Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway.

Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants.

Abnormal Error Monitoring in Math-Anxious Individuals: Evidence from Error-Related Brain Potentials.

This study used event-related brain potentials to investigate whether math anxiety is related to abnormal error monitoring processing. Seventeen high math-anxious (HMA) and seventeen low math-anxious (LMA) individuals were presented with a numerical and a classical Stroop task. Groups did not differ in terms of trait or state anxiety. We found enhanced error-related negativity (ERN) in the HMA group when subjects committed an error on the numerical Stroop task, but not on the classical Stroop task. Groups did not differ in terms of the correct-related negativity component (CRN), the error positivity component (Pe), classical behavioral measures or post-error measures. The amplitude of the ERN was negatively related to participants" math anxiety scores, showing a more negative amplitude as the score increased. Moreover, using standardized low resolution electromagnetic tomography (sLORETA) we found greater activation of the insula in errors on a numerical task as compared to errors in a nonnumerical task only for the HMA group. The results were interpreted according to the motivational significance theory of the ERN.

An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES: To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING: We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS: Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION: Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

Regional differences of physical activity and sedentary behaviour in Swiss children are not explained by socio-demographics or the built environment.

OBJECTIVE: We evaluated whether regional differences in physical activity (PA) and sedentary behaviour (SB) existed along language boundaries within Switzerland and whether potential differences would be explained by socio-demographics or environmental characteristics. METHODS: We combined data of 611 children aged 4 to 7 years from four regional studies. PA and SB were assessed by accelerometers. Information about the socio-demographic background was obtained by questionnaires. Objective neighbourhood attributes could be linked to home addresses. Multivariate regression models were used to test associations between PA and SB and socio-demographic characteristics and neighbourhood attributes. RESULTS: Children from the German compared to the French-speaking region were more physically active and less sedentary (by 10-15 %, p < 0.01). Although German-speaking children lived in a more favourable environment and a higher socioeconomic neighbourhood (differences p < 0.001), these characteristics did not explain the differences in PA behaviour between French and German speaking. CONCLUSIONS: Factors related to the language region, which might be culturally rooted were among the strongest correlates of PA and SB among Swiss children, independent of individual, social and environmental factors.

Directional and fluctuating asymmetry in finger and a-b ridge counts in psychosis: a case-control study

Background: Several studies have reported alterations in finger and a-b ridge counts, and theirderived measures of asymmetry, in schizophrenia compared to controls. Because ridges are fully formed by the end of the second trimester, they may provide clues to disturbed early development. The aim of this study was to assess these measures in a sample of patients with psychosis and normal controls.Methods: Individuals with psychosis (n = 240), and normal controls (n = 228) were drawn from a catchment-area case-control study. Differences in finger and a-b ridge count and Fluctuating Asymmetry were assessed in three group comparisons (non-affective psychosis versus controls; affective psychosis versus controls; non-affective psychosis versus affective psychosis). The analyses were performed separately for males and females. Results: There were no significant group differences for finger nor a-b ridge counts. While there were no group difference for Directional Asymmetry, for Fluctuating Asymmetry measures men with non-affective psychosis had significantly higher fluctuating asymmetry of the index finger ridge count (a) when compared to controls (FA-correlation score, p = 0.02), and (b) when compared to affective psychosis (adjusted FA-difference score, p = 0.04). Conclusion: Overall, measures of finger and a-b ridge counts, and their derived measures of directional and fluctuating asymmetry were not prominent features of psychosis in this sample. While directional asymmetry in cerebral morphology is reduced in schizophrenia, this is not reflected in dermatoglyphic variables.

Blood pressure reductions following catheter-based renal denervation are not related to improvements in adherence to antihypertensive drugs measured by urine/plasma toxicological analysis.

Renal denervation can reduce blood pressure in patients with uncontrolled hypertension. The adherence to prescribed antihypertensive medication following renal denervation is unknown. This study investigated adherence to prescribed antihypertensive treatment by liquid chromatography-high resolution tandem mass spectrometry in plasma and urine at baseline and 6 months after renal denervation in 100 patients with resistant hypertension, defined as baseline office systolic blood pressure ≥140 mmHg despite treatment with ≥3 antihypertensive agents. At baseline, complete adherence to all prescribed antihypertensive agents was observed in 52 patients, 46 patients were partially adherent, and two patients were completely non-adherent. Baseline office blood pressure was 167/88 ± 19/16 mmHg with a corresponding 24-h blood pressure of 154/86 ± 15/13 mmHg. Renal denervation significantly reduced office and ambulatory blood pressure at 6-month follow-up by 15/5 mmHg (p < 0.001/p < 0.001) and 8/4 mmHg (p < 0.001/p = 0.001), respectively. Mean adherence to prescribed treatment was significantly reduced from 85.0 % at baseline to 80.7 %, 6 months after renal denervation (p = 0.005). The blood pressure decrease was not explained by improvements in adherence following the procedure. Patients not responding to treatment significantly reduced their drug intake following the procedure. Adherence was highest for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta blockers (>90 %) and lowest for vasodilators (21 %). In conclusion, renal denervation can reduce office and ambulatory blood pressure in patients with resistant hypertension despite a significant reduction in adherence to antihypertensive treatment after 6 months.

Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Parenteral methotrexate is an effective treatment for patients with Crohn's disease, but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC. METHODS: We performed a double-blind, placebo-controlled trial to evaluate the efficacy of parenteral methotrexate (25 mg/wk) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe from 2007 through 2013. Patients were given prednisone (10 to 40 mg/d) when the study began and were randomly assigned to groups (1:1) given placebo or methotrexate (intramuscularly or subcutaneously, 25 mg weekly) for 24 weeks. The primary end point was steroid-free remission (defined as a Mayo score ≤2 with no item >1 and complete withdrawal of steroids) at week 16. Secondary endpoints included clinical remission (defined as a Mayo clinical subscore ≤2 with no item >1) and endoscopic healing without steroids at weeks 16 and/or 24, remission without steroids at week 24, and remission at both weeks 16 and 24. RESULTS: Steroid-free remission at week 16 was achieved by 19 of 60 patients given methotrexate (31.7%) and 10 of 51 patients given placebo (19.6%)-a difference of 12.1% (95% confidence interval [CI]: -4.0% to 28.1%; P = .15). The proportion of patients in steroid-free clinical remission at week 16 was 41.7% in the methotrexate group and 23.5% in the placebo group, for a difference of 18.1% (95% CI: 1.1% to 35.2%; P = .04). The proportions of patients with steroid-free endoscopic healing at week 16 were 35% in the methotrexate group and 25.5% in the placebo group-a difference of 9.5% (95% CI: -7.5% to 26.5%; P = .28). No differences were observed in other secondary end points. More patients receiving placebo discontinued the study because of adverse events (47.1%), mostly caused by UC, than patients receiving methotrexate (26.7%; P = .03). A higher proportion of patients in the methotrexate group had nausea and vomiting (21.7%) than in the placebo group (3.9%; P = .006). CONCLUSIONS: In a randomized controlled trial, parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC. However, methotrexate induced clinical remission without steroids in a significantly larger percentage of patients, resulting in fewer withdrawals from therapy due to active UC. ClinicalTrials.gov ID NCT00498589.

Incidence and Outcome of Group B Streptococcal Sepsis in Infants in Switzerland.

The incidence and outcome of group B streptococcal (GBS) sepsis were assessed prospectively between September 2011 and February 2015 in all tertiary care pediatric hospitals of Switzerland. We describe a low incidence of GBS early-onset sepsis (0.12/1000 livebirths) and a predominance of GBS late-onset sepsis (0.36/1000 livebirths), a pattern that has not been reported in other countries.

