Powering down technology

This paper will examine the issue of energy consumption resulting from the use of technology. It will identify and evaluate potential solutions currently being deployed by data center managers. In addition, the paper will recommend guidelines for reducing energy consumption for both the individual and business consumer

L’expérience professionnelle : expériences sédimentées et expériences épisodiques

On définit ici l’expérience professionnelle comme ce qui est produit sur l’homme par sa pratique, c’est-à-dire par la réalisation des tâches d’un domaine, sur un temps relativement long. On défend l’idée qu’elle présente deux modalités : les expériences « sédimentées » sont centrées sur la répétition des tâches dans leur variabilité ; les expériences » épisodiques » sur la singularité des situations rencontrées, des cas hors norme aux cas paradigmatiques. On discute l’articulation de ces deux modalités, selon les exigences différentes des types de tâches dans les domaines de travail. L’analyse de l’expérience selon ces modalités « sédimentées » et « épisodiques » articulées sert à questionner leurs apports à l’évolution des compétences, à discuter des « pathologies » possibles de l’expérience, à expliciter des conditions nécessaires aux acquisitions et à tirer quelques conséquences sur la conception de formations.Professional experience is defined as the product of practice resulting from tasks performed in a given domain of work, over a relatively long period. We put forward the idea that professional experience covers two modalities: “sedimented” experiences are centred on the repetition of tasks in all their variability; “episodic” experiences are centred on the singularity of the situations encountered, from anomalous events to paradigmatic cases. We discuss how these modalities are articulated in relation to the varying demands of the cognitive operations involved in professional tasks (memory, categorisation, analogical reasoning, decision making…). Analysis of experience depending on its “sedimented” and “episodic” modalities is used to question how they contribute to the development of competencies, discuss what may go wrong with the experience, clarify the conditions required for acquiring competencies and draw some conclusions that may prove useful in devising training programmes

Bone ultrastructure and x-ray microanalysis of aluminum-intoxicated hemodialyzed patients

Bone ultrastructure and x-ray microanalysis of aluminum-intoxicated hemodialyzed patients. In hemodialyzed patients aluminum (Al) intoxication may induce osteomalacic lesions which are mainly observed when plasma immunoreactive parathyroid hormone (iPTH) concentrations are low, and osteitis fibrosa absent. In this study, the bone tissue of eight hemodialyzed patients with elevated plasma and bone Al concentrations was examined by histomorphometry, electron microscopy, and x-ray microanalysis. Five patients (group 1) had osteomalacia and minimal osteitis fibrosa, three patients (group 2) had severe osteitis fibrosa. In group 1, Al was concentrated at the mineralizing front, in hexagonal structures measuring 200 to 1,000 Å which also contained phosphorus, but not calcium. Hydroxyapatite needles had a normal aspect. Osteoblasts appeared inactive. In group 2, Al was also present at the mineralizing layer of osteoid, but, in these cases, in small clusters next to abnormal calcium deposits. Osteoblasts appeared very active. Their mitochondria contained calcium and phosphorus granules, or amorphous material, measuring 1,500 to 2,000 Å, emitting x-rays characteristic for Al and phosphorus. These results suggest that secondary hyperparathyroidism, by stimulating the cellular activity, may increase the uptake and release of Al by the osteoblasts. The presence of Al within the mitochondria of these cells may be one of the factors inducing the mineralization defect.Ultrastructure et microanalyse x du tissu osseux de malades hémodialysés intoxiqués par l'aluminium. Chez des malades hémodialysés l'intoxication par l'aluminium (Al) peut induire des lésions ostéomalaciques qui s'observent principalement quand la concentration plasmatique de l'hormone parathyroïdienne immunoréactive (iPTH) est peu augmentée, et en l'absence d'ostéite fibreuse. Dans cette étude le tissu osseux de huit malades hémodialysés dont la concentration plasmatique et osseuse de l'Al était élevée, a été examiné par l'histomorphométrie, la microscopie électronique et la microanalyse x. Cinq malades (groupe 1) avaient une ostéomalacie et des lésions minimes d'ostéite fibreuse, trois malades (groupe 2) avaient une ostéite fibreuse sévère. Dans le groupe 1, l'Al était concentré entre ostéoïde et tissu minéralisé, dans des structures hexagonales mesurant 200 à 1000 Å, qui contenaient également du phosphore, mais pas de calcium. Les aiguilles d'hydroxyapatite avaient un aspect normal. Les ostéoblastes paraissaient peu actifs. Dans le groupe 2, l'Al était aussi présent entre ostéoïde et tissu minéralisé, mais, dans ce cas, sous forme de petits amas, près de dépôts anormaux de calcium. Les ostéoblastes semblaient très actifs. Leurs mitochondries contenaient des granules de calcium et de phosphore ou bien du matériel amorphe, mesurant 1500 à 2000 Å, dont l'émission x était caractéristique de l'Al et du phosphore. Ces résultats suggèrent que l'hyperparathyroïdie secondaire, en stimulant l'activité cellulaire, favorise la captation et le dépôt de l'Al par les ostéoblastes. La présence d'Al dans les mitochondries de ces cellules pourrait être un des facteurs à l'origine du trouble de la minéralisation

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study

Background By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fl uid, including clearance parameters. Methods In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fl uid at follow-up every 3–6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodefi cient mice to test for infectivity. We used a linear mixed-eff ect model to analyse the dynamics of virus persistence in seminal fl uid over time. Findings We enrolled 26 participants and tested 130 seminal fl uid specimens; median follow up was 197 days (IQR 187–209 days) after enrolment, which corresponded to 255 days (228–287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73–181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fl uid of –0·58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fl uid at 115 days (90% prediction interval 72–160) and 294 days (212–399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in aff ected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice. Interpretation Time to clearance of Ebola virus RNA from seminal fl uid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks

Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression

A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.No sponso

Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study.

BACKGROUND: By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fluid, including clearance parameters. METHODS: In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fluid at follow-up every 3-6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodeficient mice to test for infectivity. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time. FINDINGS: We enrolled 26 participants and tested 130 seminal fluid specimens; median follow up was 197 days (IQR 187-209 days) after enrolment, which corresponded to 255 days (228-287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73-181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fluid of -0·58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fluid at 115 days (90% prediction interval 72-160) and 294 days (212-399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in affected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice. INTERPRETATION: Time to clearance of Ebola virus RNA from seminal fluid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks. FUNDING: This study was funded by European Union's Horizon 2020 research and innovation programme, Directorate-General for International Cooperation and Development of the European Commission, Institut national de la santé et de la recherche médicale (INSERM), German Research Foundation (DFG), and Innovative Medicines Initiative 2 Joint Undertaking

Long-term follow-up of glycemic and neurological outcomes in an international series of patients with sulfonylurea-treated ABCC8 permanent neonatal diabetes

This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record OBJECTIVE ABCC8 mutations cause neonatal diabetes mellitus that can be transient (TNDM) or, less commonly, permanent (PNDM); ∼90% of individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short-term and included combinations of ABCC8-PNDM and ABCC8-TNDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM. RESEARCH DESIGN AND METHODS We studied all 24 individuals with ABCC8-PNDM diagnosed in the U.K., Italy, France, and U.S. known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analyzed using nonparametric statistical methods. RESULTS Long-term data were obtained for 21 of 24 individuals (median follow-up 10.0 [range 4.1–13.2] years). Eighteen of 21 remained on sulfonylureas without insulin at the most recent follow-up. Glycemic control improved on sulfonylureas (presulfonylurea vs. 1-year posttransfer HbA1c 7.2% vs. 5.7%, P = 0.0004) and remained excellent long-term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, P = 0.04), n = 16. Relatively high doses were used (1-year vs. 10-year dose 0.37 vs. 0.25 mg/kg/day glyburide, P = 0.50) without any severe hypoglycemia. Neurological features were reported in 13 of 21 individuals; these improved following sulfonylurea transfer in 7 of 13. The most common features were learning difficulties (52%), developmental delay (48%), and attention deficit hyperactivity disorder (38%). CONCLUSIONS Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.Wellcome Trus

Genome-wide association study of placental weight in 65,405 newborns and 113,620 parents reveals distinct and shared genetic influences between placental and fetal growth

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth