Generalized Linear Models to Forecast Malaria Incidence in Three Endemic Regions of Senegal.

Affecting millions of individuals yearly, malaria is one of the most dangerous and deadly tropical diseases. It is a major global public health problem, with an alarming spread of parasite transmitted by mosquito (Anophele). Various studies have emerged that construct a mathematical and statistical model for malaria incidence forecasting. In this study, we formulate a generalized linear model based on Poisson and negative binomial regression models for forecasting malaria incidence, taking into account climatic variables (such as the monthly rainfall, average temperature, relative humidity), other predictor variables (the insecticide-treated bed-nets (ITNs) distribution and Artemisinin-based combination therapy (ACT)) and the history of malaria incidence in Dakar, Fatick and Kedougou, three different endemic regions of Senegal. A forecasting algorithm is developed by taking the meteorological explanatory variable Xj at time t-𝓁j, where t is the observation time and 𝓁j is the lag in Xj that maximizes its correlation with the malaria incidence. We saturated the rainfall in order to reduce over-forecasting. The results of this study show that the Poisson regression model is more adequate than the negative binomial regression model to forecast accurately the malaria incidence taking into account some explanatory variables. The application of the saturation where the over-forecasting was observed noticeably increases the quality of the forecasts.

Estimation of seizure onset zone from ictal scalp EEG using independent component analysis in extratemporal lobe epilepsy.

Objective.The purpose of this study is to localize the seizure onset zone of patients suffering from drug-resistant epilepsy. During the last two decades, multiple studies proposed the use of independent component analysis (ICA) to analyze ictal electroencephalogram (EEG) recordings. This study aims at evaluating ICA potential with quantitative measurements. In particular, we address the challenging step where the components extracted by ICA of an ictal nature must be selected.Approach.We considered a cohort of 10 patients suffering from extratemporal lobe epilepsy who were rendered seizure-free after surgery. Different sets of pre-processing parameters were compared and component features were explored to help distinguish ictal components from others. Quantitative measurements were implemented to determine whether some of the components returned by ICA were located within the resection zone and thus likely to be ictal. Finally, an assistance to the component selection was proposed based on the implemented features.Main results.For every seizure, at least one component returned by ICA was localized within the resection zone, with the optimal pre-processing parameters. Three features were found to distinguish components localized within the resection zone: the dispersion of their active brain sources, the ictal rhythm power and the contribution to the EEG variance. Using the implemented component selection assistance based on the features, the probability that the first proposed component yields an accurate estimation reaches 51.43% (without assistance: 24.74%). The accuracy reaches 80% when considering the best result within the first five components.Significance.This study confirms the utility of ICA for ictal EEG analysis in extratemporal lobe epilepsy, and suggests relevant features to analyze the components returned by ICA. A component selection assistance is proposed to guide clinicians in their choice for ictal components.

-1 V bias 67 GHz bandwidth Si-contacted germanium waveguide p-i-n photodetector for optical links at 56 Gbps and beyond.

We demonstrate a 67 GHz bandwidth silicon-contacted germanium waveguide p-i-n photodetector operating at -1 V with 6.8 fF capacitance. The dark current is below 4 nA. The responsivity is 0.74 A/W at 1550 nm and 0.93 A/W at 1310 nm wavelength. 56 Gbps on-off-keying data reception is demonstrated with clear open eye diagrams in both the C-band and O-band.

High sensitivity 10Gb/s Si photonic receiver based on a low-voltage waveguide-coupled Ge avalanche photodetector.

We demonstrate low-voltage germanium waveguide avalanche photodetectors (APDs) with a gain × bandwidth product above 100GHz. A photonic receiver based on such a Ge APD, including a 0.13µm SiGe BiCMOS low-noise trans-impedance amplifier and a limiting amplifier, is realized. A 5.8dB sensitivity improvement is demonstrated at -5.9V bias at an avalanche gain of 6 through bit error ratio measurements. The absolute sensitivity in avalanche mode is -23.4dBm and -24.4dBm at a bit error ratio of 1 × 10(-12) and 1 × 10(-9) respectively.

