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Ataxia Telangiectasia (A-T) is a rare, autosomal recessive genetic disorder characterized by a variety of symptoms, including progressive neurodegeneration, telangiectasia, immunodeficiency, and an increased susceptibility to cancer. It is caused by bi-allelic mutations impacting a gene encoding a serine/threonine kinase ATM (Ataxia Telangiectasia Mutated), which plays a crucial role in DNA repair and maintenance of genomic stability. The disorder primarily affects the nervous system, leading to a range of neurological issues, including cerebellar ataxia. The cause of neurodegeneration due to mutations in ATM is still an area of investigation, and currently there is no known treatment to slow down or stop the progression of the neurological problems. In this collaboration of the A-T Children's Project (ATCP) with Charles River Discovery, we successfully developed a high-throughput assay using induced pluripotent stem cells (iPSC) from A-T donors to measure DNA damage response (DDR). By measuring the changes in levels of activated phosphorylated CHK2 (p-CHK2), which is a downstream signaling event of ATM, we were able to identify compounds that restore this response in the DDR pathway in A-T derived patient cells. Over 6,000 compounds from small molecule drug repurposing libraries were subsequently screened in the assay developed, leading to identification of several promising in vitro hits. Using the assay developed and the identified hits opens avenues to investigate potential therapeutics for A-T., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brad Margus reports a relationship with AT Childrens Project that includes: board membership. Jennifer Thornton reports a relationship with AT Childrens Project that includes: employment and non-financial support. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Venous thromboembolism (VTE) rarely occurs during childhood and, with few exceptions, should be considered as a disease of sick children. Current recommendations concerning the duration of anticoagulant treatment for paediatric VTE are essentially based on the results of clinical trials conducted in adults. Yet the underlying medical conditions, incidence, and anatomical locations of the disease, as well as the rates of unprovoked VTE, morbidity, and mortality, differ between adults and children. Unprovoked VTE is uncommon in childhood. Most children experiencing VTE present risk factors, such as the presence of a central venous catheter (CVC), cancer, chemotherapy (in particular with asparaginase or steroids), obesity, severe infection, congenital cardiopathy (notably in conjunction with hepatic venous stasis), serious trauma, an anatomical venous anomaly (such as atresia or agenesia) or a nephrotic syndrome (inducing a deficit in antithrombin or protein S), premature birth, or maternal combined oral contraception. The recent possibility of administering direct oral anticoagulants (DOAC) to children undoubtedly constitutes the greatest change in the treatment of paediatric VTE. The advantages of this therapy include the possibility of its oral administration, even in infants, the absence of any need for laboratory follow-up, and the lack of food interactions. With the approval of the direct factor Xa inhibitor rivaroxaban (by the European Medicines Agency and Health Canada), and the direct thrombin inhibitor dabigatran (by the European Medicines Agency and the US Food and Drug Administration), paediatric anticoagulant therapy is changing. Only rivaroxaban currently has a Marketing Authorisation in France for the treatment of childhood VTE., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Inclisiran, an siRNA targeting hepatic PCSK9 mRNA, administered twice-yearly (after initial and 3-month doses), substantially and sustainably reduced LDL-cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a reduced risk of major adverse cardiovascular events (MACE) is not yet established. In-silico trials applying a disease computational model to virtual patients receiving new treatments allow to emulate large scale long-term clinical trials. The SIRIUS in-silico trial programme aims to predict the efficacy of inclisiran on CV events in individuals with established atherosclerotic cardiovascular disease (ASCVD)., Methods and Results: A knowledge-based mechanistic model of ASCVD was built, calibrated, and validated to conduct the SIRIUS programme (NCT05974345) aiming to predict the effect of inclisiran on CV outcomes. The SIRIUS Virtual Population included patients with established ASCVD (previous myocardial infarction (MI), previous ischemic stroke (IS), previous symptomatic lower limb peripheral arterial disease (PAD) defined as either intermittent claudication with ankle-brachial index <0.85, prior peripheral arterial revascularization procedure, or vascular amputation) and fasting LDL-C ≥ 70 mg/dL, despite stable (≥4 weeks) well-tolerated lipid-lowering therapies.SIRIUS is an in-silico multi-arm trial programme. It follows an idealized crossover design where each virtual patient is its own control, comparing inclisiran to (i) placebo as adjunct to high-intensity statin therapy with or without ezetimibe, (ii) ezetimibe as adjunct to high-intensity statin therapy, (iii) evolocumab as adjunct to high-intensity statin therapy and ezetimibe.The co-primary efficacy outcomes are based on the time to the first occurrence of any component of 3P-MACE (composite of CV death, nonfatal MI, or nonfatal IS) and time to occurrence of CV death over 5 years., Perspectives/conclusion: The SIRIUS in-silico trial programme will provide early insights regarding potential effect of inclisiran on MACE in ASCVD patients, several years before the availability of the results from ongoing CV outcomes trials (ORION-4 and VICTORION-2-P)., Clinical Trial Registration: Clinicaltrials.gov identifier: NCT05974345., Competing Interests: Conflict of interest: Denis Angoulvant reports having received payment or honoraria for lectures, presentations, speakers bureaus or educational events from Amgen, Alnylam, Amarin, Astra Zeneca, Boehringer, BMS, Bouchara Recordati, Pfizer, Novartis, Novo Nordisk, Organon, Sanofi, Servier, Vifor. Gabriel Steg reports the following: research grants from Amarin and Sanofi. Consulting or speaking for Amarin, Amgen, BMS and Novo-Nordisk. Clinical Trials (Steering committee, CEC, DSMB) for Amarin, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Janssen, Novartis, Novo-Nordisk, Pfizer, Sanofi. Senior Associate Editor at Circulation and Chief Scientific Officer of Bioquantis Guillaume Mahé reports having received payments for consulting, speaking, or educational events from Amgen, Amarin, Bayer Healthcare, BMS, Leo Pharma, Novartis, Novo Nordisk, Pfizer and Sanofi. Bertrand Cariou reports having received payments for consulting, speaking, or educational events from Amgen, Astra Zeneca, BMS, Eli Lilly, Novartis, Novo Nordisk, Sanofi, Ultragenyx. Franck Boccara reports having received payments for consulting, speaking, or educational events from Amgen, Amarin, Novartis, Novo Nordisk, Boehringer, Servier, ViiV healthcare, Gilead and Sanofi. Pierre Amarenco reports the following: grants from the French government (PHRC: RIISC-THETIS, TST-40, SPICAF trials), Pfizer and AstraZeneca (TST trial). Speaker fee from Novartis, Viatris and Sanofi. Advisory board for Novartis and Neuraltide. Steering committee for Bayer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Patients with symptomatic lower extremity artery disease (LEAD) should have an optimal management in terms of lipid goal [i.e. controlled LDL-cholesterol (LDLc)] and medical treatment (triple therapy with an antiplatelet agent, a statin and an angiotensin-converting enzyme inhibitor or a angiotensin-receptor antagonist). Prevalence of LEAD patients with a LDLc < 0.55 g/l is unknown. Aims of this study were to: (i) describe the prevalence of patients with a LDLc < 0.55 g/l, (ii) describe the prevalence of patients with an optimal medical treatment; (iii) compare this management between patients with a vascular surgery history and those without a vascular surgery history; and (iv) evaluate the number of patients eligible for new lipid-lowering therapies according to FOURIER and REDUCE-IT criteria., Methods: In this single-center retrospective study, prevalence is expressed as numbers and percentages. Comparison of the number of well managed patients between LEAD patients with a vascular surgery history and those without was performed. Number of patients who would be eligible for FOURIER and REDUCE-IT studies were calculated., Results: Among the LEAD patients included in the analysis (n = 225), only 12.4% (n = 28) had a LDLc < 0.55 g/L. The prevalence of patients who received the optimal medical treatment was 50.7% (n = 114). There was no statistical difference in the prevalence of patients with and without vascular surgery history achieving the LDLc goal (n = 9 (10.6%) vs. n = 19 (13.6%); p = not significant). Ninety-three patients (46.0%) would be eligible for EVOLOCUMAB treatment according to the Fourier study design whereas 17 patients (8.4%) would be eligible for treatment with ICOSAPENT ETHYL according to the REDUCE-IT study design., Conclusion: A majority of LEAD patients did not reach the LDLc goals. LEAD patients with a vascular surgery history did not experience a better management whereas they had a more consistent follow-up., (© 2024. The Author(s).)

