Fluorine MR Imaging of Inflammation in Atherosclerotic Plaque in Vivo.

PURPOSE: To preliminarily test the hypothesis that fluorine 19 ((19)F) magnetic resonance (MR) imaging enables the noninvasive in vivo identification of plaque inflammation in a mouse model of atherosclerosis, with histologic findings as the reference standard. MATERIALS AND METHODS: The animal studies were approved by the local animal ethics committee. Perfluorocarbon (PFC) emulsions were injected intravenously in a mouse model of atherosclerosis (n = 13), after which (19)F and anatomic MR imaging were performed at the level of the thoracic aorta and its branches at 9.4 T. Four of these animals were imaged repeatedly (at 2-14 days) to determine the optimal detection time. Repeated-measures analysis of variance with a Tukey test was applied to determine if there was a significant change in (19)F signal-to-noise ratio (SNR) of the plaques and liver between the time points. Six animals were injected with a PFC emulsion that also contained a fluorophore. As a control against false-positive results, wild-type mice (n = 3) were injected with a PFC emulsion, and atherosclerotic mice were injected with a saline solution (n = 2). The animals were sacrificed after the last MR imaging examination, after which high-spatial-resolution ex vivo MR imaging and bright-field and immunofluorescent histologic examination were performed. RESULTS: (19)F MR signal was detected in vivo in plaques in the aortic arch and its branches. The SNR was found to significantly increase up to day 6 (P < .001), and the SNR of all mice at this time point was 13.4 ± 3.3. The presence of PFC and plaque in the excised vessels was then confirmed both through ex vivo (19)F MR imaging and histologic examination, while no signal was detected in the control animals. Immunofluorescent histologic findings confirmed the presence of PFC in plaque macrophages. CONCLUSION: (19)F MR imaging allows the noninvasive in vivo detection of inflammation in atherosclerotic plaques in a mouse model of atherosclerosis and opens up new avenues for both the early detection of vulnerable atherosclerosis and the elucidation of inflammation mechanisms in atherosclerosis.

Problems of the randomization test for AB designs

N = 1 designs imply repeated registrations of the behaviour of the same experimental unit and the measurements obtained are often few due to time limitations, while they are also likely to be sequentially dependent. The analytical techniques needed to enhance statistical and clinical decision making have to deal with these problems. Different procedures for analysing data from single-case AB designs are discussed, presenting their main features and revising the results reported by previous studies. Randomization tests represent one of the statistical methods that seemed to perform well in terms of controlling false alarm rates. In the experimental part of the study a new simulation approach is used to test the performance of randomization tests and the results suggest that the technique is not always robust against the violation of the independence assumption. Moreover, sensitivity proved to be generally unacceptably low for series lengths equal to 30 and 40. Considering the evidence available, there does not seem to be an optimal technique for single-case data analysis

Päätöspuun käyttö tutkamaalien initialisoinnissa

Suomen ilmatilaa valvotaan reaaliaikaisesti, pääasiassa ilmavalvontatutkilla. Ilmatilassa on lentokoneiden lisäksi paljon muitakin kohteita, jotka tutka havaitsee. Tutka lähettää nämä tiedot edelleen ilmavalvontajärjestelmään. Ilmavalvontajärjestelmä käsittelee tiedot, sekä lähettää ne edelleen esitysjärjestelmään. Esitysjärjestelmässä tiedot esitetään synteettisinä merkkeinä, seurantoina joista käytetään nimitystä träkki. Näiden tietojen puitteissa sekä oman ammattitaitonsa perusteella ihmiset tekevät päätöksiä. Tämän työn tarkoituksena on tutkia tutkan havaintoja träkkien initialisointipisteessä siten, että voitaisiin määritellä tyypillinen rakenne sille mikä on oikea ja mikä väärä tai huono träkki. Tämän lisäksi tulisi ennustaa, mitkä Irakeista eivät aiheudu ilma- aluksista. Saadut tulokset voivat helpottaa työtä havaintojen tulkinnassa - jokainen lintuparvi ei ole ehdokas seurannaksi. Havaintojen luokittelu voidaan tehdä joko neurolaskennalla tai päätöspuulla. Neurolaskenta tehdään neuroverkoilla, jotka koostuvat neuroneista. Päätöspuu- luokittelijat ovat oppivia tietorakenteita kuten neuroverkotkin. Yleisin päätöpuu on binääripuu. Tämän työn tavoitteena on opettaa päätöspuuluokittelija havaintojen avulla siten, että se pystyy luokittelemaan väärät havainnot oikeista. Neurolaskennan mahdollisuuksia tässä työssä ei käsitellä kuin teoreettisesti. Työn tuloksena voi todeta, että päätöspuuluokittelijat ovat erittäin kykeneviä erottamaan oikeat havainnot vääristä. Vaikka tulokset olivat rohkaiseva, lisää tutkimusta tarvitaan määrittelemään luotettavammin tekijät, jotka parhaiten suorittavat luokittelun.

Screening for ALK in non-small cell lung carcinomas: 5A4 and D5F3 antibodies perform equally well, but combined use with FISH is recommended.

OBJECTIVES: Immunohistochemistry (IHC) has become a promising method for pre-screening ALK-rearrangements in non-small cell lung carcinomas (NSCLC). Various ALK antibodies, detection systems and automated immunostainers are available. We therefore aimed to compare the performance of the monoclonal 5A4 (Novocastra, Leica) and D5F3 (Cell Signaling, Ventana) antibodies using two different immunostainers. Additionally we analyzed the accuracy of prospective ALK IHC-testing in routine diagnostics. MATERIALS AND METHODS: Seventy-two NSCLC with available ALK FISH results and enriched for FISH-positive carcinomas were retrospectively analyzed. IHC was performed on BenchMarkXT (Ventana) using 5A4 and D5F3, respectively, and additionally with 5A4 on Bond-MAX (Leica). Data from our routine diagnostics on prospective ALK-testing with parallel IHC, using 5A4, and FISH were available from 303 NSCLC. RESULTS: All three IHC protocols showed congruent results. Only 1/25 FISH-positive NSCLC (4%) was false negative by IHC. For all three IHC protocols the sensitivity, specificity, positive (PPV) and negative predictive values (NPV) compared to FISH were 96%, 100%, 100% and 97.8%, respectively. In the prospective cohort 3/32 FISH-positive (9.4%) and 2/271 FISH-negative (0.7%) NSCLC were false negative and false positive by IHC, respectively. In routine diagnostics the sensitivity, specificity, PPV and NPV of IHC compared to FISH were 90.6%, 99.3%, 93.5% and 98.9%, respectively. CONCLUSIONS: 5A4 and D5F3 are equally well suited for detecting ALK-rearranged NSCLC. BenchMark and BOND-MAX immunostainers can be used for IHC with 5A4. True discrepancies between IHC and FISH results do exist and need to be addressed when implementing IHC in an ALK-testing algorithm.

Postmortem angiography using femoral cannulation and postmortem microbiology.

Despite the undeniable advantages of postmortem angiography, numerous questions have arisen concerning the influence that the injected contrast media may exercise on biological fluids and tissues collected for toxicological and biochemical investigations. Moreover, cardiac blood for microbiological investigations cannot be obtained post-angiography. In this study, we examined whether the peripheral blood collected prior to postmortem angiography, using percutaneous access to femoral vessels after skin surface disinfection, could be suitable for microbiological investigations when postmortem angiography with femoral vessel cannulation is also performed. A total of 66 cases were included in the study and were divided into two subgroups (angiography and bacteriology group, 33 cases and control group, 33 cases). Autopsies, histology, toxicology, bacteriology, and biochemical investigations (procalcitonin, C-reactive protein, interleukin-6, and soluble triggering receptors expressed on myeloid cells type 1) were performed in all cases. No statistically significant differences between the two groups were noted, and identified category distribution (death unrelated to infection, true infection, false positive, and undetermined) was rather similar in both studied populations. These preliminary results suggest that postmortem angiography using a femoral approach does not constitute an impediment to the collection of peripheral blood for microbiology and vice versa. Moreover, the use of femoral blood for microbiology does not lead to an increased risk of doubtful results.