Spherical mesh adaptive direct search for separating quasi-uncorrelated sources by range-based independent component analysis.

It is seemingly paradoxical to the classical definition of the independent component analysis (ICA), that in reality, the true sources are often not strictly uncorrelated. With this in mind, this letter concerns a framework to extract quasi-uncorrelated sources with finite supports by optimizing a range-based contrast function under unit-norm constraints (to handle the inherent scaling indeterminacy of ICA) but without orthogonality constraints. Albeit the appealing contrast properties of the range-based function (e.g., the absence of mixing local optima), the function is not differentiable everywhere. Unfortunately, there is a dearth of literature on derivative-free optimizers that effectively handle such a nonsmooth yet promising contrast function. This is the compelling reason for the design of a nonsmooth optimization algorithm on a manifold of matrices having unit-norm columns with the following objectives: to ascertain convergence to a Clarke stationary point of the contrast function and adhere to the necessary unit-norm constraints more naturally. The proposed nonsmooth optimization algorithm crucially relies on the design and analysis of an extension of the mesh adaptive direct search (MADS) method to handle locally Lipschitz objective functions defined on the sphere. The applicability of the algorithm in the ICA domain is demonstrated with simulations involving natural, face, aerial, and texture images.

High-efficiency fiber-to-chip grating couplers realized using an advanced CMOS-compatible silicon-on-insulator platform.

A new generation of Silicon-on-Insulator fiber-to-chip grating couplers which use a silicon overlay to enhance the directionality and thereby the coupling efficiency is presented. Devices are realized on a 200 mm wafer in a CMOS pilot line. The fabricated fiber couplers show a coupling efficiency of -1.6 dB and a 3 dB bandwidth of 80 nm.

A geometric Newton method for Oja's vector field.

Newton's method for solving the matrix equation F(X) identical to AX-XX(T) AX = 0 runs up against the fact that its zeros are not isolated. This is due to a symmetry of F by the action of the orthogonal group. We show how differential-geometric techniques can be exploited to remove this symmetry and obtain a "geometric" Newton algorithm that finds the zeros of F. The geometric Newton method does not suffer from the degeneracy issue that stands in the way of the original Newton method.

Changes in the arginine-vasopressin immunoreactive systems in male mice lacking a functional aromatase gene.

In male rodents, the arginine-vasopressin-immunoreactive (AVP-ir) neurones of the bed nucleus of the stria terminalis (BNST) and medial amygdala are controlled by plasma testosterone levels (decreased after castration and restored by exogenous testosterone). AVP transcription in these nuclei is increased in adulthood by a synergistic action of the androgenic and oestrogenic metabolites of testosterone and, accordingly, androgen and oestrogen receptors are present in both BNST and medial amygdala. We used knockout mice lacking a functional aromatase enzyme (ArKO) to investigate the effects of a chronic depletion of oestrogens on the sexually dimorphic AVP system. Wild-type (WT) and ArKO male mice were perfused 48 h after an i.c.v. colchicine injection and brain sections were then processed for AVP immunocytochemistry. A prominent decrease (but not a complete suppression) of AVP-ir structures was observed in the BNST and medial amygdala of ArKO mice by comparison with the WT. Similarly, AVP-ir fibres were reduced in the lateral septum of ArKO mice and but not in the medial preoptic area, a region where the AVP system is not sexually dimorphic in rats. No change was detected in the supraoptic and suprachiasmatic nuclei. However, a decrease in AVP-ir cell numbers was however, detected in one subregion of the paraventricular nucleus. These data support the hypothesis that the steroid-sensitive sexually dimorphic AVP system of the mouse forebrain is mainly under the control of aromatized metabolites of testosterone.

In vivo manganese-enhanced magnetic resonance imaging reveals connections and functional properties of the songbird vocal control system.

Injection of manganese (Mn(2+)), a paramagnetic tract tracing agent and calcium analogue, into the high vocal center of starlings labeled within a few hours the nucleus robustus archistriatalis and area X as observed by in vivo magnetic resonance imaging. Structures highlighted by Mn(2+) accumulation assumed the expected tri-dimensional shape of the nucleus robustus archistriatalis and area X as identified by classical histological or neurochemical methods. The volume of these nuclei could be accurately calculated by segmentation of the areas highlighted by Mn(2+). Besides confirming previously established volumetric sex differences, Mn(2+) uptake into these nuclei revealed new functional sex differences affecting Mn(2+) transport. A faster transport was observed in males than in females and different relative amounts of Mn(2+) were transported to nucleus robustus archistriatalis and area X in males as compared to females. This new in vivo approach, allowing repeated measures, opens new vistas to study the remarkable seasonal plasticity in size and activity of song-control nuclei and correlate neuronal activity with behavior. It also provides new insights on in vivo axonal transport and neuronal activity in song-control nuclei of oscines.

The control of preoptic aromatase activity by afferent inputs in Japanese quail.

This review summarizes current knowledge on the mechanisms that control aromatase activity in the quail preoptic area, a brain region that plays a key role in the control of reproduction. Aromatase and aromatase mRNA synthesis in the preoptic area are enhanced by testosterone and its metabolite estradiol, but estradiol receptors of the alpha subtype are not regularly colocalized with aromatase. Estradiol receptors of the beta subtype are present in the preoptic area but it is not yet known whether these receptors are colocalized with aromatase. The regulation by estrogen of aromatase activity may be, in part, trans-synaptically mediated, in a manner that is reminiscent of the ways in which steroids control the activity of gonadotropic hormone releasing hormone neurons. Aromatase-immunoreactive neurons are surrounded by dense networks of vasotocin-immunoreactive and tyrosine hydroxylase-immunoreactive fibers and punctate structures. These inputs are in part steroid-sensitive and could therefore mediate the effects of steroids on aromatase activity. In vivo pharmacological experiments indicate that catecholaminergic depletions significantly affect aromatase activity presumably by modulating aromatase transcription. In addition, in vitro studies on brain homogenates or on preoptic-hypothalamic explants show that aromatase activity can be rapidly modulated by a variety of dopaminergic compounds. These effects do not appear to be mediated by the membrane dopamine receptors and could involve changes in the phosphorylation state of the enzyme. Together, these results provide converging evidence for a direct control of aromatase activity by catecholamines consistent with the anatomical data indicating the presence of a catecholaminergic innervation of aromatase cells. These dopamine-induced changes in aromatase activity are observed after several hours or days and presumably result from changes in aromatase transcription but rapid non-genomic controls have also been identified. The potential significance of these processes for the physiology of reproduction is critically evaluated.

Effects of lesions of the medial preoptic nucleus on the testosterone-induced metabolic changes in specific brain areas in male quail.

The effects of bilateral lesions of the medial preoptic nucleus in association with testosterone on the metabolic activity in discrete brain regions was studied quantitatively by the in vivo autoradiographic 2-deoxyglucose method. Adult male quail were castrated and then left without hormone replacement therapy or treated with testosterone or treated with testosterone and submitted to a bilateral lesion of the medial preoptic nucleus, a brain region that plays a key role in the activation of male copulatory behavior by testosterone. Treatment for about 10 days with testosterone activated the expression of the full range of male sexual behaviors and these behaviors were completely suppressed by the medial preoptic nucleus lesions. Mapping of 2-deoxyglucose uptake revealed both increases and decreases of metabolic activity in discrete brain regions associated with the systemic treatment with testosterone as well as with the lesion of the medial preoptic nucleus. Testosterone affected the oxidative metabolism in brain areas that are known to contain sex steroid receptors (such as the nucleus taeniae and the paraventricular and ventromedial nuclei of the hypothalamus) but also in nuclei that are believed to be devoid of such receptors. Effects of testosterone in these nuclei may be indirect or reflect changes in terminals of axons originating in steroid-sensitive areas. Bilateral medial preoptic nucleus lesions affected 2-deoxyglucose uptake in a variety of brain regions. Some of these regions are known to be mono-synaptically connected to the medial preoptic nucleus. Metabolic depression in these areas may reflect retrograde changes in the neurons projecting to the damaged field.The metabolic changes identified in the present study confirm the prominent role of the preoptic area in the control of sexual behavior, show that changes in the physiology of the visual system represent one of the ways through which testosterone influences the occurrence of this behavior and demonstrate that the medial preoptic nucleus has marked effects on the metabolic activity in a variety of limbic and telencephalic structures. This study also indicates that the medial preoptic nucleus affects the activity of the area ventralis of Tsai, a dopaminergic area known to send projections to a variety of hypothalamic, thalamic and mesencephalic nuclei that are implicated in the control of male sexual behavior. These data therefore support the notion that the control of the dopaminergic activity in the area ventralis of Tsai by the medial preoptic nucleus represents one of the ways through which the medial preoptic area regulates male reproductive behavior.

