Dysmegakaryopoiesis predicting response to therapy in acute myeloid leukaemia. A histologic and clinical study

With standard induction therapy between 50 to 85% of patients with Acute Myeloid Leukaemia (AML) achieve Complete Remission (CR). We investigated whether any morphological feature of bone marrow (BM) plastic embedded biopsies could predict failure of therapy. We reviewed BM plastic embedded biopsies from 54 adult patients presenting with untreated AML. The main histologic parameters analysed were cellularity, dysmegakaryopoiesis (DysM), percentage of marrow blasts and fibrosis. CR was obtained in 34 of 49 treated patients (69%). The rate of CR was significantly lower in the group of patients presenting with DysM: CR was achieved in 54% of the 28 treated patients with DysM and in 90% of the 21 treated patients without DysM (p less than 0.02). Patients with DysM had a significantly lower blood count and bone marrow blasts at presentation. Median age was not significantly different in the 2 groups. Cellularity and fibrosis were not predictive. DysM may be the hallmark of an AML subgroup with distinct clinical behaviour and lower rate of CR with conventional therapy. DysM should be carefully looked for on BM marrow biopsies and aspirate from AML patients at diagnosis.

A modified structural stress method for fatigue assessment of welded structures

Fatigue life assessment of weldedstructures is commonly based on the nominal stress method, but more flexible and accurate methods have been introduced. In general, the assessment accuracy is improved as more localized information about the weld is incorporated. The structural hot spot stress method includes the influence of macro geometric effects and structural discontinuities on the design stress but excludes the local features of the weld. In this thesis, the limitations of the structural hot spot stress method are discussed and a modified structural stress method with improved accuracy is developed and verified for selected welded details. The fatigue life of structures in the as-welded state consists mainly of crack growth from pre-existing cracks or defects. Crack growth rate depends on crack geometry and the stress state on the crack face plane. This means that the stress level and shape of the stress distribution in the assumed crack path governs thetotal fatigue life. In many structural details the stress distribution is similar and adequate fatigue life estimates can be obtained just by adjusting the stress level based on a single stress value, i.e., the structural hot spot stress. There are, however, cases for which the structural stress approach is less appropriate because the stress distribution differs significantly from the more common cases. Plate edge attachments and plates on elastic foundations are some examples of structures with this type of stress distribution. The importance of fillet weld size and weld load variation on the stress distribution is another central topic in this thesis. Structural hot spot stress determination is generally based on a procedure that involves extrapolation of plate surface stresses. Other possibilities for determining the structural hot spot stress is to extrapolate stresses through the thickness at the weld toe or to use Dong's method which includes through-thickness extrapolation at some distance from the weld toe. Both of these latter methods are less sensitive to the FE mesh used. Structural stress based on surface extrapolation is sensitive to the extrapolation points selected and to the FE mesh used near these points. Rules for proper meshing, however, are well defined and not difficult to apply. To improve the accuracy of the traditional structural hot spot stress, a multi-linear stress distribution is introduced. The magnitude of the weld toe stress after linearization is dependent on the weld size, weld load and plate thickness. Simple equations have been derived by comparing assessment results based on the local linear stress distribution and LEFM based calculations. The proposed method is called the modified structural stress method (MSHS) since the structural hot spot stress (SHS) value is corrected using information on weld size andweld load. The correction procedure is verified using fatigue test results found in the literature. Also, a test case was conducted comparing the proposed method with other local fatigue assessment methods.

Microbial diagnosis of bloodstream infection: towards molecular diagnosis directly from blood.

When a bloodstream infection (BSI) is suspected, most of the laboratory results-biochemical and haematologic-are available within the first hours after hospital admission of the patient. This is not the case for diagnostic microbiology, which generally takes a longer time because blood culture, which is to date the reference standard for the documentation of the BSI microbial agents, relies on bacterial or fungal growth. The microbial diagnosis of BSI directly from blood has been proposed to speed the determination of the etiological agent but was limited by the very low number of circulating microbes during these paucibacterial infections. Thanks to recent advances in molecular biology, including the improvement of nucleic acid extraction and amplification, several PCR-based methods for the diagnosis of BSI directly from whole blood have emerged. In the present review, we discuss the advantages and limitations of these new molecular approaches, which at best complement the culture-based diagnosis of BSI.

Being Small for Gestational Age: Does it Matter for the Neurodevelopment of Premature Infants? A Cohort Study.