Background: Tinzaparin could be easier to manage than unfractionated heparin in patients with severe renal impairment. However, clinical and pharmacologic data regarding its use in such patients are lacking., Objectives: The aims of this study were to determine, in patients with estimated glomerular filtration rate (eGFR) of <30 mL.min⁻ 1 , tinzaparin pharmacokinetics (PK) parameters using a population PK approach and bleeding and thrombotic complications., Methods: We performed a retrospective observational single-center study, including in-patients with eGFR of <30 mL.min⁻ 1 receiving prophylactic (4500 IU.d⁻ 1 ) or therapeutic (175 IU.kg⁻ 1 .d⁻ 1 ) tinzaparin. Measured anti-Xa levels were analyzed using a nonlinear mixed-effects modeling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte Carlo simulations based on the final covariate model parameter estimates., Results: Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analyzed: two-thirds received a prophylactic dose, 66% had an eGFR of <20 mL.min⁻ 1 , and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n = 199; 746 values), PK parameters, profiles, and maximum plasma concentrations were comparable with those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses over a median 9- and 7-day treatment period, respectively. No patients had thrombotic complications., Conclusion: Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment., Competing Interests: Declaration of competing interests I.G.T. has received honoraria from Aguettant, Bayer, BMS-Pfizer, Leo-Pharma, Sanofi, Stago, and Viatris. G.M. has received honoraria from Bayer Healthcare, BMS-Pfizer, Leo-Pharma, and Sanofi. P.M. has received honoraria from Bayer Healthcare, BMS-Pfizer, Leo-Pharma, and Sanofi. P.G. has received honoraria from Sanofi. All other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Lower extremity peripheral artery disease (PAD) often results from atherosclerosis, and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Individuals with T2DM exhibit a more severe manifestation and a more distal distribution of PAD compared to those without diabetes, adding complexity to the therapeutic management of PAD in this particular patient population. Indeed, the management of PAD in patients with T2DM requires a multidisciplinary and individualized approach that addresses both the systemic effects of diabetes and the specific vascular complications of PAD. Hence, cardiovascular prevention is of the utmost importance in patients with T2DM and PAD, and encompasses smoking cessation, a healthy diet, structured exercise, careful foot monitoring, and adherence to routine preventive treatments such as statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is also recommended to incorporate glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the medical management of patients with T2DM and PAD, due to their demonstrated cardiovascular benefits. However, the specific impact of these novel glucose-lowering agents for individuals with PAD remains obscured within the background of cardiovascular outcome trials (CVOTs). In this review article, we distil evidence, through a comprehensive literature search of CVOTs and clinical guidelines, to offer key directions for the optimal medical management of individuals with T2DM and lower extremity PAD in the era of GLP-1RA and SGLT2i., (© 2024. The Author(s).)

All guidelines worldwide strongly recommend exercise as a pillar of the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended for clinicians to promote and assist for the set-up of comprehensive exercise programmes to best advice in patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are narratively described based on the current best evidence. The document ends by highlighting disparities in access to supervised exercise programmes across Europe and the series of gaps for evidence requiring further research., (© 2024 the European Society of Cardiology, the European Society of Vascular Medicine, and the European Society for Vascular Surgery. Published by Oxford University Press on behalf of the European Society of Cardiology, by Hogrefe AG on behalf of European Society of Vascular Medicine and by Elsevier B.V on behalf of European Society for Vascular Surgery. All rights reserved. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.)

Investigation of the factors explaining individual differences in the acquisition of expert reading skills has become of particular interest these last decades. Non-verbal abilities, such as visual attention and executive functions play an important role in reading acquisition. Among those non-verbal factors, error-monitoring, which allows one to detect one's own errors and to avoid repeating them in the future, has been reported to be impaired in dyslexic readers. The present three-year longitudinal study aims at determining whether error-monitoring efficiency evaluated before and during reading instruction could improve the explanation of reading skills. To do so, 85 children will be followed from the last year of kindergarten to the second grade. The classic predictors of reading will be assessed at each grade level. Error-monitoring indices in domain-general and reading-related contexts will be derived from EMG data recorded during a Simon task in kindergarten and during both a Simon and a lexical decision tasks in the first and second grades. Findings concerning the role of error-monitoring on reading skills are expected to have an important impact on reading instruction to prevent reading difficulties in at-risk children and improve remediation to help children with reading difficulties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

All guidelines worldwide strongly recommend exercise as a pillar in the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research.

Background: A French intersociety consensus on behalf the Société Française de Médecine Vasculaire and the Société de Chirurgie Vasculaire et Endovasculaire was proposed in 2021 for the management of patients with lower extremity peripheral artery disease (LEAD). Recent studies have been published and an update of this consensus about the management of low-density lipoprotein cholesterol (LDLc) and hypertriglyceridemia was required., Methods: A steering committee of 12 vascular physicians and surgeons defined questions of interest about LDLc and hypertriglyceridemia management. A French expert panel voted the proposals. Consensus was considered to have been achieved if more than 80% of the responses corresponded to either "Agreement" or "Disagreement"., Results: Among the 56 experts who were asked to participate, 46 (82%) accepted. After the first round of the Delphi procedure, the 4 proposals reached consensus. The following suggestions and recommendations were approved: 1. For LEAD patients treated by the highest tolerated statin dose ± ezetimibe and who have an LDLc ≥0.70 g/L, we recommend adding a proprotein convertase subtilisin/kexin type 9 inhibitor. 2. For LEAD patients treated by statin and who have elevated triglyceride level between ≥150 mg/dL and ≤500 mg/dL, we suggest adding Icosapent Ethyl. 3. Before adding Icosapent Ethyl in LEAD patients treated with statin, we suggest looking for symptoms that may suggest atrial fibrillation. 4. For LEAD patients treated by Icosapent Ethyl and who have symptoms that suggest atrial fibrillation, we recommend performing an electrocardiogram., Conclusions: This update will help clinicians to improve LEAD patient management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

All guidelines worldwide strongly recommend exercise as a pillar in the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research., (Copyright © 2024 European Society for Vascular Surgery, The European Society of Cardiology, The European Society of Vascular Medicine. Published by Elsevier B.V. All rights reserved.)

Duplex ultrasound (DUS) is an essential tool for characterizing and monitoring arteriovenous (AV) access for hemodialysis. The aim of the work described here, requested by the French Society of Vascular Medicine in collaboration with the French-Speaking Vascular Access Society, is to propose a standardized methodology for performing and documenting DUS, taking into account the variety of AV access techniques and the problems routinely encountered. A steering committee reviewed the literature and selected the relevant references. A draft was prepared, and all items with missing or conflicting data were submitted to a Delphi consensus. The final document was discussed and approved by all participants. The principles of DUS evaluation of AV access consist of examination of the afferent artery, the anastomosis and the entire venous drainage system. DUS uses B-mode ultrasound, color flow, pulsed wave and power Doppler analysis. DUS can be used in a variety of clinical situations, which can directly influence the methodology of the examination and the interpretation of the results. Blood flow should be assessed as it correlates with the risk of thrombosis. The measurement should be adapted to the different anatomical and hemodynamic conditions encountered. Characterization of stenosis should take into account the residual diameter of the drainage vein and its hemodynamic consequences. Other complications can be assessed with a standardized DUS examination. When performed according to a rigorous methodology, DUS of the AV access allows a comprehensive assessment of its functionality and eliminates the need for further invasive diagnostic procedures., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Ischemic stroke is a major health issue. Currently, the relationship between dietary patterns and the occurrence of cardiovascular diseases including stroke is established, but the effect of systematic dietary intervention on dietary changes in ischemic stroke patients is unknown. Our objective was to compare changes in the dietary pattern of ischemic stroke patients who received a systematic diet intervention with changes in the dietary pattern of ischemic stroke patients who did not receive a systematic dietary intervention during their hospitalization., Methods: In this before-and-after study, two groups of patients with ischemic stroke were compared: Group 1 included 34 patients admitted with an ischemic stroke without a systematic dietray intervention; Group 2 included 34 patients admitted with an ischemic stroke with a systematic dietary intervention. Dietary patterns were assessed by a validated food frequency questionnaire of 19 questions (from a previously validated questionnaire of 14 questions), at the onset of stroke and at 6 months after stroke. This questionnaire allows the calculation of different scores as follows: global food score, saturated fatty acids score (SFA), unsaturated fatty acids score (UFA), fruit and vegetable score, and alcohol score., Results: Score changes were more important in group 2 than in group 1 for the global food score (7.4 ± 7 vs. 1.9 ± 6.7, p = 0.0013), the fruit and vegetable score (2 ± 2.6 vs. 0.6 ± 2.2, p = 0.0047), and the UFA score (1.8 ± 2.7 vs. 0.1 ± 3.3, p = 0.0238), whereas no significant differences were observed for the SFA score (-3.9 ± 4.9 vs. -1.6 ± 6, p = 0.1779) and the alcohol score (-0.4 ± 1.5 vs. -0.3 ± 1.1, p = 0.6960)., Conclusion: This study showed that systematic dietary intervention during hospitalization improves the dietary patterns of ischemic stroke patients. The impact on the recurrence of ischemic stroke or cardiovascular events after dietary pattern changes needs to be studied., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Besseau, Sartori, Larnier, Paillard, Laviolle and Mahé.)

Objective: The objective was to assess the accuracy and optimal threshold of the Walking Impairment Questionnaire (WIQ) and the Walking Estimated-Limitation Calculated by History (WELCH) questionnaire in identifying patients with a maximal walking distance (MWD) below or equal to 250 m., Methods: This retrospective study screened 388 consecutive patients with suspected symptomatic lower extremity arterial disease (LEAD). Collected data included the patient's history, resting ankle-brachial index, WIQ, and WELCH. MWD was assessed with a treadmill test at 2 mph (3.2 km/h) with a 10% grade. An optimized threshold for detection of MWD ≤ 250 m was determined for each questionnaire via receiver operating characteristic (ROC) curves. Subsequently, multivariate analysis was performed to build a new simple score to detect MWD ≤ 250 m., Results: The study included 297 patients (63 ± 10 years old). With a threshold of ≤ 64%, the WIQ predicted MWD ≤ 250 m with an accuracy of 71.4% (66.2, 76.5%). With a threshold of ≤ 22, the WELCH predicted a treadmill walking distance of ≤ 250 m with an accuracy of 68.7% (63.4, 74.0%). A new score with only four "yes or no" questions had an accuracy of 71.4% (66.3, 76.6%). Items on this new score consisted of the level of difficulty of walking 1 block, declared maximum walking distance, usual walking speed, and maximum duration of slow walking., Conclusion: A WIQ score ≤ 64% and a WELCH score ≤ 22 help to predict a walking distance of ≤ 250 m in a treadmill test at 2 mph (3.2 km/h) with a 10% grade. A 4-item score could be used for rapid evaluation of walking distance among patients with LEAD, but the validity of this 4-item score requires further confirmation studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tollenaere, Métairie, Le Pabic, Le Faucheur and Mahé.)

Background: Many insect species have shown dramatic declines over the last decades, as a result of man-related environmental changes. Many species which were formerly widespread are now rare. To document this trend with evidence, old records of collected specimens are vital., New Information: We provide here the data on 9752 bee (Hymenoptera: Apoidea) specimens hosted in several museums of south-east France: Musée des Confluences in Lyon, Muséum d'Histoire Naturelle de Marseille, Muséum d'Aix-en-Provence and the Muséum Départemental du Var in Toulon. Most of the specimens (9256) come from France and include data on 552 named species. For most of these specimens, the geographical location, including geographical coordinates, is based on the locality (town or village) where they were collected. The specimens were captured from the beginning of the nineteenth century to 2018. The identifications of 1377 specimens, mainly belonging to the genus Bombus , are considered reliable, as these were performed or been checked since 2009. All the other reported identifications are the original ones given by the original collectors., (Jean-Yves Meunier, Benoît Geslin, Mehdi Issertes, Gilles Mahé, Frédéric Vyghen, Harold Labrique, Yves Dutour, Vincent Poncet, Jérémy Migliore, Gabriel Nève.)

In recent years, the assessment of systolic acceleration in lower-extremity peripheral artery disease (PAD) has been brought back into the spotlight, whatever measure is used: time (in s) or acceleration (in cm.s -2 ). Acceleration time (also called systolic rise time) and maximal acceleration are two different but very useful measurements of growing interest in PAD. A background of the historical development, physics rationale, semantics, and methods of measurement, as well as their strengths and weaknesses, are discussed herein. Acceleration time is a powerful tool for predicting significant arterial stenosis or for estimating the overall impact of PAD as it is highly correlated to the ankle or toe pressure indexes. It could even become a new diagnostic criterion for critical limb ischemia. Similarly, maximal systolic acceleration ratios are highly predictive of carotid or renal stenosis. However, the literature lacks reference standards or guidelines for the assessment of such variables, and their measurement techniques seem to differ between authors. We propose herein a semantic and measurement statement order to clarify and help standardize future research.

(1) Background: Transcutaneous oxygen pressure (TcpO 2 ) is used to determine the severity of lower extremity arterial disease (LEAD). Many authors used a ratio of limb to chest TcpO 2 , also called the regional perfusion index (RPI), which should be independent of variations in oxygen delivery and reflective of local limb oxygen supply. The relevance of a reference probe-positioned TcpO 2 electrode is debated. We aimed to review the relevance of the reference probe in previous studies using rest TcpO 2 . (2) Methods: We searched Medline and the Cochrane Central Register of Controlled Trials on 22 September 2022 using keywords related to TcpO 2 , reference probe and LEAD. (3) Results/Discussion: Fifteen studies were included in the review. Nine studies investigated LEAD severity (n = 9), amputation healing predication (n = 4), surgical outcome prediction (n = 2), therapeutic effect (n = 3) and difference according to diabetic status (n = 1). Four studies investigated more than 1 indication. Among 12 (16.7%) studies using RPI, only two authors found a benefit of using RPI instead of absolute TcpO 2 . Using only univariate analysis, one author reported that RPI was significantly related to viability at 1 year, while distal TcpO 2 was not, on 13 limbs. The following year, the same author published a new study including 118 limbs that reported that RPI and absolute TcPO 2 were both prognostic factors for limb viability at 1 year using a multivariate model. (4) Conclusions: Only one study firmly supporting the use of RPI, calculated using a reference probe on the arm, to predict BKA healing. Prospective studies are needed to validate this result; for other indications there is insufficient data supporting the use of a TcpO 2 reference probe at rest.

This paper describes a currently on-going multicenter, randomized controlled trial designed to assess the efficacy of calf neuromuscular electrical stimulation (NMES) on changes in maximal walking distance in people with lower extremity peripheral artery disease (PAD), compared with a non-intervention control-group. This study (NCT03795103) encompasses five participating centers in France. PAD participants with a predominant claudication at the calf level and a maximal treadmill walking distance ≤300 m are randomized into one of the two groups: NMES group or Control group. The NMES program consists of a 12-week program of electrical stimulations at the calf-muscle level. The primary outcome of the study is the change in maximal treadmill walking distance at 12 weeks. Main secondary outcomes include changes in the pain-free treadmill walking distance; 6 min total walking distance; global positioning system (GPS)-measured outdoor walking capacity; daily physical activity level by accelerometry; self-reported walking impairment; self-reported quality of life; ankle-brachial index; and skin microvascular function, both at the forearm and calf levels. Recruitment started in September 2019 and data collection is expected to end in November 2022.

