Obstructive sleep apnoea (OSA) is a common disease that leads to daytime sleepiness and cognitive impairment. Attempts to investigate changes in brain morphology that may underlie these impairments ...have led to conflicting conclusions. This study was undertaken to aim to resolve this confusion, and determine whether OSA is associated with changes in brain morphology in a large group of patients with OSA, using improved voxel-based morphometry analysis, an automated unbiased method of detecting local changes in brain structure.
60 patients with OSA (mean apnoea hypopnoea index 55 (95% CI 48 to 62) events/h, 3 women) and 60 non-apnoeic controls (mean apnoea hypopnoea index 4 (95% CI 3 to 5) events/h, 5 women) were studied. Subjects were imaged using T1-weighted 3-D structural MRI (69 subjects at 1.5 T, 51 subjects at 3 T). Differences in grey matter were investigated in the two groups, controlling for age, sex, site and intracranial volume. Dedicated cerebellar analysis was performed on a subset of 108 scans using a spatially unbiased infratentorial template.
Patients with OSA had a reduction in grey matter volume in the right middle temporal gyrus compared with non-apnoeic controls (p<0.05, corrected for topological false discovery rate across the entire brain). A reduction in grey matter was also seen within the cerebellum, maximal in the left lobe VIIIb close to XI, extending across the midline into the right lobe.
These data show that OSA is associated with focal loss of grey matter that could contribute to cognitive decline. Specifically, lesions in the cerebellum may result in both motor dysfunction and working memory deficits, with downstream negative consequences on tasks such as driving.
Flood events cause substantial damage to urban and rural areas. Monitoring water extent during large-scale flooding is crucial in order to identify the area affected and to evaluate damage. During ...such events, spatial assessments of floodwater may be derived from satellite or airborne sensing platforms. Meanwhile, an increasing availability of smartphones is leading to documentation of flood events directly by individuals, with information shared in real-time using social media. Topographic data, which can be used to determine where floodwater can accumulate, are now often available from national mapping or governmental repositories. In this work, we present and evaluate a method for rapidly estimating flood inundation extent based on a model that fuses remote sensing, social media and topographic data sources. Using geotagged photographs sourced from social media, optical remote sensing and high-resolution terrain mapping, we develop a Bayesian statistical model to estimate the probability of flood inundation through weights-of-evidence analysis. Our experiments were conducted using data collected during the 2014 UK flood event and focus on the Oxford city and surrounding areas. Using the proposed technique, predictions of inundation were evaluated against ground-truth flood extent. The results report on the quantitative accuracy of the multisource mapping process, which obtained area under receiver operating curve values of 0.95 and 0.93 for model fitting and testing, respectively.
Abstract
Previous examinations of fully convective M-dwarf stars have highlighted enhanced rates of nanoflare activity on these distant stellar sources. However, the specific role the convective ...boundary, which is believed to be present for spectral types earlier than M2.5V, plays on the observed nanoflare rates is not yet known. Here, we utilize a combination of statistical and Fourier techniques to examine M-dwarf stellar lightcurves that lie on either side of the convective boundary. We find that fully convective M2.5V (and later subtypes) stars have greatly enhanced nanoflare rates compared with their pre-dynamo mode-transition counterparts. Specifically, we derive a flaring power-law index in the region of 3.00 ± 0.20, alongside a decay timescale of 200 ± 100 s for M2.5V and M3V stars, matching those seen in prior observations of similar stellar subtypes. Interestingly, M4V stars exhibit longer decay timescales of 450 ± 50 s, along with an increased power-law index of 3.10 ± 0.18, suggesting an interplay between the rate of nanoflare occurrence and the intrinsic plasma parameters, e.g., the underlying Lundquist number. In contrast, partially convective (i.e., earlier subtypes from M0V to M2V) M-dwarf stars exhibit very weak nanoflare activity, which is not easily identifiable using statistical or Fourier techniques. This suggests that fully convective stellar atmospheres favor small-scale magnetic reconnection, leading to implications for the flare-energy budgets of these stars. Understanding why small-scale reconnection is enhanced in fully convective atmospheres may help solve questions relating to the dynamo behavior of these stellar sources.
Increasing recognition of malformations of cortical development and continuing improvements in imaging techniques, molecular biologic techniques, and knowledge of mechanisms of brain development have ...resulted in continual improvement of the understanding of these disorders. The authors propose a revised classification based on the stage of development (cell proliferation, neuronal migration, cortical organization) at which cortical development was first affected. The categories are based on known developmental steps, known pathologic features, known genetics (when possible), and, when necessary, neuroimaging features. In those cases in which the precise developmental and genetic features are uncertain, classification is based on known relationships among the genetics, pathologic features, and neuroimaging features. The major change since the prior classification has been a shift to using genotype, rather than phenotype, as the basis for classifying disorders wherever the genotype-phenotype relationship is adequately understood. Other substantial changes include more detailed classification of congenital microcephalies, particularly those in which the genes have been mapped or identified, and revised classification of congenital muscular dystrophies and polymicrogyrias. Information on genetic testing is also included. This classification allows a better conceptual understanding of the disorders, and the use of neuroimaging characteristics allows it to be applied to all patients without necessitating brain biopsy, as in pathology-based classifications.
The development of new thermal barrier coatings (TBC's) capable of increasing the efficiency of gas-powered turbines requires an understanding of how the tensile behaviour and ductile to brittle ...transition temperature (DBTT) of MCrAlY bond coats are influenced by the coating microstructure. In this study, small punch tensile (SPT) tests were conducted on two high velocity oxy-fuel (HVOF) NiCoCrAlY coatings. Both coatings, referred to as BC1 and BC2, comprised a BCC β-NiAl matrix with FCC γ-Ni and TCP σ-Cr2Co secondary phases. Coating BC2 also contained FCC γ′-Ni3Al. Small punch tensile (SPT) tests were conducted on the coatings between RT and 750 °C. The DBTT's of coatings BC1 and BC2 were found to be 600–700 °C and 650–750 °C respectively. Lower phase fractions of γ-Ni were shown to increase the DBTT. The main mode of crack propagation in both coatings was intergranular fracture along the grain boundaries of differing phases. Schematic models were used to demonstrate the change in tensile behaviour across the DBTT and explain the influence of the coating microstructure on the fracture behaviour of both coatings.
Previous studies have shown that engineered nanomaterials can be transferred from prey to predator, but the ecological impacts of this are mostly unknown. In particular, it is not known if these ...materials can be biomagnified-a process in which higher concentrations of materials accumulate in organisms higher up in the food chain. Here, we show that bare CdSe quantum dots that have accumulated in Pseudomonas aeruginosa bacteria can be transferred to and biomagnified in the Tetrahymena thermophila protozoa that prey on the bacteria. Cadmium concentrations in the protozoa predator were approximately five times higher than their bacterial prey. Quantum-dot-treated bacteria were differentially toxic to the protozoa, in that they inhibited their own digestion in the protozoan food vacuoles. Because the protozoa did not lyse, largely intact quantum dots remain available to higher trophic levels. The observed biomagnification from bacterial prey is significant because bacteria are at the base of environmental food webs. Our findings illustrate the potential for biomagnification as an ecological impact of nanomaterials.
Summary
While murine CD4+CD39+ regulatory T cells (Treg) co‐express CD73 and hydrolyze exogenous (e) adenosine triphosphate (ATP) to immunosuppressive adenosine (ADO), surface co‐expression of CD73 ...on human circulating CD4+CD39+ Treg is rare. Therefore, the ability of human Treg to produce and utilize ADO for suppression remains unclear. Using mass spectrometry, we measured nucleoside production by subsets of human CD4+CD39+ and CD4+CD39(–)CD73+ T cells or CD19+ B cells isolated from blood of 30 volunteers and 14 cancer patients. CD39 and CD73 expression was evaluated by flow cytometry, Western blots, confocal microscopy or reverse transcription–polymerase chain reaction (RT–PCR). Circulating CD4+CD39+ Treg which hydrolyzed eATP to 5′‐AMP contained few intracytoplasmic granules and had low CD73 mRNA levels. Only ∼1% of these Treg were CD39+CD73+. In contrast, CD4+CD39negCD73+ T cells contained numerous CD73+ granules in the cytoplasm and strongly expressed surface CD73. In vitro‐generated Treg (Tr1) and most B cells were CD39+CD73+. All these CD73+ T cell subsets and B cells hydrolyzed 5′‐AMP to ADO. Exosomes isolated from plasma of normal control (NC) or cancer patients carried enzymatically active CD39 and CD73+ and, when supplied with eATP, hydrolyzed it to ADO. Only CD4+CD39+ Treg co‐incubated with CD4+CD73+ T cells, B cells or CD39+CD73+ exosomes produced ADO. Thus, contact with membrane‐tethered CD73 was sufficient for ADO production by CD4+CD39+ Treg. In microenvironments containing CD4+CD73+ T cells, B cells or CD39+CD73+ exosomes, CD73 is readily available to CD4+CD39+CD73neg Treg for the production of immunosuppressive ADO.
Aims/hypothesis
The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other ...metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells.
Methods
We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells.
Results
The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro.
Conclusions/interpretation
The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis.