MAPK and JAK-STAT pathways dysregulation in plasmablastic lymphoma

Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma with an immunoblastic/large-cell morphology and terminal B-cell differentiation. The differential diagnosis from Burkitt lymphoma, plasma cell myeloma and some variants of diffuse large B-cell lymphoma may be challenging because of the overlapping morphological, genetic and immunophenotypic features. Furthermore, the genomic landscape in PBL is not well known. To characterize the genetic and molecular heterogeneity of these tumors, we investigated 34 cases of PBL using an integrated approach, including fluorescence in situ hybridization, targeted sequencing of 94 B-cell lymphoma-related genes, and copy-number arrays. PBL were characterized by high genetic complexity including MYC translocations (87%), gains of 1q21.1-q44, trisomy 7, 8q23.2- q24.21, 11p13-p11.2, 11q14.2-q25, 12p and 19p13.3-p13.13, losses of 1p33, 1p31.1-p22.3, 13q and 17p13.3-p11.2, and recurrent mutations of STAT3 (37%), NRAS and TP53 (33%), MYC and EP300 (19%) and CARD11, SOCS1 and TET2 (11%). Pathway enrichment analysis suggested a cooperative action between MYC alterations and MAPK (49%) and JAK-STAT (40%) signaling pathways. Of note, Epstein-Barr virus (EBV)-negative PBL cases had higher mutational and copy-number load and more frequent TP53, CARD11 and MYC mutations, whereas EBVpositive PBL tended to have more mutations affecting the JAK-STAT pathway. In conclusion, these findings further unravel the distinctive molecular heterogeneity of PBL identifying novel molecular targets and the different genetic profile of these tumors in relation to EBV infection.     

Development and evaluation of SOA-based AAL services in real-life environments: A case study and lessons learned

IntroThe proper use of ICT services can support seniors in living independently longer. While such services are starting to emerge, current proprietary solutions are often expensive, covering only isolated parts of seniors’ needs, and lack support for sharing information between services and between users. For developers, the challenge is that it is complex and time consuming to develop high quality, interoperable services, and new techniques are needed to simplify the development and reduce the development costs.This paper provides the complete view of the experiences gained in the MPOWER project with respect to using model-driven development (MDD) techniques for Service Oriented Architecture (SOA) system development in the Ambient Assisted Living (AAL) domain.MethodTo address this challenge, the approach of the European research project MPOWER (2006–2009) was to investigate and record the user needs, define a set of reusable software services based on these needs, and then implement pilot systems using these services. Further, a model-driven toolchain covering key development phases was developed to support software developers through this process. Evaluations were conducted both on the technical artefacts (methodology and tools), and on end user experience from using the pilot systems in trial sites.ResultsThe outcome of the work on the user needs is a knowledge base recorded as a Unified Modeling Language (UML) model. This comprehensive model describes actors, use cases, and features derived from these. The model further includes the design of a set of software services, including full trace information back to the features and use cases motivating their design. Based on the model, the services were implemented for use in Service Oriented Architecture (SOA) systems, and are publicly available as open source software. The services were successfully used in the realization of two pilot applications. There is therefore a direct and traceable link from the user needs of the elderly, through the service design knowledge base, to the service and pilot implementations.The evaluation of the SOA approach on the developers in the project revealed that SOA is useful with respect to job performance and quality. Furthermore, they think SOA is easy to use and support development of AAL applications. An important finding is that the developers clearly report that they intend to use SOA in the future, but not for all type of projects. With respect to using model-driven development in web services design and implementation, the developers reported that it was useful. However, it is important that the code generated from the models is correct if the full potential of MDD should be achieved.The pilots and their evaluation in the trial sites showed that the services of the platform are sufficient to create suitable systems for end users in the domain.ConclusionsA SOA platform with a set of reusable domain services is a suitable foundation for more rapid development and tailoring of assisted living systems covering reoccurring needs among elderly users. It is feasible to realize a tool-chain for model-driven development of SOA applications in the AAL domain, and such a tool-chain can be accepted and found useful by software developers.     

Collaboration between general hospitals and community health services in the care of suicide attempters in Norway: a longitudinal study

Background  

The aim of this paper was to study the collaboration between emergency departments (EDs) in general hospitals and community health services (CHS) in Norway when providing psychosocial care and aftercare to patients treated in EDs following a suicide attempt. We wanted to explore the extent to which quality indicators at the hospital level measured in 1999 and 2006 could predict the presence or absence of a chain of care structure in the CHS in 2006.     

