On least favorable configurations for step-up-down tests

This paper investigates an open issue related to false discovery rate (FDR) control of step-up-down (SUD) multiple testing procedures. It has been established in earlier literature that for this type of procedure, under some broad conditions, and in an asymptotical sense, the FDR is maximum when the signal strength under the alternative is maximum. In other words, so-called "Dirac uniform configurations" are asymptotically {\em least favorable} in this setting. It is known that this property also holds in a non-asymptotical sense (for any finite number of hypotheses), for the two extreme versions of SUD procedures, namely step-up and step-down (with extra conditions for the step-down case). It is therefore very natural to conjecture that this non-asymptotical {\em least favorable configuration} property could more generally be true for all "intermediate" forms of SUD procedures. We prove that this is, somewhat surprisingly, not the case. The argument is based on the exact calculations proposed earlier by Roquain and Villers (2011), that we extend here by generalizing Steck's recursion to the case of two populations. Secondly, we quantify the magnitude of this phenomenon by providing a nonasymptotic upper-bound and explicit vanishing rates as a function of the total number of hypotheses

Bringing safe water over the last-mile: Insights from autonomous chlorine production as a scalable HTWS

According to United Nations, 1.8 billion people use a source of water that is fecally contaminated, while about 3.4 million die every year from diseases associated with pathogens in water. In order to achieve UN SDG 6 (access to safe drinking water), innovative approaches must be implemented. As providing piped-in water to every households seems out of reach, effective household water treatment solutions (HWTS), allowing families to treat their own drinking water, are very promising. Amongst the different HWTS technologies, chlorination is one of the most efficient and widespread. Sustainability and scalability of interventions targeting populations living at the bottom of the economic pyramid (BOP) can be achieved by relying on economically viable business models. Distribution of positive impact products for instance should rely on sustainable supply chains to overcome the last-mile and reach scale. Antenna Foundation (http://www.antenna.ch) develops appropriate technologies for BOP populations and helps its partners to build innovative business models to disseminate them. Antenna WATA®, a device producing sodium hypochlorite (active chlorine) by saltwater electrolysis, allows local and autonomous HWTS sourcing. The paper at hand validates this approach and presents the results achieved and challenges met by Antenna’s partners while producing, marketing and selling chlorine flasks as HWTS in developing world markets (Guinea-Conakry, Nepal, India and Pakistan). Hands-on experiences from small-scale to already scaled-up businesses provide key insights of the different steps of a growing HWTS social business. These lessons-learned should benefit social entrepreneurs from developing countries and development organizations that want to launch their own initiatives in this field

African-European contacts in the Kongo Kingdom (sixteenth-eighteenth centuries): new archaeological insights from Ngongo Mbata (Lower Congo, DRC)

Ngongo Mbata, the main and most affluent center of the Kongo kingdom’s Mbata province in the 17th century, is well known from the historical sources, but virtually unexplored in archaeological publications. Ngongo Mbata is unique in that it hosted a monumental stone building about which the historical record remains silent. This makes it particularly challenging from the point of view of historical archaeology. In this paper historical data, unpublished excavation results from the 1930s and our own fieldwork undertaken in 2012-2013 are brought together, to tell a new story of early African-European contacts in the interior of West Central Africa

Alteration of sensory-evoked metabolic and oscillatory activities in the olfactory bulb of GLAST-deficient mice

Astrocytes are key cellular elements in both the tripartite synapse and the neurovascular unit. To fulfill this dual role in synaptic activity and metabolism, they express a panel of receptors and transporters that sense glutamate. Among them, the GLT-1 and GLAST transporters are known to regulate extracellular glutamate concentrations at excitatory synapses and consequently modulate glutamate receptor signaling. These major uptake systems are also involved in energy supply to neurons. However, the functional role of GLAST in concurrent regulation of metabolic and neuronal activity is currently unknown. We took advantage of the attractive structural and functional features of the main olfactory bulb to explore the impact of GLAST on sensory information processing while probing both glutamate uptake and neuronal activity in glomeruli and deeper cellular layers, respectively. Using odor-evoked 2-deoxyglucose imaging and local field potential recordings in GLAST knockout mice, we show in vivo that deletion of GLAST alters both glucose uptake and neuronal oscillations in olfactory bulb networks

