Cholinergic, but not dopaminergic or noradrenergic, enhancement sharpens visual spatial perception in humans

The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker distance. We found that cholinergic enhancement with the cholinesterase inhibitor donepezil improved target detection, and modeling suggested that this was mainly due to a narrowing of the extent of facilitatory perceptual spatial interactions. In Experiment 2, we tested whether these effects were selective to the cholinergic system or would also be observed following enhancements of related neuromodulators dopamine or norepinephrine. Unlike cholinergic enhancement, dopamine (bromocriptine) and norepinephrine (guanfacine) manipulations did not improve performance or systematically alter the spatial profile of perceptual interactions between targets and distractors. These findings reveal mechanisms by which cholinergic signaling influences visual spatial interactions in perception and improves processing of a visual target among distractors, effects that are notably similar to those of spatial selective attention

Dysregulation of Angiopoietins Is Associated with Placental Malaria and Low Birth Weight

BACKGROUND: Placental malaria (PM) is associated with adverse pregnancy outcomes including low birth weight (LBW). However, the precise mechanisms by which PM induces LBW are poorly defined. Based on the essential role of angiopoietin (ANG)-1 and -2 in normal placental vascular development, we hypothesized that PM may result in the dysregulation of angiopoietins and thereby contribute to LBW outcomes. METHODS AND FINDINGS: In a mouse model of PM, we show that Plasmodium berghei ANKA infection of pregnant mice resulted in dysregulated angiopoietin levels and fetal growth restriction. PM lead to decreased ANG-1, increased ANG-2, and an elevated ratio of ANG-2/ANG-1 in the placenta and the serum. These observations were extended to malaria-exposed pregnant women: In a study of primigravid women prospectively followed over the course of pregnancy, Plasmodium falciparum infection was associated with a decrease in maternal plasma ANG-1 levels (P = 0.031) and an increase in the ANG-2:ANG-1 ratio (P = 0.048). ANG-1 levels recovered with successful treatment of peripheral parasitemia (P = 0.010). In a cross-sectional study of primigravidae at delivery, angiopoietin dysregulation was associated with PM (P = 0.002) and LBW (P = 0.041). Women with PM who delivered LBW infants had increased ANG-2:ANG-1 ratios (P = 0.002) compared to uninfected women delivering normal birth weight infants. CONCLUSIONS: These data support the hypothesis that dysregulation of angiopoietins is associated with PM and LBW outcomes, and suggest that ANG-1 and ANG-2 levels may be clinically informative biomarkers to identify P. falciparum-infected mothers at risk of LBW deliveries

Circulating Soluble Endoglin Levels in Pregnant Women in Cameroon and Malawi—Associations with Placental Malaria and Fetal Growth Restriction

Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng levels were higher in primigravidae than multigravidae from both Cameroon and Malawi, irrespective of malarial infection status (p<0.046 and p<0.001, respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM

Role of low Km cyclic AMP phosphodiesterase inhibition in tracheal relaxation and bronchodilation in the guinea pig.

ABSTRAC

Active megadetachment beneath the western United States

Geodetic data, interpreted in light of seismic imaging, seismicity, xenolith studies, and the late Quaternary geologic history of the northern Great Basin, suggest that a subcontinental-scale extensional detachment is localized near the Moho. To first order, seismic yielding in the upper crust at any given latitude in this region occurs via an M7 earthquake every 100 years. Here we develop the hypothesis that since 1996, the region has undergone a cycle of strain accumulation and release similar to “slow slip events” observed on subduction megathrusts, but yielding occurred on a subhorizontal surface 5–10 times larger in the slip direction, and at temperatures >800°C. Net slip was variable, ranging from 5 to 10 mm over most of the region. Strain energy with moment magnitude equivalent to an M7 earthquake was released along this “megadetachment,” primarily between 2000.0 and 2005.5. Slip initiated in late 1998 to mid-1999 in northeastern Nevada and is best expressed in late 2003 during a magma injection event at Moho depth beneath the Sierra Nevada, accompanied by more rapid eastward relative displacement across the entire region. The event ended in the east at 2004.0 and in the remainder of the network at about 2005.5. Strain energy thus appears to have been transmitted from the Cordilleran interior toward the plate boundary, from high gravitational potential to low, via yielding on the megadetachment. The size and kinematic function of the proposed structure, in light of various proxies for lithospheric thickness, imply that the subcrustal lithosphere beneath Nevada is a strong, thin plate, even though it resides in a high heat flow tectonic regime. A strong lowermost crust and upper mantle is consistent with patterns of postseismic relaxation in the southern Great Basin, deformation microstructures and low water content in dunite xenoliths in young lavas in central Nevada, and high-temperature microstructures in analog surface exposures of deformed lower crust. Large-scale decoupling between crust and upper mantle is consistent with the broad distribution of strain in the upper crust versus the more localized distribution in the subcrustal lithosphere, as inferred by such proxies as low P wave velocity and mafic magmatism

A description of the methods of the aspirin supplementation for pregnancy indicated risk reduction in nulliparas (ASPIRIN) study