Estradiol mediates effects of testosterone on vasotocin immunoreactivity in the adult quail brain.

In adult male quail, the activation of sexual behavior by testosterone (T) is mediated at the cellular level by the interaction of T metabolites with intracellular steroid receptors. In particular, the aromatization of T into an estrogen plays a key limiting role. Nonaromatizable androgens such 5alpha-dihydrotestosterone (DHT) synergize with estradiol (E2) to activate the behavior. Given that the density of vasotocin (VT) immunoreactive structures is increased by T in adult male quail and that VT injections affect male behavior, we wondered whether the expression of VT is also affected by T metabolites such as E2 and DHT. We analyzed here, in castrated male quail, the effects of a treatment with T, E2, DHT, or E2 + DHT on sexual behavior and brain VT immunoreactivity. The restoration by T of the VT immunoreactivity in the medial preoptic nucleus, bed nucleus striae terminalis, and lateral septum of castrated male quail could be fully mimicked by a treatment with E2. The androgen DHT had absolutely no effect on the VT immunoreactivity in these conditions and, at the doses used here, DHT did not synergize with E2 to enhance the density of VT immunoreactive structures. These effects of T metabolites in the brain were not fully correlated with their effects on the activation of male copulatory behavior, suggesting that the increase in VT expression in the brain does not represent a necessary step for the activation of behavior. Although VT expression in the medial preoptic nucleus and bed nucleus striae terminalis is often tightly correlated with the expression of male copulatory behavior, VT presumably does not represent simply one step in the biochemical cascade of events that is induced by T in the brain and leads to the expression of male sexual behavior.

Preoptic aromatase cells project to the mesencephalic central gray in the male Japanese quail (Coturnix japonica).

Previous tract-tracing studies demonstrated the existence of projections from the medial preoptic nucleus (POM) to the mesencephalic central gray (GCt) in quail. GCt contains a significant number of aromatase-immunoreactive (ARO-ir) fibers and punctate structures, but no ARO-ir cells are present in this region. The origin of the ARO-ir fibers of the GCt was investigated here by retrograde tract-tracing combined with immunocytochemistry for aromatase. Following injection of fluorescent microspheres in GCt, retrogradely labeled cells were found in a large number of hypothalamic and mesencephalic areas and in particular within the three main groups of ARO-ir cells located in the POM, the ventromedial nucleus of the hypothalamus, and the bed nucleus striae terminalis. Labeling of these cells for aromatase by immunocytochemistry demonstrated, however, that aromatase-positive retrogradely labeled cells are observed almost exclusively within the POM. Double-labeled cells were abundant in both the rostral and caudal parts of the POM and their number was apparently not affected by the location of the injection site within GCt. At both rostro-caudal levels of the POM, ARO-ir retrogradely labeled cells were, however, more frequent in the lateral than in the medial POM. These data indicate that ARO-ir neurons located in the lateral part of the POM may control the premotor aspects of male copulatory behavior through their projection to GCt and suggest that GCt activity could be affected by estrogens released from the terminals of these ARO-ir neurons.

Distribution of DARPP-32 immunoreactive structures in the quail brain: anatomical relationship with dopamine and aromatase.

We recently demonstrated that dopamine (DA) as well as different DA receptor agonists and antagonists are able to decrease within a few minutes the aromatase activity (AA) measured in vitro in homogenates or in explants of the quail preoptic area - hypothalamus. In addition, DA also appears to regulate AA, in vivo presumably by modifying enzyme synthesis. The cellular mechanisms and the anatomical substrate that mediate these controls of AA by DA are poorly understood. Tyrosine hydroxylase-immunoreactive (TH-ir) fibers and punctate structures have been previously observed in close vicinity of aromatase-immunoreactive (ARO-ir) cells in the quail medial preoptic nucleus (POM) and bed nucleus striae terminalis (BST) but these fibers could reflect a noradrenergic innervation. We also do not know whether aromatase cells are dopaminoceptive. The main goal of the present study was therefore to bring more information on the anatomical relationships between aromatase expressing neurons and the dopaminergic system in the quail brain. The visualization by immunocytochemistry of DA and of the D1 receptor associated protein DARPP-32 was used to address these questions. DA-ir fibers were observed in the quail forebrain and overlapped extensively with nuclei that contain high densities of ARO-ir cells such as the POM and BST. This confirms that the previously reported TH-ir innervation of ARO-ir cells is, at least in part, of dopaminergic nature. DARPP-32-immunoreactive cells were found in periventricular position throughout the hypothalamus. DARPP-32-ir cells were also observed in telencephalic and mesencephalic areas (hyperstriatum accessorium, paleostriatum, nucleus intercollicularis, optic tectum). DARPP-32-ir fibers were widespread in tel-, di-, and mes-encephalic areas. The highest densities of immunoreactive fibers were detected in the lobus parolfactorius, paleostriatum augmentatum and substantia nigra/area ventralis of Tsai. In double-labeled sections, appositions between DARPP-32 fibers and ARO-ir cells were present in the dorsolateral POM and BST but DARPP-32 immunoreactivity was not detected in the ARO-ir perikarya (no colocalization). These data confirm the presence of a dopaminoceptive structures within the main cell clusters of ARO-ir cells in the quail brain but provide no evidence that these ARO-ir cells are themselves dopaminoceptive. Because DARPP-32 is not present in all types of cells expressing DA receptors, the presence of DA receptors that would not be associated with DARPP-32 in ARO-ir cells still remains to be investigated

Vertically coupled GaInAsP--InP microring resonators.

Vertically coupled microring resonator channel-dropping filters are demonstrated in the GaInAsP-InP material system. These devices were fabricated without regrowth. In this method, low-loss single-mode waveguides are removed from the growth substrate and bonded to a GaAs transfer substrate with benzocyclobutene. This permits fabrication of vertically coupled waveguides on both sides of the epilayer. Optical quality facets are obtained by cleaving through the transfer substrate. Operation of single-mode, single-ring optical channel-dropping filters is demonstrated.

Localization and controls of aromatase in the quail spinal cord.

In adult male and female Japanese quail, aromatase-immunoreactive cells were identified in the spinal dorsal horns from the upper cervical segments to the lower caudal area. These immunoreactive cells are located mostly in laminae I-III, with additional sparse cells being present in the medial part of lamina V and, at the cervical level exclusively, in lamina X around the central canal. Radioenzyme assays based on the measurement of tritiated water release confirmed the presence of substantial levels of aromatase activity throughout the rostrocaudal extent of the spinal cord. Contrary to what is observed in the brain, this enzyme activity and the number of aromatase-immunoreactive cells in five representative segments of the spinal cord are not different in sexually mature males or females and are not influenced in males by castration with or without testosterone treatment. The aromatase activity and the numbers of aromatase-immunoreactive cells per section are higher at the brachial and thoracic levels than in the cervical and lumbar segments. These experiments demonstrate for the first time the presence of local estrogen production in the spinal cord of a higher vertebrate. This production was localized in the sensory fields of the dorsal horn, where estrogen receptors have been identified previously in several avian and mammalian species, suggesting an implication of aromatase in the modulation of sensory (particularly nociceptive) processes.