BACKGROUND: Whether being small for gestational age (SGA) increases the risk of adverse neurodevelopmental outcome in premature infants remains controversial. OBJECTIVE: to study the impact of SGA (birthweight < percentile 10) on cognition, behavior, neurodevelopmental impairment and use of therapy at 5 years old. METHODS: This population-based prospective cohort included infants born before 32 weeks of gestation. Cognition was evaluated with the K-ABC, and behavior with the Strengths and Difficulties Questionnaire (SDQ). Primary outcomes were cognitive and behavioral scores, as well as neurodevelopmental impairment (cognitive score < 2SD, hearing loss, blindness, or cerebral palsy). The need of therapy, an indirect indicator of neurodevelopmental impairment, was a secondary outcome. Linear and logistic regression models were used to analyze the association of SGA with neurodevelopment. RESULTS: 342/515 (76%) premature infants were assessed. SGA was significantly associated with hyperactivity scores of the SDQ (coefficient 0.81, p < 0.04), but not with cognitive scores, neurodevelopmental impairment or the need of therapy. Gestational age, socio-economic status, and major brain lesions were associated with cognitive outcome in the univariate and multivariate model, whereas asphyxia, sepsis and bronchopulmonary dysplasia were associated in the univariate model only. Severe impairment was associated with fetal tobacco exposition, asphyxia, gestational age and major brain lesions. Different neonatal factors were associated with the use of single or multiple therapies: children with one therapy were more likely to have suffered birth asphyxia or necrotizing enterocolitis, whereas the need for several therapies was predicted by major brain lesions. DISCUSSION: In this large cohort of premature infants, assessed at 5 years old with a complete panel of tests, SGA was associated with hyperactive behavior, but not with cognition, neurodevelopmental impairment or use of therapy. Birthweight <10th percentile alone does not appear to be an independent risk factor of neurodevelopmental adverse outcome in preterm children.

Effects of mergers and acquisitions in the paper industry

Paperiteollisuus on ollut perinteisesti fragmentoitunut toimiala, mutta viime vuosikymmenen aikana konsolidoitumisprosessi on kiihtynyt. Yrityskaupat ja fuusiot ovat muuttaneet paperiteollisuuden markkinarakennetta merkittävästi. Työn tavoitteena oli tutkia yleisesti markkinarakenteen vaikutusta liiketoiminnan tuloksiin sekä analysoida yrityskauppojen ja fuusioiden syitä, tuloksia ja rajoituksia. Tavoitteena oli myös tutkia paperiteollisuuden konsolidoitumisen vaikutuksia hintakehitykseen, hintaheilahteluihin ja kannattavuuteen. Keskeisenä syynä konsolidoitumiskehitykselle voidaan pitää uusien paperikoneiden huomattavaa investointikustannusten kasvua. Toinen tärkeä tekijä yhdentymiskehitykselle on se, että paperiteollisuus on saavuttanut elinkaaren kypsyysvaiheen Euroopassa, Pohjois-Amerikassa ja Japanissa. Yrityskauppojen ja fuusioiden motiiveja paperiteollisuudessa ovat mm. kasvu kypsillä markkinoilla, tarve parantaa taloudellista tulosta, mahdollisuus toimia globaalisti ja hyödyntää siitä saatavat edut tai mahdollisuus parempaan arvoketjun hallintaan. Näyttää siltä, että suurempien paperiteollisuusyritysten kannattavuus ei ole parempi kuin pienemmillä yrityksillä. Lisäksi useimmissa paperiteollisuuden yrityskaupoissa ja fuusioissa näyttäisi ostavan osapuolen kurssikehitys ilmoitusta seuraavana päivänä olevan negatiivinen.

From caging to rouse dynamics in polymer melts with intramolecular barriers: a critical test of the mode coupling theory

By means of computer simulations and solution of the equations of the mode coupling theory (MCT),we investigate the role of the intramolecular barriers on several dynamic aspects of nonentangled polymers. The investigated dynamic range extends from the caging regime characteristic of glass-formers to the relaxation of the chain Rouse modes. We review our recent work on this question,provide new results, and critically discuss the limitations of the theory. Solutions of the MCT for the structural relaxation reproduce qualitative trends of simulations for weak and moderate barriers. However, a progressive discrepancy is revealed as the limit of stiff chains is approached. This dis-agreement does not seem related with dynamic heterogeneities, which indeed are not enhanced by increasing barrier strength. It is not connected either with the breakdown of the convolution approximation for three-point static correlations, which retains its validity for stiff chains. These findings suggest the need of an improvement of the MCT equations for polymer melts. Concerning the relaxation of the chain degrees of freedom, MCT provides a microscopic basis for time scales from chain reorientation down to the caging regime. It rationalizes, from first principles, the observed deviations from the Rouse model on increasing the barrier strength. These include anomalous scaling of relaxation times, long-time plateaux, and nonmonotonous wavelength dependence of the mode correlators.

Implementation of CORBA interface in a wireless device

CORBA (Common Object Request Broker Architecture) on laajalle levinnyt ja teollisuudessa yleisesti käytetty hajautetun tietojenkäsittelyn arkkitehtuuri. CORBA skaalautuu eri kokoisiin tarpeisiin ja sitä voidaan hyödynntää myös sulautetuissa langattomissa laitteissa. Oleellista sulautetussa ympäristössä on rakentaa rajapinnat kevytrakenteisiksi, pysyviksi ja helposti laajennettaviksi ilman että yhteensopivuus aikaisempiin rajapintoihin olisi vaarassa. Langattomissa laitteissa resurssit, kuten muistin määrä ja prosessointiteho, ovat hyvin rajalliset, joten rajapinta tulee suunnitella ja toteuttaa optimaalisesti. Palveluiden tulee ottaa huomioon myös langattomuuden rajoitukset, kuten hitaat tiedonsiirtonopeudet ja tiedonsiirron yhteydettömän luonteen. Työssä suunniteltiin ja toteutettiin CORBA-rajapinta GSM-päätelaitteeseen, jonka on todettu täyttävän sille asetetut tavoitteet. Rajapinta tarjoaa kaikki yleisimmät GSM-terminaalin ominaisuudet ja on laajennettavissa tulevia tuotteita ja verkkotekniikoita varten. Laajennettavuutta saavutetaan esimerkiksi kuvaamalla terminaalin ominaisuudet yleisellä kuvauskielellä, kuten XML:lla (Extensible Markup Language).

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.

The Rose Bengal test in human brucellosis: a neglected test for the diagnosis of a neglected disease

Brucellosis is a highly contagious zoonosis affecting livestock and human beings. The human disease lacks pathognomonic symptoms and laboratory tests are essential for its diagnosis. However, most tests are difficult to implement in the areas and countries were brucellosis is endemic. Here, we compared the simple and cheap Rose Bengal Test (RBT) with serum agglutination, Coombs, competitive ELISA, Brucellacapt, lateral flow immunochromatography for IgM and IgG detection and immunoprecipitation with Brucella proteins. We tested 208 sera from patients with brucellosis proved by bacteriological isolation, 20 contacts with no brucellosis, and 1559 sera of persons with no recent contact or brucellosis symptoms. RBT was highly sensitive in acute and long evolution brucellosis cases and this related to its ability to detect IgM, IgG and IgA, to the absence of prozones, and to the agglutinating activity of blocking IgA at the pH of the test. RBT was also highly specific in the sera of persons with no contact with Brucella. No test in this study outperformed RBT, and none was fully satisfactory in distinguishing contacts from infected patients. When modified to test serum dilutions, a diagnostic titer >4 in RBT resulted in 87.4% sensitivity (infected patients) and 100% specificity (contacts). We discuss the limitations of serological tests in the diagnosis of human brucellosis, particularly in the more chronic forms, and conclude that simplicity and affordability of RBT make it close to the ideal test for small and understaffed hospitals and laboratories.

Present standards and future perspectives in the treatment of metastatic non-small cell lung cancer.

The development of novel effective immunotherapeutic agents and early clinical data hinting at significant activity in non-small cell lung cancer (NSCLC) has introduced yet another player in the field of management of advanced disease. At present, first-line cytotoxic chemotherapy is generally withheld pending results of molecular testing for any actionable genetic alteration that could lead to targeted treatment, and in their absence chemotherapy is prescribed as a default therapy. Phase III trials comparing head-to-head immune checkpoint inhibitors with standard platinum-based doublet chemotherapy are underway. Second-line chemotherapy is likewise being challenged in phase III trials, one of which having recently reported positive results in advanced squamous cell carcinoma. In tumors harboring actionable transforming genetic alterations such as EGFR mutations and ALK rearrangements, second- and third-generation inhibitors allow for multiple lines of targeted treatment beyond initial resistance, postponing the use of cytotoxic chemotherapy to very late lines of therapy. Chemotherapy as a longstanding but still present standard of care capable of prolonging survival, improving quality of life, and relieving symptoms sees its role increasingly restricted to clinical, immunological, and molecular subsets of patients where its activity and efficacy have never been tested prospectively.

The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study.

OBJECTIVE: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. PATIENTS AND METHODS: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. RESULTS: In all patients (Tall N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. CONCLUSIONS: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.

Accessibility, equity and the sharing of water resources

While the supply of water to dry or arid mountain regions has long been a major challenge, the on-going processes of climatic and socio-economic change currently affecting the hydrosystems of the Alps raise the spectre of renewed pressure on water resources and possible local shortages. In such a context, questions relating to fair distribution of water are all the more sensitive given the tendency to neglect the social dimension of sustainability. The present paper makes both a conceptual and empirical contribution to this debate by analysing a system of distribution that has a long experience of water scarcity management: the community governance models traditionally linked to the irrigation channels, or bisses, typical of the Swiss Alpine canton of Valais. More specifically, we evaluate these models in terms of accessibility and equity, characteristics that we use to operationalize the notion of 'fair distribution'. We examine these dimensions in three case studies with a view to highlighting the limitations of the aforementioned models. Indeed, despite their cooperative and endogenous nature, they tend to not only exclude certain members of the population, but also to reproduce rather than reduce social inequalities within the community. In general, these results challenge the rosy picture generally found in the literature relating to these community governance models.

Gamma Knife Surgery versus Linac for Brain Metastasis: Which Technique for Which Patient? Analysis of an Historical Cohort of 63 Consecutive Patients Harboring 130 Lesions

Objectives: We present the retrospective analysis of a single-institution experience for radiosurgery (RS) in brain metastasis (BM) with Gamma Knife (GK) and Linac. Methods: From July 2010 to July 2012, 28 patients (with 83 lesions) had RS with GK and 35 patients (with 47 lesions) with Linac. The primary outcome was the local progression-free survival (LPFS). The secondary outcome was the overall survival (OS). Apart a standard statistical analysis, we included a Cox regression model with shared frailty, to modulate the within-patient correlation (preliminary evaluation showed a significant frailty effect, meaning that the correlation within patient could be ignored). Results: The mean follow-up period was 11.7 months (median 7.9, 1.7-22.7) for GK and 18.1 (median 17, 7.5-28.7) for Linac. The median number of lesions per patient was 2.5 (1-9) in GK compared with 1 (1-3) in Linac. There were more radioresistant lesions (melanoma) and more lesions located in functional areas for the GK group. The median dose was 24 Gy (GK) compared with 20 Gy (Linac). The LPFS actuarial rate was as follows: for GK at 3, 6, 9, 12, and 17 months: 96.96, 96.96, 96.96, 88.1, and 81.5%, and remained stable till 32 months; for Linac at 3, 6, 12, 17, 24, and 33 months, it was 91.5, 91.5, 91.5, 79.9, 55.5, and 17.1%, respectively (p = 0.03, chi-square test). After the Cox regression analysis with shared frailty, the p-value was not statistically significant between groups. The median overall survival was 9.7 months for GK and 23.6 months for Linac group. Uni- and multivariate analysis showed a lower GPA score and noncontrolled systemic status were associated with lower OS. Cox regression analysis adjusting for these two parameters showed comparable OS rate. Conclusions: In this comparative report between GK and Linac, preliminary analysis showed that more difficult cases are treated by GK, with patients harboring more lesions, radioresistant tumors, and highly functional located. The groups look, in this sense, very heterogeneous at baseline. After a Cox frailty model, the LPFS rates seemed very similar (p < 0.05). The OS was similar, after adjusting for systemic status and GPA score (p < 0.05). The technical reasons for choosing GK instead of Linac were the anatomical location related to highly functional areas, histology, technical limitations of Linac movements, especially lower posterior fossa locations, or closeness of multiple lesions to highly functional areas optimal dosimetry with Linac

Ethnic identity construction in Chiapas: examining the role of higher intercultural education model = La construcción de la identidad étnica en Chiapas : examinando el rol de un modelo de educación superior intercultural

This study explored ethnic identity among 410 mestizo students who were attending one of three universities, which varied in their ethnic composition and their educative model. One of these universities was private and had mostly mestizo students such as the public one did. The third educative context, also public, had an intercultural model of education and the students were mixed among mestizo and indigenous. The Multigroup Ethnic Identity Measure (MEIM) was administered to high school students in order to compare their scores on ethnic identity and its components: affi rmation, belonging or commitment and exploration. Principle components factor analysis with varimax rotation and tests of mean group differences are performed. The results showed signifi cant differences between the studied groups. Scores on ethnic identity and its components were signifi cantly higher among mestizos group from University with intercultural model of education than mestizos from public and private universities of the same region. Implications of these fi ndings for education are considered, as they are the strengths as well as the limitations of this research

Quality of Qualitative Research in the Health Sciences : Analysis of the Common Criteria Present in 58 Assessment Guidelines by Expert Users

The number of qualitative research methods has grown substantially over the last twenty years, both in social sciences and, more recently, in the health sciences. This growth came with questions on the quality criteria needed to evaluate this work, and numerous guidelines were published. The latters include many discrepancies though, both in their vocabulary and construction. Many expert evaluators decry the absence of consensual and reliable evaluation tools. The authors present the results of an evaluation of 58 existing guidelines in 4 major health science fields (medicine and epidemiology; nursing and health education; social sciences and public health; psychology / psychiatry, research methods and organization) by expert users (article reviewers, experts allocating funds, editors, etc.). The results propose a toolbox containing 12 consensual criteria with the definitions given by expert users. They also indicate in which disciplinary field each type of criteria is known to be more or less essential. Nevertheless, the authors highlight the limitations of the criteria comparability, as soon as one focuses on their specific definitions. They conclude that each criterion in the toolbox must be explained to come to broader consensus and identify definitions that are consensual to all the fields examined and easily operational.