High-performance, additively-manufactured atomic spectroscopy apparatus for portable quantum technologies.

We demonstrate a miniaturised and highly robust system for performing Doppler-free spectroscopy on thermal atomic vapour for three frequencies as required for cold atom-based quantum technologies. The application of additive manufacturing techniques, together with efficient use of optical components, produce a compact, stable optical system, with a volume of 0.089 L and a weight of 120 g. The device occupies less than a tenth of the volume of, and is considerably lower cost than, conventional spectroscopic systems, but also offers excellent stability against environmental disturbances. We characterise the response of the system to changes in environmental temperature between 7 and 35 ∘C and exposure to vibrations between 0 - 2000 Hz, finding that the system can reliably perform spectroscopic measurements despite substantial vibrational noise and temperature changes. Our results show that 3D-printed optical systems are an excellent solution for portable quantum technologies.

Induced pluripotency and spontaneous reversal of cellular aging in supercentenarian donor cells.

Supercentenarians (≥110-year-old, SC) are a uniquely informative population not only because they surpass centenarians in age, but because they appear to age more slowly with fewer incidences of chronic age-related disease than centenarians. We reprogramed donor B-lymphoblastoid cell lines (LCL) derived from a 114-year-old (SC), a 43-year-old healthy disease-free control (HDC) and an 8-year-old with a rapid aging disease (Hutchinson-Gilford progeria syndrome (HGPS)) and compared SC-iPSC to HDC-iPSC and HGPS-iPSCs. Reprogramming to pluripotency was confirmed by pluripotency marker expression and differentiation to 3 germ-layers. Each iPSC clone differentiated efficiently to mesenchymal progenitor cells (MPC) as determined by surface marker expression and RNAseq analysis. We identified supercentenarian and HGPS associated gene expression patterns in the differentiated MPC lines that were not evident in the parental iPSC lines. Importantly, telomere length resetting occurred in iPSC from all donors albeit at a lower incidence in supercentenarian iPSCs. These data indicate the potential to use reprogramming to reset both developmental state and cellular age in the "oldest of the old." We anticipate that supercentenarian iPSC and their differentiated derivatives will be valuable tools for studying the underlying mechanisms of extreme longevity and disease resistance.

The cerebellum ages slowly according to the epigenetic clock.

Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages more slowly than other parts of the human body. We used both transcriptional data and genetic data to elucidate molecular mechanisms which may explain this finding. The two largest superfamilies of helicases (SF1 and SF2) are significantly over-represented (p=9.2x10-9) among gene transcripts that are over-expressed in the cerebellum compared to other brain regions from the same subject. Furthermore, SNPs that are associated with epigenetic age acceleration in the cerebellum tend to be located near genes from helicase superfamilies SF1 and SF2 (enrichment p=5.8x10-3). Our genetic and transcriptional studies of epigenetic age acceleration support the hypothesis that the slow aging rate of the cerebellum is due to processes that involve RNA helicases.

In vitro method for assessing the biomechanics of the patellofemoral joint following total knee arthroplasty.

The patellofemoral joint is a common site of pain and failure following total knee arthroplasty. A contributory factor may be adverse patellofemoral biomechanics. Cadaveric investigations are commonly used to assess the biomechanics of the joint, but are associated with high inter-specimen variability and often cannot be carried out at physiological levels of loading. This study aimed to evaluate the suitability of a novel knee simulator for investigating patellofemoral joint biomechanics. This simulator specifically facilitated the extended assessment of patellofemoral joint biomechanics under physiological levels of loading. The simulator allowed the knee to move in 6 degrees of freedom under quadriceps actuation and included a simulation of the action of the hamstrings. Prostheses were implanted on synthetic bones and key soft tissues were modelled with a synthetic analogue. In order to evaluate the physiological relevance and repeatability of the simulator, measurements were made of the quadriceps force and the force, contact area and pressure within the patellofemoral joint using load cells, pressure-sensitive film, and a flexible pressure sensor. The results were in agreement with those previously reported in the literature, confirming that the simulator is able to provide a realistic physiological loading situation. Under physiological loading, average standard deviations of force and area measurements were substantially lower and comparable to those reported in previous cadaveric studies, respectively. The simulator replicates the physiological environment and has been demonstrated to allow the initial investigation of factors affecting patellofemoral biomechanics following total knee arthroplasty.

Whole-genome sequencing of the world's oldest people.

Supercentenarians (110 years or older) are the world's oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment. The genome of one supercentenarian had a pathogenic mutation in DSC2, known to predispose to arrhythmogenic right ventricular cardiomyopathy, which is recommended to be reported to this individual as an incidental finding according to a recent position statement by the American College of Medical Genetics and Genomics. Even with this pathogenic mutation, the proband lived to over 110 years. The entire list of rare protein-altering variants and DNA sequence of all 17 supercentenarian genomes is available as a resource to assist the discovery of the genetic basis of extreme longevity in future studies.

Low torque levels can initiate a removal of the passivation layer and cause fretting in modular hip stems.

Taper connections of modular hip prostheses are at risk of fretting and corrosion, which can result in reduced implant survival. The purpose of this study was to identify the minimum torque required to initiate a removal of the passivation layer at the taper interface as a function of assembly force and axial load. Titanium stems and cobalt-chromium heads were assembled with peak impaction forces of 4.5 kN or 6.0 kN and then mounted on a materials testing machine whilst immersed in Ringer's solution. The stems were subjected to a static axial load (1 kN or 3 kN) along the taper axis. After a period of equilibration, a torque ramp from 0 to 15 Nm was manually applied and the galvanic potential was continuously recorded. Prostheses assembled with a force of 6 kN required a significantly higher torque to start a removal of the passivation layer compared to those assembled with 4.5 kN (7.23±0.55 Nm vs. 3.92±0.97 Nm, p=0.029). No influence of the axial load on the fretting behaviour was found (p=0.486). The torque levels, which were demonstrated to initiate surface damage under either assembly force, can be readily reached during activities of daily living. The damage will be intensified in situations of large weight and high activity of the patient or malpositioning of the prosthesis.

Are young people welcome in the English National Health Service?

An audit of baseline compliance with contemporary health care policies pertinent to the care of young people in hospital was undertaken in 1 large English District General Hospital. Children's and adult services within the hospital were benchmarked against the government audit tool standards. The aim of the study was to identify good and less optimum compliance to best practice policy driven benchmarks of care, using a 1-4 scale. Each clinical area within the hospital was contacted to make arrangements with members of the inter-professional team to complete the baseline benchmarking exercise. The audit was conducted over 3 days and the majority of the evidence sourced comprised of documented evidence and verbal affirmation of the individual perceptions of key informants of how the various clinical areas scored against the best practice benchmarks. Scores of policy compliance in some clinical areas of the hospital ranged from 1 not yet started (non-compliant) through to 4 you're welcome (fully compliant). The results demonstrate that many of the clinical areas within the hospital are making good efforts to ensure full compliance to policy guidelines and mandates. There are some aspects of policy standards that hospital has yet to fully embrace. This initial benchmarking exercise on behalf of 1 English hospital has revealed some areas of outstanding and good practice which have the potential to be shared.

The role of academic institutions in the development of drugs for rare and neglected diseases.

There are approximately 7,000 rare disorders, many of which are life-threatening. Diagnosis is often problematic, and therapies are few. Before the passage of the Orphan Drug Act in 1983, neither the pharmaceutical industry nor universities devoted much effort to research on rare diseases. Important changes have occurred within and outside universities that position them to play a significant role in developing orphan drugs. Several models are being employed to promote drug-related research, including disease-focused, discovery-focused, development-focused, and industry-partnership-focused approaches. However, significant barriers challenge universities' ability to fully contribute to orphan drug development. Academic institutions, along with industry, government, and not-for-profit organizations, must address these issues in order to advance the field. New initiatives designed to increase university-based orphan drug research include creating mechanisms to ensure program continuity, building research and regulatory support infrastructure, facilitating commercialization, expanding government support, and developing mutually beneficial partnerships among academe, industry, and government.

Functional benefits of ergothioneine and fruit- and vegetable-derived nutraceuticals: overview of the supplemental issue contents.

For good reason, there is increasing interest in assessing the clinical efficacy of dietary supplements, naturally occurring compounds, and nutraceuticals intended for improving health and reducing disease. This is also a pressing interest in mitigating the effects of age-dependent chronic diseases. This opportunity argues for the need to develop a clear understanding of the basic molecular mechanisms responsible for the actions of dietary biofactors that can contribute to the slowing or preventing of diseases and the possibility of enhancing these improvements by coupling them with healthy lifestyle changes.