Biomarker clusters are differentially associated with longitudinal cognitive decline in late midlife

The ability to detect preclinical Alzheimer’s disease is of great importance, as this stage of the Alzheimer’s continuum is believed to provide a key window for intervention and prevention. As Alzheimer’s disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-β42/amyloid-β40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer’s disease; (ii) mixed Alzheimer’s disease and vascular aetiology; (iii) suspected non-Alzheimer’s disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal ageing. Our results demonstrate that pathology, as indicated by biomarkers, in a preclinical timeframe is related to patterns of longitudinal cognitive decline. Such biomarker patterns may be useful for identifying at-risk populations to recruit for clinical trials

Emerging Infectious Disease leads to Rapid Population Decline of Common British Birds

Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period

The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic

Hidden fluctuations close to a quantum bicritical point

Here, we present an alternative approach for the description of quantum critical fluctuations. These are described by Langevin random fields, which are then related to the susceptibility using the fluctuation-dissipation theorem. We use this approach to characterize the physical properties arising in the vicinity of two coupled quantum phase transitions. We consider a phenomenological model based on two scalar order parameter fields locally coupled biquadratically and having a common quantum critical point as a function of a quantum tuning parameter such as pressure or magnetic field. A self-consistent treatment shows that the uniform static susceptibilities of the two order parameter fields have the same qualitative form at low temperature even where the forms are different in the absence of the biquadratic coupling.We acknowledge support from EPSRC, Corpus Christi College, the National Science Foundation Grant No. NSF DMR-1334428, and the Increase Competitiveness Program of the Ministry of Education of the Russian Federation Grant No. NUST MISiS K2-2017-024. We are grateful to Trinity College Cambridge, the Cavendish Laboratory, and the Aspen Center for Physics, supported by National Science Foundation Grant No. NSF PHY-1066293, for hospitality. S.E.R. acknowledges support from a CONFAP Newton grant

The prevention of type 2 diabetes

Type 2 diabetes mellitus (T2DM) affects more than 7% of adults in the US and leads to substantial personal and economic burden. In prediabetic states insulin secretion and action—potential targets of preventive interventions—are impaired. In trials lifestyle modification (i.e. weight loss and exercise) has proven effective in preventing incident T2DM in high-risk groups, although weight loss has the greatest effect. Various medications (e.g. metformin, thiazolidinediones and acarbose) can also prevent or delay T2DM. Whether diabetes-prevention strategies also ultimately prevent the development of diabetic vascular complications is unknown, but cardiovascular risk factors are favorably affected. Preventive strategies that can be implemented in routine clinical settings have been developed and evaluated. Widespread application has, however, been limited by local financial considerations, even though cost-effectiveness might be achieved at the population level

Differential proinflammatory responses to Aspergillus fumigatus by airway epithelial cells in vitro are protease dependent

Aspergillus fumigatus is an important human respiratory mould pathogen. In addition to a barrier function, airway epithelium elicits a robust defence against inhaled A. fumigatus by initiating an immune response. The manner by which A. fumigatus initiates this response and the reasons for the immunological heterogeneity with different isolates are unclear. Both direct fungal cell wall–epithelial cell interaction and secretion of soluble proteases have been proposed as possible mechanisms. Our aim was to determine the contribution of fungal proteases to the induction of epithelial IL-6 and IL-8 in response to different A. fumigatus isolates. Airway epithelial cells were exposed to conidia from a low or high protease-producing strain of A. fumigatus, and IL-6 and IL-8 gene expression and protein production were quantified. The role of proteases in cytokine production was further determined using specific protease inhibitors. The proinflammatory cytokine response correlated with conidia germination and hyphal extension. IL-8 induction was significantly reduced in the presence of matrix metalloprotease or cysteine protease inhibitors. With a high protease-producing strain of A. fumigatus, IL-6 release was metalloprotease dependent. Dectin-1 antagonism also inhibited the production of both cytokines. In conclusion, A. fumigatus-secreted proteases mediate a proinflammatory response by airway epithelial cells in a strain-dependent manner

Pressure-induced Anderson-Mott transition in elemental tellurium

AbstractElemental tellurium is a small band-gap semiconductor, which is always p-doped due to the natural occurrence of vacancies. Its chiral non-centrosymmetric structure, characterized by helical chains arranged in a triangular lattice, and the presence of a spin-polarized Fermi surface, render tellurium a promising candidate for future applications. Here, we use a theoretical framework, appropriate for describing the corrections to conductivity from quantum interference effects, to show that a high-quality tellurium single crystal undergoes a quantum phase transition at low temperatures from an Anderson insulator to a correlated disordered metal at around 17 kbar. Such insulator-to-metal transition manifests itself in all measured physical quantities and their critical exponents are consistent with a scenario in which a pressure-induced Lifshitz transition shifts the Fermi level below the mobility edge, paving the way for a genuine Anderson-Mott transition. We conclude that previously puzzling quantum oscillation and transport measurements might be explained by a possible Anderson-Mott ground state and the observed phase transition.</jats:p

A case of Kawasaki disease with coexistence of a parapharyngeal abscess requiring incision and drainage

Kawasaki disease (KD) causes multisystemic vasculitis but infrequently manifests with deep neck infections, such as a peritonsillar abscess, peritonsillar or deep neck cellulitis, suppurative parapharyngeal infection, or retropharyngeal abscess. As its etiology is still unknown, the diagnosis is usually made based on typical symptoms. The differential diagnosis between KD and deep neck infections is important, considering the variable head and neck manifestations of KD. There are several reports on KD patients who were initially diagnosed with retropharyngeal abscess on on computed tomography scans (CT). However, the previously reported cases did not have abscess or fluid collection on retropharyngeal aspiration. Therefore, false-positive neck CT scans have been obtained, until recently. In this case, suspected neck abscess in patients with KD unresponsive to intravenous immunoglobulin could signal the possible coexistence of suppurative cervical lymphadenitis

Short-Term Exposure to Warm Microhabitats Could Explain Amphibian Persistence with Batrachochytrium dendrobatidis

Environmental conditions can alter the outcomes of symbiotic interactions. Many amphibian species have declined due to chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), but many others persist despite high Bd infection prevalence. This indicates that Bd's virulence is lower, or it may even be a commensal, in some hosts. In the Australian Wet Tropics, chytridiomycosis extirpated Litoria nannotis from high-elevation rain forests in the early 1990 s. Although the species is recolonizing many sites, no population has fully recovered. Litoria lorica disappeared from all known sites in the early 1990 s and was thought globally extinct, but a new population was discovered in 2008, in an upland dry forest habitat it shares with L. nannotis. All frogs of both species observed during three population censuses were apparently healthy, but most carried Bd. Frogs perch on sun-warmed rocks in dry forest streams, possibly keeping Bd infections below the lethal threshold attained in cooler rain forests. We tested whether short-term elevated temperatures can hamper Bd growth in vitro over one generation (four days). Simulating the temperatures available to frogs on strongly and moderately warmed rocks in dry forests, by incubating cultures at 33°C for one hour daily, reduced Bd growth below that of Bd held at 15°C constantly (representing rain forest habitats). Even small decreases in the exponential growth rate of Bd on hosts may contribute to the survival of frogs in dry forests