Advances and challenges in umbilical cord blood and tissue bioprocessing: procurement and storage

Umbilical cord tissue and blood is banked to complement the rapidly advancing field of tissue engineering and regenerative medicine for both autologous and allogeneic therapeutic applications. Whilst many problems concerning the use of the hematopoietic and multipotential mesenchymal stromal cells contained therein may be addressed through the future development of GMP-compliant manufacturing strategies, collection and bioprocessing of these tissues can be optimised in the present to maximise clinical outcomes. In this review, we describe current procurement, processing and storage approaches for umbilical cord blood and tissue; current challenges and how these may be met to augment translation and use of therapeutics harnessing their derivatives

A simplicial gauge theory

We provide an action for gauge theories discretized on simplicial meshes, inspired by finite element methods. The action is discretely gauge invariant and we give a proof of consistency. A discrete Noether's theorem that can be applied to our setting, is also proved.Comment: 24 pages. v2: New version includes a longer introduction and a discrete Noether's theorem. v3: Section 4 on Noether's theorem has been expanded with Proposition 8, section 2 has been expanded with a paragraph on standard LGT. v4: Thorough revision with new introduction and more background materia

Neutron, electron and X-ray scattering investigation of Cr1-xVx near Quantum Criticality

The weakness of electron-electron correlations in the itinerant antiferromagnet Cr doped with V has long been considered the reason that neither new collective electronic states or even non Fermi liquid behaviour are observed when antiferromagnetism in Cr$_{1-x}$V$_{x}$ is suppressed to zero temperature. We present the results of neutron and electron diffraction measurements of several lightly doped single crystals of Cr$_{1-x}$V$_{x}$ in which the archtypal spin density wave instability is progressively suppressed as the V content increases, freeing the nesting-prone Fermi surface for a new striped charge instability that occurs at x$_{c}$=0.037. This novel nesting driven instability relieves the entropy accumulation associated with the suppression of the spin density wave and avoids the formation of a quantum critical point by stabilising a new type of charge order at temperatures in excess of 400 K. Restructuring of the Fermi surface near quantum critical points is a feature found in materials as diverse as heavy fermions, high temperature copper oxide superconductors and now even elemental metals such as Cr.Comment: 6 pages, 6 figures. Accepted to Physical Review

Severe mental illness and chronic kidney disease: a cross-sectional study in the United Kingdom

OBJECTIVE: We investigated the burden of chronic kidney disease (CKD) among patients with severe mental illness (SMI). METHODS: We identified patients with SMI among all those aged 25–74 registered in the UK Clinical Practice Research Datalink as on March 31, 2014. We compared the prevalence of CKD (two measurements of estimated glomerular filtration rate <60 mL/min/1.73 m2 for ≥3 months) and renal replacement therapy between patients with and without SMI. For patients with and without a history of lithium prescription separately, we used logistic regression to examine the association between SMI and CKD, adjusting for demographics, lifestyle characteristics, and known CKD risk factors. RESULTS: The CKD prevalence was 14.6% among patients with SMI and a history of lithium prescription (n = 4,295), 3.3% among patients with SMI and no history of lithium prescription (n = 24,101), and 2.1% among patients without SMI (n = 2,387,988; P < 0.001). The prevalence of renal replacement therapy was 0.23%, 0.15%, and 0.11%, respectively (P = 0.012). Compared to patients without SMI, the fully adjusted odds ratio for CKD was 6.49 (95% CI 5.84–7.21) for patients with SMI and a history of lithium prescription and 1.45 (95% CI 1.34–1.58) for patients with SMI and no history of lithium prescription. The higher prevalence of CKD in patients with SMI may, in part, be explained by more frequent blood testing as compared to the general population. CONCLUSION: CKD is identified more commonly among patients with SMI than in the general population

Confidential Boosting with Random Linear Classifiers for Outsourced User-generated Data

User-generated data is crucial to predictive modeling in many applications. With a web/mobile/wearable interface, a data owner can continuously record data generated by distributed users and build various predictive models from the data to improve their operations, services, and revenue. Due to the large size and evolving nature of users data, data owners may rely on public cloud service providers (Cloud) for storage and computation scalability. Exposing sensitive user-generated data and advanced analytic models to Cloud raises privacy concerns. We present a confidential learning framework, SecureBoost, for data owners that want to learn predictive models from aggregated user-generated data but offload the storage and computational burden to Cloud without having to worry about protecting the sensitive data. SecureBoost allows users to submit encrypted or randomly masked data to designated Cloud directly. Our framework utilizes random linear classifiers (RLCs) as the base classifiers in the boosting framework to dramatically simplify the design of the proposed confidential boosting protocols, yet still preserve the model quality. A Cryptographic Service Provider (CSP) is used to assist the Cloud's processing, reducing the complexity of the protocol constructions. We present two constructions of SecureBoost: HE+GC and SecSh+GC, using combinations of homomorphic encryption, garbled circuits, and random masking to achieve both security and efficiency. For a boosted model, Cloud learns only the RLCs and the CSP learns only the weights of the RLCs. Finally, the data owner collects the two parts to get the complete model. We conduct extensive experiments to understand the quality of the RLC-based boosting and the cost distribution of the constructions. Our results show that SecureBoost can efficiently learn high-quality boosting models from protected user-generated data

Isolation of digital dermatitis treponemes from hoof lesions in wild North American elk (Cervus elaphus) in Washington State, USA

Since 2008, a large increase in the numbers of cases of lameness have been seen in wild North American elk (Cervus elaphus) from Washington State, USA. The most recent cases manifested as foot lesions similar both clinically and pathologically to those seen in digital dermatitis (DD) in cattle and sheep, a disease with a bacterial etiopathogenesis. To determine whether the same bacteria considered responsible for DD are associated with elk lameness, lesion samples were subjected to bacterial isolation studies and PCR assays for three phylogroups of relevant DD treponemes. The DD treponemes were isolated from lesional tissues but not from control feet or other areas of the diseased foot (including the coronary band or interdigital space), suggesting that the bacteria are strongly associated with DD lesions and may therefore be causal. In addition, PCR analysis revealed that all three unique DD treponeme phylotypes were found in elk hoof disease, and in 23 of samples, all 3 DD-associated treponemes were present in lesions. Sequence analysis of the 16S rRNA gene showed that the elk lesion treponemes were phylogenetically almost identical to those isolated from cattle and sheep DD lesions. The isolates were particularly similar to two of the three culturable DD treponeme phylotypes: specifically, the Treponema medium/Treponema vincentii-like and Treponema phagedenis-like DD spirochetes. The third treponeme culturable phylogroup (Treponema pedis), although detected by PCR, was not isolated. This is the first report describing isolation of DD treponemes from a wildlife host, suggesting that the disease may be evolving to include a wider spectrum of cloven-hoofed animals. Copyright © 2015, American Society for Microbiology. All Rights Reserved

Changes In Apparent Molar Water Volume and DKP Solubility Yield Insights on the Hofmeister Effect

This study examines the properties of a 4 × 2 matrix of aqueous cations and anions at concentrations up to 8.0 M. The apparent molar water volume, as calculated by subtracting the mass and volume of the ions from the corresponding solution density, was found to exceed the molar volume of ice in many concentrated electrolyte solutions, underscoring the nonideal behavior of these systems. The solvent properties of water were also analyzed by measuring the solubility of diketopiperazine (DKP) in 2.000 M salt solutions prepared from the same ion combinations. Solution rankings for DKP solubility were found to parallel the Hofmeister series for both cations and anions, whereas molar water volume concurred with the cation series only. The results are discussed within the framework of a desolvation energy model that attributes solute-specific changes in equilibria to solute-dependent changes in the free energy of bulk water

Minimax Current Density Coil Design

'Coil design' is an inverse problem in which arrangements of wire are designed to generate a prescribed magnetic field when energized with electric current. The design of gradient and shim coils for magnetic resonance imaging (MRI) are important examples of coil design. The magnetic fields that these coils generate are usually required to be both strong and accurate. Other electromagnetic properties of the coils, such as inductance, may be considered in the design process, which becomes an optimization problem. The maximum current density is additionally optimized in this work and the resultant coils are investigated for performance and practicality. Coils with minimax current density were found to exhibit maximally spread wires and may help disperse localized regions of Joule heating. They also produce the highest possible magnetic field strength per unit current for any given surface and wire size. Three different flavours of boundary element method that employ different basis functions (triangular elements with uniform current, cylindrical elements with sinusoidal current and conic section elements with sinusoidal-uniform current) were used with this approach to illustrate its generality.Comment: 24 pages, 6 figures, 2 tables. To appear in Journal of Physics D: Applied Physic

Atopic eczema in adulthood and mortality: UK population–based cohort study, 1998-2016

BACKGROUND: Atopic eczema affects up to 10% of adults and is becoming more common globally. Few studies have assessed whether atopic eczema increases the risk of death. OBJECTIVE: We aimed to determine whether adults with atopic eczema were at increased risk of death overall and by specific causes and to assess whether the risk varied by atopic eczema severity and activity. METHODS: The study was a population-based matched cohort study using UK primary care electronic health care records from the Clinical Practice Research Datalink with linked hospitalization data from Hospital Episode Statistics and mortality data from the Office for National Statistics from 1998 to 2016. RESULTS: A total of 526,736 patients with atopic eczema were matched to 2,567,872 individuals without atopic eczema. The median age at entry was 41.8 years, and the median follow-up time was 4.5 years. There was limited evidence of increased hazard for all-cause mortality in those with atopic eczema (hazard ratio = 1.04; 99% CI = 1.03-1.06), but there were somewhat stronger associations (8%-14% increased hazard) for deaths due to infectious, digestive, and genitourinary causes. Differences on the absolute scale were modest owing to low overall mortality rates. Mortality risk increased markedly with eczema severity and activity. For example, patients with severe atopic eczema had a 62% increased hazard (hazard ratio = 1.62; 99% CI = 1.54-1.71) for mortality compared with those without eczema, with the strongest associations for infectious, respiratory, and genitourinary causes. CONCLUSION: The increased hazards for all-cause and cause-specific mortality were largely restricted to those with the most severe or predominantly active atopic eczema. Understanding the reasons for these increased hazards for mortality is an urgent priority