Survey of transfemoral amputee experience and priorities for the user-centered design of powered robotic transfemoral prostheses

BACKGROUND: Transfemoral amputees experience a complex host of physical, psychological, and social challenges, compounded by the functional limitations of current transfemoral prostheses. However, the specific relationships between human factors and prosthesis design and performance characteristics have not yet been adequately investigated. The present study aims to address this knowledge gap. METHODS: A comprehensive single-cohort survey of 114 unilateral transfemoral amputees addressed a broad range of demographic and clinical characteristics, functional autonomy, satisfaction and attitudes towards their current prostheses, and design priorities for an ideal transfemoral prosthesis, including the possibility of active assistance from a robotic knee unit. The survey was custom-developed based on several standard questionnaires used to assess motor abilities and autonomy in activities of daily living, prosthesis satisfaction, and quality of life in lower-limb amputees. Survey data were analyzed to compare the experience (including autonomy and satisfaction) and design priorities of users of transfemoral prostheses with versus without microprocessor-controlled knee units (MPKs and NMPKs, respectively), with a subsequent analyses of cross-category correlation, principal component analysis (PCA), cost-sensitivity segmentation, and unsupervised K-means clustering applied within the most cost-sensitive participants, to identify functional groupings of users with respect to their design priorities. RESULTS: The cohort featured predominantly younger (< 50 years) traumatic male amputees with respect to the general transfemoral amputee population, with pronounced differences in age distribution and amputation etiology (traumatic vs. non-traumatic) between MPK and NMPK groups. These differences were further reflected in user experience, with MPK users reporting significantly greater overall functional autonomy, satisfaction, and sense of prosthesis ownership than those with NMPKs, in conjunction with a decreased incidence of instability and falls. Across all participants, the leading functional priorities for an ideal transfemoral prosthesis were overall stability, adaptability to variable walking velocity, and lifestyle-related functionality, while the highest-prioritized general characteristics were reliability, comfort, and weight, with highly variable prioritization of cost according to reimbursement status. PCA and user clustering analyses revealed the possibility for functionally relevant groupings of prosthesis features and users, based on their differential prioritization of these features—with implications towards prosthesis design tradeoffs. CONCLUSIONS: This study’s findings support the understanding that when appropriately prescribed according to patient characteristics and needs in the context of a proactive rehabilitation program, advanced transfemoral prostheses promote patient mobility, autonomy, and overall health. Survey data indicate overall stability, modularity, and versatility as key design priorities for the continued development of transfemoral prosthesis technology. Finally, observed associations between prosthesis type, user experience, and attitudes concerning prosthesis ownership suggest both that prosthesis characteristics influence device acceptance and functional outcomes, and that psychosocial factors should be specifically and proactively addressed during the rehabilitation process. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12984-021-00944-x

Evaluation of total column water vapour products from satellite observations and reanalyses within the GEWEX Water Vapor Assessment

Since 2011, the Global Energy and Water cycle Exchanges (GEWEX) Water Vapor Assessment (GVAP) has provided performance analyses for state-of-the-art reanalysis and satellite water vapour products to the GEWEX Data and Analysis Panel (GDAP) and the user community in general. A significant component of the work undertaken by G-VAP is to characterise the quality and uncertainty of these water vapour records to (i) ensure full exploitation and (ii) avoid incorrect use or interpretation of results. This study presents results from the second phase of G-VAP, where we have extended and expanded our analysis of total column water vapour (TCWV) from phase 1, in conjunction with updating the G-VAP archive. For version 2 of the archive, we consider 28 freely available and mature satellite and reanalysis data products, remapped to a regular longitude– latitude grid of 2° × 2° and on monthly time steps between January 1979 and December 2019. We first analysed all records for a “common” short period of 5 years (2005–2009), focusing on variability (spatial and seasonal) and deviation from the ensemble mean. We observed that clear-sky daytime-only satellite products were generally drier than the ensemble mean, and seasonal variability/disparity in several regions up to 12 kg m−2 related to original spatial resolution and temporal sampling.This research has been supported by the Natural Environment Research Council (grant no. PR140015) and the European Space Agency (grant no. 4000131292)

Sotorasib in KRASp.G12C mutated advanced NSCLC: Real-world data from the Italian expanded access program

Background: Sotorasib showed a significant improvement of progression free survival (PFS), safety and quality of life over docetaxel in patients with KRASp.G12C-mutated advanced non-small-cell lung cancer (NSCLC) within the CodeBreak-200 study. Here we report real-world efficacy and tolerability data from NSCLC patients who received sotorasib within the Italian expanded access program (EAP). Methods: Sotorasib (960 mg, orally, once daily) was available on physician request for KRASp.G12C mutant advanced NSCLC patients. Clinical-pathological and molecular data were collected from the Italian ATLAS real-world registry. Patients underwent CT-scan and responses were evaluated by RECIST criteria. Efficacy and tolerability outcomes have been assessed. Results: A total of 196 advanced NSCLC patients were treated across 30 Italian centers. Median age was 69 years old (range 33-86). Most patients were male (61 %), former (49 %) or current smokers (43 %), with ECOG-PS 0/1 (84 %) and adenocarcinoma subtype (90 %). 45 % and 32 % of patients received sotorasib in 2nd and 3rd line, respectively. Overall, response rate was 26 % and the median duration of response was 5.7 months (95 % CI: 4.4-7.0). Median PFS and OS were 5.8 months (95 % CI: 5 - 6.5) and 8.2 months (95 % CI: 6.3 - 9.9). Grade 3-4 TRAEs occurred in 16.5 % of patients, with Grade >= 3 liver enzyme increase and TRAEs-related discontinuation reported in 12 % and 4.6 % of cases. Conclusion: Real-world data from the Italian EAP confirm the tolerability and effectiveness of sotorasib in patients with KRASp.G12C-mutated advanced NSCLC and highlight the value of the national ATLAS network as source of real-world evidence driving the clinical management of NSCLC patients

The Genetic Structure of Leishmania infantum Populations in Brazil and Its Possible Association with the Transmission Cycle of Visceral Leishmaniasis

Leishmania infantum is the etiologic agent of visceral leishmaniasis (VL) in the Americas, Mediterranean basin and West and Central Asia. Although the geographic structure of L. infantum populations from the Old World have been described, few studies have addressed the population structure of this parasite in the Neotropical region. We employed 14 microsatellites to analyze the population structure of the L. infantum strains isolated from humans and dogs from most of the Brazilian states endemic for VL and from Paraguay. The results indicate a low genetic diversity, high inbreeding estimates and a depletion of heterozygotes, which together indicate a predominantly clonal breeding system, but signs of sexual events are also present. Three populations were identified from the clustering analysis, and they were well supported by F statistics inferences and partially corroborated by distance-based. POP1 (111 strains) was observed in all but one endemic area. POP2 (31 strains) is also well-dispersed, but it was the predominant population in Mato Grosso (MT). POP3 (31 strains) was less dispersed, and it was observed primarily in Mato Grosso do Sul (MS). Strains originated from an outbreak of canine VL in Southern Brazil were grouped in POP1 with those from Paraguay, which corroborates the hypothesis of dispersal from Northeastern Argentina and Paraguay. The distribution of VL in MS seems to follow the west-east construction of the Bolivia-Brazil pipeline from Corumbá municipality. This may have resulted in a strong association of POP3 and Lutzomyia cruzi, which is the main VL vector in Corumbá, and a dispersion of this population in this region that was shaped by human interference. This vector also occurs in MT and may influence the structure of POP2. This paper presents significant advances in the understanding of the population structure of L. infantum in Brazil and its association with eco-epidemiological aspects of VL

The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction

Abstract Background: Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF. Methods: We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding). Results: The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84–1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03–1.77). Conclusions: In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability

Oral ondansetron versus domperidone for acute gastroenteritis in pediatric emergency departments: Multicenter double blind randomized controlled trial

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly