A global cloud free pixel- based image composite from Sentinel-2 data.

Large-scale land cover classification from satellite imagery is still a challenge due to the big volume of data to be processed, to persistent cloud-cover in cloud-prone areas as well as seasonal artefacts that affect spatial homogeneity. Sentinel-2 times series from Copernicus Earth Observation program offer a great potential for fine scale land cover mapping thanks to high spatial and temporal resolutions, with a decametric resolution and five-day repeat time. However, the selection of best available scenes, their download together with the requirements in terms of storage and computing resources pose restrictions for large-scale land cover mapping. The dataset presented in this paper corresponds to global cloud-free pixel based composite created from the Sentinel-2 data archive (Level L1C) available in Google Earth Engine for the period January 2017- December 2018. The methodology used for generating the image composite is described and the metadata associated with the 10 m resolution dataset is presented. The data with a total volume of 15 TB is stored on the Big Data platform of the Joint Research Centre. It can be downloaded per UTM grid zone, loaded into GIS clients and displayed easily thanks to pre-computed overviews.

Built-up area and population density: Two Essential Societal Variables to address climate hazard impact.

Scientists use Essential Climate Variables to understand and model the Earth's climate. Complementary to the Climate Variables this paper introduces global built-up area and population density, referred to as Essential Societal Variables, that can be used to model human activities and the impact of climate induced hazards on society. Climate impact scenarios inform policy makers on current and future risk and on the cost for mitigation and adaptation measures. The global built-up area and global population densities are generated from Earth observation image archives and from national population census data in the framework of the Global Human Settlement Layer (GHSL) project. The layers are produced with fine granularity for four epochs: 1975, 1990, 2000 and 2015, and will be updated on a regular basis with open satellite imagery. The paper discusses the relevance of global built-up area and population density for a number of policy areas, in particular to understand regional and global urbanization processes and for use in operational crisis management and risk assessment. The paper also provides examples of global statistics on exposure to natural hazards based on the two ESVs and their use in policy making. Finally, the paper discusses the potential of using population and built-up area for developing indicators to monitor the progress in Agenda 2030 including the Sustainable Development Goals (SDGs).

Parvalbumin-, calbindin-, and calretinin-immunoreactive hippocampal interneuron density in autism.

BACKGROUND: There has been a long-standing interest in the possible role of the hippocampus in autism and both postmortem brain and neuroimaging studies have documented varying abnormalities in this limbic system structure. AIMS: This study investigates the density of subsets of hippocampal interneurons, immunostained with the calcium binding proteins, calbindin (CB), calretinin (CR) and parvalbumin (PV) to determine whether specific subpopulations of interneurons are impacted in autism. MATERIALS AND METHODS: Unbiased stereological techniques were used to quantify the neuronal density of these immunoreactive subpopulations of gamma-aminobutyric acid-ergic (GABAergic) interneurons analyzed in the CA and subicular fields in postmortem brain material obtained from five autistic and five age-, gender- and postmortem interval-matched control cases. RESULTS: Results indicate a selective increase in the density of CB-immunoreactive interneurons in the dentate gyrus, an increase in CR-immunoreactive interneurons in area CA1, and an increase in PV-immunoreactive interneurons in areas CA1 and CA3 in the hippocampus of individuals with autism when compared with controls. DISCUSSION/CONCLUSIONS: Although our sample size is small, these findings suggest that GABAergic interneurons may represent a vulnerable target in the brains of individuals with autism, potentially impacting upon their key role in learning and information processing. These preliminary findings further suggest the need for future more expanded studies in a larger number of postmortem brain samples from cases of autism and controls.

MRI measures of temporoparietal regions show differential rates of atrophy during prodromal AD.

