The development of path integration: combining estimations of distance and heading

Efficient daily navigation is underpinned by path integration, the mechanism by which we use self-movement information to update our position in space. This process is well-understood in adulthood, but there has been relatively little study of path integration in childhood, leading to an underrepresentation in accounts of navigational development. Previous research has shown that calculation of distance and heading both tend to be less accurate in children as they are in adults, although there have been no studies of the combined calculation of distance and heading that typifies naturalistic path integration. In the present study 5-year-olds and 7-year-olds took part in a triangle-completion task, where they were required to return to the startpoint of a multi-element path using only idiothetic information. Performance was compared to a sample of adult participants, who were found to be more accurate than children on measures of landing error, heading error, and distance error. 7-year-olds were significantly more accurate than 5-year-olds on measures of landing error and heading error, although the difference between groups was much smaller for distance error. All measures were reliably correlated with age, demonstrating a clear development of path integration abilities within the age range tested. Taken together, these data make a strong case for the inclusion of path integration within developmental models of spatial navigational processing

Long-term associative learning predicts verbal short-term memory performance

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting

Sex‐specific alterations in whole body energetics and voluntary activity in heterozygous R163C malignant hyperthermia‐susceptible mice

Malignant hyperthermia (MH) is characterized by induction of skeletal muscle hyperthermia in response to a dysregulated increase in myoplasmic calcium. Although altered energetics play a central role in MH, MH‐susceptible humans and mouse models are often described as having no phenotype until exposure to a triggering agent. The purpose of this study was to determine the influence of the R163C ryanodine receptor 1 mutation, a common MH mutation in humans, on energy expenditure, and voluntary wheel running in mice. Energy expenditure was measured by indirect respiration calorimetry in wild‐type (WT) and heterozygous R163C (HET) mice over a range of ambient temperatures. Energy expenditure adjusted for body weight or lean mass was increased (P < .05) in male, but not female, HET mice housed at 22°C or when housed at 28°C with a running wheel. In female mice, voluntary wheel running was decreased (P < .05) in the HET vs WT animals when analyzed across ambient temperatures. The thermoneutral zone was also widened in both male and female HET mice. The results of the study show that the R163C mutations alters energetics even at temperatures that do not typically induce MH

Mindful Aging: The Effects of Regular Brief Mindfulness Practice on Electrophysiological Markers of Cognitive and Affective Processing in Older Adults

There is growing interest in the potential benefits of mindfulness meditation practices in terms of counteracting some of the cognitive effects associated with aging. Pursuing this question, the aim of the present study was to investigate the influence of mindfulness training on executive control and emotion regulation in older adults, by means of studying behavioral and electrophysiological changes. Participants, 55 to 75 years of age, were randomly allocated to an 8-week mindful breath awareness training group or an active control group engaging in brain training exercises. Before and after the training period, participants completed an emotional-counting Stroop task, designed to measure attentional control and emotion regulation processes. Concurrently, their brain activity was measured by means of 64-channel electroencephalography. The results show that engaging in just over 10 min of mindfulness practice five times per week resulted in significant improvements in behavioral (response latency) and electrophysiological (N2 event-related potential) measures related to general task performance. Analyses of the underlying cortical sources (Variable Resolution Electromagnetic Tomography, VARETA) indicate that this N2-related effect is primarily associated with changes in the right angular gyrus and other areas of the dorsal attention network. However, the study did not find the expected specific improvements in executive control and emotion regulation, which may be due to the training instructions or the relative brevity of the intervention. Overall, the results indicate that engaging in mindfulness meditation training improves the maintenance of goal-directed visuospatial attention and may be a useful strategy for counteracting cognitive decline associated with aging

Characterization of a fluvial aquifer at a range of depths and scales: the Triassic St Bees Sandstone Formation, Cumbria, UK

Fluvial sedimentary successions represent porous media that host groundwater and geothermal resources. Additionally, they overlie crystalline rocks hosting nuclear waste repositories in rift settings. The permeability characteristics of an arenaceous fluvial succession, the Triassic St Bees Sandstone Formation in England (UK), are described, from core-plug to well-test scale up to ~1 km depth. Within such lithified successions, dissolution associated with the circulation of meteoric water results in increased permeability (K~10−1–100 m/day) to depths of at least 150 m below ground level (BGL) in aquifer systems that are subject to rapid groundwater circulation. Thus, contaminant transport is likely to occur at relatively high rates. In a deeper investigation (> 150 m depth), where the aquifer has not been subjected to rapid groundwater circulation, well-test-scale hydraulic conductivity is lower, decreasing from K~10−2 m/day at 150–400 m BGL to 10−3 m/day down-dip at ~1 km BGL, where the pore fluid is hypersaline. Here, pore-scale permeability becomes progressively dominant with increasing lithostatic load. Notably, this work investigates a sandstone aquifer of fluvial origin at investigation depths consistent with highly enthalpy geothermal reservoirs (~0.7–1.1 km). At such depths, intergranular flow dominates in unfaulted areas with only minor contribution by bedding plane fractures. However, extensional faults represent preferential flow pathways, due to presence of high connective open fractures. Therefore, such faults may (1) drive nuclear waste contaminants towards the highly permeable shallow (< 150 m BGL) zone of the aquifer, and (2) influence fluid recovery in geothermal fields

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques

<p>Abstract</p> <p>Background</p> <p>Myeloperoxidase (MPO) -containing macrophages and neutrophils have been described at sites of plaque rupture. The presence of these cells in precursor lesions to acute rupture (thin cap atheroma, or vulnerable plaque) and within thrombi adjacent to ruptures has not been described, nor an association with iron-containing macrophages within unstable plaques.</p> <p>Methods</p> <p>We studied 61 acute ruptures, 15 organizing ruptures, 31 thin cap fibroatheromas, and 28 fibroatheromas from 72 sudden coronary death victims by immunohistochemical and histochemical techniques. Inflammatory cells were typed with anti-CD68 (macrophages), anti-BP-30 (neutrophil bactericidal glycoprotein), and anti-MPO. Iron was localized by Mallory's Prussian blue stain. In selected plaques alpha smooth muscle actin (DAKO, Carpinteria, CA, clone M0851) was performed.</p> <p>Results</p> <p>MPO positive cells were present in 79% of ruptured caps, 28% of thin cap fibroatheroma, and no fibroatheromas; neutrophils were present in 72% of ruptures, 8% of thin cap fibroatheromas, and no fibroatheromas. Iron containing foam cells were present in the caps of 93% of acute ruptures, of 85% of organizing ruptures, 20% of thin cap atheromas, and 10% of fibroatheromas. MPO positive cells were more frequent in occlusive than non-occlusive thrombi adjacent to ruptures (p = .006) and were more numerous in diabetics compared to non-diabetics (p = .002)</p> <p>Conclusion</p> <p>Unstable fibrous caps are more likely to contain MPO-positive cells, neutrophils, and iron-containing macrophages than fibrous caps of stable fibroatheromas. MPO-positive cells in thrombi adjacent to disrupted plaques are associated with occlusive thrombi and are more numerous in diabetic patients.</p

Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania

BACKGROUND: Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. METHODS: The genes for dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were used as markers, to investigate parasite resistance to SP in 141 children aged less than 5 years. Parasite DNA was extracted by Chelex method from blood samples collected and preserved on filter papers. Subsequently, polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) were applied to detect the SP resistance-associated point mutations on dhfr and dhps. Commonly reported point mutations at codons 51, 59, 108 and 164 in the dhfr and codons 437, 540 and 581 in the dhps domains were examined. RESULTS: Children infected with parasites harbouring a range of single to quintuple dhfr/dhps mutations were erratically cured with SP. However, the quintuple dhfr/dhps mutant genotypes were mostly associated with treatment failures. High proportion of SP resistance-associated point mutations was detected in this study but the adequate clinical response (89.4%) observed clinically at day 14 of follow up reflects the role of semi-immunity protection and parasite clearance in the population. CONCLUSION: In monitoring drug resistance to SP, concurrent studies on possible confounding factors pertaining to development of resistance in falciparum malaria should be considered. The SP resistance potential detected in this study, cautions on its useful therapeutic life as an interim first-line drug against malaria in Tanzania and other malaria-endemic countries