Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment

BACKGROUND: Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. STUDY DESIGN: We investigated the impact of imple- menting a protocol aiming at reducing the number of dia- gnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. RESULTS: Among the 11,503 infants born at 35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving an- tibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of dia- gnostic tests was associated with earlier antibiotic treat- ment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. CONCLUSION: Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treat- ment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.

Immunologic work up of subjects who didn't respond appropriately to a rabies post exposure prophylaxis

Background New recommendations for rabies postexposure prophylaxis (rPEP) were published by the Centers for Disease Control and Prevention and the World Health Organization in 2010. In view of these new recommendations, the adequacy of rPEP among patients consulting the travel clinic of the University Hospital of Lausanne has been investigated and 6,8% of patients have been identified as non-responders with the new rPEP regimen. In this study we have selected the non-responders for a complete immunologic work up. Method Clinical and paraclinical immunologic investigations have been done to the non- responders patients. Those investigations have been conducted to look for an increased susceptibility to infections and an immunodeficiency. The investigations included a clinical evaluation, a full blood count, measurement of the immunoglobulin levels, a numeration of the subpopulations of the lymphocytes, a HIV test and an evaluation of the humoral response to tetanus, pneumococcal, and hepatitis B vaccinations. A lymphocyte proliferation assay with rabies antigen was performed to assess the cellular immune response. Results 9 subjects with rabies antibody titers ≤0,5 IU/ml after an rPEP with 4 doses were included in this study (=non-responders). 8/9 of these non-responders had an unremarkable medical history. 9/9 of them had normal paraclinical tests that did not suggest an immunodeficiency. The results of the lymphocyte proliferation assay with rabies antigen showed a significant correlation between the level of the humoral and cellular response. Conclusion These results suggest that a 4 dose intramuscular rPEP elicits in some patients a relatively poor humoral and cellular response, even in the absence of any immunosuppression. A serology on day 21 of the rPEP seems therefore useful to identify the patients who don't respond appropriately. Those non-responders should receive additional doses until they reach an antibody titer above 0.5 IU/ml.

Mycobacterium tuberculosis Infection in Young Children: Analyzing the Performance of the Diagnostic Tests

This study evaluated the performance of the Tuberculin Skin Test (TST) and Quantiferon-TB Gold in-Tube (QFT) and the possible association of factors which may modify their results in young children (0-6 years) with recent contact with an index tuberculosis case. Materials and Methods: A cross-sectional study including 135 children was conducted in Manaus, Amazonas-Brazil. The TST and QFT were performed and the tests results were analyzed in relation to the personal characteristics of the children studied and their relationship with the index case. Results: The rates of positivity were 34.8% (TST) and 26.7% (QFT), with 14.1% of indeterminations by the QFT. Concordance between tests was fair (Kappa = 0.35 P<0.001). Both the TST and QFT were associated with the intensity of exposure (Linear OR = 1.286, P = 0.005; Linear OR = 1.161, P = 0.035 respectively) with only the TST being associated with the time of exposure (Linear OR = 1.149, P = 0.009). The presence of intestinal helminths in the TST+ group was associated with negative QFT results (OR = 0.064, P = 0.049). In the TST- group lower levels of ferritin were associated with QFT+ results (Linear OR = 0.956, P = 0.036). Conclusions: Concordance between the TST and QFT was lower than expected. The factors associated with the discordant results were intestinal helminths, ferritin levels and exposure time to the index tuberculosis case. In TST+ group, helminths were associated with negative QFT results suggesting impaired cell-mediated immunity. The TST-&QFT+ group had a shorter exposure time and lower ferritin levels, suggesting that QFT is faster and ferritin may be a potential biomarker of early stages of tuberculosis infection.

Tests of International Asset Pricing Models in Scandinavian Stock Markets

This thesis examines whether global, local and exchange risks are priced in Scandinavian countries’ equity markets by using conditional international asset pricing models. The employed international asset pricing models are the world capital asset pricing model, the international asset pricing model augmented with the currency risk, and the partially segmented model augmented with the currency risk. Moreover, this research traces estimated equity risk premiums for the Scandinavian countries. The empirical part of the study is performed using generalized method of moments approach. Monthly observations from February 1994 to June 2007 are used. Investors’ conditional expectations are modeled using several instrumental variables. In order to keep system parsimonious the prices of risk are assumed to be constant whereas expected returns and conditional covariances vary over time. The empirical findings of this thesis suggest that the prices of global and local market risk are priced in the Scandinavian countries. This indicates that the Scandinavian countries are mildly segmented from the global markets. Furthermore, the results show that the exchange risk is priced in the Danish and Swedish stock markets when the partially segmented model is augmented with the currency risk factor.

Individual differences in control of language interference in late bilinguals are mainly related to general executive abilities

Background: Recent research based on comparisons between bilinguals and monolinguals postulates that bilingualism enhances cognitive control functions, because the parallel activation of languages necessitates control of interference. In a novel approach we investigated two groups of bilinguals, distinguished by their susceptibility to cross-language interference, asking whether bilinguals with strong language control abilities ('non-switchers") have an advantage in executive functions (inhibition of irrelevant information, problem solving, planning efficiency, generative fluency and self-monitoring) compared to those bilinguals showing weaker language control abilities ('switchers"). Methods: 29 late bilinguals (21 women) were evaluated using various cognitive control neuropsychological tests [e.g., Tower of Hanoi, Ruff Figural Fluency Task, Divided Attention, Go/noGo] tapping executive functions as well as four subtests of the Wechsler Adult Intelligence Scale. The analysis involved t-tests (two independent samples). Non-switchers (n = 16) were distinguished from switchers (n = 13) by their performance observed in a bilingual picture-naming task. Results: The non-switcher group demonstrated a better performance on the Tower of Hanoi and Ruff Figural Fluency task, faster reaction time in a Go/noGo and Divided Attention task, and produced significantly fewer errors in the Tower of Hanoi, Go/noGo, and Divided Attention tasks when compared to the switchers. Non-switchers performed significantly better on two verbal subtests of the Wechsler Adult Intelligence Scale (Information and Similarity), but not on the Performance subtests (Picture Completion, Block Design). Conclusions: The present results suggest that bilinguals with stronger language control have indeed a cognitive advantage in the administered tests involving executive functions, in particular inhibition, self-monitoring, problem solving, and generative fluency, and in two of the intelligence tests. What remains unclear is the direction of the relationship between executive functions and language control abilities.

Heterogeneous products and tests for an appropriate aggregation level considering different qualities: evidence from fresh hake at Barcelona’s wholesale market

[cat] Aquest estudi destaca la importància de considerar un nivell d’agregació adequat en els anàlisis de demanda, ja que treballar utilitzant un nivell d’agregació inadequat pot donar lloc a estimacions esbiaixades. Aquest fet es mostra a través de l’anàlisi de diferents productes de lluç fresc comercialitzats a Mercabarna, el mercat majorista de Barcelona. La literatura sobre la demanda de peix tracta al lluç com un únic producte i espècie. No obstant això, en el mercat espanyol, es comercialitzen molts peixos com a lluç, els quals mostren comportaments molt diferents (des de béns inferiors fins a béns de luxe). Els resultats obtinguts, en concordança amb les observacions empíriques, demostren que l’anàlisi s’ha de realitzar amb un major grau de detall que a nivell d’espècie. Això qüestiona els resultats d’anteriors estudis de demanda i la majoria de les bases de dades, on l’observació del nivell d’agregació adequat dels productes no es té en compte.

Heterogeneous products and tests for an appropriate aggregation level considering different qualities: evidence from fresh hake at Barcelona’s wholesale market

[cat] Aquest estudi destaca la importància de considerar un nivell d’agregació adequat en els anàlisis de demanda, ja que treballar utilitzant un nivell d’agregació inadequat pot donar lloc a estimacions esbiaixades. Aquest fet es mostra a través de l’anàlisi de diferents productes de lluç fresc comercialitzats a Mercabarna, el mercat majorista de Barcelona. La literatura sobre la demanda de peix tracta al lluç com un únic producte i espècie. No obstant això, en el mercat espanyol, es comercialitzen molts peixos com a lluç, els quals mostren comportaments molt diferents (des de béns inferiors fins a béns de luxe). Els resultats obtinguts, en concordança amb les observacions empíriques, demostren que l’anàlisi s’ha de realitzar amb un major grau de detall que a nivell d’espècie. Això qüestiona els resultats d’anteriors estudis de demanda i la majoria de les bases de dades, on l’observació del nivell d’agregació adequat dels productes no es té en compte.

DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm(3) isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

The adequacy of different robust statistical tests in comparing two independent groups

In the current study, we evaluated various robust statistical methods for comparing two independent groups. Two scenarios for simulation were generated: one of equality and another of population mean differences. In each of the scenarios, 33 experimental conditions were used as a function of sample size, standard deviation and asymmetry. For each condition, 5000 replications per group were generated. The results obtained by this study show an adequate type error I rate but not a high power for the confidence intervals. In general, for the two scenarios studied (mean population differences and not mean population differences) in the different conditions analysed, the Mann-Whitney U-test demonstrated strong performance, and a little worse the t-test of Yuen-Welch.

3,4-Methylenedioxymethamphetamine enhances kainic acid convulsive susceptibility

Abstract Kainic acid (KA) causes seizures and neuronal loss in the hippocampus. The present study investigated whether a recreational schedule of 3,4-methylenedioxymethamphetamine (MDMA) favours the development of a seizure state in a model of KA-induced epilepsy and potentiates the toxicity profile of KA (20 or 30 mg/kg). Adolescent male C57BL/6 mice received saline or MDMA t.i.d. (s.c. every 3 h), on 1 day a week, for 4 consecutive weeks. Twenty-four hours after the last MDMA exposure, the animals were injected with saline or KA (20 or 30 mg/kg). After this injection, we evaluated seizures, hippocampal neuronal cell death, microgliosis, astrogliosis, and calcium binding proteins. MDMA pretreatment, by itself, did not induce neuronal damage but increased seizure susceptibility in all KA treatments and potentiated the presence of Fluoro-Jade-positive cells in CA1. Furthermore, MDMA, like KA, significantly decreased parvalbumin levels in CA1 and dentate gyrus, where it potentiated the effects of KA. The amphetamine derivative also promoted a transient decrease in calbindin and calretinin levels, indicative of an abnormal neuronal discharge. In addition, treatment of cortical neurons with MDMA (1050 μM) for 6 or 48 h significantly increased basal Ca2 +, reduced basal Na+ levels and potentiated kainate response. These results indicate that MDMA potentiates KA-induced neurodegeneration and also increases KA seizure susceptibility. The mechanism proposed includes changes in Calcium Binding Proteins expression, probably due to the disruption of intracellular ionic homeostasis, or/and an indirect effect through glutamate release.

3,4-Methylenedioxymethamphetamine enhances kainic acid convulsive susceptibility

Abstract Kainic acid (KA) causes seizures and neuronal loss in the hippocampus. The present study investigated whether a recreational schedule of 3,4-methylenedioxymethamphetamine (MDMA) favours the development of a seizure state in a model of KA-induced epilepsy and potentiates the toxicity profile of KA (20 or 30 mg/kg). Adolescent male C57BL/6 mice received saline or MDMA t.i.d. (s.c. every 3 h), on 1 day a week, for 4 consecutive weeks. Twenty-four hours after the last MDMA exposure, the animals were injected with saline or KA (20 or 30 mg/kg). After this injection, we evaluated seizures, hippocampal neuronal cell death, microgliosis, astrogliosis, and calcium binding proteins. MDMA pretreatment, by itself, did not induce neuronal damage but increased seizure susceptibility in all KA treatments and potentiated the presence of Fluoro-Jade-positive cells in CA1. Furthermore, MDMA, like KA, significantly decreased parvalbumin levels in CA1 and dentate gyrus, where it potentiated the effects of KA. The amphetamine derivative also promoted a transient decrease in calbindin and calretinin levels, indicative of an abnormal neuronal discharge. In addition, treatment of cortical neurons with MDMA (1050 μM) for 6 or 48 h significantly increased basal Ca2 +, reduced basal Na+ levels and potentiated kainate response. These results indicate that MDMA potentiates KA-induced neurodegeneration and also increases KA seizure susceptibility. The mechanism proposed includes changes in Calcium Binding Proteins expression, probably due to the disruption of intracellular ionic homeostasis, or/and an indirect effect through glutamate release.

Salmonella enterica– Mechanisms of fluoroquinolone and macrolide resistance

Salmonella enterica – Fluorokinoloni- ja makrolidiresistenssimekanisimit Vakavia salmonellainfektioita on pitkään hoidettu fluorokinoloniantibiooteilla, kuten siprofloksasiinilla. Fluorokinolonien runsas käyttö niin ihmisillä kuin eläimilläkin on kuitenkin johtanut fluorokinoloniresistenttien salmonellakantojen lisääntymiseen. Vuoteen 2002 asti kaikki matalan tason fluorokinoloniresistenssiä ilmentävät salmonellakannat olivat resistenttejä nalidiksiinihapolle, joka on vanha ensimmäisen polven kinoloniantibiootti jota ei enää käytetä infektioiden hoidossa. Vuonna 2003 havaitsimme aivan uudentyyppisen resistenssifenotyypin salmonelloissa. Kaikki uuden fenotyypin kannat osoittivat matalaa fluorokinoloniresistenssiä (MIC ≥0.125 mg/L), mutta useat kannat olivat yllättäen aikaisempaa herkempiä nalidiksiinihapolle (MIC ≤32 mg/L). Ilmiöllä on suuri merkitys salmonellan antibioottiherkkyyksien määrittämisessä, sillä jos kanta on ollut nalidiksiinihapolle herkkä, sitä on pidetty herkkänä myös fluorokinoloneille. Väitöskirjatyössä määritettiin vuosina 2003–2007 Suomessa kerättyjen kotimaisten ja ulkomaalaisten S. enterica -kantojen fluorokinoloniresistenssiä sekä tutkittiin uuden salmonellafenotyypin epidemiologiaa ja resistenssimekanismeja. Lisäksi tutkittiin salmonellan hoidossa mahdollisesti käyttökelpoisen makrolidiantibioottijohdannaisen, atsitromysiinin tehoa salmonelloihin ja erityisesti matalaa fluorokinoloniresistenssiä ilmentäviin kantoihin. Tutkimuksessa havaittiin, että matalaa fluorokinoloniresistenssiä osoittavien salmonellakantojen määrä vähenee. Lasku oli voimakkainta Kaakkois-Aasiasta tuoduissa kannoissa. Uusi resistenssifenotyyppi on plasmidivälitteinen ja qnr-geenit olivat ainoa plasmidivälitteinen kinoloniresistenssimekanismi, joka kannoista löydettiin. Myöskään kromosomaalisten gyrA, gyrB ja parE -geenien QRDR-alueelta ei löydetty fluorokinoloniresistenssiä aiheuttavia mutaatioita. Transformaatiolla osoitettiin qnr-plasmidien olevan siirtyviä ja uusi resistenssifenotyyppi saatiin ilmennettyä myös herkässä vastaanottajakannassa. Nämä tulokset osoittavat, että vaikka S. enterican qnr-fenotyyppi on toistaiseksi levinnyt pääasiassa Kaakkois-Aasiaan, se siirtyy helposti bakteerista toiseen ja tulee todennäköisesti aiheuttamaan hoito-ongelmia myös muualla maailmassa. Uudentyyppinen qnr-fenotyyppi voi olla vaikea havaita perinteisellä herkkyysmäärityksellä. Siksi laboratorioissa tulisi aina määrittää sekä siprofloksasiiniettä nalidiksiinihappoherkkyydet. Atsitromysiinin osoitettiin olevan herkkyysmääritysten mukaan tehokas salmonelloja kohtaan mukaanlukien matala-asteista fluorokinoloniresistenssiä ilmentävät bakteerikannat.

Susceptibility of fruits of the 'Valência' and 'Natal' sweet orange varieties to Guignardia citricarpa and the influence of the coexistence of healthy and symptomatic fruits

The importance of the presence of symptomatic fruits with citrus black symptoms (CBS) on the disease severity level in subsequent crop production was assessed in an orchard planted with Valência and Natal sweet orange varieties. Additionally, the period of susceptibility of the fruits of these varieties was evaluated. Fruits were covered with paper bags at the stage of 75% fallen petals and were then exposed to natural infection at weekly intervals, from October 2000 to April 2001. This process was carried out in plants where the fruits from the previous harvest had been picked as well as in plants where fruits remained until natural drop. The evaluation of disease severity used a scale that varied from 0 (absence of symptoms) to 6 (severe symptoms). It was observed that, for the Valência and Natal varieties, conidia of Phyllosticta citricarpa that had formed on the lesions of fruits from the previous harvest did not significantly increase the severity of disease on the fruits of the subsequent harvest period. In this study, the protection of the fruits until 10 weeks after petal drop did not affect the number of lesions, indicating that ascospore discharges after that date were, probably, responsible for disease severity. Fruits exposed between the 20th and 24th week after 75% of the petals had fallen were symptomatic, indicating that, at this stage, the fruits were still susceptible to the pathogen.

Susceptibility of leguminous green manure species to Rhizoctonia solani and Sclerotium rolfsii

We studied the susceptibility of species used as green manure in common bean fields to root rot (Rhizoctonia solani) and southern blight (Sclerotium rolfsii). Seeds of Crotalaria breviflora, Canavalia ensiformis, Cajanus cajan, Dolichos lablab, Stizolobium cinereum, S. aterrimum, and the bean cvs. "Pérola", "Valente" and "Carnaval" were sown in soil infested by either R. solani AG-4 or S. rolfsii in greenhouse. The emergence of D. lablab seedlings in soil infested by R. solani dropped to 62%. C. breviflora, C. ensiformis and cv. "Valente" presented the lowest root rot severity. The pathogen S. rolfsii drastically reduced seedling emergence in all species; no C. cajan and S. cinereum seedling emerged. All plant species presented high southern blight severity. We conclude that leguminous crops are not suitable as green manure for areas of bean cultivation with high R. solani and S. rolfsii populations.