BACKGROUND: MRI studies have demonstrated differential rates of atrophy in the entorhinal cortex and hippocampus during the prodromal phase of Alzheimer disease (AD). The current study was designed to determine whether a broader set of temporoparietal regions show differential rates of atrophy during the evolution of AD. METHODS: Sixteen regions of interest (ROIs) were analyzed on MRI scans obtained at baseline and follow-up in 66 subjects comprising three groups: controls = individuals who were cognitively normal at both baseline and follow-up; nonconverters = subjects with mild cognitive impairment (MCI) at both baseline and follow-up; converters had MCI at baseline but had progressed to AD at follow-up. RESULTS: Annualized percent change was analyzed with multivariate analysis of variance (MANOVA), covaried for age. The MANOVA demonstrated an effect of group (p = 0.004). Post hoc comparisons demonstrated greater rates of atrophy for converters vs nonconverters for six ROIs: hippocampus, entorhinal cortex, temporal pole, middle temporal gyrus, fusiform gyrus, and inferior temporal gyrus. Converters showed differentially greater rates of atrophy than controls in five of the same ROIs (and inferior parietal lobule). Rates of change in clinical status were correlated with the atrophy rates in these regions. Comparisons between controls and nonconverters demonstrated no differences. CONCLUSION: These results demonstrate that temporoparietal regions show differential rates of atrophy on MRI during prodromal Alzheimer disease (AD). MRI data correlate with measures of clinical severity and cognitive decline, suggesting the potential of these regions of interest as antemortem markers of prodromal AD.

Birthdates and number of neurons in the serotonergic raphe nuclei in the rat with prenatal protein malnutrition.

The effect of prenatal protein deprivation on timing of neurogenesis and on number of neurons generated in the serotonergic dorsal (DR) and median raphe (MR) nuclei of the rat was studied. These neurons are of interest because their neurogenesis occurs during the period of malnutrition and their axonal projections participate in the earliest stages of brain development. In this study, dams were maintained on a 25% casein diet or a 6% casein diet 5 weeks prior to mating and throughout pregnancy. At birth, all pups were cross-fostered to dams on a 25% casein diet. Bromodeoxyuridine, a thymidine analog that is incorporated into nuclear deoxyribonucleic acid during the cell cycle synthetic phase, was used as a marker of neurogenesis. Bromodeoxyuridine was administered on either embryonic day 11, 12, 13 or 14. On postnatal day 30, serial sections of raphe nuclei were processed with bromodeoxyuridine immunocytochemistry to determine the number of raphe cells generated on each day and with Nissl stain to determine the total number of cells generated. There were no significant differences between the two diet groups in timing of generation or in total number of cells generated, indicating that neurogenesis of these early generated neurons appears unaffected by concomitant protein deprivation.

Replication of naturally occurring woodchuck hepatitis virus deletion mutants in primary hepatocyte cultures and after transmission to naive woodchucks.

Woodchuck hepatitis virus (WHV) mutants with core internal deletions (CID) occur naturally in chronically WHV-infected woodchucks, as do hepatitis B virus mutants in humans. We studied the replication of WHV deletion mutants in primary woodchuck hepatocyte cultures and in vivo after transmission to naive woodchucks. By screening 14 wild-caught, chronically WHV-infected woodchucks, two woodchucks, WH69 and WH70, were found to harbor WHV CID mutants. Consistent with previous results, WHV CID mutants from both animals had deletions of variable lengths (90 to 135 bp) within the middle of the WHV core gene. In woodchuck WH69, WHV CID mutants represented a predominant fraction of the viral population in sera, normal liver tissues, and to a lesser extent, in liver tumor tissues. In primary hepatocytes of WH69, the replication of wild-type WHV and CID mutants was maintained at least for 7 days. Although WHV CID mutants were predominant in fractions of cellular WHV replicative intermediates, mutant covalently closed circular DNAs (cccDNAs) appeared to be a small part of cccDNA-enriched fractions. Analysis of cccDNA-enriched fractions from liver tissues of other woodchucks confirmed that mutant cccDNA represents only a small fraction of the total cccDNA pool. Four naive woodchucks were inoculated with sera from woodchuck WH69 or WH70 containing WHV CID mutants. All four woodchucks developed viremia after 3 to 4 weeks postinoculation (p.i.). They developed anti-WHV core antigen (WHcAg) antibody, lymphoproliferative response to WHcAg, and anti-WHV surface antigen. Only wild-type WHV, but no CID mutant, was found in sera from these woodchucks. The WHV CID mutant was also not identified in liver tissue from one woodchuck sacrificed in week 7 p.i. Three remaining woodchucks cleared WHV. Thus, the presence of WHV CID mutants in the inocula did not significantly change the course of acute self-limiting WHV infection. Our results indicate that the replication of WHV CID mutants might require some specific selective conditions. Further investigations on WHV CID mutants will allow us to have more insight into hepadnavirus replication.

Neuropathology of progressive cognitive decline in chronically hypertensive rhesus monkeys.

Hypertension is an identified major risk factor for cerebrovascular disease, which is second only to Alzheimer's disease as a cause of dementia in the elderly. In addition, hypertension has been associated with a more subtle, progressive decline in cognitive function for which the neuropathology is not well understood. The present study was undertaken to explore this relationship in an experimental, nonhuman primate model, with hypertension produced by a coarctation of the thoracic aorta. Since prior studies with this model have shown a progressive decline in memory function, similar to that seen in human hypertension, as well as scattered microinfarcts in the cerebral white and gray matter, this study was designed to explore the relationship between these two. In addition to microinfarcts, the hypertensive monkeys with the highest arterial blood pressure also showed minute areas of focal gliosis without infarction. The number of these focal lesions showed a significant correlation with the severity of the hypertension, but not with the behavioral deficit. For four of these hypertensive monkeys, immunostaining demonstrated a pervasive, widespread activation of microglial cells and astroglial cells in the white matter as well as evidence of leaks in the blood-brain barrier, providing a more logical substrate for the cognitive decline.

Regional cerebral correlates of global motion perception: evidence from unilateral cerebral brain damage.

We used a psychophysical task to measure sensitivity to motion direction in 50 stroke patients with unilateral brain lesions and 85 control subjects. Subjects were asked to discriminate the overall direction of motion in dynamic stochastic random dot displays in which only a variable proportion of the spots moved in a single direction while the remainder moved randomly. Behavioural and neurophysiological evidence shows that the middle temporal (MT/V5) and middle superior temporal (MST) areas in the macaque monkey are indispensably involved in the perception of this type of motion. In human subjects too, lesions in the same region disrupt performance on this task. Here we assessed more extensively the correlation between direction sensitivity for global motion and the anatomical locus of the lesion. Thresholds for perceiving the direction of global motion were impaired in the visual field contralateral to the lesion in patients with lesions in the occipitoparietal and parietotemporal areas involving the human analogue of areas MT/V5 and MST, but not by lesions in the occipito-temporal or anterior frontal areas. Patients with lesions involving the anterior temporal or parietal lobes displayed poor performance for stimuli presented in either visual field, which is consistent with the large and bilateral receptive fields in these areas in monkeys. The perception of global motion was also more impaired in the centripetal than the centrifugal direction in the hemifield contralateral to the MT/V5 lesion. Surprisingly, thresholds were normal in all patients when the displays contained static but not dynamic visual noise, suggesting that their deficit reflects an inability to filter out dynamic noise. Although frequent repeated testing of some patients whose lesion involved the human homologue of MT was accompanied by an improvement in performance, this was no greater than in other patients who received training on different motion tasks.

Density and distribution of hippocampal neurotransmitter receptors in autism: an autoradiographic study.

Neuropathological studies in autistic brains have shown small neuronal size and increased cell packing density in a variety of limbic system structures including the hippocampus, a change consistent with curtailment of normal development. Based on these observations in the hippocampus, a series of quantitative receptor autoradiographic studies were undertaken to determine the density and distribution of eight types of neurotransmitter receptors from four neurotransmitter systems (GABAergic, serotoninergic [5-HT], cholinergic, and glutamatergic). Data from these single concentration ligand binding studies indicate that the GABAergic receptor system (3[H]-flunitrazepam labeled benzodiazepine binding sites and 3[H]-muscimol labeled GABA(A) receptors) is significantly reduced in high binding regions, marking for the first time an abnormality in the GABA system in autism. In contrast, the density and distribution of the other six receptors studied (3[H]-80H-DPAT labeled 5-HT1A receptors, 3[H]-ketanserin labeled 5-HT2 receptors, 3[H]-pirenzepine labled M1 receptors, 3[H]-hemicholinium labeled high affinity choline uptake sites, 3[H]-MK801 labeled NMDA receptors, and 3[H]-kainate labeled kainate receptors) in the hippocampus did not demonstrate any statistically significant differences in binding.

Naturally occurring woodchuck hepatitis virus (WHV) deletion mutants in chronically WHV-infected woodchucks.

Deletion mutants of hepatitis B virus (HBV) are often found in chronically HBV-infected patients. It has not been possible to study the significance of such deletion mutants on liver diseases in a suitable animal model. In this study, we characterized naturally occurring deletion mutants of woodchuck hepatitis virus (WHV) in 11 chronically WHV-infected woodchucks. Deletions within the WHV preS region (nt 2992-338) had a length of 72 or 84 bp and were located in the amino terminal part of preS1. Internal deletions within the core gene (CID) had variable lengths (103 to 312 bp) and were identified within the center of this gene (nt 2021-2587). Four of seven CIDs were in-frame deletions, whereas the remaining three CIDs were out-of-frame deletions and led to the interruption of the reading frame. Sequence analysis of cloned PCR products of CIDs showed that heterogeneous WHV deletion mutants coexisted in single woodchucks. In addition, WHV genomes with double deletions in the preS1 and the core region could be found. We were unable to detect the expression of truncated core proteins in transfection experiments. The CID mutations led to a marked increase of the expression of the luciferase gene which was fused to the start codon of WHV polymerase, probably due to the shortening of the untranslated region or the removal of AUGs preceding the polymerase start codon. The characterization of naturally occurring WHV deletion mutants will allow us to study their biological and pathogenic properties in the woodchuck model in the future.

Use of fibrinolytic agents in the prevention of postoperative adhesion formation.

OBJECTIVE: To review the events leading to the formation of adhesions, to describe the development of fibrinolytic agents, to review more than a century of research on the use of fibrinolytic agents in adhesion prevention, and to look at future aspects of adhesion prevention. RESULTS: A better understanding of the pathogenesis of adhesion formation has resulted in the use of fibrinolytic agents in their prevention. Fibrinolytic agents promote fibrinolytic activity during the early period after peritoneal trauma during which an increased formation of fibrin is seen in combination with a deficiency of endogenous fibrinolytic activity. Initially, chemical attacks on fibrin (fibrolysin and hypertonic glucose), foreign digestive ferments (pepsin, trypsin, and papain), and stimulation of intraperitoneal leukocytosis (amniotic fluid) were used. Development of new thrombolytic agents was soon followed by experiments in animal adhesion models and clinical studies to examine their antiadhesion properties. Plasmin preparations (plasmin, actase, and fibrinolysin) and plasmin activators (streptokinase, urokinase, and tissue-type plasminogen activator) were found to be efficacious in preventing adhesion formation in the greater part of reviewed animal and clinical studies. CONCLUSION(S): From the current literature, it can be concluded that postoperative intraperitoneal administration of thrombolytic agents can significantly decrease adhesion formation. Given the large number of experimental studies in animals, future studies should focus on the clinical use of fibrinolytic agents in the prevention of postsurgical adhesion formation.

