Viscoelastic properties of human and bovine articular cartilage : a comparison of frequency-dependent trends

Acknowledgments The authors would like to thank Spencer C. Barnes and Hamid Sadeghi for assistance during experimentation. We would also like to thank patients donating tissue and the surgeons collecting these. Funding The equipment used in this study was funded by Arthritis Research UK (Grant number H0671). We are grateful to Arthritis Research UK for the award of a PhD studentship to Anna A. Cederlund (Grant number 19971). Arthritis Research UK had no role in the design of the study and collection, analysis and interpretation of data and in writing the manuscript.Peer reviewedPublisher PD

Breeding Season Space Use and Habitat Selection of Adult Female Scaled and Gambel\u27s Quail in West Texas

We used radiotelemetry to investigate breeding-season (1 Apr–1 Sep, 2012 and 2013) home ranges and habitat selection of adult female scaled (Callipepla squamata) and Gambel’s quail (C. gambelii) in the eastern Chihuahuan Desert, Texas. Mean breeding-season home range (95% fixed kernel) for scaled quail was 145.02 ± 23.56 ha (range = 22.03–538.24 ha) and 156.32 ± 13.04 ha (range = 66.15– 270.74 ha) for Gambel’s quail. Mean core-use area (50% fixed kernel) for scaled quail was 31.38 ± 4.80 ha (range = 4.03–111.36 ha) and 32.87 ± 2.61 ha (range = 12.19–52.36 ha) for Gambel’s quail. We found evidence of home-range overlap in neighboring females in both species. Excessive drought can suppress nesting activity. However, encourage reproductive activity in both species may be encouraged by managing riparian areas to provide adequate forage and microclimatic conditions

Effect of antihypertensive deprescribing on hospitalisation and mortality: long-term follow-up of the OPTiMISE randomised controlled trial

Background: Deprescribing of antihypertensive medications is recommended for some older patients with low blood pressure and frailty. The OPTiMISE trial showed that this deprescribing can be achieved with no differences in blood pressure control at 3 months compared with usual care. We aimed to examine effects of deprescribing on longer-term hospitalisation and mortality. Methods: This randomised controlled trial enrolled participants from 69 general practices across central and southern England. Participants aged 80 years or older, with systolic blood pressure less than 150 mm Hg and who were receiving two or more antihypertensive medications, were randomly assigned (1:1) to antihypertensive medication reduction (removal of one antihypertensive) or usual care. General practitioners and participants were aware of the treatment allocation following randomisation but individuals responsible for analysing the data were masked to the treatment allocation throughout the study. Participants were followed up via their primary and secondary care electronic health records at least 3 years after randomisation. The primary outcome was time to all-cause hospitalisation or mortality. Intention-to-treat analyses were done using Cox regression modelling. A per-protocol analysis of the primary outcome was also done, excluding participants from the intervention group who did not reduce treatment or who had medication reinstated during the initial trial 12-week follow-up period. This study is registered with the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT2016-004236-38) and the ISRCTN Registry (ISRCTN97503221). Findings: Between March 20, 2017, and Sept 30, 2018, a total of 569 participants were randomly assigned. Of these, 564 (99%; intervention=280; control=284) were followed up for a median of 4·0 years (IQR 3·7–4·3). Participants had a mean age of 84·8 years (SD 3·4) at baseline and 273 (48%) were women. Medication reduction was sustained in 109 participants at follow-up (51% of the 213 participants alive in the intervention group). Participants in the intervention group had a larger reduction in antihypertensives than the control group (adjusted mean difference –0·35 drugs [95% CI –0·52 to –0·18]). Overall, 202 (72%) participants in the intervention group and 218 (77%) participants in the control group experienced hospitalisation or mortality during follow-up (adjusted hazard ratio [aHR] 0·93 [95% CI 0·76 to 1·12]). There was some evidence that the proportion of participants experiencing the primary outcome in the per-protocol population was lower in the intervention group (aHR 0·80 [0·64 to 1·00]). Interpretation: Half of participants sustained medication reduction with no evidence of an increase in all-cause hospitalisation or mortality. These findings suggest that an antihypertensive deprescribing intervention might be safe for people aged 80 years or older with controlled blood pressure taking two or more antihypertensives

Effects of Backflow Correlation in the Three-Dimensional Electron Gas: Quantum Monte Carlo Study

The correlation energy of the homogeneous three-dimensional interacting electron gas is calculated using the variational and fixed-node diffusion Monte Carlo methods, with trial functions that include backflow and three-body correlations. In the high density regime the effects of backflow dominate over those due to three-body correlations, but the relative importance of the latter increases as the density decreases. Since the backflow correlations vary the nodes of the trial function, this leads to improved energies in the fixed-node diffusion Monte Carlo calculations. The effects are comparable to those found for the two-dimensional electron gas, leading to much improved variational energies and fixed-node diffusion energies equal to the release-node energies of Ceperley and Alder within statistical and systematic errors.Comment: 14 pages, 5 figures, submitted to Physical Review

Second-order phase transition at the phase boundary through the FeRh first-order metamagnetic phase transition

The phase coexistence present through first-order phase transitions implies the presence of phase boundary walls, which can be of finite size. Better understanding of the phase boundary wall properties will provide an insight into the dynamics of first-order phase transitions. Here, by combining x-ray photon correlation spectroscopy investigations with magnetometry measurements of magnetic relaxation through the thermally activated first-order metamagnetic phase transition present in the B2-ordered FeRh alloy, we are able to isolate the dynamic behaviour of the phase boundary wall present in this system. These investigations reveal a change in the nature of the dynamic behaviour and critical scaling of the relaxation time centred around the point of maximum phase coexistence within the phase transition. All of this behaviour can be attributed to the introduction of exchange coupling across the phase boundary wall and raises questions about the role of latent heat in dynamic behaviour of this region

