Polygenic risk for Alzheimer's disease shapes hippocampal scene-selectivity

Preclinical models of Alzheimer’s disease (AD) suggest APOE modulates brain function in structures vulnerable to AD pathophysiology. However, genome-wide association studies now demonstrate that AD risk is shaped by a broader polygenic architecture, estimated via polygenic risk scoring (AD-PRS). Despite this breakthrough, the effect of AD-PRS on brain function in young individuals remains unknown. In a large sample (N = 608) of young, asymptomatic individuals, we measure the impact of both (i) APOE and (ii) AD-PRS on a vulnerable cortico-limbic scene-processing network heavily implicated in AD pathophysiology. Integrity of this network, which includes the hippocampus (HC), is fundamental for maintaining cognitive function during ageing. We show that AD-PRS, not APOE, selectively influences activity within the HC in response to scenes, while other perceptual nodes remained intact. This work highlights the impact of polygenic contributions to brain function beyond APOE, which could aid potential therapeutic/interventional strategies in the detection and prevention of AD

Uncovering the high prevalence of bacterial burden in surgical site wounds with point‐of‐care fluorescence imaging

Detection of bacterial burden within or near surgical wounds is critical to reducing the occurrence of surgical site infection (SSI). A distinct lack of reliable methods to identify postoperative bioburden has forced reliance on clinical signs and symptoms of infection (CSS). As a result, infection management has been reactive, rather than proactive. Fluorescence imaging of bacterial burden (FL) is positioned to potentially flip that paradigm. This post hoc analysis evaluated 58 imaged and biopsied surgical site wounds from the multi-centre fluorescence imaging assessment and guidance clinical trial. Diagnostic accuracy measures of CSS and FL were evaluated. A reader study investigated the impact of advanced image interpretation experience on imaging sensitivity. Forty-four of fifty-eight surgical site wounds (75.8%) had bacterial loads >104 CFU/g (median = 3.11 × 105 CFU/g); however, only 3 of 44 were CSS positive (sensitivity of 6.8%). FL improved sensitivity of bacterial detection by 5.7-fold compared with CSS alone (P = .0005). Sensitivity improved by 11.3-fold over CSS among clinicians highly experienced with FL interpretation (P < .0001). Surgical sites that reach the stage of referral to a wound specialist frequently harbour asymptomatic high bacterial loads that delay healing and increase infection risk. Advanced imaging of pathological bacterial burden improves surgical site monitoring and may reduce the rate of SSIs

Discovery of an unknown diversity of Leucinodes species damaging Solanaceae fruits in sub-Saharan Africa and moving in trade (Insecta, Lepidoptera, Pyraloidea)

The larvae of the Old World genera Leucinodes Guenée, 1854 and Sceliodes Guenée, 1854 are internal feeders in the fruits of Solanaceae, causing economic damage to cultivated plants like Solanum melongena and S. aethiopicum . In sub-Saharan Africa five nominal species of Leucinodes and one of Sceliodes occur. One of these species, the eggplant fruit and shoot borer L. orbonalis Guenée, 1854, is regarded as regularly intercepted from Africa and Asia in Europe, North and South America and is therefore a quarantine pest on these continents. We investigate the taxonomy of African Leucinodes and Sceliodes based on morpho - logical characters in wing pattern, genitalia and larvae, as well as mitochondrial DNA, providing these data for identification of all life stages. The results suggest that both genera are congeneric, with Sceliodes syn. n. established as junior subjective synonym of Leucinodes . L. orbonalis is described from Asia and none of the samples investigated from Africa belong to this species. Instead, sub-Saharan Africa harbours a complex of eight endemic Leucinodes species. Among the former nominal species of Leucinodes (and Sceliodes ) from Africa, only L. laisalis (Walker, 1859), comb. n. ( Sceliodes ) is confirmed, with Leucinodes translucidalis Gaede, 1917, syn. n. as a junior subjective synonym. The other African Leucinodes species were unknown to science and are described as new: L. africensis sp. n. , L. ethiopica sp. n. , L. kenyensis sp. n. , L. malawiensis sp. n. , L. pseudorbonalis sp. n. , L. rimavallis sp. n. and L. ugandensis sp. n. An identification key based on male genitalia is provided for the African Leucinodes species. Most imports of Leucinodes specimens from Africa into Europe refer to Leucinodes africensis , which has been frequently imported with fruits during the last 50 years. In contrast, L. laisalis has been much less frequently re - corded, and L. pseudorbonalis as well as L. rimavallis only very recently in fruit imports from Uganda. Accordingly, interceptions of Leucinodes from Africa into other continents will need to be re-investigated for their species identity and will likely require, at least in parts, revisions of the quarantine regulations. The following African taxa are excluded from Leucinodes : Hyperanalyta Strand, 1918, syn. rev. as revised synonym of Analyta Lederer, 1863; Analyta apicalis (Hampson, 1896), comb. n. ( Leucinodes ); Lygropia aureomarginalis (Gaede, 1916), comb. n. ( Leucinodes ); Syllepte hemichionalis Mabille, 1900, comb. rev. , S. hemichionalis idalis Viette, 1958, comb. rev. and S. vagans (Tutt, 1890), comb. n. ( Aphytoceros ). Deanolis iriocapna (Meyrick, 1938), comb. n. from Indonesia is originally described and misplaced in Sceliodes , and L. cordalis (Doubleday, 1843), comb. n. ( Margaritia ) from New Zealand, L. raondry (Viette, 1981) comb. n. ( Daraba ) from Madagascar as well as L. grisealis (Kenrick, 1912), comb. n. ( Sceliodes ) from New Guinea are transferred from Sceliodes to Leucinodes . While Leucinodes is now revised from Africa, it still needs further revision in Asia.publishedVersio

Reproducing the general through the local: Lessons from poverty research

Central to research into the conduct of everyday life are issues of generalisation. This chapter focuses on three interrelated forms or manifestations of generalisation, which invoke issues around how macro-level structures and intergroup relations are reproduced through micro-level situations. First, theoretical generalisation constitutes our efforts to enlarge the significance of small-scale exemplars through research by relating local insights to the broader body of academic knowledge. Second, referential generalisation involves relating everyday artefacts produced by our research participants to the broader social context and intergroup relations at play. Third, empathetic generalisation involves promoting witnessing, recognition, and empathy towards people experiencing poverty by people who are not living in poverty. These three forms or elements of generalisation are central to the development of action strategies to address issues of poverty

Ultra-high-field fMRI reveals a role for the subiculum in scene perceptual discrimination

Recent “representational” accounts suggest a key role for the hippocampus in complex scene perception. Due to limitations in scanner field strength, however, the functional neuroanatomy of hippocampal-dependent scene perception is unknown. Here, we applied 7 T high-resolution functional magnetic resonance imaging (fMRI) alongside a perceptual oddity task, modified from nonhuman primate studies. This task requires subjects to discriminate highly similar scenes, faces, or objects from multiple viewpoints, and has revealed selective impairments during scene discrimination following hippocampal lesions. Region-of-interest analyses identified a preferential response in the subiculum subfield of the hippocampus during scene, but not face or object, discriminations. Notably, this effect was in the anteromedial subiculum and was not modulated by whether scenes were subsequently remembered or forgotten. These results highlight the value of ultra-high-field fMRI in generating more refined, anatomically informed, functional accounts of hippocampal contributions to cognition, and a unique role for the human subiculum in discrimination of complex scenes from different viewpoints

Obsidians of Pantelleria (Strait of Sicily): A Petrographic, Geochemical and Magnetic Study of Known and New Geological Sources

This paper provides new petrochemical and paleomagnetic data from obsidian sub-sources on the island of Pantelleria, exploited since the Neolithic. Data has been obtained from 14 obsidian samples from 4 locations: Fossa della Pernice (2 sites), Salto la Vecchia and Balata dei Turchi. Here, we aim to better characterize these obsidians using a cross-disciplinary and multi-analytical approach, to further understand their archaeological significance. Major element analyses (EMP) have enabled two compositional super-groups to be distinguished: (i) Fossa della Pernice, less peralkaline and (ii) Balata dei Turchi-Salto la Vecchia, distinctly more peralkaline and having almost identical chemical patterns. Trace element analyses (LA-ICP-MS) corroborate major element groupings, with the Balata dei Turchi-Salto la Vecchia super-group being further characterized by a pronounced negative europium anomaly. Glass H2O contents (FT-IR) reveal an overlap among all the sub-sources (H2O = 0.1-0.3 wt. %). Magnetic methods have refined the petrochemical groupings, permitting further distinction between Balata dei Turchi-Salto La Vecchia and the Fossa della Pernice super-groups. The occurrence of sub-microscopic (&lt; 1 μm) ferromagnetic minerals results in different magnetic susceptibility and Natural Remanent Magnetization values and allows the best distinction among the products from the chosen sites. When compared with obsidian tools excavated from Bronze-age settlements on the island of Ustica (230 km NE of Pantelleria), 12% are distinctly peralkaline, indicating their provenance to be from the Balata dei Turchi sub-source