Complications of hysteroscopy: a prospective, multicenter study.

OBJECTIVE: To estimate the incidence of complications of diagnostic and operative hysteroscopic procedures in the Netherlands and describe their nature. METHODS: Data on complications were recorded by 82 hospitals in 1997. Participating hospitals had a 100% response rate. Any unexpected events that required intraoperative or postoperative intervention were defined as complications in two groups: approach (entry-related) and technique-related (caused by surgical instruments). RESULTS: Thirty-eight complications occurred among 13,600 hysteroscopic procedures (rate 0.28%). Diagnostic hysteroscopic procedures had a significantly lower complication rate (0.13%) than operative procedures (rate 0.95%; P <.01). Fluid overloads of distention medium were recorded five times (rate 0.20%). The most frequent surgical complication was perforation of the uterine cavity (rate 0.76%). Approximately half the perforations (18 of 33) were entry-related. Bleeding caused by perforation was seen in 0.16% of cases. Incidences of complications were: intrauterine adhesiolysis 4.48%, endometrium resection 0.81%, myomectomy 0.75%, and removal of a polyp 0.38%. CONCLUSION: Diagnostic hysteroscopic procedures had very low complication rates, so are safe procedures with which to evaluate intrauterine pathology. Operative hysteroscopic procedures were more risky, but the removal of polyps had a very low complication rate (12 times lower than synechiolysis). Half the complications were entry-related, so attention has to be paid to the method of entry with the hysteroscope (ie, no unnecessary dilation of cervix and introduction of the scope under direct vision). The other half of complications were related to surgeons' experience and type of procedure.

Astrocytic hypertrophy and altered GFAP degradation with age in subcortical white matter of the rhesus monkey.

Reactive astrocytosis is a well known phenomenon that occurs in the normal aging process of the brain. While many studies indicate astrocytic hypertrophy and glial fibrillary acidic protein (GFAP) content increase with age in the hippocampal formation of certain animal models, it is unclear whether these findings are generalizable to the primate and to other areas of the brain. In this study, we quantitatively assessed age-related changes in astrocytic cell size and density in a rhesus monkey model of normal aging. By GFAP immunohistochemistry, we observed an increase in GFAP(+) cell size but not density in all subcortical white matter areas of the frontal, temporal, and parietal cortices. No significant increases in astrocyte hypertrophy were observed in any gray matter area examined. In addition, Western blotting experiments showed increases in total and degraded GFAP content with age, suggesting altered degradation and possibly production of GFAP occur with age.

Age-related neuronal loss from the substantia nigra-pars compacta and ventral tegmental area of the rhesus monkey.

This study was undertaken to document the effect of age on the volume, number, and size of neurons in the substantia nigra pars compacta (SNpc), the paranigral (VTApn), and the parabrachial pigmentosus (VTApbp) nuclei of the VTA in behaviorally well-characterized rhesus monkeys. Using a point counting technique and unbiased stereological methods, we found no significant effects of age on the volume of these dopaminergic brain stem nuclei, but there was significant age-related loss of total number of neurons in the SNpc and VTApn. The loss of neurons in the SNpc was found to be greater for neurons measuring less than 200 microm2 in cross sectional area, a size corresponding to the small GABAergic neurons in this nucleus. Age-related loss of total number of neurons in the SNpc and VTApn showed significant correlations with impairment on the delay phase of the delayed non match to sample test (DNMS), in the VTApn with impaired performance on the delayed recognition span test (DRST), and in the SNpc with impaired performance on the spatial component of reversal tasks. These correlations suggest that the loss of neurons in the SNpc and VTApn in these old monkeys may contribute to these behavioral deficits.

Microinfarction as a result of hypertension in a primate model of cerebrovascular disease.