IconHK: Using Toolbar Button Icons to Communicate Keyboard Shortcuts

International audienceWe propose a novel perspective on the design of toolbar buttons that aims to increase keyboard shortcut accessibility. IconHK implements this perspective by blending visual cues that convey keyboard shortcut information into toolbar buttons without denaturing the pictorial representation of their command. We introduce three design strategies to embed the hotkey, a visual encoding to convey the modifiers, and a magnification factor that determines the blending ratio between the pictogram of the button and the visual representation of the keyboard shortcut. Two studies examine the benefits of IconHK for end-users and provide insights from professional designers on the practicality of our approach for creating iconsets. Building on these insights, we develop a tool to assist designers in applying the IconHK design principle

Hyperparathyroïdie Primaire durant la Gtrossesse: Etude d’Un cas Chru de Strasbourg

Introduction: L’hyperparathyroïdie primaire est une anomalie des glandes parathyroïdes avec hypersécrétion de parathormone (PTH), le plus souvent secondaire à un adénome parathyroïdien. Cas clinique: Il s’agit d’une patiente de 30 ans, troisième geste, primipare qui ne présente pas d’antécédents médicochirurgicaux particuliers sauf une césarienne à 41 semaines d’aménorrhée (SA) + 4 jours sous anesthésie générale pour altération du rythme cardiaque fœtal suite à un déclenchement par prostaglandines pour rupture prolongée des membranes. La grossesse en cours a été spontanée, marquée par plusieurs épisodes de coliques néphrétiques gauches sur lithiases urinaires dès le début. La patiente a été hospitalisée à 18 semaines d’aménorrhée pour hyperalgie lors d’un de ces épisodes avec discrète dilatation pyélocalicielle gauche à 10mm, sans infection urinaire associée. Le contrôle de la douleur a nécessité l’usage de morphiniques. Les résultats biologiques étaient en faveur d’une hyperparathyroïdie primaire diagnostiquée en fin de deuxième trimestre de grossesse. Ces résultats biologiques ont été confirmés par l’imagérie (échographie et scanner cervical). A la suite de ce bilan, une parathyroidectomie partielle a été réalisée à 31 semaines d’aménorrhée et deux jours. La calcémie était légèrement supérieure à la normale à 2.60 mmol/L avec une PTH à 105 ng/L le jour de l’intervention. La lésion a été analysée en anatomopathologie et confirmait la nature d’adénome mesurant 10x8x2 mm. La calcémie corrigée a nettement diminué suite à la chirurgie. La vitalité fœtale évaluée avec le score de Manning et les cardiotocographies étaient satisfaisantes avant et après l’intervention chirurgicale. Le suivi immédiat en post chirurgie était simple : une supplémentation calcique pour environ 15 jours a été utilisée suite à une hypocalcémie secondaire. La chirurgie a permis une amélioration nette de la symptomatologie de notre patiente de façon quasi immédiate. Une césarienne sous rachianesthésie pour désir maternel en début de travail a été réalisée à 39 semaines d’aménorrhées et 6 jours, dans le contexte d’utérus cicatriciel, donnant naissance à une petite fille de 3490g et 50 cm, APGAR 10-10-10-10 avec un pH artériel au cordon à 7,28. Aucune complication materno-fœtale n’a été rapportée dans le post-partum. Un suivi endocrinologique a été proposé au post-partum ainsi qu’un suivi urologique. Discussion: Sur le plan épidémiologique, l’hyperparathyroïdie est la troisième endocrinopathie la plus fréquente dans la population générale. Les patientes atteintes ont une symptomatologie très aspécifique. Le calcium est essentiel au bon fonctionnement de l’homéostasie chez l’homme et la femme, tant sur les plans neurologique, musculaire, hémostatique, que sur les plans de la multiplication et différenciation cellulaire. Il est donc nécessaire qu’un système puisse réguler de manière constante le phosphore et le calcium dans l’organisme car les complications maternofoetales surviennent en l’absence de diagnostic précoce. Plusieurs options thérapeutiques peuvent été envisagées et proposées à la patiente allant d’un simple suivi de contrôle régulier de la calcémie à la parathyroidectomie sélective en passant par un traitement médicamenteux. Notre cas clinique illustre un traitement chirurgical efficace au troisième trimestre de grossesse. Conclusion: La parathyroidectomie pendant le 3e trimestre de grossesse est une thérapeutique efficace pour le traitement de l’hyperparathyroïdie primaire symptomatique.   Introduction: Primary hyperparathyroidism is an abnormality of the parathyroid glands with parathyroid hormone hypersecretion (PTH), most often secondary to parathyroid adenoma. Clinical case: This is a 30-year-old patient, third procedure, primiparous who has no specific medical and surgical history except a cesarean section at 41 weeks of amenorrhea (AS) + 4 days under general anesthesia for impaired fetal heart rate. triggering by prostaglandins for prolonged rupture of membranes. The current pregnancy was spontaneous, marked by several episodes of renal colic on the left on urolithiasis from the start. The patient was hospitalized at 18 weeks amenorrhea for hyperalgesia during one of these episodes with discreet left pyelocalicular dilation to 10mm, without associated urinary tract infection. Pain control required the use of opioids. The laboratory results were in favor of primary hyperparathyroidism diagnosed at the end of the second trimester of pregnancy. These laboratory results were confirmed by imaging (ultrasound and cervical scan). Following this workup, a partial parathyroidectomy was performed at 31 weeks of amenorrhea and two days. Serum calcium was slightly above normal at 2.60 mmol / L with PTH of 105 ng / L on the day of surgery. The lesion was analyzed for anatomopathology and confirmed the nature of the adenoma measuring 10x8x2 mm. The corrected serum calcium significantly decreased following the surgery. Fetal vitality assessed with Manning's score and cardiotocographies were satisfactory before and after surgery. Immediate post-surgery follow-up was simple: calcium supplementation for around 15 days was used following secondary hypocalcaemia. The surgery allowed a marked improvement in the symptoms of our patient almost immediately. A cesarean section under spinal anesthesia for maternal desire at the start of labor was performed at 39 weeks of amenorrhea and 6 days, in the context of a scarred uterus, giving birth to a baby girl of 3490g and 50 cm, APGAR 10-10-10 -10 with an arterial cord pH of 7.28. No maternal-fetal complications have been reported in the postpartum period. Endocrinological follow-up has been proposed postpartum as well as urological follow-up. Discussion: Epidemiologically, hyperparathyroidism is the third most common endocrinopathy in the general population. The affected patients have very nonspecific symptoms. Calcium is essential for the proper functioning of homeostasis in men and women, both neurologically, muscularly, hemostatically, as well as in terms of cell multiplication and differentiation. It is therefore necessary that a system can constantly regulate phosphorus and calcium in the body because maternal-fetal complications occur in the absence of early diagnosis. Several treatment options can be considered and offered to the patient, ranging from simple regular monitoring of serum calcium to selective parathyroidectomy, including drug treatment. Our clinical case illustrates an effective surgical treatment in the third trimester of pregnancy. Conclusion: Parathyroidectomy in the 3rd trimester of pregnancy is an effective therapy for the treatment of symptomatic primary hyperparathyroidism

