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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Colorectal cancer (CRC) is the third most common cancer globally. CRC risk is increased by obesity, and by its lifestyle determinants notably physical inactivity and poor nutrition. Obesity results in increased inflammation and oxidative stress which cause genomic damage and contribute to mitochondrial dysregulation and CRC risk. The mitochondrial dysfunction associated with obesity includes abnormal mitochondrial size, morphology and reduced autophagy, mitochondrial biogenesis and expression of key mitochondrial regulators. Although there is strong evidence that increased adiposity increases CRC risk, evidence for the effects of intentional weight loss on CRC risk is much more limited. In model systems, energy depletion leads to enhanced mitochondrial integrity, capacity, function and biogenesis but the effects of obesity and weight loss on mitochondria in the human colon are not known. We are using weight loss following bariatric surgery to investigate the effects of altered adiposity on mitochondrial structure and function in human colonocytes. In summary, there is strong and consistent evidence in model systems and more limited evidence in human subjects that over-feeding and/or obesity result in mitochondrial dysfunction and that weight loss might mitigate or reverse some of these effects.
The equine passport legislation is a comparatively new scheme that requires all horses to have a passport by 28th February 2005 (Defra, 2004). The equine passport is thought to have had a major impact on the industry in the United Kingdom, however the extent of this is, as yet, unknown due to the lack of current research. The UK Government hopes that the passport scheme will monitor horses that have been treated with medication and guarantee that they are not slaughtered for human consumption (Frank, 2003, Defra, 2004). Whilst the scheme originated from European food safety legislation (Ellis, 2003), the UK Government believes that there are other benefits attached to the equine passport, such as gaining comprehensive records about the equine population in the UK, which is crucial information required for epidemiological reasons (Mellor et al., 1999). The information will provide a denominator for the assessment of disease rates, and which areas of the country may be under threat.
The mammalian order Xenarthra (including the living Neotropical armadillos, anteaters, and tree sloths) has figured importantly in recent hypotheses of interordinal relationships among eutherian mammals. It has been suggested that the group shares a common ancestry both with the extant Old World order Pholidota (i.e. the pangolins or scaly-anteaters) and the extinct North American group Palaeanodonta. Furthermore, these three groups have been linked together into a monophyletic Cohort Edentata, which has been hypothesized to represent the sister-group to all other eutherians. This placement of edentates relative to the remainder of Eutheria has been supported in part by a purported difference in the morphology of the stapes in the two groups- edentates possessing a primitive, imperforate/columelliform morphology, other placentals a derived, perforate/stirrup-shaped morphology.
A recent study of stapedial morphology among mammals by Novacek and Wyss (1986) suggests that within the Xenarthra itself a perforate stapes is found among armadillos, but that the pilosa in particular (the clade including anteaters and sloths) and the order as a whole are characterized primitively by an imperforate stapes. Our studies of the xenarthran ear region (Patterson et al., in press) have uncovered new ontogenetic and paleontological evidence which contradict the findings of Novacek and Wyss. Among adults of the two extant tree sloth genera, the stapes lacks a stapedial foramen. However, in both genera, this adult imperforate morphology is derived from a perforated juvenile stapes. Novacek and Wyss ignored fossil species in their consideration of the xenarthran stapes. It has long been known that extinct ground sloths of the family Mylodontidae possessed a large stapedial foramen. Unfortunately, until now no stapes were known from the remaining ground sloth families, the Megatheriidae and the Megalonychidae. We have uncovered a complete left stapes of an early Miocene megatheriid ground sloth Eucholoeops ingens. This stapes possesses a well-developed stapedial foramen. We believe that this new paleontological evidence, combined with our information on the ontogeny of the stapes in the living genera, clearly indicates that a perforate stapes is primitive for sloths. Moreover, when we plot distributions of stapedial morphologies of both living and fossil edentates onto a phylogeny of the Edentata, we can demonstrate that the a large stapedial foramen is primitive for the Xenarthra as a whole, and probably for the entire Cohort Edentata. Such a distribution makes it unlikely that stapedial morphology can be used to separate edentates from other eutherian mammals.
We present a study of the energy levels in a FTO/TiO2/CH3NH3PbI3/Spiro solar cell device. The measurements are performed using a novel ambient pressure photoemission (APS) technique alongside Contact Potential Difference data from a Kelvin Probe. The Perovskite Solar Cell energy band diagram is demonstrated for the device in dark conditions and under illumination from a 150W Quartz Tungsten Halogen lamp. This approach provides useful information on the interaction between the different materials in this solar cell device. Additionally, non-destructive macroscopic DC and AC Surface Photovoltage Spectroscopy (SPS) studies are demonstrated of different MAPBI3 device structures to give an indication of overall device performance. AC-SPS measurements, previously used on traditional semiconductors to study the mobility, are used in this case to characterise the ability of a perovskite solar cell device to respond rapidly to chopped light. Two different device structures studied showed very different characteristics: Sample A (without TiO2): (ITO/PEDOT:PSS/polyTPD/CH3NH3PbI3/PCBM) had ∼4 times the magnitude of AC-SPS response compared to Sample B (including TiO2): (ITO/TiO2/ CH3NH3PbI3/Spiro). This demonstrates that the carrier speed characteristics of device architecture A is superior to device architecture B. The TiO2 layer has been associated with carrier trapping which is illustrated in this example. However, the DC-SPV performance of sample B is ∼5 times greater than that of sample A. The band gap of the MAPBI3 layer was determined through DC-SPS (1.57 ± 0.07 eV), Voc of the devices measured and qualitative observations made of interface trapping by DC light pulsing. The combination of these (APS, KP, AC/DC-SPV/SPS) techniques offers a more general method for measuring the energy level alignments and performance of Organic and Hybrid Solar Cell Devices.
An explanation is provided for the disruptive instability in diverted tokamaks when the safety factor
at the 95 % poloidal flux surface,
, is driven below 2.0. The instability is a resistive kink counterpart to the current-driven ideal mode that traditionally explained the corresponding disruption in limited cross-sections (Shafranov, Sov. Phys. Tech. Phys., vol. 15, 1970, p. 175) when
, the safety factor at the outermost closed flux surface, lies just below a rational value
. Experimentally, external kink modes are observed in limiter configurations as the current in a tokamak is ramped up and
decreases through successive rational surfaces. For
, the instability is always encountered and is highly disruptive. However, diverted plasmas, in which
is formally infinite in the magnetohydrodynamic (MHD) model, have presented a longstanding difficulty since the theory would predict stability, yet, the disruptive limit occurs in practice when
, reaches 2. It is shown from numerical calculations that a resistive kink mode is linearly destabilized by the rapidly increasing resistivity at the plasma edge when
. The resistive kink behaves much like the ideal kink with predominantly kink or interchange parity and no real sign of a tearing component. However, the growth rates scale with a fractional power of the resistivity near the
surface. The results have a direct bearing on the conventional edge cutoff procedures used in most ideal MHD codes, as well as implications for ITER and for future reactor options.
We present broad band photometry (B and R) of the classic shell galaxy NGC 474. Preliminary results indicate that the shells have a similar colour to and follow the same trend of colour with radius as the underlying galaxy.
Substantial healthcare resources are devoted to panic disorder (PD) and coronary heart disease (CHD); however, the association between these conditions remains controversial. Our objective was to conduct a systematic review of studies assessing the association between PD, related syndromes, and incident CHD.
Relevant studies were retrieved from Medline, EMBASE, SCOPUS and PsycINFO without restrictions from inception to January 2015 supplemented with hand-searching. We included studies that reported hazard ratios (HR) or sufficient data to calculate the risk ratio and 95% confidence interval (CI) which were pooled using a random-effects model. Studies utilizing self-reported CHD were ineligible. Twelve studies were included comprising 1 131 612 persons and 58 111 incident CHD cases.
PD was associated with the primary incident CHD endpoint [adjusted HR (aHR) 1.47, 95% CI 1.24–1.74, p < 0.00001] even after excluding angina (aHR 1.49, 95% CI 1.22–1.81, p < 0.00001). High to moderate quality evidence suggested an association with incident major adverse cardiac events (MACE; aHR 1.40, 95% CI 1.16–1.69, p = 0.0004) and myocardial infarction (aHR 1.36, 95% CI 1.12–1.66, p = 0.002). The risk for CHD was significant after excluding depression (aHR 1.64, 95% CI 1.45–1.85) and after depression adjustment (aHR 1.38, 95% CI 1.03–1.87). Age, sex, length of follow-up, socioeconomic status and diabetes were sources of heterogeneity in the primary endpoint.
Meta-analysis showed that PD was independently associated with incident CHD, myocardial infarction and MACE; however, reverse causality cannot be ruled out and there was evidence of heterogeneity.
We evaluated 222 hospitalized patients whose clinical isolates were tested using standard methods and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF). MALDI-TOF could have reduced time to appropriate therapy for 28.8% and 44.6% patients based on the treating physician's choices and stewardship team recommendations, respectively. Clinicians should be aware of scenarios in which MALDI-TOF can optimize antibiotic therapy.
Gentlemen,—It is with feelings of diffidence and trepidation that I venture to address you to-night. I have been informed that it is almost impossible to write a paper on anything new in connection with Actuarial matters, as everything bearing on the theory and practice of Life Assurance has already been written, read, and understood by all those interested in the business. However, although nowadays every Actuarial student can graduate a Mortality Table in about three different ways, and can run off lists of the Securities, in which the funds of an Office should and should not be invested, with reasons as to their choice or rejection, I think that perhaps in the department of Life Office Accounting there are still a few suggestions which can be made. I allow that the subject is not so scientific as, say, the calculation of the probable future profit to be received on a Reversion, which has been bought at an auction, or the valuation of conflicting interests in a Disentail. I am also afraid that Accounting is not thought of much importance by Actuaries, but is regarded rather, may I say, as a prosy, though easily crammed subject, to be read up before examinations.
Small liquid germanium (ℓ-Ge) droplets (0.3–0.5mm diameter) have been undercooled in a B2O3 flux a maximum of 415 ± 20°C below Tm before recalescence. Although the droplets undercooled to temperatures well below the temperature expected for metastable equilibrium with amorphous Ge, Taℓ, the solidified structures were always polycrystalline. There was no evidence of a continuous liquid-to-amorphous transition at or below Taℓ. The nucleation frequency was calculated to be ˜8 × 106 /cm 3-sec at the maximum undercooling. This should be an upper limit to the homogeneous nucleation frequency of the crystal phase since we did not establish that the nucleation was homogeneous in our experiments. However, this limiting I for Ge indicates that homogeneous nucleation of the crystal or amorphous phase would not become appreciable in nsec laser pulsing experiments until ℓ-Ge is undercooled to well below Taℓ. The structure of solidified Ge and Ge/Sn alloy droplets indicates that dendritic growth does not occur in Ge until the liquid is undercooled at least 300°C, and in Ge/Sn until the liquid is undercooled at least 250°C. Greater undercoolings lead to increased dendritic breakup, which results in grain refinement in the final structure.
We have measured the pressure dependence of the solid phase epitaxial growth (SPEG) rate of self-implanted Si (100) by using the in-situ time-resolved reflectivity technique  in a hightemperature and high-pressure diamond anvil cell (DAC). With fluid argon as the pressure transmission medium, a clean and perfectly hydrostatic pressure environment is achieved around the sample. The external heating geometry employed in the DAC provides a uniform temperature across the sample. At temperatures in the range of 530 – 550 °C and pressure up to 50 kbars (5 GPa), the growth rate is enhanced by up to a factor of ten over that at 1 atmosphere pressure. The results are characterized by a negative activation volume of approximately −3.0 cm3/mole (−27% of the atomic volume). These preliminary results show a significantly weaker pressure dependence than does the previous work of Nygren et al. , who found an activation volume of −8.7 cm3/mole. The implications of these results for the nature of the defect responsible for thermal SPEG and irradiation enhanced SPEG is discussed.
The contrast of misfit dislocations in an InGaAs layer, close to the critical thickness and capped with GaAs grown by MBE on a (001) oriented GaAs substrate has been investigated by double axis synchrotron X-radiation topography. The layer thickness variation as a function of position has been measured to a precision of 1A by matching interference fringes observed in the 004 symmetric reflection double crystal rocking curves with simulations. The misfit dislocation density is highly anisotropic, varying from zero to a high value with increasing thickness. The contrast of the dislocations in the 004, 224 and 044 reflections has been examined in detail. All of the long dislocation segments characterized were 60° in character with ½<110> Burgers vectors inclined to the specimen surface. No dislocations were found which did not appear to be of this type. A surprising difference in contrast of the background in the 224 and 224 reflections is discussed.
Relaxation in a 3μm epitaxial layer of GaAsSb on GaAs, a 1μm layer of InGaAs on InP and an InGaAs superlattice on InP has been investigated by double crystal X-ray diffractometry and double crystal X-ray synchrotron topography and found to be asymmetric. The origins of assymetric relaxation are discussed and the sensitivity of diffractometry and topography to the detection of layer relaxation compared.
Amorphous Si and Ge layers, produced by noble gas (Ar or Xe) implantation of single crystal substrates, have been crystallized in a differential scanning calorimeter (DSC). This technique allows determination of the growth velocity (which is proportional to the rate of heat evolution, ΔHac), and the total enthalpy of crystallization ΔHacAmorphous Ge was found to relax continuously to an amorphous state of lower free energy, with a total enthalpy of relaxation of 6.0 kJ.mole−1 before crystallization started. The regrowth velocity on (100) substrates,measured to be 4.2×1017 exp (−2.17eV/kT)Å/sec, is compared to other determinations. The value of ΔHac was found to be 11.66± 0.7 kJ.mole, in good agreement with ΔHac for amorphous Ge produced by other methods. For Si, ΔHac was determined to be 11.95± 0.7 kJ.mole without any evidence of heat release due to relaxation. The kinetics of crystallization measured by DSC are compared with those determined by other techniques. The effects of the implant profile on the regrowth velocity could also be observed directly in the DSC signal. The more accurate value of ΔHac allowed a more precise determination of the melting temperature of amorphous Si: Taℓ= 1420K.
The effect of pressure on self diffusion in crystalline silicon is being studied using 30Si as a tracer. Diffusion experiments have been carried out in the pressure range of 1 to 35000 atmospheres at 1000°C. The 30Si is observed to diffuse faster at high pressures, indicating a negative activation volume.
We have studied GaN films grown by atmospheric pressure metalorganic chemical vapor deposition (MOCVD) on sapphire substrates using different buffer layer structures. Surface morphology was characterized by scanning electron microscopy (SEM). Optical properties were measured using photoluminescence (PL), cathodoluminescence (CL) spectroscopy and catho-luminescence wavelength imaging (CLWI) method. It is found that the hexagonal pit-like defects in morphology are associated with the D-A/e-A transition band in the PL and CL spectra. The same correlation of morphology with optical properties is observed for the GaN films grown by selective area epitaxy (SAE). In addition, the possibility of improving optical quality by SAE is investigated. The SAE depth profile is simulated for the first time, and satisfactory results are obtained.