Energiankäytön kartoitus Lappeenrannan sementtitehtaalla.

Diplomityön tavoitteena oli kartoittaa Finnsementti Oy:n Lappeenrannan sementtitehtaan energiankäyttöä ja etsiä potentiaalisia energiansäästökohteita. Diplomityö liittyy Kauppa- ja teollisuusministeriön ja Teollisuuden ja Työnantajain Keskusliiton väliseen teollisuuden energiankäytön tehostamiseen tähtäävään puitesopimukseen, johon Finnsementti Oy on liittynyt. Diplomityön teoriaosassa tutustutaan sementin kemiaan raaka-aineista valmiisiin tuotteisiin. Lisäksi kartoitetaan sementtiteollisuuden energiansäästömahdollisuuksia laite-hankintojen ja prosessin optimointinnin kannalta. Työssä tutustutaan sementin-valmistuksessa käytettäviin laitteistoihin ja selvitetään niiden teknistä kehitystä ja energiaasäästäviä ratkaisuja. Kokeellinen osuus alkaa yksityiskohtaisella kuvauksella Lappeenrannan sementtitehtaan valmistusprosessista. Kokeellisessa osassa tutustutaan tehtaan energiankulutukseen sähkön ja polttoaineen muodossa. Lisäksi käsitellään paineilmaa ja vettä. Sähkön osalta kokeellinen osa sisältää sähkönkulutuksen historian ja sähkönjakeluverkon selvityksen lisäksi tehtaalla käytössä olevien luokittimien tehokkuustarkasteluita sähkönkulutuksen kannalta. Polttoaineen osalta diplomityö sisältää sementtiuunien energiataseiden mittaukset ja tulosten laskemisen sekä Excel-pohjaisen menetelmän kehittämisen energiataseiden laskemiseksi tulevaisuudessa. Paineilman ja veden osalta selvitetään niiden kulutusta tehtaalla ja lasketaan paineilmalle teoreettinen ominaissähkönkulutus. Luokittimien tehokkuustarkastelujen osalta havaittiin raakamyllyn luokittimen erottelu-terävyyden olevan huono verrattuna nykyaikaisiin korkeatehokkuusluokittimiin. Sementtimyllyjen luokittimien toiminnasta ei havaittu merkittäviä ongelmia. Energia-taseiden tuloksina havaittiin Lappeenrannan sementtitehtaan sementtiuunien edustavan vanhentunutta sementinvalmistustekniikkaa. Molempien uunien savukaasukanavien vuotoilmojen määrien havaittiin olevan suuret. Energiataloutta pystyttäisiin parantamaan mm. uusilla polttimilla, jolloin lämmittämättömän ensiöilman osuutta saataisiin pienentymään ja polttoaineen polttoa tehostumaan. Paineilman suhteen havaittiin kuumailman paineenalennuksen aiheuttavan turhia energiahäviöitä.

On the Adoption of Partial Least Squares in Psychological Research: Caveat Emptor

The partial least squares technique (PLS) has been touted as a viable alternative to latent variable structural equation modeling (SEM) for evaluating theoretical models in the differential psychology domain. We bring some balance to the discussion by reviewing the broader methodological literature to highlight: (1) the misleading characterization of PLS as an SEM method; (2) limitations of PLS for global model testing; (3) problems in testing the significance of path coefficients; (4) extremely high false positive rates when using empirical confidence intervals in conjunction with a new "sign change correction" for path coefficients; (5) misconceptions surrounding the supposedly superior ability of PLS to handle small sample sizes and non-normality; and (6) conceptual and statistical problems with formative measurement and the application of PLS to such models. Additionally, we also reanalyze the dataset provided by Willaby et al. (2015; doi:10.1016/j.paid.2014.09.008) to highlight the limitations of PLS. Our broader review and analysis of the available evidence makes it clear that PLS is not useful for statistical estimation and testing.

