Coronary heart disease in primary care: accuracy of medical history and physical findings in patients with chest pain - a study protocol for a systematic review with individual patient data.

BACKGROUND: Chest pain is a common complaint in primary care, with coronary heart disease (CHD) being the most concerning of many potential causes. Systematic reviews on the sensitivity and specificity of symptoms and signs summarize the evidence about which of them are most useful in making a diagnosis. Previous meta-analyses are dominated by studies of patients referred to specialists. Moreover, as the analysis is typically based on study-level data, the statistical analyses in these reviews are limited while meta-analyses based on individual patient data can provide additional information. Our patient-level meta-analysis has three unique aims. First, we strive to determine the diagnostic accuracy of symptoms and signs for myocardial ischemia in primary care. Second, we investigate associations between study- or patient-level characteristics and measures of diagnostic accuracy. Third, we aim to validate existing clinical prediction rules for diagnosing myocardial ischemia in primary care. This article describes the methods of our study and six prospective studies of primary care patients with chest pain. Later articles will describe the main results. METHODS/DESIGN: We will conduct a systematic review and IPD meta-analysis of studies evaluating the diagnostic accuracy of symptoms and signs for diagnosing coronary heart disease in primary care. We will perform bivariate analyses to determine the sensitivity, specificity and likelihood ratios of individual symptoms and signs and multivariate analyses to explore the diagnostic value of an optimal combination of all symptoms and signs based on all data of all studies. We will validate existing clinical prediction rules from each of the included studies by calculating measures of diagnostic accuracy separately by study. DISCUSSION: Our study will face several methodological challenges. First, the number of studies will be limited. Second, the investigators of original studies defined some outcomes and predictors differently. Third, the studies did not collect the same standard clinical data set. Fourth, missing data, varying from partly missing to fully missing, will have to be dealt with.Despite these limitations, we aim to summarize the available evidence regarding the diagnostic accuracy of symptoms and signs for diagnosing CHD in patients presenting with chest pain in primary care. REVIEW REGISTRATION: Centre for Reviews and Dissemination (University of York): CRD42011001170.

Complete immunization against Trypanosoma cruzi verified in individual mice by complement-mediated lysis

Experimental systems to assay immunity against Trypanosoma cruzi usually demonstrate partial resistance without excluding the establishment of sub-patent infections in protected animals. To test whether Swiss mice immunized with attenuated parasites might develop complete resistance against virulent T. cruzi, experiments were performed involving challenge with low numbers of parasites, enhancement of local inflammation and the combination of natural and acquired resistance. Absence of infection was established after repeated negative parasitological tests (including xenodiagnosis and hemoculture), and lack of lytic antibody was tested by complement mediated lysis. Immunization with 10(7) attenuated epimastigotes conferred protection against the development of high levels of parasitemia after challenge with Tulahuen strain, but was unable to reduce the number of infected animals. However, when a strong, delayed-type hypersensitivity reaction was triggered at the site of infection by injecting a mixture of virulent and attenuated T. cruzi, a significant proportion of immunized animals remained totally free of virulent infection. The same result was obtained when the immunization experiment was performed in four month old Swiss mice, displaying a relatively high natural resistance and challenged with wild, vector-borne parasites. These experiments demonstrate that complete resistance against T. cruzi can be obtained in a significant proportion of animals, under conditions which replicate natural, vector delivered infection by the parasite.

Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease (PR) and reverse transcriptase (RT) inhibitors may display impaired infectivity and replication capacity. The individual contributions of mutated HIV-1 PR and RT to infectivity, replication, RT activity, and protein maturation (herein referred to as "fitness") in recombinant viruses were investigated by separately cloning PR, RT, and PR-RT cassettes from drug-resistant mutant viral isolates into the wild-type NL4-3 background. Both mutant PR and RT contributed to measurable deficits in fitness of viral constructs. In peripheral blood mononuclear cells, replication rates (means +/- standard deviations) of RT recombinants were 72.5% +/- 27.3% and replication rates of PR recombinants were 60.5% +/- 33.6% of the rates of NL4-3. PR mutant deficits were enhanced in CEM T cells, with relative replication rates of PR recombinants decreasing to 15.8% +/- 23.5% of NL4-3 replication rates. Cloning of the cognate RT improved fitness of some PR mutant clones. For a multidrug-resistant virus transmitted through sexual contact, RT constructs displayed a marked infectivity and replication deficit and diminished packaging of Pol proteins (RT content in virions diminished by 56.3% +/- 10.7%, and integrase content diminished by 23.3% +/- 18.4%), a novel mechanism for a decreased-fitness phenotype. Despite the identified impairment of recombinant clones, fitness of two of the three drug-resistant isolates was comparable to that of wild-type, susceptible viruses, suggestive of extensive compensation by genomic regions away from PR and RT. Only limited reversion of mutated positions to wild-type amino acids was observed for the native isolates over 100 viral replication cycles in the absence of drug selective pressure. These data underscore the complex relationship between PR and RT adaptive changes and viral evolution in antiretroviral drug-resistant HIV-1.

Desenvolupament d'eines per l'apliació de l'aprenentatge basat en projectes a l'enginyeria tècnica de telecomunicacions

El projecte d'innovació docent s'emmarca dintre de la línia de treball de l'Escola Politècnica Superior de Castelldefels. Aquesta escola, des de els seus inicis ha destacat per la seva aposta per la innovació docent i l'aplicació de mètodes pedagògics pioners arreu d'Espanya. El sistema d'ensenyament basat en el seguiment individualitzat de l'estudiant, facilitat per una bona relació professor/nombre d'estudiants (grups de 40 o 20 estudiants), l'avaluació continuada, que parteix de les activitats acadèmiques realitzades en una matèria, i l'avaluació curricular, que atén el rendiment global de l'estudiant, fan que el sistema fomenti el treball regular al mateix temps que l'informa en tot moment del seu progrés acadèmic. Per un altre banda, dintre del sistema educatiu de la nostra escola podem destacar l'aplicació de l'Aprenentatge Basat en Projectes (PBL), aplicat inicialment als estudis de Segon Cicle. D'acord amb aquest model, els alumnes aprenen realitzant projectes en grup. Les intervencions del professorat i els materials del curs estan orientats a donar suport a les necessitats dels projectes que es desenvolupen a cada moment. Tot seguint la línia de treball de l'escola i la seva adequació als criteris determinats en el Espai Europeu d'Educació Superior, aquest projecte segueix tres línies d’actuació: (1) incideix en l'aplicació del PBL dintre d'assignatures Optatives i en assignatures de primers cursos de la Titulació d'Enginyeria de Telecomunicacions, (2) estimular l’alumnat, a través de treballs interdisciplinaris i la utilització de les noves tecnologies, (3) generació de documentació adaptada als nous plans d’estudi. Aquestes línies d’actuació es desenvolupen per motivar els alumnes en els estudis d'enginyeria que estan cursant i fer-los veure l'aplicabilitat, en el camp de la recerca, de gran quantitat dels coneixements que van adquirint durant la seva formació dintre de la Universitat.

Establiment d’un laboratori d’habilitats clíniques a la facultat de medicina de la Universitat de Barcelona

Per tal de millorar l'aprenentatge, actualment deficitari de les habilitats clíniques i dels procediments pràctics, la facultat va decidir implementar un laboratori d’habilitats. La Facultat de Medicina ha fet una important inversió per tal d’adequar un espai físic i adquirir diferents materials. En paral·lel es van identificar quines habilitats havien de ser ensenyats en el laboratori d’acord amb les dèficits observats prèviament. Es va dissenyar un curs optatiu sobre habilitats clíniques pels nostres estudiants de medicina i es van seleccionar i entrenar els diferents professors. El curs s’ha desenvolupat durant els tres últims anys. S'ha investigat el grau d’acceptació d’aquesta eina pels estudiants i professors utilitzant diferents tipus d’enquestes. Més de 300 estudiants de medicina per any han estat formats en el laboratori en diferents activitats, participant 20 professors i havent-se oferit diferents tallers sobre habilitats clíniques i procediments pràctics. Pels estudiants el laboratori es una excel·lent eina per incrementar la seva competència individual en habilitats clíniques i que es necessari estendre-la a tots els estudiants. Pels professors, el laboratori es una eina molt útil per millorar l’ensenyament clínic L'experiència ha estat molt positiva i molt útil en el procés de canvi curricular que es desenvolupa actualment a la nostra facultat. La nostra experiència pot servir de model per altres facultats de medicina de l’estat.

Assessing ageing of individual T lymphocytes: mission impossible?

Effector T lymphocytes are the progeny of a limited number of antigen-specific precursor cells and it has been estimated that clonotypic human T cells may expand million fold on their way reaching high cell numbers that are sufficient for immune protection. Moreover, memory T cell responses are characterized by repetitive expansion of antigen-specific T cell clonotypes, and limitations in the proliferative capacity could lead to immune senescence. Because telomeres progressively shorten as a function of cell division, telomere length is a powerful indicator of the replicative in vivo history of human T lymphocytes. In this review, we summarize observations made over the last decade on telomere length dynamics of well-defined T cell populations derived from healthy donors and patients with infectious disease or cancer. We focus on T cell differentiation, T cell ageing, and natural and vaccine induced immune responses. We also discuss the scientific evidence for in vivo replicative senescence of antigen-specific T cells, and evaluate the available methods for measuring telomere lengths and telomerase activity, and their potential and limitations to increase our understanding of T cell physiology.

Change in individual growth rate and its link to gill-net fishing in two sympatric whitefish species

Size-selective fishing is expected to affect traits such as individual growth rate, but the relationship between the fishery-linked selection differentials and the corresponding phenotypic changes is not well understood. We analysed a 25-year monitoring survey of sympatric populations of the two Alpine whitefish Coregonus albellus and C. fatioi. We determined the fishing-induced selection differentials on growth rates, the actual change of growth rates over time, and potential indicators of reproductive strategies that may change over time. We found marked declines in adult growth rate and significant selection differentials that may partly explain the observed declines. However, when comparing the two sympatric species, the selection differentials on adult growth were stronger in C. albellus while the decline in adult growth rate seemed more pronounced in C. fatioi. Moreover, the selection differential on juvenile growth was significant in C. albellus but not in C. fatioi, while a significant reduction in juvenile growth over the last 25 years was only found in C. fatioi. Our results suggest that size-selective fishing affects the genetics for individual growth in these whitefish, and that the link between selection differentials and phenotypic changes is influenced by species-specific factors.

Las Bodegas españolas y su adaptación a los cambios del mercado a finales del siglo XX: análisis lingüístico de la publicidad

El sector vitivinícola español ha experimentado una serie de transformaciones en los últimos años, especialmente derivada de la caída del consumo interno y la creciente competencia en los mercados. Esto ha provocado que las bodegas españolas tuvieran que adaptarse a las nuevas circunstancias mediante la aplicación de modernas políticas de marketing. El objetivo principal del estudio es conocer el grado de aplicación de éstas, mediante la comparación y el análisis lingüístico de distintos tipos de incursiones publicitarias en medios impresos especializados, tratando aspectos como la frecuencia específica, la variación léxica, las categorías semánticas y las familias de palabras más utilizadas. La principal conclusión es que las bodegas españolas emprendieron un proceso de adaptación tardía, pasando de mensajes sencillos, sin imagen y relacionados con el sistema productivo, a otros mucho más elaborados, con imagen y nuevos términos que pretenden transmitir que estamos ante un producto de calidad.

Habitat, breeding performance, diet and individual age in Swiss barn owls (Tyto alba)

Intensification of farming over the past 50 years has homogenised the landscape structure and contributed to the decline of bird populations in Europe. To better target the conservation of the Barn Owl Tyto alba, we assessed the influence of the landscape structure on breeding performance in western Switzerland. The analyses considered a 23-year data set of breeding parameters collected in an area dominated by intensive agriculture. Using a Geographic Information System approach, landscape characteristics were described around 194 nest sites. Our analyses showed that nest-box occupancy, laying date, clutch and brood size, egg volume and probability of producing a second annual clutch were not significantly associated with any of the eight principal landscape variables (agricultural land, woodland, urban area, hedgerows, cereals, sugar beet, maize and meadow). Nevertheless, the probability that a breeding pair occupied a nest-box decreased the more roads there were surrounding the nest-box. The absence of strong associations between habitat features and breeding parameters suggests that prey availability may be relatively similar between the different breeding sites. In our study area Barn Owls can always find suitable foraging habitats around most nest-boxes.

Singling out individual inventors from patent data

An increasing number of studies have sprung up in recent years seeking to identify individual inventors from patent data. Different heuristics have been suggested to use their names and other information disclosed in patent documents in order to find out “who is who” in patents. This paper contributes to this literature by setting forth a methodology to identify them using patents applied to the European Patent Office (EPO hereafter). As in the large part of this literature, we basically follow a three-steps procedure: (1) the parsing stage, aimed at reducing the noise in the inventor’s name and other fields of the patent; (2) the matching stage, where name matching algorithms are used to group possible similar names; (3) the filtering stage, where additional information and different scoring schemes are used to filter out these potential same inventors. The paper includes some figures resulting of applying the algorithms to the set of European inventors applying to the EPO for a large period of time.

Individual versus standard quality of life assessment in a phase II clinical trial in mesothelioma patients: feasibility and responsiveness to clinical changes.

BACKGROUND: In patients with malignant pleural mesothelioma undergoing a multimodality therapy, treatment toxicity may outweigh the benefit of progression-free survival. The subjective experience across different treatment phases is an important clinical outcome. This study compares a standard with an individual quality of life (QoL) measure used in a multi-center phase II trial. PATIENTS AND METHODS: Sixty-one patients with stage I-III technically operable pleural mesothelioma were treated with preoperative chemotherapy, followed by pleuropneumonectomy and subsequent radiotherapy. QoL was assessed at baseline, at day 1 of cycle 3, and 1, 3 and 6 months post-surgery by using the Rotterdam Symptom Checklist (RSCL) and the Schedule for the Evaluation of Quality of Life-Direct Weighting (SEIQoL-DW), a measure that is based on five individually nominated and weighted QoL-domains. RESULTS: Completion rates were 98% (RSCL) and 92% (SEIQoL) at baseline and 98%/89% at cycle 3, respectively. Of the operated patients (N=45) RSCL and SEIQoL were available from 86%/72%, 93%/74%, and 94%/76% at months 1, 3, and 6 post-surgery. Average assessment time for the SEIQoL was 24min compared to 8min needed for the RSCL. Median changes from baseline indicate that both RSCL QoL overall score and SEIQoL index remained stable during chemotherapy with a clinically significant deterioration (change>or=8 points) 1 month after surgery (median change of -66 and -14 for RSCL and SEIQoL, respectively). RSCL QoL overall scores improved thereafter, but remained beneath baseline level until 6 months after surgery. SEIQoL scores improved to baseline-level at month 3 after surgery, but worsened again at month 6. RSCL QoL overall score and SEIQoL index were moderately correlated at baseline (r=.30; p<or=.05) and at 6-month follow-up (r=.42; p<or=.05) but not at the other time points. CONCLUSION: The SEIQoL assessment seems to be feasible within a phase II clinical trial, but may require more effort from staff. More distinctive QoL changes in accordance with clinical changes were measured with the RSCL. Our findings suggest that the two measures are not interchangeable: the RSCL is to favor when mainly information related to the course of disease- and treatment is of interest.

Quality assurance in the EORTC 22033-26033/CE5 phase III randomized trial for low grade glioma: the digital individual case review.

INTRODUCTION: The phase III EORTC 22033-26033/NCIC CE5 intergroup trial compares 50.4 Gy radiotherapy with up-front temozolomide in previously untreated low-grade glioma. We describe the digital EORTC individual case review (ICR) performed to evaluate protocol radiotherapy (RT) compliance. METHODS: Fifty-eight institutions were asked to submit 1-2 randomly selected cases. Digital ICR datasets were uploaded to the EORTC server and accessed by three central reviewers. Twenty-seven parameters were analysed including volume delineation, treatment planning, organ at risk (OAR) dosimetry and verification. Consensus reviews were collated and summary statistics calculated. RESULTS: Fifty-seven of seventy-two requested datasets from forty-eight institutions were technically usable. 31/57 received a major deviation for at least one section. Relocation accuracy was according to protocol in 45. Just over 30% had acceptable target volumes. OAR contours were missing in an average of 25% of cases. Up to one-third of those present were incorrectly drawn while dosimetry was largely protocol compliant. Beam energy was acceptable in 97% and 48 patients had per protocol beam arrangements. CONCLUSIONS: Digital RT plan submission and review within the EORTC 22033-26033 ICR provide a solid foundation for future quality assurance procedures. Strict evaluation resulted in overall grades of minor and major deviation for 37% and 32%, respectively.