Potentiometric and conductometric studies on the system acid-isopolytungstate and the formation of lanthanum tungstates

The stoichiometry of the polyanions formed by the action of nitric acid on sodium tungstate (< 0.01M) has been studied by means of electrometric techniques involving pH-potentiometric and conductometric titrations. The well defined inflections and breaks in the titration curves provide evidence for the existence of the polyanions, para-W12O41(10-) and meta-W12O39(6-) corresponding to the ratio of H+:WO4(2-) as 7:6 and 9:6 in the pH ranges 5.7-6.0 and 3.6-4.1, respectively. The interaction of lanthanum nitrate with sodium tungstate solutions, at specific pH levels 8.0, 5.9 and 4.0 was also studied by pH and conductometric titrations, in aqueous and alcoholic media, with each of the reagents alternatively used as titrant. The electrometric experiments provide definite evidence of the formation of normal-La2O3.3WO3, para-5La2O3.36WO3 and meta-La2O3.12WO3 tungstates in the vicinity of pH 6.3, 5.0 and 4.2, respectively. Analytical investigations on the precipitates formed confirm the results of the electrometric study.

Imaging of Dopamine and Serotonin Transporters. Pre-clinical Studies with Radiotracers for Positron Emission Tomography

The action of the neurotransmitters dopamine (DA) and serotonin (5-HT) at synapses is terminated by their rapid reuptake into presynaptic nerve endings via plasma membrane dopamine (DAT) and serotonin (SERT) transporters. Alterations in the function of these transporters have been suggested as a feature of several neurological and neuropsychiatric diseases, such as Parkinson’s disease (PD), depression, and anxiety. A suitable clinical method for studying these transporters non-invasively in vivo is positron emission tomography (PET) utilizing radiopharmaceuticals (tracers) labelled with short-lived positron-emitting radionuclides. The aim of this study was to evaluate in rats two novel radiotracers, [¹⁸F]beta -CFT-FP and ¹⁸FFMe-McN, for imaging DAT and SERT, respectively, using in vitro, ex vivo and in vivo methods. Substituting an N-methyl in [¹⁸F]beta-CFT, a well known DAT tracer, with a ¹⁸Ffluoropropyl group significantly changed the properties of the tracer. [¹⁸F]beta- CFT showed slow kinetics and metabolism, and a high specific uptake in the striatum, whereas [¹⁸F]beta-CFT-FP showed fast kinetics and metabolism, and a moderate specific uptake in the striatum. [¹⁸F]betaCFT-FP was selective for DAT; but [¹⁸F]beta-CFT also bound to the noradrenaline transporter. [¹⁸F]beta-CFT-FP may be a suitable PET tracer for imaging the striatal DAT sites, but a tracer with a higher affinity is needed for imaging extrastriatal DAT sites. In rats, ¹⁸FFMe-McN showed high target-to-non-target ratios, specificity and selectivity for SERT, but slow kinetics. However, ¹⁸FFMe-McN reveals potential for imaging SERT, at least in pre-clinical studies. In addition, the sensitivities of [¹⁸F]beta CFT and [¹⁸ F]FDOPA (a precursor of DA) for detecting mild nigrostriatal hypofunction were compared in an animal model of PD. The uptake of [¹⁸F]FDOPA was significantly affected by compensatory effects in dopaminergic cells, whereas [¹⁸F]beta-CFT was more sensitive and therefore more suitable for PET studies of mild dopaminergic symptoms. In conclusion, both novel tracers, [¹⁸F]-CFT-FP and ¹⁸FFMe-McN, have potential, but are not optimal PET tracers for DAT and SERT imaging in rats, respectively. [¹⁸F]beta-CFT is superior to [18F]FDOPA for imaging mild nigral lesions in rat brains.

