guidelines have yet to be finalised. Previous discussions about their nature have taken place in the absence of a systematic analysis of the potential environmental impacts of pharmaceuticals. This study attempts to address this deficiency via a review of existing ecotoxicity data. Acute ecotoxicity data relating to >100 human pharmaceuticals have been collated. They suggest a lack of acute effects at Daphnia > fish. Chronic effects data were limited and this was identified as a shortcoming. This was reinforced by observations of large differences between acute and chronic responses to steroids in fish. The availability of UK usage data permitted risk characterisation i.e., calculation of PEC/PNEC1 ratios for >60 compounds. Under "worst-case" fate assumptions of no human metabolism, passage of all material to drain, no removal during wastewater treatment and no surface water dilution of effluent, the large majority of pharmaceuticals yielded PEC/PNEC ratios worst-case" assumptions (as above and no removal during drinking water treatment) revealed I70 values (based on ingestion of 2 litres/day for 70 years) generally equivalent to worst-case" exposure estimations

On compound locomotive engines

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Beyond the barrier: Female Genital Schistosomiasis as a potential risk factor for HIV-1 acquisition.

Female genital schistosomiasis (FGS) results from egg-deposition in the female reproductive tract primarily by the waterborne parasite Schistosoma (S.) haematobium, and less commonly by Schistosoma (S.) mansoni. FGS affects an estimated 20-56 million women worldwide, mostly in sub-Saharan Africa. There is cross-sectional evidence of increased HIV-1 prevalence in schistosomiasis-infected women, but a causal relationship between FGS and either HIV-1 acquisition or transmission has not been fully established. Beyond the pathognomonic breach in the cervicovaginal barrier caused by FGS, this narrative review explores potential mechanisms for a synergistic relationship between S. haematobium infection, FGS, and HIV-1 acquisition through vaginal inflammation and target cell recruitment

Repercusiones económicas de la exoneración de impuestos municipales a empresas pesqueras de Bilwi, Enero-junio, 2013

El presente trabajo de investigación está relacionado con el “Análisis de las repercusiones Económicas de la exoneración de impuestos municipales por el Estado de Nicaragua a empresas pesqueras de Bilwi”, basado en la reforma a la Ley de concertación tributaria Ley “822”(LCT), los impuestos del 2% por exportación de productos del mar procesados con valor agregado que pagaban las empresas pesqueras y que hoy en día han dejado de percibir, lo que repercute negativamente en los planes, programas y proyectos que planifica y ejecuta la alcaldía municipal. El tipo de estudio es Mixto, descriptivo, retrospectivo, de corte transversal y para la recopilación de información se formularon y aplicaron guías de entrevistas y encuestas abiertas. Los principales resultados de esta investigación señalan que la alcaldía municipal dejó de percibir ingresos económicos estimados en dos millones cuatro mil trecientos setenta cinco mil con cuatro centavos (C$2, 004,375.04), provenientes de las cinco empresas pesqueras que operan en la ciudad de Bilwi, presentando un déficit en las inversiones públicas de Un millón de córdobas, (1,000,000.00) durante el año 2013. El MHCP, transfiere anualmente la suma de C$ 8,733,407.27 córdobas al gobierno municipal de Bilwi , para compensar la cantidad exonerado por el Estado a las empresas pesqueras en calidad de impuestos por exportación de productos del mar, pero esta cantidad apenas cubre el 47% del monto total que deberían pagar las empresas durante el semestre, 2013

An ultrasonics based system for the extraction of range and bearing data for multiple targets

With the increasing use of automatically guided vehicles and a requirement for greater flexibility from fixed robots there is a need for a system which can locate and map the position of objects within a defined workspace in real time. The purpose of this research is to design and evaluate a system which will provide a possible solution to this problem using ultrasonics and to investigate the applicability of different signal processing strategies to the enhancement of such data

A trans-acting cyclase off-loading strategy for non-ribosomal peptide synthetases

The terminal step in the biosynthesis of nonribosomal peptides is the hydrolytic release and, frequently, macrocyclization of an aminoacyl-S-thioester by an embedded thioesterase. The surugamide biosynthetic pathway is composed of two nonribosomal peptide synthetase (NRPS) assembly lines in which one produces surugamide A, which is a cyclic octapeptide, and the other produces surugamide F, a linear decapeptide. The terminal module of each system lacks an embedded thioesterase, which led us to question how the peptides are released from the assembly line (and cyclized in the case of surugamide A). We characterized a cyclase belonging to the β-lactamase superfamily in vivo, established that it is a trans-acting release factor for both compounds, and verified this functionality in vitro with a thioester mimic of linear surugamide A. Using bioinformatics, we estimate that ∼11% of filamentous Actinobacteria harbor an NRPS system lacking an embedded thioesterase and instead employ a trans-acting cyclase. This study improves the paradigmatic understanding of how nonribosomal peptides are released from the terminal peptidyl carrier protein and adds a new dimension to the synthetic biology toolkit

Prevalence and causes of prescribing errors: the prescribing outcomes for trainee doctors engaged in clinical training (PROTECT) study

Objectives Study objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing. Method A three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors' self-efficacy were established. Results 4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p&#60;0.001), surgical (p = &#60;0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p&#60;0.001), a greater number of prescribed medicines (p&#60;0.001) and the months December and June (p&#60;0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen. Conclusions Prescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these.</p