The right dorsolateral prefrontal cortex prevents post-error slowing

Adjusting behavior following the detection of inappropriate actions allows flexible adaptation to task demands and environmental contingencies during goal-directed behaviors. Post-error behavioral adjustments typically consist in adopting more cautious response mode, which manifests as a slowing down of response speed. Although converging evidence involves the dorsolateral prefrontal cortex (DLPFC) in post-error behavioral adjustment, whether and when the left or right DLPFC is critical for post-error slowing (PES), as well as the underlying brain mechanisms, remain highly debated. To resolve these issues, we used single-pulse transcranial magnetic stimulation in healthy human adults to disrupt the left or right DLPFC selectively at various delays within the 30-180ms interval following false alarms commission, while participants preformed a standard visual Go/NoGo task. PES significantly increased after TMS disruption of the right, but not the left DLPFC at 150ms post-FA response. We discuss these results in terms of an involvement of the right DLPFC in reducing the detrimental effects of error detection on subsequent behavioral performance, as opposed to implementing adaptative error-induced slowing down of response speed.

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

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

Uma abordagem robusta de cálculo aplicada a um sistema potenciométrico de medida de concentrações hidrogeniônicas em soluções aquosas

The data analyzed in this work were generated following the methodology developed by Molina et al.(J. Electroanal. Chem., 1979) for the calibration of a potentiometric system of measurement of hydrogen-ion concentrations resulting from neutralizations, at 25 ºC, of acidic or alkaline solutions at constant ionic strength (0.1 mol.l-1) held with NaClO4. The observed data present a serious deviation in relation to the mathematical model derived from the Nernst equation, for pH values ranging from 3 to 11, where pH=-log[H+]. We show that the minimization of the sum of the absolute values of the residuals gives estimates that are not influenced by outlying values.

3D Surface Modeling From Point Clouds

The goal of this thesis is to implement software for creating 3D models from point clouds. Point clouds are acquired with stereo cameras, monocular systems or laser scanners. The created 3D models are triangular models or NURBS (Non-Uniform Rational B-Splines) models. Triangular models are constructed from selected areas from the point clouds and resulted triangular models are translated into a set of quads. The quads are further translated into an estimated grid structure and used for NURBS surface approximation. Finally, we have a set of NURBS surfaces which represent the whole model. The problem wasn’t so easy to solve. The selected triangular surface reconstruction algorithm did not deal well with noise in point clouds. To handle this problem, a clustering method is introduced for simplificating the model and removing noise. As we had better results with the smaller point clouds produced by clustering, we used points in clusters to better estimate the grids for NURBS models. The overall results were good when the point cloud did not have much noise. The point clouds with small amount of error had good results as the triangular model was solid. NURBS surface reconstruction performed well on solid models.

Effect of the structure of commercial poly(ethylene oxide-b-propylene oxide) demulsifier bases on the demulsification of water-in-crude oil emulsions: elucidation of the demulsification mechanism

Water-in-crude oil emulsions are formed during petroleum production and asphaltenes play an important role in their stabilization. Demulsifiers are added to destabilize such emulsions,however the demulsification mechanism is not completely known. In this paper, the performances of commercial poly(ethylene oxide-b-propylene oxide) demulsifiers were studied using synthetic water-in-oil emulsions and model-systems (asphaltenes in organic solvent). No change in the asphaltene aggregate size induced by the demulsifier was observed. The demulsification performance decreased as the asphaltene aggregate size increased, so it can be suggested that the demulsification mechanism is correlated to the voids between the aggregates adsorbed on the water droplets surface.

