Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of the Cohen-Mansfield Agitation Inventory Observational (CMAI-O) Tool

Behaviours associated with agitation are common in people living with dementia. The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item scale widely used to assess agitation completed by a proxy (family carer or staff member). However, proxy informants introduce possible reporting bias when blinding to the treatment arm is not possible, and potential accuracy issues due to irregular contact between the proxy and the person with dementia over the reporting period. An observational measure completed by a blinded researcher may address these issues, but no agitation measures with comparable items exist. This study developed and validated observational version of the CMAI (CMAI-O) and assessed its validity as an alternative or complementary measure of agitation. We recruited 726 participants with dementia from 50 care homes as part of a clinical trial. The CMAI-O and an additional observational measure of agitation (Pittsburgh Agitation Scale; PAS) were completed. Measures of agitation, functional status, and neuropsychiatric symptoms were completed with staff proxies. The CMAI-O showed adequate internal consistency (α = .61), criterion validity with the PAS ( r = .79, p = <.001), incremental validity in predicting quality of life beyond the Functional Assessment Staging of Alzheimer’s disease ( β = 1.83, p < .001 at baseline) and discriminant validity from the Neuropsychiatric Inventory Apathy subscale ( r = .004, p = .902). The CMAI-O is a promising research tool for independently measuring agitation in people with dementia in care homes. Its use alongside the CMAI could provide a more robust understanding of agitation amongst residents with dementia.
Impact of Universal Antiretroviral Treatment Eligibility on Rapid Treatment Initiation Among Young Adolescents with Human Immunodeficiency Virus in Sub-Saharan Africa

Received 21 June 2019; editorial decision 11 September 2019; accepted 19 October 2019; published online November 4, 2019. O. T. and E. B. contributed equally to this work. Correspondence: Ellen Brazier, Institute for Implementation Science in Population Health, City University of New York, 55 W 125th St, New York, NY 10027 (ellen.brazier@sph.cuny.edu). The Journal of Infectious Diseases 2019;XX:1–9 © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/infdis/jiz547 Impact of Universal Antiretroviral Treatment Eligibility on Rapid Treatment Initiation Among Young Adolescents with Human Immunodeficiency Virus in Sub-Saharan Africa
Statistical aspects of environmental risk assessment of GM plants for effects on non-target organisms

Previous European guidance for environmental risk assessment of genetically modiﬁed plants emphasized the concepts of statistical power but provided no explicit requirements for the provision of statistical power analyses. Similarly, whilst the need for good experimental designs was stressed, no minimum guidelines were set for replication or sample sizes. Furthermore, although substantial equivalence was stressed as central to risk assessment, no means of quantiﬁcation of this concept was given. This paper suggests several ways in which existing guidance might be revised to address these problems. One approach explored is the ‘bioequivalence’ test, which has the advantage that the error of most concern to the consumer may be set relatively easily. Also, since the burden of proof is placed on the experimenter, the test promotes high-quality, well-replicated experiments with sufﬁcient statistical power. Other recommendations cover the speciﬁcation of effect sizes, the choice of appropriate comparators, the use of positive controls, meta-analyses, multivariate analysis and diversity indices. Speciﬁc guidance is suggested for experimental designs of ﬁeld trials and their statistical analyses. A checklist for experimental design is proposed to accompany all environmental risk assessments.
Effect of aging on muscle mitochondrial substrate utilization in humans

Significance Approximately 40% of Americans over the age of 65 suffer from impaired glucose tolerance or type 2 diabetes; however, the pathogenesis of aging-associated reductions in glucose metabolism is poorly understood. Aging is associated with muscle insulin resistance, increased intramyocellular fat content, and reductions in rates of muscle mitochondrial activity. To further examine the potential role of age-associated alterations in mitochondrial metabolism, we applied a novel method to assess muscle specific rates of mitochondrial glucose and fat oxidation and demonstrate that aging is also associated with a marked inability of mitochondria to switch from lipid to glucose oxidation on insulin stimulation, which may further contribute to dysregulated glucose and lipid metabolism in the elderly. Previous studies have implicated age-associated reductions in mitochondrial oxidative phosphorylation activity in skeletal muscle as a predisposing factor for intramyocellular lipid (IMCL) accumulation and muscle insulin resistance (IR) in the elderly. To further investigate potential alterations in muscle mitochondrial function associated with aging, we assessed basal and insulin-stimulated rates of muscle pyruvate dehydrogenase (VPDH) flux relative to citrate synthase flux (VCS) in healthy lean, elderly subjects and healthy young body mass index- and activity-matched subjects. VPDH/VCS flux was assessed from the 13C incorporation from of infused [1-13C] glucose into glutamate [4-13C] relative to alanine [3-13C] assessed by LC-tandem MS in muscle biopsies. Insulin-stimulated rates of muscle glucose uptake were reduced by 25% (P < 0.01) in the elderly subjects and were associated with ∼70% (P < 0.04) increase in IMCL, assessed by 1H magnetic resonance spectroscopy. Basal VPDH/VCS fluxes were similar between the groups (young: 0.20 ± 0.03; elderly: 0.14 ± 0.03) and increased approximately threefold in the young subjects following insulin stimulation. However, this increase was severely blunted in the elderly subjects (young: 0.55 ± 0.04; elderly: 0.18 ± 0.02, P = 0.0002) and was associated with an ∼40% (P = 0.004) reduction in insulin activation of Akt. These results provide new insights into acquired mitochondrial abnormalities associated with aging and demonstrate that age-associated reductions in muscle mitochondrial function and increased IMCL are associated with a marked inability of mitochondria to switch from lipid to glucose oxidation during insulin stimulation.
University of Groningen GMP manufacturing of Vvax001, a therapeutic anti-HPV vaccine based on recombinant viral particles Jorritsma-Smit,

Therapeutic vaccination is being explored as a treatment strategy for the treatment of patients with primary or metastatic tumours. We developed a vaccine targeted to Human papillomavirus (HPV)induced tumours based on recombinant Semliki Forest virus (rSFV) encoding a fusion protein of the E6 and E7 proteins of HPV type 16. To enable a phase I clinical trial with this vaccine, Vvax001, a Good Manufacturing Practice (GMP)-compliant manufacturing process was set up and clinical material was produced. Upstream production of the clinical material resulted in viral titers from 2.4 x 10 to 1.3 x 10 infectious particles/ mL in the harvest. The total volume of 6.0 liter crude virus was purified in 13 consecutive downstream purification runs. The mean titer after purification was 4.0 x 10 infectious particles/ mL and the mean recovery was 19%. Finally, clinical material was filled at a target concentration of 1.25 x 10 infectious particles/mL. Release testing included tests for viral titer and virus identity, biological activity, sterility, bacterial endotoxins, adventitious viruses and absence of replication competent virus. The product complied with all specifications and was released for use as an investigational medicinal product. This is the first GMP production process developed for a SFV-based therapeutic vaccine. The vaccine, Vvax001 is targeted to HPV and has shown promising results in preclinical studies. The GMPproduced Vvax001 material met the quality criteria and was of sufficient quantity to enable assessment of its immunogenicity, safety and efficacy in a clinical setting.
Estimation of 2006 Northern Hemisphere contrail coverage using MODIS data

A modified automated contrail detection algorithm (CDA) using five infrared channels available from the Moderate Resolution Imaging Spectrometer onboard the Aqua satellite is used to determine linear contrail coverage over the Northern Hemisphere during 2006. Commercial aircraft flight data are employed to filter false contrail detections by the CDA. The Northern Hemisphere annual mean linear contrail coverage ranges from 0.07% to 0.40% for three different CDA sensitivities. Based on visual analyses, the medium sensitivity CDA provides the best estimate of linear contrail coverage, which averages 0.13%. If scaled to the Southern Hemisphere, the global mean coverage would be 0.07%. Coverage is greatest during winter and least during the summer with maximum coverage over the North Atlantic. Less coverage is observed over heavy European and American traffic areas, likely as a result of difficulties in detecting linear contrails that overlap with each other and with older contrail cirrus. These results are valuable for evaluating the representation of contrails and contrail cirrus within global climate models and for retrieving contrail optical properties and radiative forcing.
A 10-years fog climatology of Germany and the Alpine region based on satellite data - preliminary results

A European fog climatology of fog frequency and fog properties which is based on a 10-years time series of NOAA-AVHRR data is under preparation. In this paper, preliminary results are presented. A fog map for 63 days provides a clear distinction of fog frequency in Europe: The pre-alpine basins reveal the highest fog frequency, a secondary maximum is observed for the river valleys of the lower mountain ranges and the fog minimum is located in the transition zone between the maritime coastal fog of the North Sea and the area of continental valley fog of the river valleys. The potential of VIS and MIR data for the calculation of fog optical and microphysical properties are discussed in the scope of a case study.
Geodynamic evolution of an Alpine terrane—the Austroalpine basement to the south of the Tauern Window as a part of the Adriatic Plate (eastern Alps)