Introduction: This study aims to evaluate changes in the arterial spectral Doppler waveform in a canine artery stenosis model., Methods: Canine femoral artery stenosis models were established in 12 beagle dogs. Doppler waveforms were recorded in the femoral artery preoperatively and postoperatively in the femoral artery and at the ankle after formation of a 50%, 70%, and 90% stenosis or occlusion. Major descriptors for arterial Doppler waveform were used to analyse waveforms., Results: The proportion of multiphasic waveforms proximal to a moderate stenosis decreased compared to normal baseline, although the difference was not statistically significant, whereas the decreases at the stenosis, distal to the stenosis, and at the ankle were significant ( p < 0.05). The decreases in arteries with a more severe stenosis or occlusion were significant at all locations ( p < 0.05). The proportion of high resistive waveforms decreased significantly at the ankle in the arteries with a moderate stenosis (50%) ( p = 0.002), but the decreases proximal to, at, and distal to the stenosis were not significant. The decreases were significant at all locations in the arteries with a more severe stenosis ( p < 0.05). The decrease was significant at the ankle in the arteries with an occlusion ( p < 0.001) but not significant pre, at, and post an occlusion., Conclusions: Phasicity and resistance of Doppler waveforms alter in canine femoral arteries with a stenosis. Phasicity change seems more sensitive in response to an arterial stenosis than resistance change. Additional information on arterial resistance could be obtained using end-diastolic ratios, resistive indices, and potentially end-systolic notch velocity measurements.

Objectives: Ankle-brachial index (ABI) is commonly used for screening lower extremity peripheral artery disease (PAD) according to the international guidelines. Arterial Doppler waveform recordings is a tool to diagnose and assess PAD severity. We hypothesized that ABI measurement could be simplified by measuring only the pressure where the best arterial flow is recorded. The aim of this study was to evaluate the concordance between ABI performed according to the American Heart Association guidelines (AHA-ABI) and ABI measured according to best arterial waveform (FLOW-ABI)., Design: This was a monocentric cross-sectional study., Methods: We included patients with exertional limb symptoms suspected of PAD. Arterial Doppler waveforms and ABI were acquired on both lower extremities at the pedis and tibial posterior arteries. Each arterial waveform was classified using the Saint-Bonnet classification. Concordances were analyzed with the kappa coefficient (confidence interval 95%). Exercise PAD study was registered n° NCT03186391., Results: In total, one hundred and eighty-eight patients (62+/-12 years and 26.8+/-4.5 kg/m 2 ) with exertional limb symptoms were included from May 2016 to June 2019. On each extremity, FLOW-ABI had excellent concordance for the diagnosis of PAD with the AHA-ABI with a kappa of 0.95 (95% CI: 0.90, 0.99) in the right extremity and 0.91 (95% CI: 0.86, 0.97) in the left extremity., Conclusion: There is almost perfect concordance between AHA-ABI and FLOW-ABI. Thus, ABI can be simplified into five pressure measurements instead of seven in patient suspected of PAD with exertional limb symptoms. The question remains in patients with chronic limb ischemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Métairie, Tollenaere, Lanéelle, Le Faucheur, Le Pabic, Omarjee and Mahé.)

Low molecular weight heparins (LMWHs) are recommended by international guidelines for at least 6 months in patients with cancer-associated thromboembolism (CAT). Direct oral anticoagulants (DOACs) have been proposed as an alternative to LMWH. In clinical practice, the specialists in charge of CAT have to decide which anticoagulant to prescribe. An electronic survey tool, including vignettes and questions, was sent to members of the French Society of Vascular Medicine, the French-speaking association for supportive care in oncology and the Investigation Network On Venous Thrombo-Embolism. Among the 376 respondents, LMWHs were reported as the first choice by most specialists. The prescription of DOACs within the first 3 weeks of CAT diagnosis was highly dependent on the cancer site: 5.9%, 18.6% and 24.5% in patients with locally advanced colorectal, lung and breast cancer, respectively. The determinants were mostly related to cancer (site and stage or evolution) and to anticancer treatments. For 61% of physicians, some anticancer treatments were contraindications to DOACs. However, almost 90% of physicians considered switching to DOAC after a median 3-month period of LMWHs. In daily practice, LMWHs and DOACs are now considered by specialists of CAT; the decision is mostly driven by the site of cancer. The role of anticancer treatments in the decision remains to be investigated.

Limb-girdle muscular dystrophy type R3 (LGMD R3) is a rare genetic disorder characterized by a progressive proximal muscle weakness and caused by mutations in the SGCA gene encoding alpha-sarcoglycan (α-SG). Here, we report the results of a mechanistic screening ascertaining the molecular mechanisms involved in the degradation of the most prevalent misfolded R77C-α-SG protein. We performed a combinatorial study to identify drugs potentializing the effect of a low dose of the proteasome inhibitor bortezomib on the R77C-α-SG degradation inhibition. Analysis of the screening associated to artificial intelligence-based predictive ADMET characterization of the hits led to identification of the HDAC inhibitor givinostat as potential therapeutical candidate. Functional characterization revealed that givinostat effect was related to autophagic pathway inhibition, unveiling new theories concerning degradation pathways of misfolded SG proteins. Beyond the identification of a new therapeutic option for LGMD R3 patients, our results shed light on the potential repurposing of givinostat for the treatment of other genetic diseases sharing similar protein degradation defects such as LGMD R5 and cystic fibrosis., Competing Interests: Authors NM, JD, MG, DP, and NS were employed by the company KANTIFY. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hoch, Bourg, Degrugillier, Bruge, Benabides, Pellier, Tournois, Mahé, Maignan, Dawe, Georges, Papazian, Subramanian, Simon, Fanen, Delevoye, Richard and Nissan.)

