Reconfigurable elastic metamaterials: Engineering dispersion with beyond nearest neighbors (article)

This is the final version. Available on open access from the American Physical Society via the DOI in this recordThe research data supporting this publication are openly available in ORE at https://doi.org/10.24378/exe.4564We design, simulate, and experimentally characterize a reconfigurable elastic metamaterial with beyond-nearest-neighbor (BNN) coupling. The structure is composed from the popular British model-construction system Meccano and supports backward waves with opposite directions of phase and group velocities. We experimentally verify three distinct configurations and acoustically infer their spatial vibration spectra.Royal Commission for the Exhibition of 1851Defence Science and Technology Laboratory (Dstl)Engineering and Physical Sciences Research Council (EPSRC)QinetiQ Ltd

Proteolytic shedding of the prion protein via activation of metallopeptidase ADAM10 reduces cellular binding and toxicity of amyloid-β oligomers

The cellular prion protein (PrPC) is a key neuronal receptor for amyloid-β oligomers (AβO), mediating their neurotoxicity, which contributes to the neurodegeneration in Alzheimer's disease (AD). Similarly to the amyloid precursor protein (APP), PrPC is proteolytically cleaved from the cell surface by a disintegrin and metalloprotease, ADAM10. We hypothesized that ADAM10-modulated PrPC shedding would alter the cellular binding and cytotoxicity of AβO. Here, we found that in human neuroblastoma cells, activation of ADAM10 with the muscarinic agonist carbachol promotes PrPC shedding and reduces the binding of AβO to the cell surface, which could be blocked with an ADAM10 inhibitor. Conversely, siRNA-mediated ADAM10 knockdown reduced PrPC shedding and increased AβO binding, which was blocked by the PrPC-specific antibody 6D11. The retinoic acid receptor analog acitretin, which up-regulates ADAM10, also promoted PrPC shedding and decreased AβO binding in the neuroblastoma cells and in human induced pluripotent stem cell (iPSC)-derived cortical neurons. Pretreatment with acitretin abolished activation of Fyn kinase and prevented an increase in reactive oxygen species caused by AβO binding to PrPC Besides blocking AβO binding and toxicity, acitretin also increased the non-amyloidogenic processing of APP. However, in the iPSC-derived neurons, Aβ and other amyloidogenic processing products did not exhibit a reciprocal decrease upon acitretin treatment. These results indicate that by promoting the shedding of PrPC in human neurons, ADAM10 activation prevents the binding and cytotoxicity of AβO, revealing a potential therapeutic benefit of ADAM10 activation in AD

Assessing Internet addiction using the parsimonious Internet addiction components model - a preliminary study [forthcoming]

Internet usage has grown exponentially over the last decade. Research indicates that excessive Internet use can lead to symptoms associated with addiction. To date, assessment of potential Internet addiction has varied regarding populations studied and instruments used, making reliable prevalence estimations difficult. To overcome the present problems a preliminary study was conducted testing a parsimonious Internet addiction components model based on Griffiths’ addiction components (2005), including salience, mood modification, tolerance, withdrawal, conflict, and relapse. Two validated measures of Internet addiction were used (Compulsive Internet Use Scale [CIUS], Meerkerk et al., 2009, and Assessment for Internet and Computer Game Addiction Scale [AICA-S], Beutel et al., 2010) in two independent samples (ns = 3,105 and 2,257). The fit of the model was analysed using Confirmatory Factor Analysis. Results indicate that the Internet addiction components model fits the data in both samples well. The two sample/two instrument approach provides converging evidence concerning the degree to which the components model can organize the self-reported behavioural components of Internet addiction. Recommendations for future research include a more detailed assessment of tolerance as addiction component

Uncemented and cemented primary total hip arthroplasty in the Swedish Hip Arthroplasty Register: Evaluation of 170,413 operations

BACKGROUND AND PURPOSE: Since the introduction of total hip arthroplasty (THA) in Sweden, both components have most commonly been cemented. A decade ago the frequency of uncemented fixation started to increase, and this change in practice has continued. We therefore analyzed implant survival of cemented and uncemented THA, and whether the modes of failure differ between the two methods of fixation. PATIENTS AND METHODS: All patients registered in the Swedish Hip Arthroplasty Register between 1992 and 2007 who received either totally cemented or totally uncemented THA were identified (n = 170,413). Kaplan-Meier survival analysis with revision of any component, and for any reason, as the endpoints was performed. Cox regression models were used to calculate risk ratios (RRs) for revision for various reasons, adjusted for sex, age, and primary diagnosis. RESULTS: Revision-free 10-year survival of uncemented THA was lower than that of cemented THA (85% vs. 94%, p < 0.001). No age or diagnosis groups benefited from the use of uncemented fixation. Cox regression analysis confirmed that uncemented THA had a higher risk of revision for any reason (RR = 1.5, 95% CI: 1.4-1.6) and for aseptic loosening (RR = 1.5, CI: 1.3-1.6). Uncemented cup components had a higher risk of cup revision due to aseptic loosening (RR = 1.8, CI: 1.6-2.0), whereas uncemented stem components had a lower risk of stem revision due to aseptic loosening (RR = 0.4, CI: 0.3-0.5) when compared to cemented components. Uncemented stems were more frequently revised due to periprosthetic fracture during the first 2 postoperative years than cemented stems (RR = 8, CI: 5-14). The 5 most common uncemented cups had no increased risk of revision for any reason when compared with the 5 most commonly used cemented cups (RR = 0.9, CI: 0.6-1.1). There was no significant difference in the risk of revision due to infection between cemented and uncemented THA. INTERPRETATION: Survival of uncemented THA is inferior to that of cemented THA, and this appears to be mainly related to poorer performance of uncemented cups. Uncemented stems perform better than cemented stems; however, unrecognized intraoperative femoral fractures may be an important reason for early failure of uncemented stems. The risk of revision of the most common uncemented cup designs is similar to that of cemented cups, indicating that some of the problems with uncemented cup fixation may have been solved.Open Access - This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the source is credited

Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Multiple randomized controlled trials (RCTs) have examined the cardiovascular effects of omega-3 fatty acids and have provided unexplained conflicting results. A meta-analysis of these RCTs to estimate efficacy and safety and potential sources of heterogeneity may be helpful.</p> <p>Methods</p> <p>The Cochrane library, MEDLINE, and EMBASE were systematically searched to identify all interventional trials of omega-3 fatty acids compared to placebo or usual diet in high-risk cardiovascular patients. The primary outcome was all-cause mortality and secondary outcomes were coronary restenosis following percutaneous coronary intervention and safety. Meta-analyses were carried out using Bayesian random-effects models, and heterogeneity was examined using meta-regression.</p> <p>Results</p> <p>A total of 29 RCTs (n = 35,144) met our inclusion criteria, with 25 reporting mortality and 14 reporting restenosis. Omega-3 fatty acids were not associated with a statistically significant decreased mortality (relative risk [RR] = 0.88, 95% Credible Interval [CrI] = 0.64, 1.03) or with restenosis prevention (RR = 0.89, 95% CrI = 0.72, 1.06), though the probability of some benefit remains high (0.93 and 0.90, respectively). However in meta-regressions, there was a >90% probability that larger studies and those with longer follow-up were associated with smaller benefits. No serious safety issues were identified.</p> <p>Conclusions</p> <p>Although not reaching conventional statistical significance, the evidence to date suggests that omega-3 fatty acids may result in a modest reduction in mortality and restenosis. However, caution must be exercised in interpreting these benefits as results were attenuated in higher quality studies, suggesting that bias may be at least partially responsible. Additional high quality studies are required to clarify the role of omega-3 fatty acid supplementation for the secondary prevention of cardiovascular disease.</p

How individuals change language

Languages emerge and change over time at the population level though interactions between individual speakers. It is, however, hard to directly observe how a single speaker's linguistic innovation precipitates a population-wide change in the language, and many theoretical proposals exist. We introduce a very general mathematical model that encompasses a wide variety of individual-level linguistic behaviours and provides statistical predictions for the population-level changes that result from them. This model allows us to compare the likelihood of empirically-attested changes in definite and indefinite articles in multiple languages under different assumptions on the way in which individuals learn and use language. We find that accounts of language change that appeal primarily to errors in childhood language acquisition are very weakly supported by the historical data, whereas those that allow speakers to change incrementally across the lifespan are more plausible, particularly when combined with social network effects