Young HIV-Infected Children and Their Adult Caregivers Prefer Tablets to Syrup Antiretroviral Medications in Africa

Background: Provision of anti-retroviral therapy (ART) for HIV-infected children is complicated using syrup formulations, which are costlier than tablets, harder to transport and store and difficult for health-workers to prescribe and caregivers to administer. Dispersible/crushable tablets may be more appropriate. We studied the acceptability of syrups and scored tablets among young children who used both in the AntiRetroviral Research fOr Watoto (ARROW) trial. Methods: ARROW is an ongoing randomized trial of paediatric ART monitoring and treatment strategies in 1206 children in Uganda and Zimbabwe. 405 children initially received syrups of combination ART including Nevirapine, Zidovudine, Abacavir and Lamivudine before changing, when reaching the 12-,15 kg weightband, to scored adult-dose tablets prescribed according to WHO weightband tables. Caregiver expectations and experiences were collected in questionnaires at their last visit on syrups and after 8 and 24 weeks on tablets. Results: Questionnaires were completed by caregivers of 267 children (median age 2.9 years (IQR 2.5, 3.4)). At last visit on syrups, 79 % caregivers reported problems with syrups, mostly related to number, weight, transportation and conspicuousness of bottles. Difficulties taking tablets were expected by 127(48%) caregivers; however, after 8 and 24 weeks, only 26 % and 18 % reported their children had problems with tablets and no problems were reported with transportation/conspicuousness. Taste, swallowing or vomiting were reported as problems ‘sometimes/often ’ for 14%, 9%

Ex vivo correction of selenoprotein N deficiency in rigid spine muscular dystrophy caused by a mutation in the selenocysteine codon

Premature termination of translation due to nonsense mutations is a frequent cause of inherited diseases. Therefore, many efforts were invested in the development of strategies or compounds to selectively suppress this default. Selenoproteins are interesting candidates considering the idiosyncrasy of the amino acid selenocysteine (Sec) insertion mechanism. Here, we focused our studies on SEPN1, a selenoprotein gene whose mutations entail genetic disorders resulting in different forms of muscular diseases. Selective correction of a nonsense mutation at the Sec codon (UGA to UAA) was undertaken with a corrector tRNASec that was engineered to harbor a compensatory mutation in the anticodon. We demonstrated that its expression restored synthesis of a full-length selenoprotein N both in HeLa cells and in skin fibroblasts from a patient carrying the mutated Sec codon. Readthrough of the UAA codon was effectively dependent on the Sec insertion machinery, therefore being highly selective for this gene and unlikely to generate off-target effects. In addition, we observed that expression of the corrector tRNASec stabilized the mutated SEPN1 transcript that was otherwise more subject to degradation. In conclusion, our data provide interesting evidence that premature termination of translation due to nonsense mutations is amenable to correction, in the context of the specialized selenoprotein synthesis mechanism

Asymmetric magnetic relaxation behavior of domains and domain walls observed through the FeRh first-order metamagnetic phase transition

The phase coexistence present through a first-order phase transition means there will be finite regions between the two phases where the structure of the system will vary from one phase to the other, known as a phase boundary wall. This region is said to play an important but unknown role in the dynamics of the first-order phase transitions. Here, by using both x-ray photon correlation spectroscopy and magnetometry techniques to measure the temporal isothermal development at various points through the thermally activated first-order metamagnetic phase transition present in the near-equiatomic FeRh alloy, we are able to isolate the dynamic behavior of the domain walls in this system. These investigations reveal that relaxation behavior of the domain walls changes when phase coexistence is introduced into the system and that the domain-wall dynamics is different to the macroscale behavior. We attribute this to the effect of the exchange coupling between regions of either magnetic phase changing the dynamic properties of domain walls relative to bulk regions of either phase. We also believe this behavior comes from the influence of the phase boundary wall on other magnetic objects in the system

Magnetic unmixing of first-order reversal curve diagrams using principal component analysis

We describe a quantitative magnetic unmixing method based on principal component analysis (PCA) of first-order reversal curve (FORC) diagrams. For PCA we resample FORC distributions on grids that capture diagnostic signatures of single-domain (SD), pseudo-single-domain (PSD), and multidomain (MD) magnetite, as well as of minerals such as hematite. Individual FORC diagrams are recast as linear combinations of end-member (EM) FORC diagrams, located at user-defined positions in PCA space. The EM selection is guided by constraints derived from physical modeling and imposed by data scatter. We investigate temporal variations of two EMs in bulk North Atlantic sediment cores collected from the Rockall Trough and the Iberian Continental Margin. Sediments from each site contain a mixture of magnetosomes and granulometrically distinct detrital magnetite. We also quantify the spatial variation of three EM components (a coarse silt-sized MD component, a fine silt-sized PSD component, and a mixed clay-sized component containing both SD magnetite and hematite) in surficial sediments along the flow path of the North Atlantic Deep Water (NADW). These samples were separated into granulometric fractions, which helped constrain EM definition. PCA-based unmixing reveals systematic variations in EM relative abundance as a function of distance along NADW flow. Finally, we apply PCA to the combined dataset of Rockall Trough and NADW sediments, which can be recast as a four-EM mixture, providing enhanced discrimination between components. Our method forms the foundation of a general solution to the problem of unmixing multi-component magnetic mixtures, a fundamental task of rock magnetic studies.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC grant agreement 320750.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/2015GC00590