Altered Patterns of Fungal Keratitis at a London Ophthalmic Referral Hospital: An Eight-Year Retrospective Observational Study.

PURPOSE: In previous studies of fungal keratitis (FK) from temperate countries, yeasts were the predominant isolates, with ocular surface disease (OSD) being the leading risk factor. Since the 2005-2006 outbreak of contact lens (CL)-associated Fusarium keratitis, there may have been a rise in CL-associated filamentary FK in the United Kingdom. This retrospective case series investigated the patterns of FK from 2007 to 2014. We compared these to 1994-2006 data from the same hospital. DESIGN: Retrospective observational study. METHODS: All cases of FK presenting to Moorfields Eye Hospital between 2007 and 2014 were identified. The definition of FK was either a fungal organism isolated by culture or fungal structures identified by light microscopy (LM) of scrape material, histopathology, or in vivo corneal confocal microscopy (IVCM). Main outcome measure was cases of FK per year. RESULTS: A total of 112 patients had confirmed FK. Median age was 47.2 years. Between 2007 and 2014, there was an increase in annual numbers of FK (Poisson regression, P = .0001). FK was confirmed using various modalities: 79 (70.5%) by positive culture, 16 (14.3%) by LM, and 61 (54.5%) by IVCM. Seventy-eight patients (69.6%) were diagnosed with filamentary fungus alone, 28 (25%) with yeast alone, and 6 (5.4%) with mixed filamentary and yeast infections. This represents an increase in the proportion of filamentary fungal infections from the pre-2007 data. Filamentary fungal and yeast infections were associated with CL use and OSD, respectively. CONCLUSIONS: The number of FK cases has increased. This increase is due to CL-associated filamentary FK. Clinicians should be aware of these changes, which warrant epidemiologic investigations to identify modifiable risk factors

Long-term Late Cretaceous oxygen-and carbonisotope trends and planktonic foraminiferal turnover: A new record from the southern midlatitudes

© 2016 Geological Society of America. The ~35-m.y.-long Late Cretaceous greenhouse climate has been the subject of a number of studies, with emphasis on the Cenomanian-Turonian and late Campanian-Maastrichtian intervals. By contrast, far less information is available for the Turonian-early Campanian interval, even though it encompasses the transition out of the extreme warmth of the Cenomanian-Turonian greenhouse climate optimum and includes an ~3-m.y.-long mid-Coniacian-mid-Santonian interval when planktonic foraminifera underwent a large-scale, but poorly understood, turnover. This study presents ~1350 δ18O and δ13C values of wellpreserved benthic and planktonic foraminifera and of the <63 μm size fraction from the Exmouth Plateau off Australia (eastern Indian Ocean). These data provide: (1) the most continuous, highly resolved, and stratigraphically well-constrained record of longterm trends in Late Cretaceous oxygen-and carbon-isotope ratios from the southern midlatitudes, and (2) new information on the paleoecological preferences of planktonic foraminiferal taxa. The results indicate persistent warmth from the early Turonian until the mid-Santonian, cooling from the mid-Santonian through the mid-Campanian, and short-term climatic variability during the late Campanian-Maastrichtian. Moreover, our results suggest the cause of Coniacian-Santonian turnover among planktonic foraminifera may have been the diversification of a temperature-and/or salinity-tolerant genus (Marginotruncana), and the cause of the Santonian-early Campanian extinction of Dicarinella and Marginotruncana may have been surface-ocean cooling and competition with globotruncanids

NODAL/TGFβ signalling mediates the self-sustained stemness induced by PIK3CAH1047R homozygosity in pluripotent stem cells

Activating PIK3CA mutations are known “drivers” of human cancer and developmental overgrowth syndromes. We recently demonstrated that the "hotspot" PIK3CAH1047R variant exerts unexpected allele dose-dependent effects on stemness in human pluripotent stem cells (hPSCs). In the present study, we combine high-depth transcriptomics, total proteomics and reverse-phase protein arrays to reveal potentially disease-related alterations in heterozygous cells, and to assess the contribution of activated TGFβ signalling to the stemness phenotype of homozygous PIK3CAH1047R cells. We demonstrate signalling rewiring as a function of oncogenic PI3K signalling strength, and provide experimental evidence that self-sustained stemness is causally related to enhanced autocrine NODAL/TGFβ signalling. A significant transcriptomic signature of TGFβ pathway activation in heterozygous PIK3CAH1047R was observed but was modest and was not associated with the stemness phenotype seen in homozygous mutants. Notably, the stemness gene expression in homozygous PIK3CAH1047R iPSCs was reversed by pharmacological inhibition of NODAL/TGFβ signalling, but not by pharmacological PI3Kα pathway inhibition. Altogether, this provides the first in-depth analysis of PI3K signalling in human pluripotent stem cells and directly links strong PI3K activation to developmental NODAL/TGFβ signalling. This work illustrates the importance of allele dosage and expression when artificial systems are used to model human genetic disease caused by activating PIK3CA mutations

