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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.
Inequalities in mental health treatment access and outcomes for minority ethnic and religious groups in the UK have been recognized for more than a decade; however, work to address these at an operational level is still emerging. In recognition of the need for culturally adapted therapies, researchers at the University of Leeds developed and piloted an adapted therapy for Muslim clients, based on behavioural activation (BA), an existing evidence-based psychosocial treatment for depression. Therapists and supervisors at Touchstone, Leeds have been trained to deliver the culturally adapted approach, which supports Muslim clients who choose to use ‘positive religious coping’ as a resource for health. This paper describes the key elements of the intervention and how it is being delivered in practice to increase service uptake and recovery in Muslim communities.
In the 1980s, John Reynolds postulated that a parametrically polymorphic function is an ad-hoc polymorphic function satisfying a uniformity principle. This allowed him to prove that his set-theoretic semantics has a relational lifting which satisfies the Identity Extension Lemma and the Abstraction Theorem. However, his definition (and subsequent variants) has only been given for specific models. In contrast, we give a model-independent axiomatic treatment by characterising Reynolds’ definition via a universal property, and show that the above results follow from this universal property in the axiomatic setting.
In the multi-volume work The Heritage of Sufism covering an entire millennium of Persianate Sufism, Leonard Lewisohn recognizes the difficulty of undertaking a “comprehensive coverage of all the mystical contexts” that characterize Sufi heritage within the span of a single study. Covering the expansive idea of a “spiritual and cultural renaissance” in Persian society between 1200 and 1500 the work identifies Sufism as a major catalyst for these developments. The religious climate of Persia in the aforementioned period was intensely influenced by Sufi traditions led by masters like Jalaluddin Rumi (d. 1273), Nimatullah Wali (d. 1431), Hafez Shirazi (d. 1389), Saadi (d. 1292), and Saiyid Ali Hamadani (d. 1384) among many others. Their works and activities shaped pre-Safavid Persia in a manner which scholars have characterized as a “renaissance” — in literature, arts, Islamic sciences, philosophy, music and mystical scholarship. One can grasp Lewisohn's emphasis on the impossibility of covering comprehensively all dimensions of this Sufi tradition between the covers of a single volume. Certain important aspects remain unexplored, even though they are critical towards understanding the heritage of Persian Sufism.
In an interesting parallel, South Asia presents before us similar difficulties of undertaking a comprehensive study of a Sufi heritage in this region. Within the same time frame, before the rise of the Mughal Empire — the South Asian equivalent of the mighty Safavids — Sufi activities spread across north India, and also the South, particularly the Deccan region. This paper will look into certain aspects connected to the rise of Sufi networks in the Deccan in the thirteenth and fourteenth centuries, at a time when Deccan's Sanskritized cultural world experienced the coming of a north Indian Persian tradition. In spite of some obvious similarities with the Iranian situation, the focus will be less on such sweeping categories as “renaissance”. Rather the article will seek to engage with a different set of questions more relevant to the idea of a Sufi heritage.
What roles did Sufi saints and, later, their shrines play in creating a heritage? Was this idea sustained only through tangible traces of their shrines? Or can it be located in the intangible idea of mystical rituals and practices, like sama? How did the chain of spiritual succession ensure the continuity of this heritage?
Background: Cerebral palsy (CP) is a debilitating disorder (1). Based on neuromotor impairments it is divided to spastic, dyskinetic and ataxic types (2). Inborn Errors of Metabolism (IEMs), monogenic and chromosomal disorders mimic CP (3). We aimed to identify causal genetic variants in patients with atypical dyskinetic CP in whom known IEMs were ruled out. Timely diagnosis is essential for proper management, especially in conditions that mimic CP and are treatable. Methods: We enrolled 23 patients with unexplained atypical dyskinetic CP, for whole exome sequencing. Variants were filtered against public and in-house databases to identify variants predicted as damaging (in silico tools and ACMG criteria). We applied a virtual gene panel of known and suspected CP and movement disorder genes and investigated each sample. Results: The participants presented with symptoms including: spasticity, dystonia, choera-athetosis, ataxia and cognitive delays. We identified 23 diagnoses: 13 dominant,6 recessive and 4 X-linked. 12 patients had movement disorders. In 4, the diagnoses enabled targeted treatment (neurotransmitter supplements in Unverricht Lundborg diseases (CSTB) and PAK3 deficiency, deep brain stimulation in GNAO1 deficiency, medical diet in Glutaric Aciduria (GCDH). Conclusions: Whole Exome Sequencing contributes to establishing diagnosis in patients with atypical dyskinetic CP resulting in precision medicine and improved health outcomes.
Steady methane/air laminar premixed flames stabilised on a cylindrical bluff body subjected to a continuous rotation are analysed using joint direct numerical simulations (DNS) and experiments. DNS are carried out using a 19 species scheme for methane/air combustion and a lumped model to predict the cylinder temperature. Rotation of the cylinder induces a symmetry breaking of the flow, and leads to two distinct flame branches in the wake of the cylinder. DNS are validated against experiments in terms of flame topologies and velocity fields. DNS are then used to analyse flame structures and thermal effects. The location and structure of the two flames are differently modified by rotation and heat transfer: a superadiabatic flame branch stabilises close to the hot cylinder and burns preheated fresh gases while a subadiabatic branch is quenched over a large zone and anchors far downstream of the cylinder. Local flame structures are shown to be controlled to first order by the local enthalpy defect or excess due to heat transfer between the cylinder and the flow. An analysis of the local wall heat flux around the cylinder shows that, for low rotation speeds, the superadiabatic flame branch contributes to wall heat fluxes that considerably exceed typical values found for classical flame/wall interactions. However, for high rotation speeds, fluxes decrease because the cylinder is surrounded by a layer of burned gases that dilute incoming reactants and shield it from the flame.
The Late Caledonian granites of Donegal are all intruded into metasediments of the Dalradian Supergroup of Neoproterozoic age, which were metamorphosed and deformed during the Grampian Phase of the Caledonian orogeny at c. 470-460 m.y. They were intruded in a singular pulse well after the main tectonic event, apparently peaking at 407-402 m.y.; importantly after the strong collision of Laurentia with Baltica on closure of the Iapetus Ocean. The plutons are mainly made up of granodiorite and granite, and are all ‘I’ type, but different to Cordilleran ‘I’ types of the eastern Pacific margin. Major element chemistry indicates they are high-K calc-alkaline rocks with a large range in SiO2 content. However three of the plutons (Fanad, Thorr, Ardara), have very high Ba and Sr contents, even higher than Mainland Scotland counterparts; they are high Ba-Sr plutons. Three plutons (Barnesmore, Rosses, Trawenagh Bay) are evolved and are low-Ba-Sr types, while one (Main Donegal) has atypical, intermediate characteristics. The origin of the magmas is still much debated; here we suggest slab breakoff on Iapetus Ocean closure accounts for the special compositions of these magmas and the other major features of Late Caledonian granitic magmatism, including the singular intrusion peak and the associated appinite-lamprophyre suite.
Carbon fiber reinforced plastic (CFRP) is an expensive composite which has become valuable material as the demand for this composite increased in the industries. It is suitable to be used in automotive, aerospace, and aircraft because of its properties which is stronger than steel and also stiffer than titanium while retaining its lighter weight. However machining of CFRP is a mess to machinist due to its nature which is abrasive. The paper presents the wear mechanism on solid carbide cutting tool during milling CFRP. The wear mechanism is observed under dry and chilled air machining. The machining parameters tested were at cutting speed of 200 m/min with constant feed rate and depth of cut. For both dry and chilled air machining, it is observed that carbide cutting tool experienced abrasive wear which has been influenced by abrasive powdering chips and fibers during milling CFRP. Under microscope and scanning electron microscope, the abrasive wear is represented by shiny and polish area on the cutting tool respectively. This abrasive wear is observed higher under dry machining compared to the chilled air machining which was due to the heat generated during machining. Thus, chilled air has a potential of improving machinability of CFRP by using solid carbide cutting tool.
Titanium carbonitride (TiCN) is a popular hard coating for carbide cutting tools in various applications. This paper studied the influence of the carbon content and coating composition within TiCxN1−x coatings with regard to their adhesive strength on tungsten carbide substrate and subsequently, the performance of cutting tool in the dry turning of stainless steel. Among all the TiCxN1−x coatings, the TiCN coating has exhibited the highest adhesivity onto a substrate, followed by a TiC coating and lastly, a TiN coating. It was found that the adhesive strength of TiCN coating increased with the carbon content. The C/N ratio or C–N bond is a vital contributor to the adhesivity of the TiCxN1−x coating rather than the C or N atoms in the TiCxN1−x coating. It was found that the coating was delaminated before the exposure of substrate material. Hence, coating with higher adhesivity will promote longer tool life.
A carbide cutting tool is widely used in machining process due to its availability and being cheaper than a better performance cutting tool, such as cubic boron nitride. The carbide cutting tool also has substantial hardness and toughness that is suitable to be applied in intermittent cutting. This paper presents the case study of a wear mechanism experienced on the cutting edge of the coated and uncoated carbide tools in turning and milling processes. The wear mechanisms of carbide cutting tools were investigated in machining Inconel 718, titanium alloy Ti–6Al–4V extra-low interstitial, and aluminum metal matrix composite (AlSi/AlN MMC) at their high cutting speed regime. The tools failed primarily due to wear on the flank and rake faces. The failure mode of the carbide cutting tools was similar regardless of the machining operations and coating is believed to enhance the tool life, but once removed, the tool fails similar to that with the uncoated tool.
