Determination of Cholic and Chenodeoxycholic Acid in Serum: Evaluation of Two Commercial Radioimmunoassay Methods

Peer Reviewe

The Kinect project: group motion-based gaming for people living with dementia

Engaging in enjoyable activities is an essential part of well-being, but people with dementia can find participation increasingly difficult. Motion-based technologies can provide meaningful engagement in a wide range of activities, but for people with dementia to take advantage of these devices requires a good understanding of how best to select and present these activities to this population. The objective of this study was to explore the use of motion-based technology (Xbox Kinect) as a group activity for people with dementia who attend adult day programs. This qualitative study took place in an adult day program for older adults with age-related challenges. Participants (n=23) were observed while playing a digital bowling game presented on Xbox Kinect one hour per week for a period of 20 weeks, to capture naturalistic data. Field notes generated through observations were transcribed and analyzed to identify emerging themes. The findings revealed three predominant themes which illustrate the potential of motion-based technology as a group activity for people with dementia who attend adult day programs: (a) the importance of having a trained trainer, (b) learning vs. mastery, and (c) playing ‘independently together’. People with dementia can learn to play games presented on motion-based technology and enjoy doing so. Furthermore, using the technology in a group setting fostered an encouraging and supportive environment which further contributed to the leisure experience. However, to be used most effectively, staff must be trained to set-up and interact with the technology, as well as introduce, teach, and support people with dementia to use it

Barriers and facilitators to adherence to group exercise in institutionalized older people living with dementia: a systematic review

Objectives Research suggests targeted exercise is important for people living with dementia, especially those living in residential care. The aim of this review was to collect and synthesize evidence on the known barriers and facilitators to adherence to group exercise of institutionalized older people living with dementia. Methods We searched all available electronic databases. Additionally, we searched trial registries (clinicaltrial.gov, and WHO ICTRP) for ongoing studies. We searched for and included papers from January 1990 until September 2017 in any language. We included randomized, non-randomized trials. Studies were not eligible if participants were either healthy older people or people suffering from dementia but not living in an institution. Studies were also excluded if they were not focused on barriers and facilitators to adherence to group exercise. Results Using narrative analysis, we identified the following themes for barriers: bio-medical reasons and mental wellbeing and physical ability, relationships dynamics, and socioeconomic reasons. The facilitators were grouped under the following thematic frames: bio-medical benefits and benefits related to physical ability, feelings and emotions and confidence improvements, therapist and group relationships dynamics and activity related reasons. Conclusions We conclude that institutionalized older people living with dementia, even those who are physically frail, incontinent and/or have mild dementia can demonstrate certain level of exercise adherence, and therefore can respond positively to exercise programs. Tailored, individually-adjusted and supported physical activity, led by a knowledgeable, engaging and well communicating therapist/facilitator improves the adherence to group exercise interventions of institutionalized older people living with dementia

Integrative Genomics Identifies the Molecular Basis of Resistance to Azacitidine Therapy in Myelodysplastic Syndromes

© 2017 The Author(s) Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle. Non-responder HPC quiescence is mediated by integrin α5 (ITGA5) signaling and their hematopoietic potential improved by combining AZA with an ITGA5 inhibitor. AZA response is associated with the induction of an inflammatory response in HPCs in vivo. By molecular bar coding and tracking individual clones, we found that, although AZA alters the sub-clonal contribution to different lineages, founder clones are not eliminated and continue to drive hematopoiesis even in complete responders

Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6–8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response

Roofer: An Engineered Management System (EMS) for Bituminous Built-Up Roofs

Each of the U.S. anned services branches has a very large inventory of roofs with bituminous built-up membranes. Roof repairs and reconstruction are steadily increasing as the roofs approach the end of their service lives, making it increasingly important to better manage maintenance funds. Currently, there is need for a systematic procedure to detennine priorities and select repair strategies that will ensure a maximum return on investment. In response to this problem, the U.S. Anny Construction Engineering Research Laboratory (USACERL), with the assistance of the U.S. Army Cold Regions Research and Engineering Laboratory (USACRREL) and the U.S. Anny Engineering and Housing Support Center (USAEHSC), has developed ROOFER, a roofing maintenance management system. ROOFER provides military installations with a practical decision-making procedure to identify problems and select maintenance and repair strategies for roofs with bituminous membranes.U.S. Army Corps of Engineers Construction Engineering Research Laborator

Failure to reach hematopoietic allogenic stem cell transplantation in patients with myelodysplastic syndromes planned for transplantation : a population-based study

The only potential cure for patients with myelodysplastic syndrome (MDS) is allogeneic hematopoietic stem cell transplantation (HCT). However, a proportion of patients who are HCT candidates do not finally get transplanted. This population-based study aimed to characterize HCT candidates were attempting to reach HCT fail and to identify causes and risk factors for failure. Data were collected from (1) the national Swedish registry, enrolling 291 transplant candidates between 2009-2018, and (2) Karolinska University Hospital, enrolling 131 transplantation candidates between 2000 and 2018. Twenty-five % (nation-wide) and 22% (Karolinska) failed to reach HCT. Reasons for failure to reach HCT were progressive and refractory disease (47%), no donor identified (22%), identification of comorbidity (18%), and infectious complications (14%). Factors associated with failure to reach HCT were IPSS-R cytogenetic risk-group very poor, mixed MDS/MPN disease, low blast count (0-4.9%), and low hemoglobin levels (&amp;lt;= 7.9 g/dL). Transplanted patients had a longer overall survival (OS) compared to patients who failed to reach transplantation (83 months versus 14 months; p &amp;lt; 0.001). The survival advantage was seen for the IPSS-R risk groups intermediate, high, and very high. This study demonstrated that a high proportion of HCT-candidates fail to reach HCT and underlines the difficulties associated with bridging MDS patients to HCT.Funding Agencies|Karolinska InstituteKarolinska Institutet</p

Embracing first-person perspectives in soma-based design

A set of prominent designers embarked on a research journey to explore aesthetics in movement-based design. Here we unpack one of the design sensitivities unique to our practice: A strong first person perspective-where the movements, somatics and aesthetic sensibilities of the designer, design researcher and user are at the forefront. We present an annotated portfolio of design exemplars and a brief introduction to some of the design methods and theory we use, together substantiating and explaining the first-person perspective. At the same time, we show how this felt dimension, despite its subjective nature, is what provides rigor and structure to our design research. Our aim is to assist researchers in soma-based design and designers wanting to consider the multiple facets when designing for the aesthetics of movement. The applications span a large field of designs, including slow introspective, contemplative interactions, arts, dance, health applications, games, work applications and many others

Single-Cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy

Altres ajuts: Cellex Foundation, CEL007; Asociación Española Contra el Cáncer, AC18/000002Alterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy in myeloid malignancies. Hypomethylating agents (HMAs), such as azacitidine (AZA), have become standard-of-care therapy to treat myelodysplastic syndromes (MDS), myeloid neoplasms that can evolve into acute myeloid leukemia (AML). However, our capacity to identify who will respond to HMAs, and the duration of response, remains limited. To shed light on this question, we have leveraged the unprecedented analytical power of single-cell technologies to simultaneously map the genome and immunoproteome of MDS samples throughout clinical evolution. We were able to chart the architecture and evolution of molecular clones in precious paired bone marrow MDS samples at diagnosis and post-treatment to show that a combined imbalance of specific cell lineages with diverse mutational profiles is associated with the clinical response of MDS patients to hypomethylating therapy