The El Nino event of 2015-2016: climate anomalies and their impact on groundwater resources in East and Southern Africa

The impact of climate variability on groundwater storage has received limited attention despite widespread dependence on groundwater as a resource for drinking water, agriculture and industry. Here, we assess the climate anomalies that occurred over Southern Africa (SA) and East Africa, south of the Equator (EASE), during the major El Niño event of 2015–2016, and their associated impacts on groundwater storage, across scales, through analysis of in situ groundwater piezometry and Gravity Recovery and Climate Experiment (GRACE) satellite data. At the continental scale, the El Niño of 2015–2016 was associated with a pronounced dipole of opposing rainfall anomalies over EASE and Southern Africa, north–south of ∼12∘ S, a characteristic pattern of the El Niño–Southern Oscillation (ENSO). Over Southern Africa the most intense drought event in the historical record occurred, based on an analysis of the cross-scale areal intensity of surface water balance anomalies (as represented by the standardised precipitation evapotranspiration index – SPEI), with an estimated return period of at least 200 years and a best estimate of 260 years. Climate risks are changing, and we estimate that anthropogenic warming only (ignoring changes to other climate variables, e.g. precipitation) has approximately doubled the risk of such an extreme SPEI drought event. These surface water balance deficits suppressed groundwater recharge, leading to a substantial groundwater storage decline indicated by both GRACE satellite and piezometric data in the Limpopo basin. Conversely, over EASE during the 2015–2016 El Niño event, anomalously wet conditions were observed with an estimated return period of ∼10 years, likely moderated by the absence of a strongly positive Indian Ocean zonal mode phase. The strong but not extreme rainy season increased groundwater storage, as shown by satellite GRACE data and rising groundwater levels observed at a site in central Tanzania. We note substantial uncertainties in separating groundwater from total water storage in GRACE data and show that consistency between GRACE and piezometric estimates of groundwater storage is apparent when spatial averaging scales are comparable. These results have implications for sustainable and climate-resilient groundwater resource management, including the potential for adaptive strategies, such as managed aquifer recharge during episodic recharge events

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2

Spatial Kramers-Kronig relations and the reflection of waves

Copyright © 2015, Rights Managed by Nature Publishing GroupAuthor version of article. The version of record is available from the publisher via DOI: 10.1038/nphoton.2015.106When a planar dielectric medium has a permittivity profile that is an analytic function in the upper or lower half of the complex position plane x=x'+ix'' then the real and imaginary parts of its permittivity are related by the spatial Kramers-Kronig relations. We find that such a medium will not reflect radiation incident from one side, whatever the angle of incidence. Using the spatial Kramers-Kronig relations, one can derive a real part of a permittivity profile from some given imaginary part (or vice versa) such that the reflection is guaranteed to be zero. This result is valid for both scalar and vector wave theories and may have relevance for designing materials that efficiently absorb radiation or for the creation of a new type of anti-reflection surface.Engineering and Physical Sciences Research Council (EPSRC

The selection landscape and genetic legacy of ancient Eurasians

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes 1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans

A call for transparent reporting to optimize the predictive value of preclinical research

The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress

The relative contribution of shape and colour to object memory

The current studies examined the relative contribution of shape and colour in object representations in memory. A great deal of evidence points to the significance of shape in object recognition, with the role of colour being instrumental under certain circumstances. A key but yet unanswered question concerns the contribution of colour relative to shape in mediating retrieval of object representations from memory. Two experiments (N=80) used a new method to probe episodic memory for objects and revealed the relative contribution of colour and shape in recognition memory. Participants viewed pictures of objects from different categories, presented one at a time. During a practice phase, participants performed yes/no recognition with some of the studied objects and their distractors. Unpractised objects shared shape only (Rp–Shape), colour only (Rp–Colour), shape and colour (Rp–Both), or neither shape nor colour (Rp–Neither), with the practised objects. Interference effects in memory between practised and unpractised items were revealed in the forgetting of related unpractised items – retrieval-induced forgetting. Retrieval-induced forgetting was consistently significant for Rp–Shape and Rp–Colour objects. These findings provide converging evidence that colour is an automatically encoded object property, and present new evidence that both shape and colour act simultaneously and effectively to drive retrieval of objects from long-term memory

Reporting and Methods in Clinical Prediction Research: A Systematic Review

Walter Bouwmeester and colleagues investigated the reporting and methods of prediction studies in 2008, in six high-impact general medical journals, and found that the majority of prediction studies do not follow current methodological recommendations