The authors investigated the agreement between StepWatch3™ (SW3) and ActiGraph™ wGT3X+ monitors for measuring step-based metrics in patients with peripheral artery disease and older adults. In 23 patients with peripheral artery disease and 38 older participants, the authors compared the metrics obtained during an outdoor (400-m track) walking session (step count) and a 7-day free-living period (step count and 60/30/5/1-min maximal or peak step accumulation) using the SW3 (ankle) and the wGT3X+ (hip) with the low-frequency extension filter enabled (wGT3X+/LFE) or not (wGT3X+/N). During outdoor walking session, agreement was high, particularly for wGT3X+/LFE: correlations ≥.98, median absolute percentage errors <1%, and significant equivalence using a ± 15% equivalence zone or narrower. In free living, no wGT3X+ method was equivalent to SW3 for step count. The wGT3X+/LFE was equivalent to SW3 regarding all step accumulation metrics using a ± 20% equivalence zone or narrower, with median absolute percentage errors <11%. The wGT3X+/LFE method is the best option for comparisons with SW3 in peripheral artery disease and older adults.

Context: Ankle-brachial index (ABI) and toe-brachial index (TBI) are the recommended tests for the diagnosis of lower extremity peripheral artery disease (PAD) and the assessment of its severity, whereas Doppler ultrasound (DUS) is usually used to localize vascular lesions. However, the performance of DUS as an alternative to TBI and ABI measurement is unknown., Objective: The goals were (i) to evaluate the correlation between DUS parameters of distal arteries of the lower extremities with TBI in patients with PAD; (ii) to evaluate the correlation between DUS parameters of distal arteries with ABI; and (iii) to assess the diagnostic accuracy of maximal acceleration time of pedal arteries to detect toe pressure ≤30 mmHg., Methods: An observational retrospective study was conducted for 1 year on patients with the diagnosis of PAD on DUS. Demographic data, ABI, TBI, and DUS parameters of the dorsal pedis and lateral plantar arteries (DPA and LPA) were recorded., Results: Seventy-seven patients with 88 limbs were included, aged 69 [interquartile range: 11 years] with 28.6% of diabetic patients. The highest acceleration time of either DPA or LPA (AT max ) was the most correlated to TBI on both univariate ( r = -0.78, p < 0.0001) and multivariate analysis ( p < 0.0001). DUS parameters had a weaker correlation with ABI. AT max > 215 ms showed high diagnosis accuracy to a toe pressure of 30 mmHg or less [sensitivity of 86% [0.57-0.98] and negative predictive value of 97% [0.89-1.00]]., Conclusion: AT max demonstrates a high correlation with TBI in patients with PAD, and high diagnostic accuracy for detection of critical limb ischemia. Based on these results, AT max can represent the next step in evaluating PAD severity with DUS, in patients with advanced lower extremity PAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Trihan, Mahé, Croquette, Coutant, Thollot, Guillaumat and Lanéelle.)

Background: Direct oral anticoagulants (DOAC) use remains challenging in obese patients treated for Venous-Thrombo-Embolism (VTE) due to the paucity of prospective and dedicated studies., Objective: To assess rivaroxaban and apixaban concentrations at different time-points after intake, in obese patients followed at a thrombosis center and treated for VTE; to define factors associated with DOAC levels outside the on-therapy ranges; and to evaluate bleeding and thrombosis rates during follow-up., Methods: Observational prospective study in two French University hospitals. Apixaban or rivaroxaban concentrations were measured after the first visit, regardless of last intake in obese patients receiving DOAC for VTE. Concentrations were compared to published reference values for non-obese patients. Demographic, clinical, biological and therapeutic data were collected. Univariate and multivariate analyses were performed to identify factors associated to DOAC concentrations outside the on-therapy ranges., Results: Out of the 146 patients included, 22 (15%) had DOAC concentrations outside the on-therapy ranges, mainly in the rivaroxaban group (n = 17). Age ≤ 63 years, use of rivaroxaban and time since last intake ≤8 h were associated with DOAC concentrations outside the on-therapy ranges, in multivariable analysis. During the median follow-up of 16 months, two (1%) patients receiving apixaban had recurrent VTE. No patient had major bleeding, 11 (8%) patients had minor bleeding., Conclusion: In this specific prospective bi-centric study dedicated to VTE obese patients, use of DOACs at fixed doses led to concentrations similar to those of non-obese patients in a high proportion of patients, without any effect of the BMI, and with risk-benefit profile comparable to non-obese patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Nothing is known about the interest of the combination of exercise tests to diagnose Lower-extremity Peripheral Artery Disease (LEPAD). The aim of this study was to assess if combining exercise testing criteria [post-exercise Ankle-Brachial Index (ABI) + exercise-oximetry (exercise-TcPO2)] improves the detection of lower limbs arterial stenoses as compared with post-exercise ABI using American Heart Association (AHA) criteria, or exercise-TcPO2 alone. Material and Methods: In a prospective monocentric study, consecutive patients with exertional-limb pain and normal resting-ABI referred to our vascular center (Rennes, France) were assessed from May 2016 to February 2018. All included patients had a computed tomography angiography (CTA), a resting-ABI, a post-exercise ABI and an exercise-TcPO2. AHA post-exercise criteria, new validated post-exercise criteria (post-exercise ABI decrease ≥18.5%, post-exercise ABI decrease <0.90), and Delta from Rest of Oxygen Pressure (Total-DROP) ≤-15mmHg (criterion for exercise-TcPO2) were used to diagnose arterial stenoses ≥50%. For the different combinations of exercise testing criteria, sensitivity or specificity or accuracies were compared with McNemar's test. Results: Fifty-six patients (mean age 62 ± 11 years old and 84% men) were included. The sensitivity of the combination of exercise testing criteria (post-exercise ABI decrease ≥18.5%, or post-exercise ABI decrease <0.90 or a Total-DROP ≤-15mmHg) was significantly higher (sensitivity = 81% [95% CI, 71-92]) than using only one exercise test (post-exercise AHA criteria (sensitivity = 57% [43-70]) or exercise-TcPO2 alone (sensitivity = 59% [45-72]). Conclusions: Combination of post-exercise ABI with Exercise-TcPO2 criteria shows better sensitivity to diagnose arterial stenoses compared with the AHA post-exercise criteria alone or Exercise-TcPO2 criteria used alone. A trend of a better accuracy of this combined strategy was observed but an external validation should be performed to confirm this diagnostic strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stivalet, Paisant, Belabbas, Le Faucheur, Landreau, Le Pabic, Omarjee and Mahé.)