Toimintolaskennan soveltuminen Fingrid Verkko Oy:n kustannuslaskentaan

Tutkimuksen tavoitteena oli selvittää toimintolaskennan soveltuvuus esimerkkiyritykseen. Lähtökohtana oli kiinteiden kustannusten kohdistaminen tuotteille ja tuotekustannusten parempi hallinta.Lopputuloksiin on tässä casetutkimuksessa ennen kaikkea päästy kyseisen Fingrid Verkko Oy:n nykyistä laskentaa tutkimalla. Toimintolaskentakirjallisuuden ja artikkeleiden pohjalta laadittiin teoriaosuus, minkä tarkoituksena oli antaa riittävää tietoa yritykselle toimintolaskennasta sekä sen soveltamisesta. Tutkimuksessa päädyttiin kahteen merkittävään lopputulokseen. Ensinnäkin siihen, että toimintoperusteinen kustannuslaskentaa ei voida toteuttaa yrityksessä pilottiprojektin omaisesti kohdistettuna yksittäiseen tuotteeseen. Haluttaessa kertaluontoisesti jälkilaskennalla testata toimintolaskennan tuotteiden kannattavuuksia, täytyy koko yrityksen ja tässä tapauksessa myös konsernin osallistua projektiin. Toiseksi toimintolaskennan todettiin olevan yleensäkin epäsopiva yritykselle. Huomioitavaa on yrityksen prosessin luonne, jossa jokainen tuote on erillinen tilaus tai projekti. Yrityksen kustannuslaskentaa tulee kuitenkin kehittää, ratkaisu tähän voisi olla nykyisen laskentatavan tarkentaminen siten että kiinteistä kustannuksista osa saataisiin kohdennettua resurssien ajankäytön mukaan nykyisille kustannuspaikoille.

Feature Selection, Ranking of Each Feature and Classification for the Diagnosis of Community Acquired Legionella Pneumonia

Diagnosis of community acquired legionella pneumonia (CALP) is currently performed by means of laboratory techniques which may delay diagnosis several hours. To determine whether ANN can categorize CALP and non-legionella community-acquired pneumonia (NLCAP) and be standard for use by clinicians, we prospectively studied 203 patients with community-acquired pneumonia (CAP) diagnosed by laboratory tests. Twenty one clinical and analytical variables were recorded to train a neural net with two classes (LCAP or NLCAP class). In this paper we deal with the problem of diagnosis, feature selection, and ranking of the features as a function of their classification importance, and the design of a classifier the criteria of maximizing the ROC (Receiving operating characteristics) area, which gives a good trade-off between true positives and false negatives. In order to guarantee the validity of the statistics; the train-validation-test databases were rotated by the jackknife technique, and a multistarting procedure was done in order to make the system insensitive to local maxima.

Regression-based techniques for statistical decision making in single-case designs

The present study evaluates the performance of four methods for estimating regression coefficients used to make statistical decisions regarding intervention effectiveness in single-case designs. Ordinary least squares estimation is compared to two correction techniques dealing with general trend and one eliminating autocorrelation whenever it is present. Type I error rates and statistical power are studied for experimental conditions defined by the presence or absence of treatment effect (change in level or in slope), general trend, and serial dependence. The results show that empirical Type I error rates do not approximate the nominal ones in presence of autocorrelation or general trend when ordinary and generalized least squares are applied. The techniques controlling trend show lower false alarm rates, but prove to be insufficiently sensitive to existing treatment effects. Consequently, the use of the statistical significance of the regression coefficients for detecting treatment effects is not recommended for short data series.

Impact of round-the-clock CSF Gram stain on empirical therapy for suspected central nervous system infections.

The impact of round-the-clock cerebrospinal fluid (CSF) Gram stain on overnight empirical therapy for suspected central nervous system (CNS) infections was investigated. All consecutive overnight CSF Gram stains between 2006 and 2011 were included. The impact of a positive or a negative test on empirical therapy was evaluated and compared to other clinical and biological indications based on institutional guidelines. Bacterial CNS infection was documented in 51/241 suspected cases. Overnight CSF Gram stain was positive in 24/51. Upon validation, there were two false-positive and one false-negative results. The sensitivity and specificity were 41 and 99 %, respectively. All patients but one had other indications for empirical therapy than Gram stain alone. Upon obtaining the Gram result, empirical therapy was modified in 7/24, including the addition of an appropriate agent (1), addition of unnecessary agents (3) and simplification of unnecessary combination therapy (3/11). Among 74 cases with a negative CSF Gram stain and without formal indication for empirical therapy, antibiotics were withheld in only 29. Round-the-clock CSF Gram stain had a low impact on overnight empirical therapy for suspected CNS infections and was associated with several misinterpretation errors. Clinicians showed little confidence in CSF direct examination for simplifying or withholding therapy before definite microbiological results.

Decreasing Proportion of Recent Infections among Newly Diagnosed HIV-1 Cases in Switzerland, 2008 to 2013 Based on Line-Immunoassay-Based Algorithms.

BACKGROUND: HIV surveillance requires monitoring of new HIV diagnoses and differentiation of incident and older infections. In 2008, Switzerland implemented a system for monitoring incident HIV infections based on the results of a line immunoassay (Inno-Lia) mandatorily conducted for HIV confirmation and type differentiation (HIV-1, HIV-2) of all newly diagnosed patients. Based on this system, we assessed the proportion of incident HIV infection among newly diagnosed cases in Switzerland during 2008-2013. METHODS AND RESULTS: Inno-Lia antibody reaction patterns recorded in anonymous HIV notifications to the federal health authority were classified by 10 published algorithms into incident (up to 12 months) or older infections. Utilizing these data, annual incident infection estimates were obtained in two ways, (i) based on the diagnostic performance of the algorithms and utilizing the relationship 'incident = true incident + false incident', (ii) based on the window-periods of the algorithms and utilizing the relationship 'Prevalence = Incidence x Duration'. From 2008-2013, 3'851 HIV notifications were received. Adult HIV-1 infections amounted to 3'809 cases, and 3'636 of them (95.5%) contained Inno-Lia data. Incident infection totals calculated were similar for the performance- and window-based methods, amounting on average to 1'755 (95% confidence interval, 1588-1923) and 1'790 cases (95% CI, 1679-1900), respectively. More than half of these were among men who had sex with men. Both methods showed a continuous decline of annual incident infections 2008-2013, totaling -59.5% and -50.2%, respectively. The decline of incident infections continued even in 2012, when a 15% increase in HIV notifications had been observed. This increase was entirely due to older infections. Overall declines 2008-2013 were of similar extent among the major transmission groups. CONCLUSIONS: Inno-Lia based incident HIV-1 infection surveillance proved useful and reliable. It represents a free, additional public health benefit of the use of this relatively costly test for HIV confirmation and type differentiation.

Clinico-Pathological discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n ¼ 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.

Fluoroscopic-Guided Radial Endobronchial Ultrasound Without Guide Sheath For Peripheral Pulmonary Lesions: A Safe And Efficient Combination.

BACKGROUND: Several guidelines recommend computed tomography scans for populations with high-risk for lung cancer. The number of individuals evaluated for peripheral pulmonary lesions (PPL) will probably increase, and with it non-surgical biopsies. Associating a guidance method with a target confirmation technique has been shown to achieve the highest diagnostic yield, but the utility of bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy as guidance without a guide sheath has not been reported. METHODS: We conducted a retrospective analysis of bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy procedures for the investigation of PPL performed by experienced bronchoscopists with no specific previous training in this particular technique. Operator learning curves and radiological predictors were assessed for all consecutive patients examined during the first year of application of the technique. RESULTS: Fifty-one PPL were investigated. Diagnostic yield and visualization yield were 72.5 and 82.3% respectively. The diagnostic yield was 64.0% for PPL ≤20mm, and 80.8% for PPL>20mm. No false-positive results were recorded. The learning curve of all diagnostic tools showed a DY of 72.7% for the first sub-group of patients, 81.8% for the second, 72.7% for the third, and 81.8% for the last. CONCLUSION: Bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy as guidance is safe and simple to perform, even without specific prior training, and diagnostic yield is high for PPL>and ≤20mm. Based on these findings, this method could be introduced as a first-line procedure for the investigation of PPL, particularly in centers with limited resources.

Clinico-Pathological discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n ¼ 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.