Effects of a soft robotic exosuit on the quality and speed of overground walking depends on walking ability after stroke

\ua9 2023, BioMed Central Ltd., part of Springer Nature.Background: Soft robotic exosuits can provide partial dorsiflexor and plantarflexor support in parallel with paretic muscles to improve poststroke walking capacity. Previous results indicate that baseline walking ability may impact a user’s ability to leverage the exosuit assistance, while the effects on continuous walking, walking stability, and muscle slacking have not been evaluated. Here we evaluated the effects of a portable ankle exosuit during continuous comfortable overground walking in 19 individuals with chronic hemiparesis. We also compared two speed-based subgroups (threshold: 0.93 m/s) to address poststroke heterogeneity. Methods: We refined a previously developed portable lightweight soft exosuit to support continuous overground walking. We compared five minutes of continuous walking in a laboratory with the exosuit to walking without the exosuit in terms of ground clearance, foot landing and propulsion, as well as the energy cost of transport, walking stability and plantarflexor muscle slacking. Results: Exosuit assistance was associated with improvements in the targeted gait impairments: 22% increase in ground clearance during swing, 5\ub0 increase in foot-to-floor angle at initial contact, and 22% increase in the center-of-mass propulsion during push-off. The improvements in propulsion and foot landing contributed to a 6.7% (0.04 m/s) increase in walking speed (R 2 = 0.82). This enhancement in gait function was achieved without deterioration in muscle effort, stability or cost of transport. Subgroup analyses revealed that all individuals profited from ground clearance support, but slower individuals leveraged plantarflexor assistance to improve propulsion by 35% to walk 13% faster, while faster individuals did not change either. Conclusions: The immediate restorative benefits of the exosuit presented here underline its promise for rehabilitative gait training in poststroke individuals

Stability analysis and quasinormal modes of Reissner Nordstr{\o}m Space-time via Lyapunov exponent

We explicitly derive the proper time $(\tau)$ principal Lyapunov exponent ($\lambda_{p}$) and coordinate time ($t$) principal Lyapunov exponent ($\lambda_{c}$) for Reissner Nordstr{\o}m (RN) black hole (BH) . We also compute their ratio. For RN space-time, it is shown that the ratio is $\frac{\lambda_{p}}{\lambda_{c}}=\frac{r_{0}}{\sqrt{r_{0}^2-3Mr_{0}+2Q^2}}$ for time-like circular geodesics and for Schwarzschild BH it is $\frac{\lambda_{p}}{\lambda_{c}}=\frac{\sqrt{r_{0}}}{\sqrt{r_{0}-3M}}$. We further show that their ratio $\frac{\lambda_{p}}{\lambda_{c}}$ may vary from orbit to orbit. For instance, Schwarzschild BH at innermost stable circular orbit(ISCO), the ratio is $\frac{\lambda_{p}}{\lambda_{c}}\mid_{r_{ISCO}=6M}=\sqrt{2}$ and at marginally bound circular orbit (MBCO) the ratio is calculated to be $\frac{\lambda_{p}}{\lambda_{c}}\mid_{r_{mb}=4M}=2$. Similarly, for extremal RN BH the ratio at ISCO is $\frac{\lambda_{p}}{\lambda_{c}}\mid_{r_{ISCO}=4M}=\frac{2\sqrt{2}}{\sqrt{3}}$. We also further analyse the geodesic stability via this exponent. By evaluating the Lyapunov exponent, it is shown that in the eikonal limit , the real and imaginary parts of the quasi-normal modes of RN BH is given by the frequency and instability time scale of the unstable null circular geodesics.Comment: Accepted in Pramana, 07/09/201

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Combination schemes for turning point prediction

We propose new forecast combination schemes for predicting turning points of business cycles. The combination schemes deal with the forecasting performance of a given set of models and possibly providing better turning point predictions. We consider turning point predictions generated by autoregressive (AR) and Markov-Switching AR models, which are commonly used for business cycle analysis. In order to account for parameter uncertainty we consider a Bayesian approach to both estimation and prediction and compare, in terms of statistical accuracy, the individual models and the combined turning point predictions for the United States and Euro area business cycles

Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease

BACKGROUND:Recently, a large meta-analysis including over 28,000 participants identified nine different loci with association to serum uric acid (UA) levels. Since elevated serum UA levels potentially cause gout and are a possible risk factor for coronary artery disease (CAD) and myocardial infarction (MI), we performed two large case-control association analyses with participants from the German MI Family Study. In the first study, we assessed the association of the qualitative trait gout and ten single nucleotide polymorphisms (SNP) markers that showed association to UA serum levels. In the second study, the same genetic polymorphisms were analyzed for association with CAD. METHODS AND FINDINGS:A total of 683 patients suffering from gout and 1,563 healthy controls from the German MI Family Study were genotyped. Nine SNPs were identified from a recently performed genome-wide meta-analysis on serum UA levels (rs12129861, rs780094, rs734553, rs2231142, rs742132, rs1183201, rs12356193, rs17300741 and rs505802). Additionally, the marker rs6855911 was included which has been associated with gout in our cohort in a previous study. SNPs rs734553 and rs6855911, located in SLC2A9, and SNP rs2231142, known to be a missense polymorphism in ABCG2, were associated with gout (p=5.6*10(-7), p=1.1*10(-7), and p=1.3*10(-3), respectively). Other SNPs in the genes PDZK1, GCKR, LRRC16A, SLC17A1-SLC17A3, SLC16A9, SLC22A11 and SLC22A12 failed the significance level. None of the ten markers were associated with risk to CAD in our study sample of 1,473 CAD cases and 1,241 CAD-free controls. CONCLUSION:SNP markers in SLC2A9 and ABCG2 genes were found to be strongly associated with the phenotype gout. However, not all SNP markers influencing serum UA levels were also directly associated with the clinical manifestation of gout in our study sample. In addition, none of these SNPs showed association with the risk to CAD in the German MI Family Study