A Mystery Unraveled: Non-tumorigenic pluripotent stem cells in human adult tissues

Embryonic stem cells and induced pluripotent stem cells have emerged as the gold standard of pluripotent stem cells and the class of 10 stem cell with the highest potential for contribution to regenerative and therapeutic application; however, their translational use is often impeded by teratoma formation, commonly associated with pluripotency. We discuss a population of nontumorigenic pluripotent stem cells, termed Multilineage Differentiating Stress Enduring (Muse) cells, which offer an innovative and 15 exciting avenue of exploration for the potential treatment of various human diseases. Areas covered: This review discusses the origin of Muse cells, describes in detail their various unique characteristics, and considers future avenues of their application and investigation with respect to what is currently known 20 of adult pluripotent stem cells in scientific literature. We begin by defining cell potency, then discussing both mesenchymal and various reported populations of pluripotent stem cells, and finally, delving into Muse cells and what sets them apart from their contemporaries. Expert opinion: Muse cells derived from adipose tissue (Muse-AT) are 25 efficiently, routinely and painlessly isolated from human lipoaspirate material, exhibit tripoblastic differentiation both spontaneously and under media-specific induction, and do not form teratomas. We describe qualities specific to Muse-ATcells and their potential impact on the field of regenerative medicine and cell therapy.Fil: Simerman, Ariel A.. University of California; Estados UnidosFil: Perone, Marcelo Javier. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Gimeno, Maria Laura. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Dumesic, Daniel A.. University of California; Estados UnidosFil: Chazenblak, Gregorio D.. University of California; Estados Unido

The effects of clinical task interruptions on subsequent performance of a medication pre-administration task

There is a surge of research exploring the role of task interruptions in the manifestation of primary task errors both in controlled experimental settings, and safety critical workplaces such as healthcare. Despite such research providing valuable insights into the disruptive properties of task interruption, and, the importance of considering the likely disruptive consequences of clinical task interruptions in healthcare environments, there is an urgent need for an approach that best mimics complex working environments such as healthcare, whilst allowing better control over experimental variables with minimal constraints. We propose that this can be achieved with ecologically sensitive experimental tasks designed to have high levels of experimental control so that theoretical as well as practical parameters and factors can be tested. We developed a theoretically and ecologically informed procedural memory-based task - the CAMROSE Medication Pre-Administration Task. Results revealed significantly more sequence errors were made on low, moderate and high complex conditions compared to no interruption condition. There was no significant difference in non-sequence errors. Findings reveal the importance of developing ecologically valid tasks to explore non-observable characteristics of clinical task interruptions. Both theoretical and possible practical implications are discussed

Hsp21potentiates antifungal drug tolerance in Candida albicans

Peer reviewedPublisher PD

Quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 1: Individual participant data meta-analysis and health economic analysis.

INTRODUCTION: The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (qfFN) concentration, in combination with clinical risk factors. METHODS AND ANALYSIS: The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts) which quantifies fFN in a vaginal swab. In part 1 of the study, we will develop and internally validate a prognostic model using an individual participant data (IPD) meta-analysis of existing studies containing women with symptoms of preterm labour alongside fFN measurements and pregnancy outcome. An economic analysis will be undertaken to assess potential cost-effectiveness of the qfFN prognostic model. The primary endpoint will be the ability of the prognostic model to rule out spontaneous preterm birth within 7 days. Six eligible studies were identified by systematic review of the literature and five agreed to provide their IPD (n=5 studies, 1783 women and 139 events of preterm delivery within 7 days of testing). ETHICS AND DISSEMINATION: The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). PROSPERO REGISTRATION NUMBER: CRD42015027590. VERSION: Protocol version 2, date 1 November 2016