Applications of graph transformation in tools for domain-specific modeling languages

The use of domain-specific languages (DSLs) has been proposed as an approach to cost-e ectively develop families of software systems in a restricted application domain. Domain-specific languages in combination with the accumulated knowledge and experience of previous implementations, can in turn be used to generate new applications with unique sets of requirements. For this reason, DSLs are considered to be an important approach for software reuse. However, the toolset supporting a particular domain-specific language is also domain-specific and is per definition not reusable. Therefore, creating and maintaining a DSL requires additional resources that could be even larger than the savings associated with using them. As a solution, di erent tool frameworks have been proposed to simplify and reduce the cost of developments of DSLs. Developers of tool support for DSLs need to instantiate, customize or configure the framework for a particular DSL. There are di erent approaches for this. An approach is to use an application programming interface (API) and to extend the basic framework using an imperative programming language. An example of a tools which is based on this approach is Eclipse GEF. Another approach is to configure the framework using declarative languages that are independent of the underlying framework implementation. We believe this second approach can bring important benefits as this brings focus to specifying what should the tool be like instead of writing a program specifying how the tool achieves this functionality. In this thesis we explore this second approach. We use graph transformation as the basic approach to customize a domain-specific modeling (DSM) tool framework. The contributions of this thesis includes a comparison of di erent approaches for defining, representing and interchanging software modeling languages and models and a tool architecture for an open domain-specific modeling framework that e ciently integrates several model transformation components and visual editors. We also present several specific algorithms and tool components for DSM framework. These include an approach for graph query based on region operators and the star operator and an approach for reconciling models and diagrams after executing model transformation programs. We exemplify our approach with two case studies MICAS and EFCO. In these studies we show how our experimental modeling tool framework has been used to define tool environments for domain-specific languages.

Transcriptional Profiling of Organ‐Specific Autoimmunity in Human

Our understanding of the pathogenesis of organ‐specific autoinflammation has been restricted by limited access to the target organs. Peripheral blood, however, as a preferred transportation route for immune cells, provides a window to assess the entire immune system throughout the body. Transcriptional profiling with RNA stabilizing blood collection tubes reflects in vivo expression profiles at the time the blood is drawn, allowing detection of the disease activity in different samples or within the same sample over time. The main objective of this Ph.D. study was to apply gene‐expression microarrays in the characterization of peripheral blood transcriptional profiles in patients with autoimmune diseases. To achieve this goal a custom cDNA microarray targeted for gene‐expression profiling of human immune system was designed and produced. Sample collection and preparation was then optimized to allow gene‐expression profiling from whole‐blood samples. To overcome challenges resulting from minute amounts of sample material, RNA amplification was successfully applied to study pregnancy related immunosuppression in patients with multiple sclerosis (MS). Furthermore, similar sample preparation was applied to characterize longitudinal genome‐wide expression profiles in children with type 1 diabetes (T1D) associated autoantibodies and eventually clinical T1D. Blood transcriptome analyses, using both the ImmunoChip cDNA microarray with targeted probe selection and genome‐wide Affymetrix U133 Plus 2.0 oligonucleotide array, enabled monitoring of autoimmune activity. Novel disease related genes and general autoimmune signatures were identified. Notably, down‐regulation of the HLA class Ib molecules in peripheral blood was associated with disease activity in both MS and T1D. Taken together, these studies demonstrate the potential of peripheral blood transcriptional profiling in biomedical research and diagnostics. Imbalances in peripheral blood transcriptional activity may reveal dynamic changes that are relevant for the disease but might be completely missed in conventional cross‐sectional studies.

In vivo imaging of vascular adhesion protein 1 - preclinical studies with positron emission tomography

The golden standard in nuclear medicine imaging of inflammation is the use of radiolabeled leukocytes. Although their diagnostic accuracy is good, the preparation of the leukocytes is both laborious and potentially hazardous for laboratory personnel. Molecules involved in leukocyte migration could serve as targets for the development of inflammation imaging agents. An excellent target would be a molecule that is absent or expressed at low level in normal tissues, but is induced or up-regulated at the site of inflammation. Vascular adhesion protein-1 (VAP-1) is a very promising target for in vivo imaging, since it is translocated to the endothelial cell surface when inflammation occurs. VAP-1 functions as an endothelial adhesion molecule that participates in leukocyte recruitment to inflamed tissues. Besides being an adhesion molecule, VAP-1 also has enzymatic activity. In this thesis, the targeting of VAP-1 was studied by using Gallium-68 (68Ga) labeled peptides and an Iodine-124 (124I) labeled antibody. The peptides were designed based on molecular modelling and phage display library searches. The new imaging agents were preclinically tested in vitro, as well as in vivo in animal models. The most promising imaging agent appeared to be a peptide belonging to the VAP-1 leukocyte ligand, Siglec-9 peptide. The 68Ga-labeled Siglec-9 peptide was able to detect VAP-1 positive vasculature in rodent models of sterile skin inflammation and melanoma by positron emission tomography. In addition to peptides, the 124I-labeled antibody showed VAP-1 specific binding both in vitro and in vivo. However, the estimated human radiation dose was rather high, and thus further preclinical studies in disease models are needed to clarify the value of this imaging agent. Detection of VAP-1 on endothelium was demonstrated in these studies and this imaging approach could be used in the diagnosis of inflammatory conditions as well as melanoma. These studies provide a proof-of-concept for PET imaging of VAP-1 and further studies are warranted.

Free Prostate-specific Antigen Forms and Kallikrein-related Peptidase 2: Tools for Prostate Cancer Diagnostics

Prostate-specific antigen (PSA) is a marker that is commonly used in estimating prostate cancer risk. Prostate cancer is usually a slowly progressing disease, which might not cause any symptoms whatsoever. Nevertheless, some cases of cancer are aggressive and need to be treated before they become life-threatening. However, the blood PSA concentration may rise also in benign prostate diseases and using a single total PSA (tPSA) measurement to guide the decision on further examinations leads to many unnecessary biopsies, over-detection, and overtreatment of indolent cancers which would not require treatment. Therefore, there is a need for markers that would better separate cancer from benign disorders, and would also predict cancer aggressiveness. The aim of this study was to evaluate whether intact and nicked forms of free PSA (fPSA-I and fPSA-N) or human kallikrein-related peptidase 2 (hK2) could serve as new tools in estimating prostate cancer risk. First, the immunoassays for fPSA-I and free and total hK2 were optimized so that they would be less prone to assay interference caused by interfering factors present in some blood samples. The optimized assays were shown to work well and were used to study the marker concentrations in the clinical sample panels. The marker levels were measured from preoperative blood samples of prostate cancer patients scheduled for radical prostatectomy. The association of the markers with the cancer stage and grade was studied. It was found that among all tested markers and their combinations especially the ratio of fPSA-N to tPSA and ratio of free PSA (fPSA) to tPSA were associated with both cancer stage and grade. They might be useful in predicting the cancer aggressiveness, but further follow-up studies are necessary to fully evaluate the significance of the markers in this clinical setting. The markers tPSA, fPSA, fPSA-I and hK2 were combined in a statistical model which was previously shown to be able to reduce unnecessary biopsies when applied to large screening cohorts of men with elevated tPSA. The discriminative accuracy of this model was compared to models based on established clinical predictors in reference to biopsy outcome. The kallikrein model and the calculated fPSA-N concentrations (fPSA minus fPSA-I) correlated with the prostate volume and the model, when compared to the clinical models, predicted prostate cancer in biopsy equally well. Hence, the measurement of kallikreins in a blood sample could be used to replace the volume measurement which is time-consuming, needs instrumentation and skilled personnel and is an uncomfortable procedure. Overall, the model could simplify the estimation of prostate cancer risk. Finally, as the fPSA-N seems to be an interesting new marker, a direct immunoassay for measuring fPSA-N concentrations was developed. The analytical performance was acceptable, but the rather complicated assay protocol needs to be improved until it can be used for measuring large sample panels.

The Finnish Paper Workers' Union at a crossroads: Labor union representativeness in a changing environment, 1980-2008

