Aligning daily activities with personality: towards a recommender system for improving wellbeing

Recommender Systems have not been explored to a great extentfor improving health and subjective wellbeing. Recent advances inmobile technologies and user modelling present the opportunityfor delivering such systems, however the key issue is understand-ing the drivers of subjective wellbeing at an individual level. Inthis paper we propose a novel approach for deriving personalizedactivity recommendations to improve subjective wellbeing by maxi-mizing the congruence between activities and personality traits. Toevaluate the model, we leveraged a rich dataset collected in a smart-phone study, which contains three weeks of daily activity probes,the Big-Five personality questionnaire and subjective wellbeingsurveys. We show that the model correctly infers a range of activ-ities that are ’good’ or ’bad’ (i.e. that are positively or negativelyrelated to subjective wellbeing) for a given user and that the derivedrecommendations greatly match outcomes in the real-world

Diagnostic accuracy of biomarkers and imaging for bone turnover in renal osteodystrophy

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry.MethodsWe obtained fasting blood samples from 69 patients with CKD stages 4-5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD.ResultsLevels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.ConclusionsThe biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX

Immunophenotypic analysis of cell cycle status in acute myeloid leukaemia: relationship to cytogenetics, genotype and clinical outcome

Cell cycle status may play an important role in directing patient therapy. We therefore determined the cell cycle status of leukaemic cells by immunophenotypic analysis of bone marrow trephine biopsies from 181 patients with acute myeloid leukaemia (AML) and correlated the results with biological features and clinical outcome. There was considerable heterogeneity between patients. The presenting white cell count significantly correlated with the proportion of non-quiescent cells (P < 0·0001), of cycling cells beyond G1 (P < 0·0001) and the speed of cycling (P < 0·0001). Profiles in acute promyelocytic leukaemia (APL) differed from non-APL and were consistent with more differentiated cells with reduced proliferative potential, but no significant differences were observed between non-APL cytogenetic risk groups. NPM1 mutations but not FLT3 internal tandem duplication (FLT3ITD ) were significantly associated with a higher proportion of cells beyond G1 (P = 0·002) and faster speed of cycling (P = 0·003). Resistance to standard cytosine arabinoside and daunorubicin induction chemotherapy was significantly related to a slower speed of cycling (P = 0·0002), as was a higher relapse rate (P = 0·05), but not with the proportion of non-quiescent cells or actively cycling cells. These results show a link between the cycling speed of AML cells and the response to chemotherapy, and help to identify a group with a very poor prognosis

Expression of Growth Factors and Growth Factor Receptor in Non-healing and Healing Ischaemic Ulceration

AbstractObjectivesTo characterise the histological and cytokinetic characteristics of purely ischaemic ulcers and the processes that underpin healing following successful revascularisation.DesignProspective observational study.Materials and methodsBiopsies were taken immediately pre- and 6 weeks following successful revascularisation of solely ischaemic ulceration. They were evaluated for morphological differences using H&E staining for the platelet derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), TGFβreceptorIII (TGFβRIII), transforming growth factor beta 1 and 3 (TGFβ1 and TGFβ3) and von Willebrand factor (vWF) expression using immunohistochemistry. Localisation and quantification of these growth factors and receptors was assessed systematically by three independent investigators who were blinded to the timing of biopsy.ResultsPre-operatively, small vessel vasculitis, necrosis and infection with a profuse neutrophil and macrophage infiltrate was observed in all samples. Post-operative biopsies revealed a proliferation of new capillaries in and around the ulcer edge and base. vWF staining confirmed an endothelial layer within these new vessels. Following successful revascularisation there was less infection and inflammation with minimal vasculitis. These newly formed capillaries had increased staining for TGFβ3, PDGFR and TGFβRIII with staining for PDGFR also localised to dermal fibroblasts which were larger and more numerous. Accelerated epithelial cell proliferation was observed with detachment from the underlying dermis.ConclusionsHealing of purely ischaemic ulcers is characterised by vasculogenesis associated with increased presence of the proangiogenic cytokines PDGF and TGFβ3. These findings show promise for the use of growth factor manipulation to aid healing in ischaemic ulcers

Posterior Mediastinal Hematoma after a Fall from Standing Height: A Case Report

Posterior Mediastinal Hematomas (PMHs) secondary to a fall from standing height are uncommon, with only one previous case reported in the literature. We describe a case of a 78-year-old male with multiple medical comorbidities, who was transferred to Montreal General Hospital (MGH) with a posterior mediastinal hematoma (PMH) after sustaining a fall from standing height. On initial assessment, the patient was hemodynamically stable and complained of mild chest pain, dyspnea, fatigue, and diaphoresis. The patient's airway was secured via endotracheal intubation fearing impending respiratory compromise secondary to an enlarging PMH. The patient was admitted to ICU where over the next 3 days he was managed conservatively via careful monitoring of his hemodynamic and hematologic indices. Repeat CT scanning indicated reduction in size of the PMH. The patient was discharged on hospital day eight. This case describes the assessment, evaluation, and conservative management of PMH in a complicated patient receiving prior anticoagulation. A review of the literature regarding the epidemiology of PMH and the management of both unstable and stable PMHs is also presented

A Phase I trial of talazoparib in patients with advanced hematologic malignancies

Aim: The objective of this study was to establish the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of talazoparib. Patients & methods: This Phase I, two-cohort, dose-escalation trial evaluated talazoparib monotherapy in advanced hematologic malignancies (cohort 1: acute myeloid leukemia/myelodysplastic syndrome; cohort 2: chronic lymphocytic leukemia/mantle cell lymphoma). Results: Thirty-three (cohort 1: n = 25; cohort 2: n = 8) patients received talazoparib (0.1-2.0 mg once daily). The MTD was exceeded at 2.0 mg/day in cohort 1 and at 0.9 mg/day in cohort 2. Grade ≥3 adverse events were primarily hematologic. Eighteen (54.5%) patients reported stable disease. Conclusion: Talazoparib is relatively well tolerated in hematologic malignancies, with a similar MTD as in solid tumors, and shows preliminary anti leukemic activity.Clinical trial registration: NCT01399840 (ClinicalTrials.gov)