Design and Analysis of Forward Error Control Coding and Signaling for Guaranteeing QoS in Wireless Broadcast Systems

Broadcasting systems are networks where the transmission is received by several terminals. Generally broadcast receivers are passive devices in the network, meaning that they do not interact with the transmitter. Providing a certain Quality of Service (QoS) for the receivers in heterogeneous reception environment with no feedback is not an easy task. Forward error control coding can be used for protection against transmission errors to enhance the QoS for broadcast services. For good performance in terrestrial wireless networks, diversity should be utilized. The diversity is utilized by application of interleaving together with the forward error correction codes. In this dissertation the design and analysis of forward error control and control signalling for providing QoS in wireless broadcasting systems are studied. Control signaling is used in broadcasting networks to give the receiver necessary information on how to connect to the network itself and how to receive the services that are being transmitted. Usually control signalling is considered to be transmitted through a dedicated path in the systems. Therefore, the relationship of the signaling and service data paths should be considered early in the design phase. Modeling and simulations are used in the case studies of this dissertation to study this relationship. This dissertation begins with a survey on the broadcasting environment and mechanisms for providing QoS therein. Then case studies present analysis and design of such mechanisms in real systems. The mechanisms for providing QoS considering signaling and service data paths and their relationship at the DVB-H link layer are analyzed as the first case study. In particular the performance of different service data decoding mechanisms and optimal signaling transmission parameter selection are presented. The second case study investigates the design of signaling and service data paths for the more modern DVB-T2 physical layer. Furthermore, by comparing the performances of the signaling and service data paths by simulations, configuration guidelines for the DVB-T2 physical layer signaling are given. The presented guidelines can prove useful when configuring DVB-T2 transmission networks. Finally, recommendations for the design of data and signalling paths are given based on findings from the case studies. The requirements for the signaling design should be derived from the requirements for the main services. Generally, these requirements for signaling should be more demanding as the signaling is the enabler for service reception.

Professional development among educators pursuing a B.Ed. program in special education in Tanzania : a study of motives and perceived outcomes

Implementation of different policies and plans aiming at providing education for all is a challenge in Tanzania. The need for educators and professionals with relevant knowledge and qualifications in special education is substantial. Teacher education does not equip educators with sufficient knowledge and skills in special education and professional development programs in special education are few in number. Up to 2005 no degree programs in special education at university level were available in Tanzania. The B.Ed. Special Education program offered by the Open University of Tanzania in collaboration with Åbo Akademi University in Finland was one of the efforts aimed at addressing the big national need for teachers and other professionals with degree qualifications in special education. This pilot program offered unique possibilities to study professional development in Tanzania. The research group in this study consisted of the group of students who participated in the degree program 2005-2007. The study is guided by three theoretical perspectives: individual, social and societal. The individual perspective emphasizes psychological factors as motives, motivation, achievement, self-directed behavior and personal growth. Within social perspective, professional development is viewed as situated within the social and cultural context. The third perspective, the societal, focuses on change, reforms, innovations and transformation of school systems and societies. Accordingly, professional development is viewed as an individual, social and societal phenomenon. The overall aim of the study is to explore the participants’ motives for participating in a B.Ed. Special Education program and the perceived outcomes of the program in terms of professional development. In order to achieve the objectives of the study, a case study approach was adopted. Questionnaires and semi-structured interviews were administered in three waves between January 2007 and February 2009 to the 35 educators participating in the B.Ed. Special Education program. The findings of the study reveal that the participants expressed motives which were related to job performance, knowledge, skills, academic degree and career. Also altruistic motives were expressed by the participants in terms of helping and supporting students with special needs and their communities. The perceived outcomes of the program were in line with the expressed motives. However, the results indicate that the participants also learned new skills, as interaction skills and guidance and counseling skills. Increased self-confidence was also mentioned as an outcome. The participants also got deepened understanding of disability issues. In addition, they learned strategies for creating awareness of persons with disability in the communities. Thus the findings of the study indicate positive outcomes of the program in terms of professional development. The conclusion of the study is that individual, social and societal factors interact when it comes to explaining why Tanzanian educators in special education choose to pursue a degree program in special education. The individual motives, as increased knowledge and better prospects of career development interact with the social and societal motives to help and support vulnerable student groups. The study contributes to increased understanding of the complexity of professional development and of the realities educators meet when educational reforms are implemented in a developing country.