Tribology is a phenomenon concerning the relative motion between at least two amalgamating surfaces. In the machining process, surface roughness is the most important element for studying this occurrence, which contributes to the evaluation of part quality. This paper will provide detailed analysis for better understanding of tribological during the machining process of Inconel 718 alloy using a multi-layer TiAlN/AlCrN-coated carbide ball end inserted in dry cutting condition. The analysis focused on the relationship of tool wear with cutting temperature, cutting force, and surface integrity. Results found that the cutting temperature increased around 7.5% and surface roughness of machined surface improved about 10.3% when the cutting speed increased. Flaking at the rake face and notching at the flank face were determined as the main tool failures during milling Inconel 718. Furthermore, high friction between the tool–workpiece interfaces during machining was due to the build-up edge (BUE) formation that causes an alteration in microstructure at machine surface.
Dental microwear analyses of ungulates and other large herbivores rely on correlations of diet and microwear among extant ungulates, primarily ruminants. Microwear is considered a ‘taxon-free’ method of paleodietary analysis. The properties of food are associated with causality of microwear, but the possibility that heritable properties of the consumer (tooth morphologies, masticatory dynamics, enamel mechanical properties, digestive physiologies) may introduce bias is not considered. Using an observer blind method of light microscopy, we examined the distribution of microwear features on the molars of eight species of ruminants and perissodactyls. Grazing and browsing ruminants had statistically different numbers of scratches forming discrete data clusters. Perissodactyls differ in the numbers of scratches and pits but without discrete browser and grazer clusters. Microwear features were distributed homogeneously across ruminant molars and strongly predictive of diet from the labial edge of the molar to the lingual edge. Microwear was heterogeneously distributed across perissodactyl molars with more pits on the labial edge and more scratches on the lingual edge. In perissodactyls, microwear sampled from the labial edge was strongly predictive of diet, while microwear sampled from other areas were not. Discriminant function analyses of microwear assigned individual molars to diets (browser and grazer) and clades (ruminant and perissodactyl) with similar success (70–73%) indicating that phylogeny and diet influence microwear equally. Rhino microwear was more sensitive to clade membership while other perissodactyl microwear was more sensitive to diet. Although it is not clear what heritable variables may phylogenetically bias dental microwear, extant ruminants may not be appropriate models for the microwear of other large herbivores.
We show that the syntactically rich notion of strictly positive families can be reduced to a core type theory with a fixed number of type constructors exploiting the novel notion of indexed containers. As a result, we show indexed containers provide normal forms for strictly positive families in much the same way that containers provide normal forms for strictly positive types. Interestingly, this step from containers to indexed containers is achieved without having to extend the core type theory. Most of the construction presented here has been formalized using the Agda system.
Induction recursion offers the possibility of a clean, simple and yet powerful meta-language for the type system of a dependently typed programming language. At its crux, induction recursion allows us to define a universe, that is a set U of codes and a decoding function T : U → D which assigns to every code u : U, a value T, u of some type D, e.g. the large type Set of small types or sets. The name induction recursion refers to the build-up of codes in U using inductive clauses, simultaneously with the definition of the function T, by structural recursion on codes.
Our contribution is to (i) bring out explicitly algebraic structure which is less visible in the original type-theoretic presentation – in particular showing how containers and monads play a pivotal role within induction recursion; and (ii) use these structures to present a clean and high level definition of induction recursion suitable for use in functional programming.
To evaluate the primary and long-term surgical outcomes of patients with postinflammatory medial meatal fibrosis.
A retrospective study was conducted of 14 ears (in 12 patients) with postinflammatory medial meatal fibrosis managed surgically. Outcome measures were primary (i.e. less than six months) and long-term (i.e. greater than five years) closure of the air–bone gap, and the incidence of otorrhoea and restenosis.
At primary review, the mean air–bone gap ± standard deviation had decreased from 29.9 ± 11.6 dB to 12 ± 8.4 dB (p < 0.0006). Seven (50 per cent) ears had closure of the air–bone gap to within 10 dB. However, for the 9 ears receiving long-term review, the mean air–bone gap ± standard deviation increased to 19.3 ± 15.2 dB; there was no significant difference between this result and pre-operative values (p = 0.06). Of the 9 long-term review ears, 3 (33 per cent) showed closure of the air–bone gap to within 10 dB. Recurrent otorrhoea was the most common complication, occurring in 5 of the 9 long-term review ears (56 per cent); in addition, 3 (33 per cent) of these 9 ears developed restenosis.