Nasal ketamine for paediatric premedication

Ketamine in a dose of 6 mg · kg⁻¹ was nasally administered in 86 healthy children (ASA I and II), aged from two to five years undergoing elective general, urological or plastic surgery, 20 to 40 min before the scheduled surgery time. These children were compared with 62 others, also aged from two to five years, in whom promethazine and meperidine, 1 mg · kg⁻¹ of each, were injected im. Sedation was started as excellent in 48 and as adequate in 19 children in the ketamine group, compared with nine and 12 respectively in Group 2 (P < 0.05), while salivation was similar in both groups. We conclude that nasal ketamine is an alternative to im preanaesthetic sedation administration in children aged from two to five years. Vingt à quarante minutes avant la chirurgie, de la kétamine 6 mg · kg⁻¹ est administrée par voie nasale à 86 enfants en bonne santé (ASA I et II), agés de deux à cinq ans programmés pour une intervention urologique ou plastique non urgente sous anesthésie générale. On compare ces enfants à 62 autres enfants du même age, auxquels on a injecté par la voie i.m., soit de la mépéridine, soit de la prométhazine, à la dose de 1 mg · kg⁻¹. La sédation est jugée excellente pour 48 et adéquate pour 19 des enfants du groupe kétamine, comparativement à 9 et 12 des enfants du groupe 2 (P < 0,05), alors que la salivation est identique dans les deux groupes. Nous en concluons que la kétamine nasale est une alternative a la prémédication intramusculaire pour des enfants de deux à cinq ans.     

Premedication with metoclopramide decreases the frequency of methohexital induced hiccup

Metoclopramide is one of many drugs that have been recommended for the treatment of intractable hiccup. Methohexital may produce hiccup during induction of general anesthesia. 211 women received methohexital for induction and maintenance of general anesthesia for short gynaecological procedures. All the patients were premedicated with fentanyl, diazepam and atropine. 109 patients were randomly selected to receive metoclopramide before induction of anesthesia; the remaining 102 patients served as a control group, and were anesthetized without metoclopramide premedication. The frequency of hiccup was compared between the two groups. 7 patients had hiccup in the metoclopramide premedicated group, as compared to 17 patients in the control group. This difference was statistically significant. We conclude that metoclopramide reduces the frequency of methohexital induced hiccup, and recommend that metoclopramide be routinely used for the premedication of methohexital injection.(Stav A, Weksler N, Berman M: premedication with metcoclopramide decreases the frequency of methohexital induced hiccup. J Anesth 6: 17–20, 1992)     

Consumer-Based Activity Trackers as a Tool for Physical Activity Monitoring in Epidemiological Studies During the COVID-19 Pandemic: Development and Usability Study

BackgroundConsumer-based physical activity trackers have increased in popularity. The widespread use of these devices and the long-term nature of the recorded data provides a valuable source of physical activity data for epidemiological research. The challenges include the large heterogeneity between activity tracker models in terms of available data types, the accuracy of recorded data, and how this data can be shared between different providers and third-party systems.ObjectiveThe aim of this study is to develop a system to record data on physical activity from different providers of consumer-based activity trackers and to examine its usability as a tool for physical activity monitoring in epidemiological research. The longitudinal nature of the data and the concurrent pandemic outbreak allowed us to show how the system can be used for surveillance of physical activity levels before, during, and after a COVID-19 lockdown.MethodsWe developed a system (mSpider) for automatic recording of data on physical activity from participants wearing activity trackers from Apple, Fitbit, Garmin, Oura, Polar, Samsung, and Withings, as well as trackers storing data in Google Fit and Apple Health. To test the system throughout development, we recruited 35 volunteers to wear a provided activity tracker from early 2019 and onward. In addition, we recruited 113 participants with privately owned activity trackers worn before, during, and after the COVID-19 lockdown in Norway. We examined monthly changes in the number of steps, minutes of moderate-to-vigorous physical activity, and activity energy expenditure between 2019 and 2020 using bar plots and two-sided paired sample t tests and Wilcoxon signed-rank tests.ResultsCompared to March 2019, there was a significant reduction in mean step count and mean activity energy expenditure during the March 2020 lockdown period. The reduction in steps and activity energy expenditure was temporary, and the following monthly comparisons showed no significant change between 2019 and 2020. A small significant increase in moderate-to-vigorous physical activity was observed for several monthly comparisons after the lockdown period and when comparing March-December 2019 with March-December 2020.ConclusionsmSpider is a working prototype currently able to record physical activity data from providers of consumer-based activity trackers. The system was successfully used to examine changes in physical activity levels during the COVID-19 period.     

Sexual Orientation,Sexual Arousal,and Finger Length Ratios in Women

Archives of Sexual Behavior - In general, women show physiological sexual arousal to both sexes. However, compared with heterosexual women, homosexual women are more aroused to their preferred sex,...