Exploring Patterns of Activities of Daily Living in the Home Environment

Background: Senior citizens tend to live longer and longer independently. Judging whether a senior person is still capable of living on his own is often based on the occurrence of incidents, with all consequences thereof. In the specific case of early dementia, the symptoms are not immediately apparent and the occurrence and severity of incidents progress gradually over time. In this case, the children or grandchildren are burdened by the question whether or not the elderly adult can still live safely and independently in his or her own home. This decision is only based on input obtained through incidental visits. We believe that the capability of independent living can only be objectively judged, by a health professional, if long term objective information on the elderly person's daily activities of living (ADL) is available

Status and performance of the THD2 bench in multi-deformable mirror configuration

The architecture of exoplanetary systems is relatively well known inward to 1 AU thanks to indirect techniques, which have allowed characterization of thousands of exoplanet orbits, masses and sometimes radii. The next step is the characterization of exoplanet atmospheres at long period, which requires direct imaging capability. While the characterization of a handful of young giant planets is feasible with dedicated instruments like SPHERE/VLT, GPI/Gemini, SCExAO/Subaru and soon with the coronagraphic capabilities aboard JWST, the spectroscopic study of mature giant planets and lower mass planets (Neptune-like, Super Earths) requires the achievement of better coronagraphic performance. While space-based coronagraph on WFIRST-AFTA might start this study at low spectroscopic resolution, dedicated projects on large space telescope and on the ELT will be required for a more complete spectroscopic study of these faint planets. To prepare these future instruments, we developed a high contrast imaging bench called THD, then THD2 for the upgraded version using multi-DM configuration. The THD2 bench is designed to test and compare coronagraphs as well as focal plane wavefront sensors and wavefront control techniques. It can simulate the beam provided by a space telescope and soon the first stage of adaptive optics behind a ground-based telescope. In this article, we describe in details the THD2 bench and give the results of a recent comparison study of the chromatic behavior for several coronagraph on the THD2.Comment: 9 pages, 5 figures, 1 Table, AO4ELT 2017 conference proceedin

Imbalanced Folate and Vitamin B12 in the Third Trimester of Pregnancy and its Association with Birthweight and Child Growth up to 2 Years

Scope: Folic acid supplementation during pregnancy may lead to an imbalance when vitamin B12 intake is low (folate trap) and may affect child’s growth. Methods: The authors study the association between third trimester maternal intakes of folate and B12 and birthweight and postnatal growth of 2632 infants from the KOALA Birth Cohort Study. Plasma vitamin biomarkers are measured in 1219 women. Results: Imbalanced total intakes (folate > 430 µg day−1 combined with B12 < 5.5 µg day−1) are not associated with birthweight [ adj (95% CI) = –14.87 (–68.87, 39.13)] compared with high intakes of both. Imbalanced intake is associated with a lower z score of weight at 1–2 years [ adj = –0.14 (–0.25, –0.03)]. Having red blood cell folate > 745 nmol L−1 and plasma B12 < 172 pmol L−1 is not associated with birthweight [ adj = –7.10 (–97.90, 83.71) g]. Maternal dietary B12 intake [ adj = –9.5 (–15.6, –3.3)] and plasma methylmalonic acid [ adj = 234 (43, 426)] are associated with birthweight. Conclusion: Low maternal dietary B12 intake and elevated methylmalonic acid rather than imbalanced vitamins are associated with higher birthweight, suggesting that low maternal B12 can predispose the infants for later obesity

Optimal sensor placement for measuring physical activity with a 3D accelerometer

Accelerometer-based activity monitors are popular for monitoring physical activity. In this study, we investigated optimal sensor placement for increasing the quality of studies that utilize accelerometer data to assess physical activity. We performed a two-staged study, focused on sensor location and type of mounting. Ten subjects walked at various walking speeds on a treadmill, performed a deskwork protocol, and walked on level ground, while simultaneously wearing five ProMove2 sensors with a snug fit on an elastic waist belt. We found that sensor location, type of activity, and their interaction-effect affected sensor output. The most lateral positions on the waist belt were the least sensitive for interference. The effect of mounting was explored, by making two subjects repeat the experimental protocol with sensors more loosely fitted to the elastic belt. The loose fit resulted in lower sensor output, except for the deskwork protocol, where output was higher. In order to increase the reliability and to reduce the variability of sensor output, researchers should place activity sensors on the most lateral position of a participant's waist belt. If the sensor hampers free movement, it may be positioned slightly more forward on the belt. Finally, sensors should be fitted tightly to the body

Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells.

Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications.We thank M. Jaeger (Radboudumc) for kindly providing flourescein isothiocyanate-labelled Candida albicans. D. Williams (East Tennessee State University) provided the β-glucan we used in our initial experiments. H. Lemmers (Radboudumc) kindly prepared the purified lipopolysaccharide used for stimulation of primary human monocytes and macrophages. Part of the figures were prepared using (among other software) Biorender.com. B.N. is supported by a National Health and Medical Research Council (Australia) Investigator Grant (APP1173314). This work was supported by National Institutes of Health grants R01 HL144072, R01 CA220234 and P01 HL131478, as well as a Vici grant from the Dutch Research Council NWO and an ERC Advanced Grant (all to W.J.M.M.). M.G.N. was supported by a Spinoza grant from Dutch Research Council NWO and an ERC Advanced Grant (#833247).S

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. Materials and methods: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged &lt;40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. Results: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs &lt;30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. Conclusions: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.</p

Architecture and performance of the KM3NeT front-end firmware

The KM3NeT infrastructure consists of two deep-sea neutrino telescopes being deployed in the Mediterranean Sea. The telescopes will detect extraterrestrial and atmospheric neutrinos by means of the incident photons induced by the passage of relativistic charged particles through the seawater as a consequence of a neutrino interaction. The telescopes are configured in a three-dimensional grid of digital optical modules, each hosting 31 photomultipliers. The photomultiplier signals produced by the incident Cherenkov photons are converted into digital information consisting of the integrated pulse duration and the time at which it surpasses a chosen threshold. The digitization is done by means of time to digital converters (TDCs) embedded in the field programmable gate array of the central logic board. Subsequently, a state machine formats the acquired data for its transmission to shore. We present the architecture and performance of the front-end firmware consisting of the TDCs and the state machine

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 - 4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 - 1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. This article is protected by copyright. All rights reserved