Abstract The Austroalpine basement underwent a multistage Precambrian to Tertiary evolution. Meta-magmatic rocks occur in pre-Early Ordovician and post-Early Ordovician units. Protolith zircon ages and whole-rock trace element data define two magmatic evolution lines. An older trend with Th/Yb typical of subduction-related metamorphism, started by 590 Ma N-MORB-type and 550–530 Ma volcanic arc basalt-type basic suites which mainly involved depleted mantle sources, and was continued by mainly crustal-source 470–450 Ma acid magmatic suites. A presumably younger evolution by tholeiitic MORB-type and 430 Ma alkaline within-plate basalt-type suites is characterized by an intraplate mantle metasomatism and multicomponent sources. These magmatic trends can be related to a Neoproterozoic to Ordovician active margin and a subsequent Palaeo-Tethys passive margin along the north-Gondwanan periphery. During Variscan collision, the Austroalpine basement underwent multiphase deformation and metamorphism. Early deformation involved non-coaxial shearing with formation of sheath folds and calcsilicategneiss bodies in some regions. Syndeformational clockwise P–T paths in lower basement parts passed high-pressure and high-temperature amphibolite-facies stages and are interpreted by a Devonian to Carboniferous crustal stacking. A post-collisional Permian thermal event is documented by pegmatite intrusions, LP-HT assemblages and monazite ages. Ductile overprinting under greenschist-facies conditions during the Cretaceous is indicated by foliated pegmatites and monazite ages in samples with retrogressed garnet. The emplacement of the Oligocene Rieserferner pluton was controlled by sinistral shear zone deformation along the Defereggen–Antholz–Vals line. Shear zone activity ceased at 15 Ma and was superseded by brittle strike-slip movements along NW and SE trending faults.
Magnetotail response to prolonged southward IMF Bz intervals: Loading, unloading, and continuous magnetospheric dissipation

[1] The response of the Earth's magnetotail to prolonged southward interplanetary magnetic field (IMF) has been determined for the three Geotail magnetotail seasons from November to April, 1999–2002. We examine the total magnetotail pressure PT,tail = B2/2μ0 + NikTi because variations should be similar in this parameter in the lobes and in the plasma sheet. We found 13 events when IMF Bz remained southward for 8 hours or longer and Geotail was located within the magnetotail farther than 10 RE downstream. All 13 events were subdivided into separate intervals characterized as (1) loading, if the tail total pressure increased more than 100%; (2) unloading, if the total pressure decreased by more than 50%; and (3) what we term here continuous magnetospheric dissipation (CMD), if the tail total pressure increased by less than 100% and/or decreased less than 50% during the entire mode interval. In total, 37 loading, 37 unloading, and 28 CMD events were found. The plasma sheet magnetic flux transfer rate, ϕEarth ≈ vx · Bz, and plasma bulk velocity has been analyzed to determine the steadiness of the plasma sheet convection. Plasma sheet convection was found to be highly disturbed and intense plasma flows (BBFs and FBs) were observed during all convection states. However, the occurence rate and amplitude of plasma flows distinguish loading-unloading and continuous dissipation periods from each other. BBFs seem to be more numerous (135) but weaker (about 500 km/s) during continuous dissipation intervals compared with BBFs existing during unloading mode (61 and 660 km/s). Finally, it was found that CMD-type convection is more likely when the mean southward IMF Bz > −5 nT, while loading-unloading is more likely when IMF Bz < −5 nT.
Dysregulation of the secretory pathway connects Alzheimer ' s 1 disease genetics to aggregate formation 2 3

15 A hallmark of amyloid disorders, such as Alzheimer’s disease, is aggregation of secreted proteins. However, it 16 is largely unclear how the hundreds of secretory pathway proteins contribute to amyloid formation. We developed 17 a systems biology framework that integrates expression data with protein-protein interaction networks to 18 successfully estimate a tissue’s fitness for producing specific secreted proteins. Using this framework, we 19 analyzed the fitness of the secretory pathway of various brain regions and cell types for synthesizing the 20 Alzheimer’s disease-associated amyloid-precursor protein (APP). While none of the key amyloidogenic pathway 21 components were differentially expressed in AD brain, we found the deposition of Aβ is associated with 22 repressed expression of the secretory pathway components proximal to APP. Concurrently, we detected 23 systemic up-regulation of the secretory pathway components proximal to βand γ-secretases in AD brains. Our 24 analyses suggest that perturbations from 3 high confidence AD risk genes cascade through the secretory 25 machinery support network for APP and into the endocytosis pathway. Thus, we present a model where 26 amyloidogenesis is associated with dysregulation of dozens of secretory pathway components supporting APP, 27 which could yield novel therapeutic targets for the treatment of AD. 28 29
Peptidoglycan cross-linking activity of L,D-transpeptidases from Clostridium difficile and inactivation of theses enzymes by -lactams

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Peptidoglycan cross-linking activity of L,D-transpeptidases from Clostridium difficile and inactivation of theses enzymes by β-lactams Laetitia Sütterlin, Zainab Edoo, Jean-Emmanuel Hugonnet, Jean-Luc Mainardi, Michel Arthur
Toward Compact ConvNets via Structure-Sparsity Regularized Filter Pruning

The success of convolutional neural networks (CNNs) in computer vision applications has been accompanied by a significant increase of computation and memory costs, which prohibits their usage on resource-limited environments, such as mobile systems or embedded devices. To this end, the research of CNN compression has recently become emerging. In this paper, we propose a novel filter pruning scheme, termed structured sparsity regularization (SSR), to simultaneously speed up the computation and reduce the memory overhead of CNNs, which can be well supported by various off-the-shelf deep learning libraries. Concretely, the proposed scheme incorporates two different regularizers of structured sparsity into the original objective function of filter pruning, which fully coordinates the global output and local pruning operations to adaptively prune filters. We further propose an alternative updating with Lagrange multipliers (AULM) scheme to efficiently solve its optimization. AULM follows the principle of alternating direction method of multipliers (ADMM) and alternates between promoting the structured sparsity of CNNs and optimizing the recognition loss, which leads to a very efficient solver ( $2.5\times $ to the most recent work that directly solves the group sparsity-based regularization). Moreover, by imposing the structured sparsity, the online inference is extremely memory-light since the number of filters and the output feature maps are simultaneously reduced. The proposed scheme has been deployed to a variety of state-of-the-art CNN structures, including LeNet, AlexNet, VGGNet, ResNet, and GoogLeNet, over different data sets. Quantitative results demonstrate that the proposed scheme achieves superior performance over the state-of-the-art methods. We further demonstrate the proposed compression scheme for the task of transfer learning, including domain adaptation and object detection, which also show exciting performance gains over the state-of-the-art filter pruning methods.
Do Economic Crises Lead Tourists to Closer Destinations? An Analysis of Italy's Regional Data

This article investigates whether the distance between origin and destination has played an increased role in shaping Italy’s domestic tourism flows during the recent years of economic recession. Indeed, the occurrence of closer tourism destinations, as a consequence of the economic crisis, has been recently suggested by a number of authors who obtain their results from micro-data and, more specifically, from surveys. Differently, we study this issue through aggregate official data. Our dataset is made of inter-regional tourism flows among Italian regions over the 2000-12 period; across this period, 2008 to 2012 are years of economic recession. The analytical tool employed is a gravity model. Our results document that distance played a more and more relevant role during the recession.
Migration and Democratization in Brazil: The Case of Electoral Participation and Competition

Deepening democratization in Brazil has coincided with sustained flows of domestic migration. This raises an important question of whether migration deepens or depresses democratic development in migrant-sending regions. Whereas earlier perspectives view migration as a political "brain drain," we contend that out-migration can generate resources that promote democratic processes back home. We investigate the role of migration in two aspects of democratization: electoral participation and competition. The analyses are based on spatial panel data models of mayoral election results across all municipalities between 1996 and 2012. The results show that migration increases electoral participation and competition in migrant-sending localities in Brazil. This study also identifies the sociopolitical context that conditions the impact of migration: the effect is most often present in the context of rural-urban migration and is more pronounced in sending localities with less democratic political structures than those with more democratic structures. Moreover, using spatial network models, we find evidence for the transmission of political remittances from migration destination municipalities to origin municipalities. The present study extends the research on the "migration-development nexus" to the political arena, thus demonstrating the value of integrating demographic processes into explanations of political change. dense of a closest of dense to classify into urban, intermediary, and
Origin of Calcium carbonate granules found in buried soils and Quaternary deposits

The ovoid calcium carbonate granules of less than 2 mm in size commonly found by molluscan specialists and soil micromorphologists are usually interpreted as coming from either earthworms or arionid slugs, or both. In this paper the granules are examined in detail, with a view to better understanding their origins and dynamics. Through collection and experiments, it is shown conclusively that both animals produce calcium carbonate granules of the right size range. The two types have distinctive morphologies, however, and most of the granules observed in soils and sediments are clearly identifiable as coming from earthworms. This arises from a far greater production rate: worms are capable of shedding granules at the rate of 1–3 per week, whereas Arion ater only yields around 40 granules < 250 μm on death. The granules survive digestive processes, so heavy predation of earthworms by various animals and birds means that there is a constant recycling of the granules in the biosphere.
Unsupervised Discovery of Non-linear Structure Using Contrastive Backpropagation

We describe a way of modelling high-dimensional data-vectors by using an unsupervised, non-linear, multilayer neural network in which the activity of each neuron-like unit makes an additive contribution to a global energy score that indicates how surprised the network is by the data-vector. The connection weights which determine how the activity of each unit depends on the activities in earlier layers are learned by minimizing the energy assigned to data-vectors that are actually observed and maximizing the energy assigned to " confabulations " that are generated by perturbing an observed data-vector in a direction that decreases its energy under the current model. The backpropagation algorithm (Rumelhart et al., 1986) trains the units in the intermediate layers of a feedforward neural net to represent features of the input vector that are useful for predicting the desired output. This is achieved by propagating information about the discrepancy between the actual output and the desired output backwards through the net to compute how to change the connection weights in a 1