Ten adult cynomolgus monkeys were studied as a non-human primate model of hypertensive cerebrovascular disease. Seven were made hypertensive by surgical coarctation of the aorta and three served as unoperated controls. After survival periods of 8-30 months, the brains were serially sectioned and surveyed for neuropathological changes. The most conspicuous change was minute areas of microinfarction in the white and gray matter. The lesions were of irregular shape with an average maximum diameter of less than 0.5 mm. They were slightly larger in the gray than in the white matter and appeared to be of different ages. Their area of predilection was the white matter of the forebrain, with smaller numbers in the cerebral cortex and scattered lesions elsewhere in the forebrain, brain stem and cerebellum. These microinfarcts did not correspond to usually described lesions in the human brain in hypertension or in other animal models of hypertensive cerebrovascular disease. We suggest that they represent an early change in the natural history of hypertensive neuropathology.

Human immunodeficiency virus infection, inducible nitric oxide synthase expression, and microglial activation: pathogenetic relationship to the acquired immunodeficiency syndrome dementia complex.

The regional expression of immune-mediated and neurotoxic events in the human immunodeficiency virus (HIV)-infected brain in relationship to the acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) and brain pathology remains uncertain. The extent of gp41, inducible nitric oxide synthase (iNOS), and HLA-DR expression was examined in the frontal lobe and basal ganglia of 25 patients at varying stages of ADC. The expression of gp41 and iNOS was present predominantly in perivascular cells and most often in the basal ganglia. Staining for gp41 correlated significantly with iNOS in the basal ganglia, whereas the severity of staining for gp41 and iNOS in the basal ganglia and white matter was significantly greater in subjects with moderate to severe dementia compared with those with milder impairment. The degree of macrophage staining in the white matter and basal ganglia also correlated significantly with ADC severity and was more abundant than gp41 or iNOS staining, particularly in the white matter. Logistic regression analysis revealed that staining for iNOS and gp41 increased linearly with ADC severity and was significantly more abundant in the basal ganglia compared with the white matter. Double-immunolabeling studies colocalized iNOS predominantly to macrophage/microglia and to gp41-positive cells. The expression of iNOS and gp41 in the basal ganglia combined with immune activation contributes to the development and progression of the clinical syndrome.

Immunization of woodchucks with plasmids expressing woodchuck hepatitis virus (WHV) core antigen and surface antigen suppresses WHV infection.

DNA vaccination can induce humoral and cellular immune response to viral antigens and confer protection to virus infection. In woodchucks, we tested the protective efficacy of immune response to woodchuck hepatitis core antigen (WHcAg) and surface antigen (WHsAg) of woodchuck hepatitis virus (WHV) elicited by DNA-based vaccination. Plasmids pWHcIm and pWHsIm containing WHV c- or pre-s2/s genes expressed WHcAg and WHsAg in transient transfection assays. Pilot experiments in mice revealed that a single intramuscular injection of 100 microgram of plasmid pWHcIm DNA induced an anti-WHcAg titer over 1:300 that was enhanced by boost injections. However, two injections of 100 microgram of pWHcIm did not induce detectable anti-WHcAg in woodchucks. With an increase in the dose to 1 mg of pWHcIm per injection, transient anti-WHcAg response and WHcAg-specific proliferation of peripheral mononuclear blood cells (PMBCs) appeared in woodchucks after repeated immunizations. Four woodchucks vaccinated with pWHcIm were challenged with 10(4) or 10(5) of the WHV 50% infective dose. They remained negative for markers of WHV replication (WHV DNA and WHsAg) in peripheral blood and developed anti-WHs in week 5 after challenge. In contrast, woodchucks not immunized or immunized with the control vector pcDNA3 developed acute WHV infection. Two woodchucks immunized with 1 mg of pWHsIm developed WHsAg-specific proliferative response of PBMCs but no measurable anti-WHsAg response. A rapid anti-WHsAg response developed during week 2 after virus challenge. Neither woodchuck developed any signs of WHV infection. These data indicate that DNA-based vaccination with WHcAg and WHsAg can elicit immunity to WHV infection.