Selection of adequate optimization criteria in chromatographic separations

Computer-assisted optimization of chromatographic separations is still a fruitful activity. In fact, advances in computerized data handling should make the application of systematic optimization strategies much easier. However, in most contemporary applications, the optimization criterion is not considered to be a key issue (Vanbel, J Pharm Biomed, 21:603–610, 1999). In this paper, an update of the importance of selecting adequate criteria in chromatographic separation is presented

Forty years studying British politics : the decline of Anglo-America

The still present belief some 40 years ago that British politics was both exceptional and superior has been replaced by more theoretically sophisticated analyses based on a wider and more rigorously deployed range of research techniques, although historical analysis appropriately remains important. The American influence on the study of British politics has declined, but the European Union dimension has not been fully integrated. The study of interest groups has been in some respects a fading paradigm, but important questions related to democratic health have still to be addressed. Public administration has been supplanted by public policy, but economic policy remains under-studied. A key challenge for the future is the study of the management of expectations

Pharmacological inhibition of leukotrienes in an animal model of bleomycin-induced acute lung injury

Leukotrienes are increased locally in idiopathic pulmonary fibrosis. Furthermore, a role for these arachidonic acid metabolites has been thoroughly characterized in the animal bleomycin model of lung fibrosis by using different gene knock-out settings. We investigated the efficacy of pharmacological inhibition of leukotrienes activity in the development of bleomycin-induced lung injury by comparing the responses in wild-type mice with mice treated with zileuton, a 5-lipoxygenase inhibitor and MK-571, a cys-leukotrienes receptor antagonist. Mice were subjected to intra-tracheal administration of bleomycin or saline and were assigned to receive either MK-571 at 1 mg/Kg or zileuton at 50 mg/Kg daily. One week after bleomycin administration, BAL cell counts, lung histology with van Gieson for collagen staining and immunohistochemical analysis for myeloperoxidase, IL-1 and TNF-α were performed. Following bleomycin administration both MK-571 and zileuton treated mice exhibited a reduced degree of lung damage and inflammation when compared to WT mice as shown by the reduction of:(i) loss of body weight, (ii) mortality rate, (iii) lung infiltration by neutrophils (myeloperoxidase activity, BAL total and differential cell counts), (iv) lung edema, (v) histological evidence of lung injury and collagen deposition, (vi) lung myeloperoxidase, IL-1 and TNF-α staining. This is the first study showing that the pharmacological inhibition of leukotrienes activity attenuates bleomycin-induced lung injury in mice. Given our results as well as those coming from genetic studies, it might be considered meaningful to trial this drug class in the treatment of pulmonary fibrosis, a disease that still represents a major challenge to medical treatment

A systematic review of techniques and interventions for improving adherence to inclusion and exclusion criteria during enrolment into randomised controlled trials

<p>Abstract</p> <p>Background</p> <p>Enrolment of patients into a randomised controlled trial (RCT) in violation of key inclusion or exclusion criteria, may lead to excess avoidable harm. The purpose of this paper was to systematically identify and review techniques and interventions proven to prevent or avoid inappropriate enrolment of patients into RCTs.</p> <p>Methods</p> <p>EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, online abstract repositories, and conference websites were searched. Experts were contacted and bibliographies of retrieved papers hand-searched. The search cut-off date was 31 August 2009.</p> <p>Results</p> <p>No primary publications were found. We identified one study in the grey literature (conference abstracts and presentations) reporting the results of an evaluation of the effectiveness of an intervention designed to prevent or avoid inappropriate enrolment of patients into an RCT. In the context of a multicentre trial, use of a dummy enrolment run-in phase was shown to reduce enrolment errors significantly (<it>P </it>< 0.001), from 16.1% during the run-in phase to < 1% after trial initiation.</p> <p>Conclusions</p> <p>Our systematic search yielded only one technique or intervention shown to improve adherence to eligibility criteria during enrolment into RCTs. Given the potential harm involved in recruiting patients into a clinical trial in violation of key eligibility criteria, future research is needed to better inform those conducting clinical trials of how best to prevent enrolment errors</p

New ophthalmosaurid ichthyosaurs from the European lower cretaceous demonstrate extensive ichthyosaur survival across the Jurassic–Cretaceous boundary

Background Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events affected this group during its history: one during the latest Triassic, one at the Jurassic–Cretaceous boundary (JCB), and one (resulting in total extinction) at the Cenomanian-Turonian boundary. The JCB was believed to eradicate most of the peculiar morphotypes found in the Late Jurassic, in favor of apparently less specialized forms in the Cretaceous. However, the record of ichthyosaurs from the Berriasian–Barremian interval is extremely limited, and the effects of the end-Jurassic extinction event on ichthyosaurs remains poorly understood. Methodology/Principal Findings Based on new material from the Hauterivian of England and Germany and on abundant material from the Cambridge Greensand Formation, we name a new ophthalmosaurid, Acamptonectes densus gen. et sp. nov. This taxon shares numerous features with Ophthalmosaurus, a genus now restricted to the Callovian–Berriasian interval. Our phylogenetic analysis indicates that Ophthalmosauridae diverged early in its history into two markedly distinct clades, Ophthalmosaurinae and Platypterygiinae, both of which cross the JCB and persist to the late Albian at least. To evaluate the effect of the JCB extinction event on ichthyosaurs, we calculated cladogenesis, extinction, and survival rates for each stage of the Oxfordian–Barremian interval, under different scenarios. The extinction rate during the JCB never surpasses the background extinction rate for the Oxfordian–Barremian interval and the JCB records one of the highest survival rates of the interval. Conclusions/Significance There is currently no evidence that ichthyosaurs were affected by the JCB extinction event, in contrast to many other marine groups. Ophthalmosaurid ichthyosaurs remained diverse from their rapid radiation in the Middle Jurassic to their total extinction at the beginning of the Late Cretaceous

Repeat prenatal corticosteroid prior to preterm birth: a systematic review and individual participant data meta-analysis for the PRECISE study group (prenatal repeat corticosteroid international IPD study group: assessing the effects using the best level of evidence) - study protocol

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND The aim of this individual participant data (IPD) meta-analysis is to assess whether the effects of repeat prenatal corticosteroid treatment given to women at risk of preterm birth to benefit their babies are modified in a clinically meaningful way by factors related to the women or the trial protocol. METHODS/DESIGN The Prenatal Repeat Corticosteroid International IPD Study Group: assessing the effects using the best level of Evidence (PRECISE) Group will conduct an IPD meta-analysis. The PRECISE International Collaborative Group was formed in 2010 and data collection commenced in 2011. Eleven trials with up to 5,000 women and 6,000 infants are eligible for the PRECISE IPD meta-analysis. The primary study outcomes for the infants will be serious neonatal outcome (defined by the PRECISE International IPD Study Group as one of death (foetal, neonatal or infant); severe respiratory disease; severe intraventricular haemorrhage (grade 3 and 4); chronic lung disease; necrotising enterocolitis; serious retinopathy of prematurity; and cystic periventricular leukomalacia); use of respiratory support (defined as mechanical ventilation or continuous positive airways pressure or other respiratory support); and birth weight (Z-scores). For the children, the primary study outcomes will be death or any neurological disability (however defined by trialists at childhood follow up and may include developmental delay or intellectual impairment (developmental quotient or intelligence quotient more than one standard deviation below the mean), cerebral palsy (abnormality of tone with motor dysfunction), blindness (for example, corrected visual acuity worse than 6/60 in the better eye) or deafness (for example, hearing loss requiring amplification or worse)). For the women, the primary outcome will be maternal sepsis (defined as chorioamnionitis; pyrexia after trial entry requiring the use of antibiotics; puerperal sepsis; intrapartum fever requiring the use of antibiotics; or postnatal pyrexia). DISCUSSION Data analyses are expected to commence in 2011 with results publicly available in 2012.Caroline A Crowther ... Tanya K Bubner ... Philippa F Middleton ... Lisa Yelland ... Sasha Zhang ... et al

Surface pretreatment for prolonged survival of cemented tibial prosthesis components: full- vs. surface-cementation technique

BACKGROUND: One of few persisting problems of cemented total knee arthroplasty (TKA) is aseptic loosening of tibial component due to degradation of the interface between bone cement and metallic tibial shaft component, particularly for surface cemented tibial components. Surface cementation technique has important clinical meaning in case of revision and for avoidance of stress shielding. Degradation of the interface between bone cement and bone may be a secondary effect due to excessive crack formation in bone cement starting at the opposite metallic surface. METHODS: This study was done to prove crack formation in the bone cement near the metallic surface when this is not coated. We propose a newly developed coating process by PVD layering with SiO(x )to avoid that crack formation in the bone cement. A biomechanical model for vibration fatigue test was done to simulate the physiological and biomechanical conditions of the human knee joint and to prove excessive crack formation. RESULTS: It was found that coated tibial components showed a highly significant reduction of cement cracking near the interface metal/bone cement (p < 0.01) and a significant reduction of gap formation in the interface metal-to-bone cement (p < 0.05). CONCLUSION: Coating dramatically reduces hydrolytic- and stress-related crack formation at the prosthesis interface metal/bone cement. This leads to a more homogenous load transfer into the cement mantle which should reduce the frequency of loosening in the interfaces metal/bone cement/bone. With surface coating of the tibial component it should become possible that surface cemented TKAs reveal similar loosening rates as TKAs both surface and stem cemented. This would be an important clinical advantage since it is believed that surface cementing reduces metaphyseal bone loss in case of revision and stress shielding for better bone health

Medical students’ preparedness for professional activities in early clerkships

Background Sufficient preparedness is important for transitions to workplace participation and learning in clinical settings. This study aims to analyse medical students’ preparedness for early clerkships using a three-dimensional, socio-cognitive, theory-based model of preparedness anchored in specific professional activities and their supervision level. Methods Medical students from a competency-based undergraduate curriculum were surveyed about preparedness for 21 professional activities and level of perceived supervision during their early clerkships via an online questionnaire. Preparedness was operationalized by the three dimensions of confidence to carry out clerkship activities, being prepared through university teaching and coping with failure by seeking support. Factors influencing preparedness and perceived stress as outcomes were analysed through step-wise regression. Results Professional activities carried out by the students (n = 147; 19.0%) and their supervision levels varied. While most students reported high confidence to perform the tasks, the activity-specific analysis revealed important gaps in preparation through university teaching. Students regularly searched for support in case of difficulty. One quarter of the variance of each preparedness dimension was explained by self-efficacy, supervision quality, amount of prior clerkship experience and nature of professional activities. Preparedness contributed to predicting perceived stress. Conclusions The applied three-dimensional concept of preparedness and the task-specific approach provided a detailed and meaningful view on medical students’ workplace participation and experiences in early clerkships