This thesis consists of four articles and an introductory section. The main research questions in all the articles refer to the changes in the representativeness of the Finnish Paper Workers' Union. Representativeness stands for the entire entity of external, internal, legal and reputational factors that enable the labor union to represent its members and achieve its goals. This concept is based on an extensive reading of quantitative and qualitative industrial relations literature, which includes works based on Marxist labor-capital relations (such as Hyman's industrial relations studies), and more recent union density studies as well as gender- and ethnic diversity-based 'union revitalization' studies. Müller-Jentsch's German studies of industrial relations have been of particular importance as well as Streeck's industrial unionism and technology studies. The concept of representativeness is an attempt to combine the insights of these diverse strands of literature and bring the scientific discussion of labor unions back to the core of a union's function: representing its members. As such, it can be seen as a theoretical innovation. The concept helps to acknowledge both the heterogeneity of the membership and the totality of a labor union organization. The concept of representativeness aims to move beyond notions of 'power'. External representativeness can be expressed through the position of the labor union in the industrial relations system and the economy. Internal representativeness focuses on the aspects of labor unions that relate to the function of the union as an association with members, such as internal democracy. Legal representativeness lies in the formal legal position of the union – its rights and instruments. This includes collective bargaining legislation, co-decision rules and industrial conflict legislation. Reputational representativeness is related to how the union is seen by other actors and the general public, and can be approximated using data on strike activity. All these aspects of representativeness are path-dependent, and show the results of previous struggles over issues. The concept of representativeness goes beyond notions of labor union power and symbolizes an attempt to bring back the focus of industrial relations studies to the union's basic function of representing its members. The first article shows in detail the industrial conflict of the Finnish paper industry in 2005. The intended focus was the issue of gender in the negotiations over a new collective agreement, but the focal point of the industrial conflict was the issue of outsourcing and how this should be organized. Also, the issue of continuous shifts as an issue of working time was very important. The drawn-out conflict can be seen as a struggle over principles, and under pressure the labor union had to concede ground on the aforementioned issues. The article concludes that in this specific conflict, the union represented its' female members to a lesser extent, because the other issues took such priority. Furthermore, because of the substantive concessions. the union lost some of its internal representativeness, and the stubbornness of the union may have even harmed the reputation of the union. This article also includes an early version of the representativeness framework, through which this conflict is analyzed. The second article discusses wage developments, union density and collective bargaining within the context of representativeness. It is shown that the union has been able to secure substantial benefits for its members, regardless of declining employment. Collective agreements have often been based on centralized incomes policies, but the paper sector has not always joined these. Attention is furthermore paid to the changing competition of the General Assembly, with a surprisingly strong position of the Left Alliance still. In an attempt to replicate analysis of union density measures, an analysis of sectoral union density shows that similar factors as in aggregate data influence this measure, though – due to methodological issues – the results may not be robust. On this issue, it can be said that the method of analysis for aggregate union density is not suitable for sectoral union density analysis. The increasingly conflict-ridden industrial relations predicted have not actually materialized. The article concludes by asking whether the aim of ever-increasing wages is a sustainable one in the light of the pressures of globalization, though wage costs are a relatively small part of total costs. The third article discusses the history and use of outsourcing in the Finnish paper industry. It is shown using Hyman's framework of constituencies that over time, the perspective of the union changed from 'members of the Paper Workers' Union' to a more specific view of who is a core member of the union. Within the context of the industrial unionism that the union claims to practice, this is an important change. The article shows that the union more and more caters for a core group, while auxiliary personnel is less important to the union's identity and constituencies, which means that the union's internal representativeness has decreased. Maintenance workers are an exception; the union and employers have developed a rotating system that increases the efficient allocation of these employees. The core reason of the exceptional status of maintenance personnel is their high level of non-transferable skills. In the end it is debatable whether the compromise on outsourcing solves the challenges facing the industry. The fourth article shows diverging discourses within the union with regard to union-employer partnership for competitiveness improvements and instruments of local union representatives. In the collective agreement of 2008, the provision regulating wage effects of significant changes in the organization or content of work was thoroughly changed, though this mainly reflected decisions by the Labor Court on the pre-2008 version of the provision. This change laid bare the deep rift between the Social Democratic and Left Alliance (ex-Communist) factions of the union. The article argues that through the changed legal meaning of the provision, the union was able to transform concession bargaining into a basis for partnership. The internal discontent about this issue is nonetheless substantial and a threat to the unity of the union, both locally and at the union level. On the basis of the results of the articles, other factors influencing representativeness, such as technology and EU law and an overview of the main changes in the Finnish paper industry, it is concluded that, especially in recent years, the Finnish Paper Workers' Union has lost some of its representativeness. In particular, the loss of the efficiency of strikes is noted, the compromise on outsourcing which may have alienated a substantial part of the union's membership, and the change in the collective agreement of 2008 have caused this decline. In the latter case, the internal disunion on that issue shows the constraints of the union's internal democracy. Furthermore, the failure of the union to join the TEAM industrial union (by democratic means), the internal conflicts and a narrow focus on its own sector may also hurt the union in the future, as the paper industry in Finland is going through a structural change. None of these changes in representativeness would have been so drastic without the considerable pressure of globalization - in particular changing markets, changing technology and a loss of domestic investments to foreign investments, which in the end have benefited the corporations more than the Finnish employees of these corporations. Taken together, the union risks becoming socially irrelevant in time, though it will remain formally very strong on the basis of its institutional setting and financial situation.

