Noninvasive techniques in assessing coronary artery disease

Conventional invasive coronary angiography is the clinical gold standard for detecting of coronary artery stenoses. Noninvasive multidetector computed tomography (MDCT) in combination with retrospective ECG gating has recently been shown to permit visualization of the coronary artery lumen and detection of coronary artery stenoses. Single photon emission tomography (SPECT) perfusion imaging has been considered the reference method for evaluation of nonviable myocardium, but magnetic resonance imaging (MRI) can accurately depict structure, function, effusion, and myocardial viability, with an overall capacity unmatched by any other single imaging modality. Magnetocardiography (MCG) provides noninvasively information about myocardial excitation propagation and repolarization without the use of electrodes. This evolving technique may be considered the magnetic equivalent to electrocardiography. The aim of the present series of studies was to evaluate changes in the myocardium assessed with SPECT and MRI caused by coronary artery disease, examine the capability of multidetector computed tomography coronary angiography (MDCT-CA) to detect significant stenoses in the coronary arteries, and MCG to assess remote myocardial infarctions. Our study showed that in severe, progressing coronary artery disease laser treatment does not improve global left ventricular function or myocardial perfusion, but it does preserve systolic wall thickening in fixed defects (scar). It also prevents changes from ischemic myocardial regions to scar. The MCG repolarization variables are informative in remote myocardial infarction, and may perform as well as the conventional QRS criteria in detection of healed myocardial infarction. These STT abnormalities are more pronounced in patients with Q-wave infarction than in patients with non-Q-wave infarctions. MDCT-CA had a sensitivity of 82%, a specificity of 94%, a positive predictive value of 79%, and a negative predictive value of 95% for stenoses over 50% in the main coronary arteries as compared with conventional coronary angiography in patients with known coronary artery disease. Left ventricular wall dysfunction, perfusion defects, and infarctions were detected in 50-78% of sectors assigned to calcifications or stenoses, but also in sectors supplied by normally perfused coronary arteries. Our study showed a low sensitivity (sensitivity 63%) in detecting obstructive coronary artery disease assessed by MDCT in patients with severe aortic stenosis. Massive calcifications complicated correct assessment of the lumen of coronary arteries.

Imaging of knee injuries with special focus on tibial plateau fractures

Acute knee injury is a common event throughout life, and it is usually the result of a traffic accident, simple fall, or twisting injury. Over 90% of patients with acute knee injury undergo radiography. An overlooked fracture or delayed diagnosis can lead to poor patient outcome. The major aim of this thesis was retrospectively to study imaging of knee injury with a special focus on tibial plateau fractures in patients referred to a level-one trauma center. Multi-detector computed tomography (MDCT) findings of acute knee trauma were studied and compared to radiography, as well as whether non-contrast MDCT can detect cruciate ligaments with reasonable accuracy. The prevalence, type, and location of meniscal injuries in magnetic resonance imaging (MRI) were evaluated, particularly in order to assess the prevalence of unstable meniscal tears in acute knee trauma with tibial plateau fractures. The possibility to analyze with conventional MRI the signal appearance of menisci repaired with bioabsorbable arrows was also studied. The postoperative use of MDCT was studied in surgically treated tibial plateau fractures: to establish the frequency and indications of MDCT and to assess the common findings and their clinical impact in a level-one trauma hospital. This thesis focused on MDCT and MRI of knee injuries, and radiographs were analyzed when applica-ble. Radiography constitutes the basis for imaging acute knee injury, but MDCT can yield information beyond the capabilities of radiography. Especially in severely injured patients , sufficient radiographs are often difficult to obtain, and in those patients, radiography is unreliable to rule out fractures. MDCT detected intact cruciate ligaments with good specificity, accuracy, and negative predictive value, but the assessment of torn ligaments was unreliable. A total of 36% (14/39) patients with tibial plateau fracture had an unstable meniscal tear in MRI. When a meniscal tear is properly detected preoperatively, treatment can be combined with primary fracture fixation, thus avoiding another operation. The number of meniscal contusions was high. Awareness of the imaging features of this meniscal abnormality can help radiologists increase specificity by avoiding false-positive findings in meniscal tears. Postoperative menisci treated with bioabsorbable arrows showed no difference, among different signal intensities in MRI, among menisci between patients with operated or intact ACL. The highest incidence of menisci with an increased signal intensity extending to the meniscal surface was in patients whose surgery was within the previous 18 months. The results may indicate that a rather long time is necessary for menisci to heal completely after arrow repair. Whether the menisci with an increased signal intensity extending to the meniscal surface represent improper healing or re-tear, or whether this is just the earlier healing feature in the natural process remains unclear, and further prospective studies are needed to clarify this. Postoperative use of MDCT in tibial plateau fractures was rather infrequent even in this large trauma center, but when performed, it revealed clinically significant information, thus benefitting patients in regard to treatment.

Cyclosporine population pharmacokinetics in pediatric renal transplant recipients

Cyclosporine is an immunosuppressant drug with a narrow therapeutic index and large variability in pharmacokinetics. To improve cyclosporine dose individualization in children, we used population pharmacokinetic modeling to study the effects of developmental, clinical, and genetic factors on cyclosporine pharmacokinetics in altogether 176 subjects (age range: 0.36–20.2 years) before and up to 16 years after renal transplantation. Pre-transplantation test doses of cyclosporine were given intravenously (3 mg/kg) and orally (10 mg/kg), on separate occasions, followed by blood sampling for 24 hours (n=175). After transplantation, in a total of 137 patients, cyclosporine concentration was quantified at trough, two hours post-dose, or with dose-interval curves. One-hundred-four of the studied patients were genotyped for 17 putatively functionally significant sequence variations in the ABCB1, SLCO1B1, ABCC2, CYP3A4, CYP3A5, and NR1I2 genes. Pharmacokinetic modeling was performed with the nonlinear mixed effects modeling computer program, NONMEM. A 3-compartment population pharmacokinetic model with first order absorption without lag-time was used to describe the data. The most important covariate affecting systemic clearance and distribution volume was allometrically scaled body weight i.e. body weight**3/4 for clearance and absolute body weight for volume of distribution. The clearance adjusted by absolute body weight declined with age and pre-pubertal children (< 8 years) had an approximately 25% higher clearance/body weight (L/h/kg) than did older children. Adjustment of clearance for allometric body weight removed its relationship to age after the first year of life. This finding is consistent with a gradual reduction in relative liver size towards adult values, and a relatively constant CYP3A content in the liver from about 6–12 months of age to adulthood. The other significant covariates affecting cyclosporine clearance and volume of distribution were hematocrit, plasma cholesterol, and serum creatinine, explaining up to 20%–30% of inter-individual differences before transplantation. After transplantation, their predictive role was smaller, as the variations in hematocrit, plasma cholesterol, and serum creatinine were also smaller. Before transplantation, no clinical or demographic covariates were found to affect oral bioavailability, and no systematic age-related changes in oral bioavailability were observed. After transplantation, older children receiving cyclosporine twice daily as the gelatine capsule microemulsion formulation had an about 1.25–1.3 times higher bioavailability than did the younger children receiving the liquid microemulsion formulation thrice daily. Moreover, cyclosporine oral bioavailability increased over 1.5-fold in the first month after transplantation, returning thereafter gradually to its initial value in 1–1.5 years. The largest cyclosporine doses were administered in the first 3–6 months after transplantation, and thereafter the single doses of cyclosporine were often smaller than 3 mg/kg. Thus, the results suggest that cyclosporine displays dose-dependent, saturable pre-systemic metabolism even at low single doses, whereas complete saturation of CYP3A4 and MDR1 (P-glycoprotein) renders cyclosporine pharmacokinetics dose-linear at higher doses. No significant associations were found between genetic polymorphisms and cyclosporine pharmacokinetics before transplantation in the whole population for which genetic data was available (n=104). However, in children older than eight years (n=22), heterozygous and homozygous carriers of the ABCB1 c.2677T or c.1236T alleles had an about 1.3 times or 1.6 times higher oral bioavailability, respectively, than did non-carriers. After transplantation, none of the ABCB1 SNPs or any other SNPs were found to be associated with cyclosporine clearance or oral bioavailability in the whole population, in the patients older than eight years, or in the patients younger than eight years. In the whole population, in those patients carrying the NR1I2 g.-25385C–g.-24381A–g.-205_-200GAGAAG–g.7635G–g.8055C haplotype, however, the bioavailability of cyclosporine was about one tenth lower, per allele, than in non-carriers. This effect was significant also in a subgroup of patients older than eight years. Furthermore, in patients carrying the NR1I2 g.-25385C–g.-24381A–g.-205_-200GAGAAG–g.7635G–g.8055T haplotype, the bioavailability was almost one fifth higher, per allele, than in non-carriers. It may be possible to improve individualization of cyclosporine dosing in children by accounting for the effects of developmental factors (body weight, liver size), time after transplantation, and cyclosporine dosing frequency/formulation. Further studies are required on the predictive value of genotyping for individualization of cyclosporine dosing in children.

The association between student characteristics and the development of clinical reasoning in a graduate-entry, PBL medical programme

This study sought to assess the extent to which the entry characteristics of students in a graduate-entry medical programme predict the subsequent development of clinical reasoning ability. Subjects comprised 290 students voluntarily recruited from three successive cohorts of the University of Queensland's MBBS Programme. Clinical reasoning was measured once a year over a period of three years using two methods, a set of 10 Clinical Reasoning Problems (CRPs) and the Diagnostic Thinking Inventory (DTI). Data on gender, age at entry into the programme, nature of primary degree, scores on selection criteria (written examination plus interview) and academic performance in the first two years of the programme were recorded for each student, and their association with clinical reasoning skill analysed using univariate and multivariate analysis. Univariate analysis indicated significant associations between CRP score, gender and primary degree with a significant but small association between DTI and interview score. Stage of progression through the programme was also an important predictor of performance on both indicators. Subsequent multivariate analysis suggested that female gender is a positive predictor of CRP score independently of the nature of a subject's primary degree and stage of progression through the programme, although these latter two variables are interdependent. Positive predictors of clinical reasoning skill are stage of progression through the MBBS programme, female gender and interview score. Although the nature of a student's primary degree is important in the early years of the programme, evidence suggests that by graduation differences between students' clinical reasoning skill due to this factor have been resolved.

Appendiceal sonography in children: A retrospective analysis as a platform for potential implementation of diagnostic categories

- Background Sonography is an important diagnostic tool in children with suspected appendicitis. Reported accuracy and appendiceal visualisation rates vary significantly, as does the management of equivocal ultrasound findings. The aim of this study was to audit appendiceal sonography at a tertiary children's hospital, and provide baseline data for a future prospective study. - Summary of work Records of children who underwent ultrasound studies for possible appendicitis between January 2008 and December 2010 were reviewed. Variables included patient demographics, sonographic appendix characteristics, and secondary signs. Descriptive statistics and analysis using ANOVA, Mann-Whitney U test, and ROC curves were performed. Mater Human Research Ethic Committee approval was granted. - Summary of results There were 457 eligible children. Using a dichotomous diagnostic model (including equivocal results), sensitivity was 89.6%, specificity 91.6%, and diagnostic yield of 40.7%. ROC curve analysis of a 6mm diameter cut-off was 0.88 AUC (95% CI 0.80 to 0.95). - Discussion and conclusions Sonography is an accurate test for acute appendicitis in children, with a high sensitivity and negative predictive value. A diameter of 6mm as an absolute cut-off in a binary model can lead to false findings. Results were compared with available literature. Recent publications propose categorising diameter1 and integrating secondary signs2 to improve accuracy and provide more meaningful results to clinicians. This study will be a benchmark for future studies with multiple diagnostic categorisation.

Parathyroid hormone as an outcome indicator in old age

Serum parathyroid hormone (PTH) and vitamin D are the major regulators of extracellular calcium homeostasis. The inverse association between PTH and vitamin D and the common age-related elevation of the PTH concentration are well known phenomena. However, the confounding or modifying factors of this relationship and their impact on the response of PTH levels to vitamin D supplementation need further investigation. Clinical conditions such as primary hyperparathyroidism (PHPT), renal failure and vitamin D deficiency, characterized by an elevation of the PTH concentration, have been associated with impaired long-term health outcomes. Curative treatments for these conditions have also been shown to decreases PTH concentration and attenuate some of the adverse health effects. In PHPT it has also been commonly held that hypercalcaemia, the other hallmark of the disease, is the key mediator of the adverse health outcomes. In chronic kidney disease the systemic vascular disease has been proposed to have the most important impact on general health. Some evidence also indicates that vitamin D may have significant extraskeletal actions. However, the frank elevation of PTH concentration seen in advanced PHPT and in end-stage renal failure have also been suggested to be at least partly causally related to an increased risk of death as well as cognitive dysfunction. However, the exact mechanisms have remained unclear. Furthermore, the predictive value of elevated PTH in unselected older populations has been less well studied. The studies presented in this thesis investigated the impact of age and mobility on the responses of PTH levels to vitamin D deficiency and supplementation. Furthermore, the predictive value of PTH for long-term survival and cognitive decline was addressed in an unselected population of older people. The hypothesis was that age and chronic immobility are related to a persistently blunted elevation of PTH concentration, even in the presence of chronic vitamin D deficiency, and to attenuated responses of PTH to vitamin D supplementation. It was also further hypothesized that a slightly elevated or even high-normal PTH concentration is an independent indicator of an increased risk of death and cognitive decline in the general aged population. The data of this thesis are based on three samples: a meta-analysis of published vitamin D supplementation trials, a randomized placebo controlled six-month vitamin D supplementation trial, and a longitudinal prospective cohort study on a general aged population. Based on a PubMed search, a meta-analysis of 52 clinical trials with 6 290 adult participants was performed to evaluate the impact of age and immobility on the responses of PTH to 25-OHD levels and vitamin D supplementation. A total of 218 chronically immobile, very old inpatients were also enrolled into a vitamin D supplementation trial. Mortality data for these patients was also collected after a two-year follow-up. Finally, data from the Helsinki Aging Study, which followed three random age cohorts (75, 80 and 85 years) until death in almost all subjects, was used to evaluate the predictive value of PTH for long-term survival and cognitive decline. This series of studies demonstrated that in older people without overt renal failure or severe hypercalcaemia, serum 25-OHD and PTH were closely associated, but this relationship was also affected by age and immobility. Furthermore, a substantial proportion of old chronically bedridden patients did not respond to vitamin D deficiency by elevating PTH, and the effect of a high-dose (1200 IU/d) six-month cholecalciferol supplementation on the PTH concentration was minor. This study demonstrated longitudinally for the first time that the blunted PTH also persisted over time. Even a subtle elevation of PTH to high-normal levels predicted impaired long-term health outcomes. Slightly elevated PTH concentrations indicated an increased risk of clinically significant cognitive decline and death during the last years of life in a general aged population. This association was also independent of serum ionized calcium (Ca2+) and the estimated glomerular filtration rate (GFR). A slightly elevated PTH also indicated impaired two-year survival during the terminal years of frail elderly subjects independently of Ca2+, GFR, and of 25-OHD levels. The interplay between PTH and vitamin D in the regulation of calcium homeostasis is more complex than has been generally considered. In addition to muskuloskeletal health parathyroid hormone is also related to the maintenance of other important domains of health in old age. Higher PTH concentrations, even within conventional laboratory reference ranges, seem to be an independent indicator of an increased risk of all-cause and of cardiovascular mortality, independently of established cardiovascular risk factors, disturbances in mineral metabolism, and renal failure. Limited and inconsistent evidence supports the role of vitamin D deficiency-related lack of neuroprotective effects over the causal association between PTH and impaired cognitive functions. However, the causality of these associations remains unclear. The clinical implications of the observed relationships remain to be elucidated by future studies interfering with PTH concentrations, especially by long-term interventions to reduce PTH.

29Si NMR chemical shifts in silicates

29Si chemical shifts in a wide variety of silicates in crystalline, glassy and gel states have been related to a parameter, P, which takes into account the electronegativity and the structural description of the silicate units as well as the ionic potential of the modifier cation. The relation, δ(ppm)=28.4 [1−exp(−P)]−110.5, besides having predictive value, satisfactorily accounts for all the available chemical-shifts data on silicates and shows the right kind of limiting behaviour, with δ approaching the Q0 value at large P.

Poststroke survival and ischemic stroke recurrence : the cerebral small-vessel disease perspective

The aim of the present study was to investigate the influence of different manifestations of cerebral SVD on poststroke survival and ischemic stroke recurrence in long-term follow-up. The core imaging features of small-vessel disease (SVD) are confluent and extensive white matter changes (WMC) and lacunar infarcts. These are associated with minor motor deficits but a major negative influence on cognition, mood, and functioning in daily life, resulting from small-vessel lesions in the fronto-subcortical brain network. These sub-studies were conducted as part of the Helsinki Stroke Aging Memory (SAM) study. The SAM cohort consisted of 486 consecutive patients aged 55 to 85 years who were admitted to Helsinki University Central Hospital with acute ischemic stroke. The study included comprehensive clinical, neuropsychological, psychiatric and radiological assessment three months poststroke. The patients were followed up up for 12 years using extensive national registers. The effect of different manifestations of cerebral SVD on poststroke survival and stroke recurrence was analyzed controlling for factors such as age, education, and cardiovascular risk factors. Poststroke dementia and cognitive impairment relate to poor long-term survival. In particular, deficits in executive functions as well as visuospatial and constructional abilities predict poor outcome. The predictive value of cognitive deficits is further underlined by the finding that depression-executive dysfunction syndrome (DES), but not depression in itself, is associated with poor poststroke survival. Delirium is not independently associated with increased risk for long-term poststroke mortality, although it is associated with poststroke dementia. Furthermore, acute index stroke attributable to SVD is associated with poorer long-term survival and a higher risk for cardiac death than other stroke subtypes. Severe WMC, a surrogate of SVD, is independently related to an increased risk of stroke recurrence at five years. In summary, cognitive poststroke outcomes reflecting changes in the executive network brain, and the presence of cerebral SVD are important determinants of poststroke mortality and ischemic stroke recurrence, regardless of whether SVD is the cause of the index stroke or a condition concurrent to some other etiology.

Lypsylehmän energiataseen mallintaminen tuotoskauden alkuvaiheessa

Energiataseen mallinnus on osa KarjaKompassi-hankkeeseen liittyvää kehitystyötä. Tutkielman tavoitteena oli kehittää lypsylehmän energiatasetta etukäteen ennustavia ja tuotoskauden aikana saatavia tietoja hyödyntäviä matemaattisia malleja. Selittävinä muuttujina olivat dieetti-, rehu-, maitotuotos-, koelypsy-, elopaino- ja kuntoluokkatiedot. Tutkimuksen aineisto kerättiin 12 Suomessa tehdyistä 8 – 28 laktaatioviikon pituisesta ruokintakokeesta, jotka alkoivat heti poikimisen jälkeen. Mukana olleista 344 lypsylehmästä yksi neljäsosa oli friisiläis- ja loput ayshire-rotuisia. Vanhempien lehmien päätiedosto sisälsi 2647 havaintoa (koe * lehmä * laktaatioviikko) ja ensikoiden 1070. Aineisto käsiteltiin SAS-ohjelmiston Mixed-proseduuria käyttäen ja poikkeavat havainnot poistettiin Tukeyn menetelmällä. Korrelaatioanalyysillä tarkasteltiin energiataseen ja selittävien muuttujien välisiä yhteyksiä. Energiatase mallinnettiin regressioanalyysillä. Laktaatiopäivän vaikutusta energiataseeseen selitettiin viiden eri funktion avulla. Satunnaisena tekijänä mallissa oli lehmä kokeen sisällä. Mallin sopivuutta aineistoon tarkasteltiin jäännösvirheen, selitysasteen ja Bayesin informaatiokriteerin avulla. Parhaat mallit testattiin riippumattomassa aineistossa. Laktaatiopäivän vaikutusta energiataseeseen selitti hyvin Ali-Schaefferin funktio, jota käytettiin perusmallina. Kaikissa energiatasemalleissa vaihtelu kasvoi laktaatioviikosta 12. alkaen, kun havaintojen määrä väheni ja energiatase muuttui positiiviseksi. Ennen poikimista käytettävissä olevista muuttujista dieetin väkirehuosuus ja väkirehun syönti-indeksi paransivat selitysastetta ja pienensivät jäännösvirhettä. Ruokinnan onnistumista voidaan seurata maitotuotoksen, maidon rasvapitoisuuden ja rasva-valkuaissuhteen tai EKM:n sisältävillä malleilla. EKM:n vakiointi pienensi mallin jäännösvirhettä. Elopaino ja kuntoluokka olivat heikkoja selittäjiä. Malleja voidaan hyödyntää karjatason ruokinnan suunnittelussa ja seurannassa, mutta yksittäisen lehmän energiataseen ennustamiseen ne eivät sovellu.

Molecular profile of oligodendrogliomas in young patients

Several studies on molecular profiling of oligodendrogliomas (OGs) in adults have shown a distinctive genetic pattern characterized by combined deletions of chromosome arms 1 p and 19q, O6-methylguanine-methyltransferase (MGMT) methylation, and isocitrate dehydrogenase 1 (IDH1) mutation, which have potential diagnostic, prognostic, and even therapeutic relevance. OGs in pediatric and young adult patients are rare and have been poorly characterized on a molecular and biological basis, and it remains uncertain whether markers with prognostic significance in adults also have predictive value in these patients. Fourteen cases of OGs in young patients (age, <= 25 years) who received a diagnosis over 7 years were selected (7 pediatric patients age <= 18 years and 7 young adults aged 19-25 years). The cases were evaluated for 1p/19q status, MGMT promoter methylation, p53 mutation, and IDH1 mutation. None of the pediatric cases showed 1p/19q deletion. In young adults, combined 1p/19q loss was observed in 57% and isolated 1p loss in 14% of cases. The majority of cases in both subgroups (71% in each) harbored MGMT gene promoter methylation. TP53 and IDH1 mutations were not seen in any of the cases in both the groups. To our knowledge, this is the first study to show that molecular profile of OGs in pediatric and young adult patients is distinct. Further large-scale studies are required to identify additional clinically relevant genetic alterations in this group of patients.

Low cost calibrated mechanical noisemaker for hearing screening of neonates in resource constrained settings

Background & objectives: There is a need to develop an affordable and reliable tool for hearing screening of neonates in resource constrained, medically underserved areas of developing nations. This study valuates a strategy of health worker based screening of neonates using a low cost mechanical calibrated noisemaker followed up with parental monitoring of age appropriate auditory milestones for detecting severe-profound hearing impairment in infants by 6 months of age. Methods: A trained health worker under the supervision of a qualified audiologist screened 425 neonates of whom 20 had confirmed severe-profound hearing impairment. Mechanical calibrated noisemakers of 50, 60, 70 and 80 dB (A) were used to elicit the behavioural responses. The parents of screened neonates were instructed to monitor the normal language and auditory milestones till 6 months of age. This strategy was validated against the reference standard consisting of a battery of tests - namely, auditory brain stem response (ABR), otoacoustic emissions (OAE) and behavioural assessment at 2 years of age. Bayesian prevalence weighted measures of screening were calculated. Results: The sensitivity and specificity was high with least false positive referrals for. 70 and 80 dB (A) noisemakers. All the noisemakers had 100 per cent negative predictive value. 70 and 80 dB (A) noisemakers had high positive likelihood ratios of 19 and 34, respectively. The probability differences for pre- and post- test positive was 43 and 58 for 70 and 80 dB (A) noisemakers, respectively. Interpretation & conclusions: In a controlled setting, health workers with primary education can be trained to use a mechanical calibrated noisemaker made of locally available material to reliably screen for severe-profound hearing loss in neonates. The monitoring of auditory responses could be done by informed parents. Multi-centre field trials of this strategy need to be carried out to examine the feasibility of community health care workers using it in resource constrained settings of developing nations to implement an effective national neonatal hearing screening programme.

Detección oportuna de niños en riesgo pre-lector : ponderación del valor potencial de instrumentos de evaluación de la consciencia fonológica

Se evalúan validez, confiabilidad y nivel de dificultad de instrumentos de evaluación de la conciencia fonológica, a fin de analizar su potencialidad como herramientas de detección oportuna, de pre-lectores en riesgo en una muestra de niños que crecen en un ambiente de vulnerabilidad social. Los instrumentos se seleccionaron en función de los dos niveles de CF: unidad lingüística y nivel de dificultad. Se ponderó la validez del instrumento mediante la técnica de análisis de contenido de investigaciones previas. Obtuvo buena confiabilidad (alpha de Cronbach: 0.84) y potencialidad discriminativa. Se hallan niveles diferenciales de dificultad en la resolución de las distintas tareas en pre-lectores en riesgo en comparación con buenos lectores de la misma edad. El análisis de regresión simple destaca el valor predictivo de las tareas de evaluación seleccionadas en este estudio sobre el posterior nivel alcanzado por los niños en habilidades básicas de la lectura.

Contribution of Resource-Based View and Entrepreneurial Orientation on Small Firm Growth

[EN] This research provides a useful framework for identifying a small firms’ propensity to engage in entrepreneurial orientation. We examine the impact of the Entrepreneurial Orientation (EO) as a main resource and capability on small firm’ growth. The growth seems to come out as an important demonstration of the entrepreneurial orientation of small firms (Davidsson, 1989; Green and Brown, 1997; Janney and Gregory, 2006). Thus, this research builds on prior conceptual research that suggests a positive integration between entrepreneurial orientation and resource-based view. In the first instance, the research will focus on reviewing literature in the emerging area of entrepreneurial orientation as it applies to growth oriented small firms and resource-based view of the firm. Secondly, an empirical study was developed based on a stratified sample of small firms of manufacturing industry. Data were submitted to a multivariate statistical analysis and a linear regression model was performed in order to predict the influence of the resources and capabilities on small firms’ growth. In this sense, we consider the construct growth as a dependent variable and the ones relates with resources and capabilities (entrepreneur resources, firm resources, networks and EO) as independent variables. The research results suggest a set of resources and capabilities that promote the growth of the small firms. Also, the EO seems to have a predictive value on growth. Explaining variables related with resources and capabilities and EO were identified as essential in growth oriented small firms. It was still possible to conclude that the entrepreneurial firms which grew seem to have resources and develop more capabilities and take advantage in the search for those competences. This attitude reflects on the EO of the firm. This study has important implication for both researchers and practitioners. It highlights the necessity of firms to develop superior EO of all their members and also to invest on better resources and consequently superior capabilities as a way of reaching higher levels of growth. While previous authors have attempted to analyse certain aspects of this process (linkage between entrepreneurial orientation and growth), this research developed a framework that combines these and others factors (resource-based view) pertinent to growth oriented small firms. The results support the necessity to identify explicative variables of multiple levels to explain the growth of small firms. The adoption of an entrepreneurial orientation as an indispensable variable to the growth oriented small firms seems pertinent.

Diagnosis of invasive candidiasis by enzyme-linked immunosorbent assay using the N-terminal fragment of Candida albicans hyphal wall protein I

Background: The diagnosis of invasive candidiasis is difficult because there are no specific clinical manifestations of the disease and colonization and infection are difficult to distinguish. In the last decade, much effort has been made to develop reliable tests for rapid diagnosis of invasive candidiasis, but none of them have found widespread clinical use. Results: Antibodies against a recombinant N-terminal fragment of the Candida albicans germ tube-specific antigen hyphal wall protein 1 (Hwp1) generated in Escherichia coli were detected by both immunoblotting and ELISA tests in a group of 36 hematological or Intensive Care Unit patients with invasive candidiasis and in a group of 45 control patients at high risk for the mycosis who did not have clinical or microbiological data to document invasive candidiasis. Results were compared with an immunofluorescence test to detect antibodies to C. albicans germ tubes (CAGT). The sensitivity, specificity, positive and negative predictive values of a diagnostic test based on the detection of antibodies against the N-terminal fragment of Hwp1 by immunoblotting were 27.8 %, 95.6 %, 83.3 % and 62.3 %, respectively. Detection of antibodies to the N-terminal fragment of Hwp1 by ELISA increased the sensitivity (88.9 %) and the negative predictive value (90.2 %) but slightly decreased the specificity (82.6 %) and positive predictive values (80 %). The kinetics of antibody response to the N-terminal fragment of Hwp1 by ELISA was very similar to that observed by detecting antibodies to CAGT. Conclusion: An ELISA test to detect antibodies against a recombinant N-terminal fragment of the C. albicans germ tube cell wall antigen Hwp1 allows the diagnosis of invasive candidiasis with similar results to those obtained by detecting antibodies to CAGT but without the need of treating the sera to adsorb the antibodies against the cell wall surface of the blastospore.

Desenvolvimento e validação de modelo preditivo e avaliação de testes de diagnóstico por classe latente para o parasitismo por L. chagasi em cães atendidos no Hospital Veterinário Universitário da UFPI, Teresina

A leishmaniose visceral americana (LVA) é uma doença em expansão no Brasil, para a qual se dispõem de poucas, e aparentemente ineficientes, estratégias de controle. Um dos grandes problemas para a contenção da leishmaniose visceral americana é a falta de um método acurado de identificação dos cães infectados, considerados os principais reservatórios da doença no meio urbano. Neste sentido, a caracterização de marcadores clínico-laboratoriais da infecção neste reservatório e a avaliação mais adequada do desempenho de testes para diagnóstico da infecção podem contribuir para aumentar a efetividade das estratégias de controle da LVA. Com isso, o presente estudo tem dois objetivos principais: (1) desenvolver e validar um modelo de predição para o parasitismo por Leishmania chagasi em cães, baseado em resultados de testes sorológicos e sinais clínicos e (2) avaliar a sensibilidade e especificidade de critérios clínicos, sorológicos e parasitológicos para detecção de infecção canina por L. chagasi mediante análise de classe latente. O primeiro objetivo foi desenvolvido a partir de estudo em que foram obtidos dados de exames clínico, sorológico e parasitológico de todos os cães, suspeitos ou não de LVA, atendidos no Hospital Veterinário Universitário da Universidade Federal do Piauí (HVU-UFPI), em Teresina, nos anos de 2003 e 2004, totalizando 1412 animais. Modelos de regressão logística foram construídos com os animais atendidos em 2003 com a finalidade de desenvolver um modelo preditivo para o parasitismo com base nos sinais clínicos e resultados de sorologia por Imunofluorescência Indireta (IFI). Este modelo foi validado nos cães atendidos no hospital em 2004. Para a avaliação da área abaixo da curva ROC (auROC), sensibilidade, especificidade, valores preditivos positivo (VPP), valores preditivos negativo (VPN) e acurácia global, foram criados três modelos: um somente baseado nas variáveis clínicas, outro considerando somente o resultado sorológico e um último considerando conjuntamente a clínica e a sorologia. Dentre os três, o último modelo apresentou o melhor desempenho (auROC=90,1%, sensibilidade=82,4%, especificidade=81,6%, VPP=73,4%, VPN=88,2% e acurácia global=81,9%). Conclui-se que o uso de modelos preditivos baseados em critérios clínicos e sorológicos para o diagnóstico da leishmaniose visceral canina pode ser de utilidade no processo de avaliação da infecção canina, promovendo maior agilidade na contenção destes animais com a finalidade de reduzir os níveis de transmissão. O segundo objetivo foi desenvolvido por meio de um estudo transversal com 715 cães de idade entre 1 mês e 13 anos, com raça variada avaliados por clínicos veterinários no HVU-UFPI, no período de janeiro a dezembro de 2003. As sensibilidades e especificidades de critérios clínicos, sorológicos e parasitológicos para detecção de infecção canina por Leishmania chagasi foram estimadas por meio de análise de classe latente, considerando quatro modelos de testes e diferentes pontos de corte. As melhores sensibilidades estimadas para os critérios clínico, sorológico e parasitológico foram de 60%, 95% e 66%, respectivamente. Já as melhores especificidades estimadas para os critérios clínico, sorológico e parasitológico foram de 77%, 90% e 100%, respectivamente. Conclui-se que o uso do exame parasitológico como padrão-ouro para validação de testes diagnósticos não é apropriado e que os indicadores de acurácia dos testes avaliados são insuficientes e não justificam que eles sejam usados isoladamente para diagnóstico da infecção com a finalidade de controle da doença.