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Monitoring lactoferrin iron levels by fluorescence resonance energy transfer: A combined chemical and computational study

Three forms of lactoferrin (Lf) that differed in their levels of iron loading (Lf, LfFe, and LfFe2) were simultaneously labeled with the fluorophores AF350 and AF430. All three resulting fluorescent lactoferrins exhibited fluorescence resonance energy transfer (FRET), but they all presented different FRET patterns. Whereas only partial FRET was observed for Lf and LfFe, practically complete FRET was seen for the holo form (LfFe2). For each form of metal-loaded lactoferrin, the AF350–AF430 distance varied depending on the protein conformation, which in turn depended on the level of iron loading. Thus, the FRET patterns of these lactoferrins were found to correlate with their iron loading levels. In order to gain greater insight into the number of fluorophores and the different FRET patterns observed (i.e., their iron levels), a computational analysis was performed. The results highlighted a number of lysines that have the greatest influence on the FRET profile. Moreover, despite the lack of an X-ray structure for any LfFe species, our study also showed that this species presents modified subdomain organization of the N-lobe, which narrows its iron-binding site. Complete domain rearrangement occurs during the LfFe to LfFe2 transition. Finally, as an example of the possible applications of the results of this study, we made use of the FRET fingerprints of these fluorescent lactoferrins to monitor the interaction of lactoferrin with a healthy bacterium, namely Bifidobacterium breve. This latter study demonstrated that lactoferrin supplies iron to this bacterium, and suggested that this process occurs with no protein internalization.This work was supported by MINECO and FEDER (projects CTQ2012-32236, CTQ2011-23336, and BIO2012-39682-C02-02) and BIOSEARCH SA. F.C. and V.M.R. are grateful to the Spanish MINECO for FPI fellowships

Elevated Ratio of Urinary Metabolites of Thromboxane and Prostacyclin Is Associated with Adverse Cardiovascular Events in ADAPT

Results from prevention trials, including the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT), have fueled discussion about the cardiovascular (CV) risks associated with non-steroidal anti-inflammatory drugs (NSAIDs). We tested the hypotheses that (i) adverse CV events reported among ADAPT participants (aged 70 years and older) are associated with increased ratio of urine 11-dehydrothromboxane B2 (Tx-M) to 2′3-donor–6-keto-PGF1 (PGI-M) attributable to NSAID treatments; (ii) coincident use of aspirin (ASA) would attenuate NSAID-induced changes in Tx-M/PGI-M ratio; and (iii) use of NSAIDs and/or ASA would not alter urine or plasma concentrations of F2-isoprostanes (IsoPs), in vivo biomarkers of free radical damage. We quantified urine Tx-M and PGI-M, and urine and plasma F2-IsoPs from 315 ADAPT participants using stable isotope dilution assays with gas chromatography/mass spectrometry, and analyzed these data by randomized drug assignment and self-report compliance as well as ASA use. Adverse CV events were significantly associated with higher urine Tx-M/PGI-M ratio, which seemed to derive mainly from lowered PGI-M. Participants taking ASA alone had reduced urine Tx-M/PGI-M compared to no ASA or NSAID; however, participants taking NSAIDs plus ASA did not have reduced urine Tx-M/PGI-M ratio compared to NSAIDs alone. Neither NSAID nor ASA use altered plasma or urine F2-IsoPs. These data suggest a possible mechanism for the increased risk of CV events reported in ADAPT participants assigned to NSAIDs, and suggest that the changes in the Tx-M/PGI-M ratio was not substantively mitigated by coincident use of ASA in individuals 70 years or older

Symmetrical Corticobasal Syndrome Caused by a Novel c.314dup Progranulin Mutation

Corticobasal syndrome (CBS) is characterised by asymmetrical parkinsonism and cognitive impairment. The underlying pathology varies between corticobasal degeneration, progressive supranuclear palsy, Alzheimer’s disease, Creutzfeldt–Jakob disease and frontotemporal lobar degeneration sometimes in association with GRN mutations. A 61-year-old male underwent neurological examination, neuropsychological assessment, MRI, and HMPAO-SPECT at our medical centre. After his death at the age of 63, brain autopsy, genetic screening and mRNA expression analysis were performed. The patient presented with slow progressive walking disabilities, non-fluent language problems, behavioural changes and forgetfulness. His family history was negative. He had primitive reflexes, rigidity of his arms and postural instability. Later in the disease course he developed dystonia of his left leg, pathological crying, mutism and dysphagia. Neuropsychological assessment revealed prominent ideomotor and ideational apraxia, executive dysfunction, non-fluent aphasia and memory deficits. Neuroimaging showed symmetrical predominant frontoparietal atrophy and hypoperfusion. Frontotemporal lobar degeneration (FTLD)-TDP type 3 pathology was found at autopsy. GRN sequencing revealed a novel frameshift mutation c.314dup, p.Cys105fs and GRN mRNA levels showed a 50% decrease. We found a novel GRN mutation in a patient with an atypical (CBS) presentation with symmetric neuroimaging findings. GRN mutations are an important cause of CBS associated with FTLD-TDP type 3 pathology, sometimes in sporadic cases. Screening for GRN mutations should also be considered in CBS patients without a positive family history