Endoscopic biliary procedures: studies on cannulation and stenting

Deep cannulation is a prerequisite for successful endoscopic retrograde cholangiopancreatography (ERCP) procedures. Of the biliary procedures, stenting is one of the most common. This study was carried out to investigate current and controversial issues regarding biliary cannulation and stenting. The double guidewire (DGW) technique was studied to analyze its safety and feasibility in biliary cannulation as a single procedure and as a part of the novel three-step cannulation protocol. Female gender was evaluated in regard to difficult cannulation. The use of an angled and a straight tipped guidewire in biliary cannulation was studied in a prospective, randomized trial. Additionally, the patency of the novel antireflux plastic biliary stent was compared to the patency of the conventional plastic biliary stent in a prospective, randomized setting. The DGW method seems safe and feasible as an alternative cannulation technique in biliary cannulation. Female gender was not associated significantly with difficult biliary cannulation in our study, although the cannulation times seemed to be longer and the alternative cannulation techniques seemed to be needed more often in females than males. According to the results of this thesis, an angled tipped guidewire may facilitate biliary cannulation. In controversy to the previous result presented in the literature, the antireflux plastic biliary stent tested herein should not be used, as the patency of the stent was significantly shorter compared to the conventional plastic stent.

Promoting Customer Loyalty Through a Telecommunication Specific CRM Framework

The objective of this thesis is to find new methods to promote customer loyalty in the telecommunication industry. The study was made on the appointment of Tecnotree Corporation, which operates in a telecommunication software business. This thesis comprises of a theoretical section, which includes the presentation of relevant theoretical background and of an empirical section, which is mostly based on interviews and professional opinions. One of the most important aspects of customer relationship management (CRM) is building customer loyalty. Telecommunication markets are becoming saturated in an increasing number of markets. Customer acquisition is no longer a way to grow; companies need to hold on to their existing customers. Companies are always looking for new ways to avoid churning customers. These new methods are searched from recent studies and they are discussed with marketing professionals from operators. Current CRM lacks the ability to extract data efficiently from databases. Social media’s utilization is also in its early stages. It contains a lot of possibilities, but also things that can be risky for companies. In order to obtain full advantage of the new methods companies are required to invest considerable amounts of time and money to develop new systems, but not all companies are ready for the change.

The Effects of Anesthetic Induced Loss of Consciousness on Quantitative Electroen Cephalogram, and Bispectral and Spectral Entropy Indices. Studies on Healthy Male

Changes in the electroencephalography (EEG) signal have been used to study the effects of anesthetic agents on the brain function. Several commercial EEG based anesthesia depth monitors have been developed to measure the level of the hypnotic component of anesthesia. Specific anesthetic related changes can be seen in the EEG, but still it remains difficult to determine whether the subject is consciousness or not during anesthesia. EEG reactivity to external stimuli may be seen in unconsciousness subjects, in anesthesia or even in coma. Changes in regional cerebral blood flow, which can be measured with positron emission tomography (PET), can be used as a surrogate for changes in neuronal activity. The aim of this study was to investigate the effects of dexmedetomidine, propofol, sevoflurane and xenon on the EEG and the behavior of two commercial anesthesia depth monitors, Bispectral Index (BIS) and Entropy. Slowly escalating drug concentrations were used with dexmedetomidine, propofol and sevoflurane. EEG reactivity at clinically determined similar level of consciousness was studied and the performance of BIS and Entropy in differentiating consciousness form unconsciousness was evaluated. Changes in brain activity during emergence from dexmedetomidine and propofol induced unconsciousness were studied using PET imaging. Additionally, the effects of normobaric hyperoxia, induced during denitrogenation prior to xenon anesthesia induction, on the EEG were studied. Dexmedetomidine and propofol caused increases in the low frequency, high amplitude (delta 0.5-4 Hz and theta 4.1-8 Hz) EEG activity during stepwise increased drug concentrations from the awake state to unconsciousness. With sevoflurane, an increase in delta activity was also seen, and an increase in alpha- slow beta (8.1-15 Hz) band power was seen in both propofol and sevoflurane. EEG reactivity to a verbal command in the unconsciousness state was best retained with propofol, and almost disappeared with sevoflurane. The ability of BIS and Entropy to differentiate consciousness from unconsciousness was poor. At the emergence from dexmedetomidine and propofol induced unconsciousness, activation was detected in deep brain structures, but not within the cortex. In xenon anesthesia, EEG band powers increased in delta, theta and alpha (8-12Hz) frequencies. In steady state xenon anesthesia, BIS and Entropy indices were low and these monitors seemed to work well in xenon anesthesia. Normobaric hyperoxia alone did not cause changes in the EEG. All of these results are based on studies in healthy volunteers and their application to clinical practice should be considered carefully.

Cardiac Troponin Specific Autoantibodies: Analytical Tools for Exploring Their Impact on Cardiac Troponin I Testing

Cardiac troponin (cTn) I and T are the recommended biomarkers for the diagnosis and risk stratification of patients with suspected acute coronary syndrome (ACS), a major cause of cardiovascular death and disability worldwide. It has recently been demonstrated that cTn-specific autoantibodies (cTnAAb) can negatively interfere with cTnI detection by immunoassays to the extent that cTnAAb-positive patients may be falsely designated as cTnI-negative. The aim of this thesis was to develop and optimize immunoassays for the detection of both cTnI and cTnAAb, which would eventually enable exploring the clinical impact of these autoantibodies on cTnI testing and subsequent patient management. The extent of cTnAAb interference in different cTnI assay configurations and the molecular characteristics of cTnAAbs were investigated in publications I and II, respectively. The findings showed that cTnI midfragment targeting immunoassays used predominantly in clinical practice are affected by cTnAAb interference which can be circumvented by using a novel 3+1-type assay design with three capture antibodies against the N-terminus, midfragment and C-terminus and one tracer antibody against the C-terminus. The use of this assay configuration was further supported by the epitope specificity study, which showed that although the midfragment is most commonly targeted by cTnAAbs, the interference basically encompasses the whole molecule, and there may be remarkable individual variation at the affected sites. In publications III and IV, all the data obtained in previous studies were utilized to develop an improved version of an existing cTnAAb assay and a sensitive cTnI assay free of this specific analytical interference. The results of the thesis showed that approximately one in 10 patients with suspected ACS have detectable amounts of cTnAAbs in their circulation and that cTnAAbs can inhibit cTnI determination when targeted against the binding sites of assay antibodies used in its immunological detection. In the light of these observations, the risk of clinical misclassification caused by the presence of cTnAAbs remains a valid and reasonable concern. Because the titers, affinities and epitope specificities of cTnAAbs and the concentration of endogenous cTnI determine the final effect of circulating cTnAAbs, appropriately sized studies on their clinical significance are warranted. The new cTnI and cTnAAb assays could serve as analytical tools for establishing the impact of cTnAAbs on cTnI testing and also for unraveling the etiology of cTn-related autoimmune responses.

Long-term habituation (LTH) in the crab Chasmagnathus: a model for behavioral and mechanistic studies of memory

A decade of studies on long-term habituation (LTH) in the crab Chasmagnathus is reviewed. Upon sudden presentation of a passing object overhead, the crab reacts with an escape response that habituates promptly and for at least five days. LTH proved to be an instance of associative memory and showed context, stimulus frequency and circadian phase specificity. A strong training protocol (STP) (³15 trials, intertrial interval (ITI) of 171 s) invariably yielded LTH, while a weak training protocol (WTP) (£10 trials, ITI = 171 s) invariably failed. STP was used with a presumably amnestic agent and WTP with a presumably hypermnestic agent. Remarkably, systemic administration of low doses was effective, which is likely to be due to the lack of an endothelial blood-brain barrier. LTH was blocked by inhibitors of protein and RNA synthesis, enhanced by protein kinase A (PKA) activators and reduced by PKA inhibitors, facilitated by angiotensin II and IV and disrupted by saralasin. The presence of angiotensins and related compounds in the crab brain was demonstrated. Diverse results suggest that LTH includes two components: an initial memory produced by spaced training and mainly expressed at an initial phase of testing, and a retraining memory produced by massed training and expressed at a later phase of testing (retraining). The initial memory would be associative, context specific and sensitive to cycloheximide, while the retraining memory would be nonassociative, context independent and insensitive to cycloheximide

Developmental norms for eight instruments used in the neuropsychological assessment of children: studies in Brazil

Norms for a battery of instruments, including Denckla's and Garfield's tests of Motor Persistence, Benton's Right-Left Discrimination, two recall modalities (Immediate and Delayed) of the Bender Test, Wechsler's Digit Span, the Color Span Test and the Human Figure Drawing Test, were developed for the neuropsychological assessment of children in the greater Rio de Janeiro area. Additionally, the behavior of each child was assessed with the Composite Teacher Rating Scale (Brito GNO and Pinto RCA (1991) Journal of Clinical and Experimental Neuropsychology, 13: 417-418). A total of 398 children (199 boys and 199 girls balanced for age) with a mean age of 9.3 years (SD = 2.8), who were attending a public school in Niterói, were the subjects of this study. Gender and age had significant effects on performance which depended on the instrument. Nonachievers performed worse than achievers in most neuropsychological tests. Comparison of our data to the available counterparts in the United States revealed that American children outperformed Brazilian children on the Right-Left Discrimination, Forward Digit Span, Color Span and Human Figure Drawing Tests. Further analysis showed that the neurobehavioral data consist of different factorial dimensions, including Human Body Representation, Motor Persistence of the Legs, Orbito-Orobuccal Motor Persistence, Attention-Memory, Visuospatial Memory, Neuropsychomotor Speed, Hyperactivity-Inattention, and Anxiety-Negative Socialization. We conclude that gender and age should be taken into account when using the normative data for most of the instruments studied in the present report. Furthermore, we stress the need for major changes in the Brazilian public school system in order to foster the development of secondary cognitive abilities in our children

Gender effects on esophageal motility

It has been suggested that there are no gender effects on esophageal motility. However, in previous studies the subjects did not perform multiple swallows and the quantitative features of esophageal contractions were not evaluated. In order to investigate the gender effects on esophageal motility we studied 40 healthy normal volunteers, 20 men aged 37 ± 15 years (mean ± SD), and 20 women aged 38 ± 14 years. We used the manometric method with an eight-lumen polyvinyl catheter and continuous perfusion. The upper and lower esophageal sphincter pressures were measured by the rapid pull-through method. With the catheter positioned with one lumen opening in the lower esophageal sphincter, and the others at 5, 10 and 15 cm above the sphincter, ten swallows of a 5-ml water bolus alternated with ten dry swallows were performed. Statistical analysis was done by the Student t-test and Mann-Whitney test. Gender differences (P<0.05) were observed for wet swallows in the duration of contractions 5 cm above the lower esophageal sphincter (men: 3.7 ± 0.2 s, women: 4.5 ± 0.3 s, mean ± SEM), and in the velocity of contractions from 15 to 10 cm above the lower esophageal sphincter (men: 4.7 ± 0.3 cm/s, women: 3.5 ± 0.2 cm/s). There was no difference (P>0.05) in sphincter pressure, duration and percentage of complete lower esophageal sphincter relaxation, amplitude of contractions, or in the number of failed, multipeaked and synchronous contractions. We conclude that gender may cause some differences in esophageal motility which, though of no clinical significance, should be taken into consideration when interpreting esophageal motility tests.

Amplification of 9q34 in childhood adrenocortical tumors: a specific feature unrelated to ethnic origin or living conditions

Adrenocortical tumors (ACT) in children under 15 years of age exhibit some clinical and biological features distinct from ACT in adults. Cell proliferation, hypertrophy and cell death in adrenal cortex during the last months of gestation and the immediate postnatal period seem to be critical for the origin of ACT in children. Studies with large numbers of patients with childhood ACT have indicated a median age at diagnosis of about 4 years. In our institution, the median age was 3 years and 5 months, while the median age for first signs and symptoms was 2 years and 5 months (N = 72). Using the comparative genomic hybridization technique, we have reported a high frequency of 9q34 amplification in adenomas and carcinomas. This finding has been confirmed more recently by investigators in England. The lower socioeconomic status, the distinctive ethnic groups and all the regional differences in Southern Brazil in relation to patients in England indicate that these differences are not important to determine 9q34 amplification. Candidate amplified genes mapped to this locus are currently being investigated and Southern blot results obtained so far have discarded amplification of the abl oncogene. Amplification of 9q34 has not been found to be related to tumor size, staging, or malignant histopathological features, nor does it seem to be responsible for the higher incidence of ACT observed in Southern Brazil, but could be related to an ACT from embryonic origin.