Over time, the success of surgery for postinflammatory medial meatal fibrosis diminishes. This was demonstrated in the present study by progressive post-operative hearing decline and a high prevalence of otorrhoea and restenosis.
Entamoeba moshkovskii and Entamoeba dispar are microscopically indistinguishable from the pathogenic species Entamoeba histolytica. Although sporadic cases of human infection with E. moshkovskii have been reported, the amoeba is still considered primarily as a free-living amoeba. A cross-sectional study was carried out among Orang Asli communities in 3 different states of Peninsular Malaysia. Fecal samples were examined by formalin-ether sedimentation and trichrome staining techniques and then single-round PCR assay was used to detect E. moshkovskii. Out of 500 fecal samples examined microscopically, 93 (18·6%) samples were positive for E. histolytica/E. dispar/E. moshkovskii complex cysts and/or trophozoites. PCR products were detected in 106 fecal samples. E. moshkovskii isolates were detected in 13 (12·3%) fecal samples. Of the 13 E. moshkovskii-positive samples, 5 were of single isolation of E. moshkovskii, 6 were also positive for E. dispar, and only 2 samples were positive for E. dispar and E. histolytica. Moreover, 3 E. moshkovskii-positive samples were collected from symptomatic individuals while the remaining 10 samples were from asymptomatic subjects. This is the first report on the identification of E. moshkovskii in Malaysia. Further studies are needed to confirm the pathogenicity of E. moshkovskii infection and determine the epidemiology among Orang Asli communities in Malaysia.
We report the electrochemical behavior of various layered oxides in Li cells. A series of LiNiyMnyCozO2 materials (with z=1-2y) was synthesized by “chimie douce” and investigated as positive electrodes in rechargeable lithium batteries. Electrochemical performances of LiNiyMnyCozO2 oxides are tested cell using non-aqueous 1M LiPF6 dissolved in EC-DEC. Charge discharge profiles are investigated as a function of the rate capability, the voltage window and the synthesis parameters of the cathode. A relation is found between the gravimetric capacity and the cation disorder of materials as indicated by magnetometry analysis.
The extraction of recombination lifetime from the current-vol tage characteristics of diode structures containing Si1−xGex strained layers is discussed. Electrical measurements are used in conjunction with computer simulations to extract minority carrier lifetime in Si1−xGex layers with various oxygen concentrations. The minority carrier lifetime in Si1−xGex increases from several psec at an oxygen concentration of 2×1020 cm−3, to greater than 0.5 μs at concentrations below 3×1017 cm−3. The structures are analyzed for sensitivity of the current characteristics to Si1−xGex minority carrier lifetime. Calculations predict that the maximum lifetime which can be extracted from such structures is greater than 100 μsec. However, due to limitations imposed by perimeter currents, the maximum lifetime which can be extracted from our diode structures is on the order of 3 μsec. Maximizing area to perimeter ratio of the diode structures and moving the Si1−xGex-SiO2 interface away from the active device region is required in order to increase the maximum extracted lifetime from such structures.
The electrical characteristics of DBD have been studied using four different
barriers. These barriers are Pyrex glass, Mylar, porous alumina
Al2O3 plates and ceramic plates of composition (50% MgO:50%
Al2O3). It has been found that the type and the internal
composition of the dielectric barriers affect the formation of the DBD
modes. Using glass or Mylar as a dielectric causes the formation of the
filamentary DBD mode. While using porous alumina plates leads to the
generation of the discharge in APGD mode. A quasiglow mode is obtained when
a ceramic of composition (50% MgO:50% Al2O3) is used. The
effect of using one dielectric barrier, on the DBD characteristics has also
been studied. Antisymmetric behavior of the current waveform is obtained
when one dielectric barrier is placed on the life electrode.
Statins have been shown to increase endothelial progenitor cells (EPCs) in patients with cardiovascular disease. However, there is no similar study that has been done on the patients recovering from cerebrovascular disease. We present the largest prospective study of statin therapy on EPC levels of patients recovering from stroke.
Our study subjects were treated with rosuvastatin (10 mg/day) over a period of 12 weeks. Blood was collected from these patients periodically and EPC levels were measured along with other biochemical parameters.
Results and Conclusions:
Our study shows that rosuvastatin treatment significantly reduces the low density lipoprotein (LDL) levels in the patients over the 12 weeks. However, we did not find any corresponding changes in the EPC levels during this time period. Earlier reports indicated that statin use could increase EPC proliferation. Our research, however, indicates that the in-vivo effects of rosuvastatin are not similar to those of previous reports. There may be several reasons for this lack of congruence between these two studies, including age of the study population, predominantly low high density lipoprotein (HDL) levels in our subjects and effects from other concomitant medications.