Autism Spectrum Disorders in Gender Dysphoric Children and Adolescents

Only case reports have described the co-occurrence of gender identity disorder (GID) and autism spectrum disorders (ASD). This study examined this co-occurrence using a systematic approach. Children and adolescents (115 boys and 89 girls, mean age 10.8, SD = 3.58) referred to a gender identity clinic received a standardized assessment during which a GID diagnosis was made and ASD suspected cases were identified. The Dutch version of the Diagnostic Interview for Social and Communication Disorders (10th rev., DISCO-10) was administered to ascertain ASD classifications. The incidence of ASD in this sample of children and adolescents was 7.8% (n = 16). Clinicians should be aware of co-occurring ASD and GID and the challenges it generates in clinical management

Ett Intelligent Beslutsstöd

Denna fallstudie syftar till att undersöka effekterna av ett intelligent beslutsstöd på beslutsprocessen i en konsultverksamhet. Vi har utvecklat ett intelligent beslutsstöd och sedan undersökt beslutsprocessen vid kompetensmatchning av konsulter och kundförfrågningar. Vår forskningsfråga är således: Hur kan beslutsprocessen vid kompetensmatchning påverkas av ett intelligent beslutsstöd i en konsultverksamhet? Det finns studier som visar effekten av ett vanligt beslutsstöd och beslutsforskaretror att mer utvecklade beslutsstöd har potential. Dock studeras inte denna typ av intelligent beslutsstöd vanligtvis i kombination med beslutsprocessen. Syftet med studien är att bidra till forskningsläget, på grund av bristen på forskning inom detta område. För att undersöka detta fall behövde vi samla in kvalitativa data, som gjordes med semistrukturerade intervjuer och observationer, före och efter införandet av ett intelligent beslutsstöd. När vi analyserade den insamlade datan användes en kvalitativ innehållsanalys för att hitta teman och kategorier, som vi sedan jämförde resultaten före och efter meden teoretisk referensram. Vi fann att det intelligenta beslutsstödet kunde tillgängliggöra informationen i beslutsprocessen som kunde frigöra tid. Utifrån det kunde tiden istället fokusera på utvärdering. Detta ledde till att beslutsprocessen blev mer rationell i tre av fyra steg. Avslutningsvis fann vi att det intelligenta beslutsstödet hjälpte beslutsprocessen att bli mer rationell.This case study aims to investigate the impact of an intelligent decision support system on the decisionmaking in a consulting firm. We have developed an intelligent decision support system and then investigated the decision-making when competence matching consultants and customer requests. Thus, our research question: How can the decision-making process when competence matching be affected by an intelligent decision support system in a consulting business? Studies shows the effect of an ordinary decision support system, and decision scientists thinks that more evolved decision support system has potential. However, this type of intelligent decision support system is not usually researched in combination with the decision-making process. The purpose of this study is to contribute to the gap of missing research in this area. To investigate this case, we needed to collect qualitative data, which was done with semi structured interviews and observations, before and after the introduction of the intelligent decision support system. When analyzing our data, we used a qualitative content analysis to find themes and categories, which we then compared the before and after results with theoretical input. We found that the intelligent decision support system could enable the information in the decisionmaking process which could make more time available. With that extra time, the focus of the time could shift to evaluation. This led the decision-making process to become more rational in three of four steps. In conclusion we found that the intelligent decision support system helped the decision-making process to become more rational

Ett Intelligent Beslutsstöd

Denna fallstudie syftar till att undersöka effekterna av ett intelligent beslutsstöd på beslutsprocessen i en konsultverksamhet. Vi har utvecklat ett intelligent beslutsstöd och sedan undersökt beslutsprocessen vid kompetensmatchning av konsulter och kundförfrågningar. Vår forskningsfråga är således: Hur kan beslutsprocessen vid kompetensmatchning påverkas av ett intelligent beslutsstöd i en konsultverksamhet? Det finns studier som visar effekten av ett vanligt beslutsstöd och beslutsforskaretror att mer utvecklade beslutsstöd har potential. Dock studeras inte denna typ av intelligent beslutsstöd vanligtvis i kombination med beslutsprocessen. Syftet med studien är att bidra till forskningsläget, på grund av bristen på forskning inom detta område. För att undersöka detta fall behövde vi samla in kvalitativa data, som gjordes med semistrukturerade intervjuer och observationer, före och efter införandet av ett intelligent beslutsstöd. När vi analyserade den insamlade datan användes en kvalitativ innehållsanalys för att hitta teman och kategorier, som vi sedan jämförde resultaten före och efter meden teoretisk referensram. Vi fann att det intelligenta beslutsstödet kunde tillgängliggöra informationen i beslutsprocessen som kunde frigöra tid. Utifrån det kunde tiden istället fokusera på utvärdering. Detta ledde till att beslutsprocessen blev mer rationell i tre av fyra steg. Avslutningsvis fann vi att det intelligenta beslutsstödet hjälpte beslutsprocessen att bli mer rationell.This case study aims to investigate the impact of an intelligent decision support system on the decisionmaking in a consulting firm. We have developed an intelligent decision support system and then investigated the decision-making when competence matching consultants and customer requests. Thus, our research question: How can the decision-making process when competence matching be affected by an intelligent decision support system in a consulting business? Studies shows the effect of an ordinary decision support system, and decision scientists thinks that more evolved decision support system has potential. However, this type of intelligent decision support system is not usually researched in combination with the decision-making process. The purpose of this study is to contribute to the gap of missing research in this area. To investigate this case, we needed to collect qualitative data, which was done with semi structured interviews and observations, before and after the introduction of the intelligent decision support system. When analyzing our data, we used a qualitative content analysis to find themes and categories, which we then compared the before and after results with theoretical input. We found that the intelligent decision support system could enable the information in the decisionmaking process which could make more time available. With that extra time, the focus of the time could shift to evaluation. This led the decision-making process to become more rational in three of four steps. In conclusion we found that the intelligent decision support system helped the decision-making process to become more rational

Ett Intelligent Beslutsstöd

Denna fallstudie syftar till att undersöka effekterna av ett intelligent beslutsstöd på beslutsprocessen i en konsultverksamhet. Vi har utvecklat ett intelligent beslutsstöd och sedan undersökt beslutsprocessen vid kompetensmatchning av konsulter och kundförfrågningar. Vår forskningsfråga är således: Hur kan beslutsprocessen vid kompetensmatchning påverkas av ett intelligent beslutsstöd i en konsultverksamhet? Det finns studier som visar effekten av ett vanligt beslutsstöd och beslutsforskare tror att mer utvecklade beslutsstöd har potential. Dock studeras inte denna typ av intelligent beslutsstöd vanligtvis i kombination med beslutsprocessen. Syftet med studien är att bidra till forskningsläget, på grund av bristen på forskning inom detta område. För att undersöka detta fall behövde vi samla in kvalitativa data, som gjordes med semistrukturerade intervjuer och observationer, före och efter införandet av ett intelligent beslutsstöd. När vi analyserade den insamlade datan användes en kvalitativ innehållsanalys för att hitta teman och kategorier, som vi sedan jämförde resultaten före och efter med en teoretisk referensram. Vi fann att det intelligenta beslutsstödet kunde tillgängliggöra informationen i beslutsprocessen som kunde frigöra tid. Utifrån det kunde tiden istället fokusera på utvärdering. Detta ledde till att beslutsprocessen blev mer rationell i tre av fyra steg. Avslutningsvis fann vi att det intelligenta beslutsstödet hjälpte beslutsprocessen att bli mer rationell.This case study aims to investigate the impact of an intelligent decision support system on the decisionmaking in a consulting firm. We have developed an intelligent decision support system and then investigated the decision-making when competence matching consultants and customer requests. Thus, our research question: How can the decision-making process when competence matching be affected by an intelligent decision support system in a consulting business? Studies shows the effect of an ordinary decision support system, and decision scientists thinks that more evolved decision support system has potential. However, this type of intelligent decision support system is not usually researched in combination with the decision-making process. The purpose of this study is to contribute to the gap of missing research in this area. To investigate this case, we needed to collect qualitative data, which was done with semi structured interviews and observations, before and after the introduction of the intelligent decision support system. When analyzing our data, we used a qualitative content analysis to find themes and categories, which we then compared the before and after results with theoretical input. We found that the intelligent decision support system could enable the information in the decisionmaking process which could make more time available. With that extra time, the focus of the time could shift to evaluation. This led the decision-making process to become more rational in three of four steps. In conclusion we found that the intelligent decision support system helped the decision-making process to become more rational

Identification of HDAC10 Inhibitors that Modulate Autophagy in Transformed Cells

Histone deacetylases (HDACs) are a family of 18 epigenetic modifiers that fall into 4 classes. Histone deacetylase inhibitors (HDACi) are valid tools to assess HDAC functions. HDAC6 and HDAC10 belong to the class IIb subgroup of the HDAC family. The targets and biological functions of HDAC10 are ill-defined. This lack of knowledge is due to a lack of specific and potent HDAC10 inhibitors with cellular activity. Here, we have synthesized and characterized piperidine-4-acrylhydroxamates as potent and highly selective inhibitors of HDAC10. This was achieved by targeting the acidic gatekeeper residue Glu274 of HDAC10 with a basic piperidine moiety that mimics the interaction of the polyamine substrate of HDAC10. We have confirmed the binding modes of selected inhibitors using X-ray crystallography. Promising candidates were selected based on their specificity by in vitro profiling using recombinant HDACs. The most promising HDAC10 inhibitors 10c and 13b were tested for specificity in acute myeloid leukemia (AML) cells with the FLT3-ITD oncogene. By immunoblot experiments we assessed the hyperacetylation of histones and tubulin-α, which are class I and HDAC6 substrates, respectively. As validated test for HDAC10 inhibition we used flow cytometry assessing autolysosome formation in neuroblastoma and AML cells. We demonstrate that 10c and 13b inhibit HDAC10 with high specificity over HDAC6 and with no significant impact on class I HDACs. The accumulation of autolysosomes is not a consequence of apoptosis and 10c and 13b are not toxic for normal human kidney cells. These data show that 10c and 13b are nanomolar inhibitors of HDAC10 with high specificity. Thus, our new HDAC10 inhibitors are tools to identify the downstream targets and functions of HDAC10 in cells

Virulence-associated protein A from Rhodococcus equi is an intercompartmental pH-neutralising virulence factor

Professional phagocytic cells such as macrophages are a central part of innate immune defence. They ingest microorganisms into membrane-bound compartments (phagosomes), which acidify and eventually fuse with lysosomes, exposing their contents to a microbicidal environment. Gram-positive Rhodococcus equi can cause pneumonia in young foals and in immunocompromised humans. The possession of a virulence plasmid allows them to subvert host defence mechanisms and to multiply in macrophages. Here, we show that the plasmid-encoded and secreted virulence-associated protein A (VapA) participates in exclusion of the proton-pumping vacuolar-ATPase complex from phagosomes and causes membrane permeabilisation, thus contributing to a pH-neutral phagosome lumen. Using fluorescence and electron microscopy, we show that VapA is also transferred from phagosomes to lysosomes where it permeabilises the limiting membranes for small ions such as protons. This permeabilisation process is different from that of known membrane pore formers as revealed by experiments with artificial lipid bilayers. We demonstrate that, at 24 hr of infection, virulent R. equi is contained in a vacuole, which is enriched in lysosome material, yet possesses a pH of 7.2 whereas phagosomes containing a vapA deletion mutant have a pH of 5.8 and those with virulence plasmid-less sister strains have a pH of 5.2. Experimentally neutralising the macrophage endocytic system allows avirulent R. equi to multiply. This observation is mirrored in the fact that virulent and avirulent R. equi multiply well in extracts of purified lysosomes at pH 7.2 but not at pH 5.1. Together these data indicate that the major function of VapA is to generate a pH-neutral and hence growth-promoting intracellular niche. VapA represents a new type of Gram-positive virulence factor by trafficking from one subcellular compartment to another, affecting membrane permeability, excluding proton-pumping ATPase, and consequently disarming host defences

The impact of COVID-19 pandemic on the diagnosis and management of inborn errors of metabolism: A global perspective

Quantitative estimates for the global impact of COVID-19 on the diagnosis and management of patients with inborn errors of metabolism (IEM) are lacking. We collected relevant data from 16 specialized medical centers treating IEM patients in Europe, Asia and Africa. The median decline of reported IEM related services in March 1st-May 31st 2020 compared to the same period in 2019 were as high as 60-80% with a profound impact on patient management and care for this vulnerable patient group. More representative data along with outcome data and guidelines for managing IEM disorders under such extraordinary circumstances are needed.status: publishe