Background: Preterm birth (PTB) remains the leading cause of neonatal mortality and long term disability throughout the world. Though complex in its origins, a growing body of evidence suggests that first trimester administration of low dose aspirin (LDA) may substantially reduce the rate of PTB.Methods: Hypothesis: LDA initiated in the first trimester reduces the risk of preterm birth. Study Design Type: Prospective randomized, placebo-controlled, double-blinded multi-national clinical trial conducted in seven low and middle income countries. Trial will be individually randomized with one-to-one ratio (intervention/control) Population: Nulliparous women between the ages of 14 and 40, with a singleton pregnancy between 6 0/7 weeks and 13 6/7 weeks gestational age (GA) confirmed by ultrasound prior to enrollment, no more than two previous first trimester pregnancy losses, and no contraindications to aspirin.Intervention: Daily administration of low dose (81 mg) aspirin, initiated between 6 0/7 weeks and 13 6/7 weeks GA and continued to 36 0/7 weeks GA, compared to an identical appearing placebo. Compliance and outcomes will be assessed biweekly.Outcomes: Primary outcome: Incidence of PTB (birth prior to 37 0/7 weeks GA). Secondary outcomes Incidence of preeclampsia/eclampsia, small for gestational age and perinatal mortality.Discussion: This study is unique as it will examine the impact of LDA early in pregnancy in low-middle income countries with preterm birth as a primary outcome. The importance of developing low-cost, high impact interventions in low-middle income countries is magnified as they are often unable to bear the financial costs of treating illness

Intra-week spatial-temporal patterns of crime

Since its original publication, routine activity theory has proven most instructive for understanding temporal patterns in crime. The most prominent of the temporal crime patterns investigated is seasonality: crime (most often assault) increases during the summer months and decreases once routine activities are less often outside. Despite the rather widespread literature on the seasonality of crime, there is very little research investigating temporal patterns of crime at shorter time intervals such as within the week or even within the day. This paper contributes to this literature through a spatial-temporal analysis of crime patterns for different days of the week. It is found that temporal patterns are present for different days of the week (more crime on weekends, as would be expected) and there is a spatial component to that temporal change. Specifically, aside from robbery and sexual assault at the micro-spatial unit of analysis (street segments) the spatial patterns of crime changed. With regard to the spatial pattern changes, we found that assaults and theft from vehicle had their spatial patterns change in predictable ways on Saturdays: assaults increased in the bar district and theft from vehicles increased in the downtown and recreational car park areas

Stillbirths: recall to action in high-income countries.

Variation in stillbirth rates across high-income countries and large equity gaps within high-income countries persist. If all high-income countries achieved stillbirth rates equal to the best performing countries, 19,439 late gestation (28 weeks or more) stillbirths could have been avoided in 2015. The proportion of unexplained stillbirths is high and can be addressed through improvements in data collection, investigation, and classification, and with a better understanding of causal pathways. Substandard care contributes to 20-30% of all stillbirths and the contribution is even higher for late gestation intrapartum stillbirths. National perinatal mortality audit programmes need to be implemented in all high-income countries. The need to reduce stigma and fatalism related to stillbirth and to improve bereavement care are also clear, persisting priorities for action. In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts. Programmes at community and country level need to improve health in disadvantaged families to address these inequities.Mater Research Institute – The University of Queensland provided infrastructure and funding for the research team to enable this work to be undertaken. The Canadian Research Chair in Psychosocial Family Health provided funding for revision of the translation of the French web-based survey of care providers.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/S0140-6736(15)01020-

The Equifinality of Archaeological Networks: an Agent-Based Exploratory Lab Approach

When we find an archaeological network, how can we explore the necessary versus contingent processes at play in the formation of that archaeological network? Given a set of circumstances or processes, what other possible network shapes could have emerged? This is the problem of equifinality, where many different means could potentially arrive at the same end result: the networks that we observe. This paper outlines how agent-based modelling can be used as a laboratory for exploring different processes of archaeological network formation. We begin by describing our best guess about how the (ancient) world worked, given our target materials (here, the networks of production and patronage surrounding the Roman brick industry in the hinterland of Rome). We then develop an agent-based model of the Roman extractive economy which generates different kinds of networks under various assumptions about how that economy works. The rules of the simulation are built upon the work of Bang (2006; 2008) who describes a model of the Roman economy which he calls the ‘imperial Bazaar’. The agents are allowed to interact, and the investigators compare the kinds of networks this description generates over an entire landscape of economic possibilities. By rigorously exploring this landscape, and comparing the resultant networks with those observed in the archaeological materials, the investigators will be able to employ the principle of equifinality to work out the representativeness of the archaeological network and thus the underlying processes

Obesity, physical activity, and the urban environment: public health research needs

Persistent trends in overweight and obesity have resulted in a rapid research effort focused on built environment, physical activity, and overweight. Much of the focus of this research has been on the design and form of suburbs. It suggests that several features of the suburban built environment such as low densities, poor street connectivity and the lack of sidewalks are associated with decreased physical activity and an increased risk of being overweight. But compared to suburban residents, inner city populations have higher rates of obesity and inactivity despite living in neighborhoods that are dense, have excellent street connectivity and who's streets are almost universally lined with sidewalks. We suggest that the reasons for this apparent paradox are rooted in the complex interaction of land use, infrastructure and social factors affecting inner city populations. Sometimes seemingly similar features are the result of very different processes, necessitating different policy responses to meet these challenges. For example, in suburbs, lower densities can result from government decision making that leads to restrictive zoning and land use issues. In the inner city, densities may be lowered because of abandonment and disinvestment. In the suburbs, changes in land use regulations could result in a healthier built environment. In inner cities, increasing densities will depend on reversing economic trends and investment decisions that have systematically resulted in distressed housing, abandoned buildings and vacant lots. These varying issues need to be further studied in the context of the totality of urban environments, incorporating what has been learned from other disciplines, such as economics and sociology, as well as highlighting some of the more successful inner city policy interventions, which may provide examples for communities working to improve their health. Certain disparities among urban and suburban populations in obesity and overweight, physical activity and research focus have emerged that are timely to address. Comparable research on the relationship of built environment and health is needed for urban, especially inner city, neighborhoods