Clinical Chorioamnionitis and Neurodevelopment at 5 Years of Age in Children Born Preterm: The EPIPAGE-2 Cohort Study.

OBJECTIVE To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm. STUDY DESIGN EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 24+0 and 34+6 weeks following preterm labor (PTL) or preterm premature rupture of membranes (PPROM). Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with at least two of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the non-independence of twins and missing data by generalized estimating equation models and multiple imputations, respectively. RESULTS Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed respectively to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (adjusted odds ratio = 0.9, 95%CI: 0.5-1.8). CONCLUSION We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born before 35 weeks of gestation after PTL or PPROM

Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease

The mechanisms underlying preferential atrophy of the striatum in Huntington's disease (HD) are unknown. One hypothesis is that a set of gene products preferentially expressed in the striatum could determine the particular vulnerability of this brain region to mutant huntingtin (mHtt). Here, we studied the striatal protein µ-crystallin (Crym). Crym is the NADPH-dependent p38 cytosolic T3-binding protein (p38CTBP), a key regulator of thyroid hormone (TH) T3 (3,5,3′-triiodo-l-thyronine) transportation. It has been also recently identified as the enzyme that reduces the sulfur-containing cyclic ketimines, which are potential neurotransmitters. Here, we confirm the preferential expression of the Crym protein in the rodent and macaque striatum. Crym expression was found to be higher in the macaque caudate than in the putamen. Expression of Crym was reduced in the BACHD and Knock-in 140CAG mouse models of HD before onset of striatal atrophy. We show that overexpression of Crym in striatal medium-size spiny neurons using a lentiviral-based strategy in mice is neuroprotective against the neurotoxicity of an N-terminal fragment of mHtt in vivo. Thus, reduction of Crym expression in HD could render striatal neurons more susceptible to mHtt suggesting that Crym may be a key determinant of the vulnerability of the striatum. In addition our work points to Crym as a potential molecular link between striatal degeneration and the THs deregulation reported in HD patient