A survey of people with foot problems related to rheumatoid arthritis and their educational needs

Background Up to 50% of people with rheumatoid arthritis (RA) have foot symptoms at diagnosis, hence early foot health intervention is recommended and this should include patient education. This study identifies, for the first time, the foot health education (FHE) needs of people with RA. Methods An online survey of people with RA (n = 543) captured quantitative data in relation to the aims, methods of delivery, content, timing and accessibility of FHE. Results The majority concurred about the aims of FHE. Verbal delivery and websites were the most common methods. Written and verbal FHE were perceived to be the most effective methods. The point of diagnosis was the preferred time to receive it. Lack of access to FHE included minimal focus on foot health during consultations by both health practitioners and patients with RA. Participant gender, age, disease duration and living situation had a statistically significant influence on the results. Conclusion Foot health education is rarely considered within the medical consultation. There is a lack of patient and/or health professional awareness of this need with a detrimental impact on foot health. Patients require health professionals to identify their foot education health needs. Tailored foot health education should begin at initial diagnosis

Methanobactin and the Link Between Copper and Bacterial Methane Oxidation

Methanobactins (mbs) are low-molecular-mass (<1,200 Da) copper-binding peptides, or chalkophores, produced by many methane-oxidizing bacteria (methanotrophs). These molecules exhibit similarities to certain iron-binding siderophores but are expressed and secreted in response to copper limitation. Structurally, mbs are characterized by a pair of heterocyclic rings with associated thioamide groups that form the copper coordination site. One of the rings is always an oxazolone and the second ring an oxazolone, an imidazolone, or a pyrazinedione moiety. The mb molecule originates from a peptide precursor that undergoes a series of posttranslational modifications, including (i) ring formation, (ii) cleavage of a leader peptide sequence, and (iii) in some cases, addition of a sulfate group. Functionally, mbs represent the extracellular component of a copper acquisition system. Consistent with this role in copper acquisition, mbs have a high affinity for copper ions. Following binding, mbs rapidly reduce Cu2+ to Cu1+. In addition to binding copper, mbs will bind most transition metals and near-transition metals and protect the host methanotroph as well as other bacteria from toxic metals. Several other physiological functions have been assigned to mbs, based primarily on their redox and metal-binding properties. In this review, we examine the current state of knowledge of this novel type of metal-binding peptide. We also explore its potential applications, how mbs may alter the bioavailability of multiple metals, and the many roles mbs may play in the physiology of methanotrophs

Search for Dark Matter Annihilation in the Galactic Center with IceCube-79

The Milky Way is expected to be embedded in a halo of dark matter particles, with the highest density in the central region, and decreasing density with the halo-centric radius. Dark matter might be indirectly detectable at Earth through a flux of stable particles generated in dark matter annihilations and peaked in the direction of the Galactic Center. We present a search for an excess flux of muon (anti-) neutrinos from dark matter annihilation in the Galactic Center using the cubic-kilometer-sized IceCube neutrino detector at the South Pole. There, the Galactic Center is always seen above the horizon. Thus, new and dedicated veto techniques against atmospheric muons are required to make the southern hemisphere accessible for IceCube. We used 319.7 live-days of data from IceCube operating in its 79-string configuration during 2010 and 2011. No neutrino excess was found and the final result is compatible with the background. We present upper limits on the self-annihilation cross-section, \left, for WIMP masses ranging from 30 GeV up to 10 TeV, assuming cuspy (NFW) and flat-cored (Burkert) dark matter halo profiles, reaching down to $\simeq 4 \cdot 10^{-24}$ cm$^3$ s$^{-1}$, and $\simeq 2.6 \cdot 10^{-23}$ cm$^3$ s$^{-1}$ for the $\nu\overline{\nu}$ channel, respectively.Comment: 14 pages, 9 figures, Submitted to EPJ-C, added references, extended limit overvie