Identification of the origin of catecholaminergic inputs to HVc in canaries by retrograde tract tracing combined with tyrosine hydroxylase immunocytochemistry.

The telencephalic nucleus HVc (sometimes referred to as the high vocal center) plays a key role in the production and perception of birdsong. Although many afferent and efferent connections to this nucleus have been described, it has been clear for many years, based on chemical neuroanatomical criteria, that there are projections to this nucleus that remain undescribed. A variety of methods including high performance liquid chromatography, immunohistochemistry and receptor autoradiography have identified high levels of catecholamine transmitters, the presence of enzymes involved in the synthesis of catecholamines such as tyrosine hydroxylase and a variety of catecholamine receptor sub-types in the HVc of several songbird species. However, no definitive projections to HVc have been described from cells groups known to synthesize catecholamines. These projections were analyzed in the present study by retrograde tract tracing combined with immunocytochemistry for tyrosine hydroxylase. The origin of the catecholaminergic inputs to HVc were determined based exclusively on birds in which injections of the retrograde tracer (latex fluospheres) were confined within the cytoarchitectonic boundaries of the nucleus. Retrogradely transported latex fluospheres were found mainly in cells of two dopaminergic nuclei, the mesencephalic central gray (A11) and, to a lesser extend, the area ventralis of Tsai (A10; homologous to the ventral tegmental area of mammals). A few retrogradely-labelled cells were also found in the noradrenergic nucleus subceruleus (A6). Most of these retrogradely-labelled cells were also tyrosine hydroxylase-positive. Other catecholaminergic nuclei were devoid of retrograde label. These data converge with others studies to indicate that HVc receives discrete dopaminergic and noradrenergic inputs. These inputs may influence the steroid regulation of HVc, attentional processes related to song and modulate sensory inputs to the song system.

Filter synthesis for periodically coupled microring resonators.

The theory of filter synthesis using periodically coupled microring resonators is developed as a means to overcome the fabrication sensitivities inherent in conventional higher-order filters, while still achieving desirable spectral characteristics. Each resonator in the array can compensate for deficiencies in any of the others. These filters exhibit a boxlike shape and very high extinction ratios.

Wavelength conversion in GaAs micro-ring resonators.

Tightly confined, low-loss waveguides in highly nonlinear materials permit nonlinear optical interactions to occur over much shorter distances than do fibers. The nonlinear interactions are further enhanced in resonators. Both theory and experiment of enhanced four-wave mixing in micro-ring resonators are presented that can be used for many applications. A conversion efficiency of 14% achievable with only 10-mW peak pump power is predicted under realizable conditions. The experiment, the first one to the authors' knowledge in nonlinear optics performed in micro-rings, shows, even in a lossy GaAs/AlGaAs ring, a 26-dB improvement in the conversion efficiency compared with that of an equivalent straight waveguide, in agreement with theory.

Effects of naloxone on the acquisition and expression of appetitive and consummatory sexual behavior in male Japanese quail.

Previous studies in Japanese quail indicate that central administration of the opioid antagonist naloxone enhances consummatory sexual behavior (CSB). This effect could be related either to a decrease in sexual satiety or to previously documented stimulatory effects of naloxone on GnRH. The present studies were performed to investigate these two possibilities and to explore for the first time opioid involvement in the expression and acquisition of appetitive aspects of sexual behavior (ASB) in castrated, testosterone-treated Japanese quail. Although no effects on either ASB or CSB were observed in response to peripheral naloxone injections, a significant increase in CSB was observed in males receiving central injections of naloxone. Central injections of naloxone had no effect on the acquisition of a social proximity response used to measure ASB. However, compared to controls a greater number of naloxone-treated birds copulated in the test arena on the first day. Overall, these results indicate an inhibitory role for opioids in CSB, and suggest that opioids are differentially involved in different aspects of sexual behavior.