Background: Arterial Doppler flow waveform analysis is a tool recommended for the management of lower extremity peripheral arterial disease (PAD). To standardize the waveform analysis, classifications have been proposed. Neural networks have shown a great ability to categorize data. The aim of the present study was to use an existing neural network to evaluate the potential for categorization of arterial Doppler flow waveforms according to a commonly used classification., Methods: The Pareto efficient ResNet-101 (ResNet-101) neural network was chosen to categorize 424 images of arterial Doppler flow waveforms according to the Simplified Saint-Bonnet classification. As a reference, the inter-operator variability between two trained vascular medicine physicians was also assessed. Accuracy was expressed in percentage, and agreement was assessed using Cohen's Kappa coefficient., Results: After retraining, ResNet-101 was able to categorize waveforms with 83.7 ± 4.6% accuracy resulting in a kappa coefficient of 0.79 (0.75-0.83) (CI 95%), compared with a kappa coefficient of 0.83 (0.79-0.87) (CI 95%) between the two physicians., Conclusion: This study suggests that the use of transfer learning on a pre-trained neural network is feasible for the automatic classification of images of arterial Doppler flow waveforms.

This experiment was designed to investigate conceptual links directly through a word-picture matching task in children. Participants were asked to indicate between two pictures the one depicting the same concept as the newly learned L2 word (target). One of the two pictures was the target, while the other was either semantically related to it or was unrelated. To investigate whether learning methods modulate L2 word processing, two learning methods were compared: an L2-photograph method and an L1-L2 method. Results showed a semantic interference effect only with the L2-photograph method: Children responded more slowly in the related condition than in the unrelated one. The learning method modulated L2 word processing and L2 word meaning was not necessarily accessed through L1 mediation in the first steps of learning. The method used paves the way for the direct investigation of conceptual links., (© 2021 The British Psychological Society.)

Background: Diet strongly influences cardiovascular risk. Dietary evaluation is a major issue in cardiovascular prevention, but few simple tools are available. Our team previously validated a short food frequency questionnaire; a new version of this questionnaire (Cardiovascular Dietary Questionnaire 2 [CDQ-2]) is easier to complete and more reliable., Aims: To validate CDQ-2 in comparison with the original version, and to test its reproducibility., Methods: CDQ-2 has 17 closed-ended questions; it provides a global dietary score that is a combination of specific scores for saturated, monounsaturated and omega-3 fatty acids, and fruit and vegetables. CDQ-2 was validated against the original version in two groups, who completed both questionnaires: 99 patients with cardiovascular risk factors and 50 healthy subjects. Reproducibility was assessed with 27 health professionals who completed the questionnaire twice, with a 1-month interval., Results: The correlation coefficients of the scores between the two questionnaires ranged from 0.65 (monounsaturated fatty acids) to 0.93 (fruit and vegetables) (all P<0.001). The percentage of subjects classified in the same quartile by both questionnaires ranged from 56% (omega-3 fatty acids) to 78% (fruit and vegetables). The percentage of subjects classified in the same or adjacent quartile ranged from 91% to 99%. The intraclass correlation coefficients, which assessed reproducibility, ranged from 0.61 (fruit and vegetables) to 0.88 (saturated fatty acids) (P<0.001)., Conclusions: This new version of the short dietary questionnaire shows good reproducibility and correlations with the original version; use and reliability are improved, which makes CDQ-2 a valuable tool for cardiovascular prevention., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Numerous studies report that poor readers display low performance in naming tasks. However, very few studies have investigated the development of naming skills along with the development of reading fluency and its variability in typically developing children. In this study, we used electro-encephalographic (EEG) recordings acquired during letter and picture naming tasks to investigate how naming skills develop and, possibly, interact with age and reading level variations. Ninety-three children aged 7-12 years named letters and pictures under an EEG recording, and their reading performance was assessed. ERP results on amplitudes show that age and reading level have similar effects on the entire letter naming time-course. By contrast, age and reading level have different effects on the picture naming time-course, with a specific effect of reading level on the N1 time-interval, associated with visuo-conceptual processing and an effect of both age and reading on later time-windows. On the microstate analysis, age remains the only predictor of the variance in global electric field at scalp for both letter and picture naming indicating that reading skill is not related to a modulation of the mental processes underlying naming., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The objective of the study was to investigate the effect of recovery time on walking capacity (WC) throughout repeated maximal walking bouts in symptomatic lower-extremity peripheral artery disease (PAD). The effect of recovery time on WC (maximal walking time) was determined in 21 participants with PAD in three experimental conditions [recovery time from 0.5 to 9.5 min + a self-selected recovery time (SSRT)]: 1 ) 11 repeated sequences of two treadmill walking bouts (TW-ISO); 2 ) a single sequence of seven treadmill walking bouts (TW-CONS); 3 ) a single sequence of seven outdoor walking bouts (OW-CONS). Exercise transcutaneous oxygen pressure changes were continuously recorded as an indirect measure of ischemia. An individual recovery time (IRT) beyond which WC did not substantially increased was determined in participants with a logarithmic fit. At the group level, mixed models showed a significant effect ( P < 0.001) of recovery time on WC restoration. At the participant level, strong logarithmic relationships were found (median significant R 2 ≥ 0.78). The median SSRT corresponded to a median work-to-rest ratio >1:1 (i.e., a lower recovery time in view of the corresponding previous walking time) and was related to unrecovered ischemia and a WC restoration level of <80%. A median work-to-rest ratio of ≤1:2 allowed full recovery of ischemia and full restoration of WC. The IRT ratio was between 1:1 and 1:2 and corresponded to the start of recovery from ischemia. Recovery time affects the restoration level of WC during repeated maximal walking bouts in symptomatic PAD. Meaningful variations in WC restoration were related to specific levels of work-to-rest ratios. NEW & NOTEWORTHY This study demonstrated that there is a significant and mostly logarithmic effect of recovery time on walking capacity in people with symptomatic PAD. This study revealed that a median work-to-rest ratio >1:1 leads to the resumption of walking with unrecovered ischemia and precludes the restoration of full walking capacity, whereas a work-to-rest ratio ≤1:2 allowed walking capacity to fully be restored.

Radiologists, and doctors in general, need relevant information for the quantification and characterization of pulmonary structures damaged by severe diseases, such as the Coronavirus disease 2019 (COVID-19). Texture-based analysis in scope of other pulmonary diseases has been used to screen, monitor, and provide valuable information for several kinds of diagnoses. To differentiate COVID-19 patients from healthy subjects and patients with other pulmonary diseases is crucial. Our goal is to quantify lung modifications in two pulmonary pathologies: COVID-19 and idiopathic pulmonary fibrosis (IPF). For this purpose, we propose the use of a three-dimensional multiscale fuzzy entropy (MFE3D) algorithm. The three groups tested (COVID-19 patients, IPF, and healthy subjects) were found to be statistically different for 9 scale factors ( p < 0.01 ). A complexity index (CI) based on the sum of entropy values is used to classify healthy subjects and COVID-19 patients showing an accuracy of 89.6 % , a sensitivity of 96.1 % , and a specificity of 76.9 % . Moreover, 4 different machine-learning models were also used to classify the same COVID-19 dataset for comparison purposes., (© 2021 Elsevier Ltd. All rights reserved.)

Background/objectives: Peripheral arterial disease is a frequent and severe disease with high cardiovascular morbidity and mortality. However, female patients appear to be undertreated., Objectives: The primary goal was to compare the prescription of optimal medical treatment (OMT) of peripheral arterial disease between women and men in primary health care., Material and Methods: An observational retrospective study was based on the data collected from general practitioners (GP) office in Brittany., Results: The study included 100 patients, aged 71 ± 10 years old, with 24% of women. Compared to men, women received the OMT less frequently (29.2% vs. 53.9%, p = 0.038), especially after 75 years old. Antiplatelet therapy was largely prescribed (100%), statins less frequently (70.8% women vs. 85.5% men), and prescription of renin-angiotensin-aldosterone system inhibitors was still not optimal in the two genders (41.7% women vs. 61.9% men). Active smoking is important for both women and men (33% and 30% respectively)., Conclusion: Optimal medical treatment of peripheral artery disease is insufficiently prescribed, especially in women in this region of France.

Background: Anticoagulants are the recommended treatment for venous thromboembolic disease (VTE). The mode of anticoagulant administration may influence compliance, and therefore the effectiveness of the treatment. Unlike in atrial fibrillation or cancer-associated thrombosis, there is only limited data on patient preferences regarding the choice of anticoagulation in VTE. This study aims to evaluate patient preferences regarding anticoagulants in terms of administration: types (oral or injectable treatment) and number of doses or injections per day. Patients and Methods: This is a national survey through a questionnaire sent by e-mail to 1936 French vascular physicians between February and April 2019. They recorded the responses for each patient admitted for VTE. Results: Three hundred and eleven (response rate of 16%) of the 1936 contacted physicians responded for 364 patients. Among these, there were 167 fully completed questionnaires. Most patients (63%) express concerns about VTE and prefer oral treatment (81.5%), justified by the ease of administration (74%) and a fear of the injections (22%). When patients were taking more than three oral treatments they statistically chose injectable treatment more often (54%) than oral treatment (25%, p = 0.002). Patients who chose injectable treatment were also older (70 ± 16 vs. 58 ± 17 years old, p = 0.001). There was no statistically difference in anticoagulation preference according to gender or to the expected duration of treatment (6 weeks, 3 months, 6 months or unlimited). When oral treatment was preferred (81%), most chose oral treatment without dose adjustment and biomonitoring (74.3%). Among them, very few (5.8%) preferred a twice-daily intake. Conclusion: Patient preference in terms of anticoagulant treatment in VTE disease is in favor of oral treatment without adjustment or biomonitoring and with once-daily intake. When an injectable treatment is chosen, a prolonged duration of treatment does not seem to be a constraint for the patient. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT03889457]., Competing Interests: GM has received fees as speaker from Bristol-Myers-Squibb, Leo Pharma, GSK, and Bayer. DL has received fees as speaker from Bristol-Myers-Squibb, Leo Pharma, and Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lanéelle, Le Brun, Mauger, Guillaumat, Le Pabic, Omarjee, Mahé and SFMV VTE Study Group.)

Purpose: This study aimed to determine and compare the accuracy of different activity monitors in assessing intermittent outdoor walking in both healthy and clinical populations through the development and validation of processing methodologies., Methods: In study 1, an automated algorithm was implemented and tested for the detection of short (≤1 min) walking and stopping bouts during prescribed walking protocols performed by healthy subjects in environments with low and high levels of obstruction. The following parameters obtained from activity monitors were tested, with different recording epochs0.1s/0.033s/1s/3s/10s and wearing locationsscapula/hip/wrist/ankle: GlobalSat DG100 (GS) and Qstarz BT-Q1000XT/-Q1000eX (QS) speed; ActiGraph wGT3X+ (AG) vector magnitude (VM) raw data, VM counts, and steps; and StepWatch3 (SW) steps. Furthermore, linear mixed models were developed to estimate walking speeds and distances from the monitors parameters. Study 2 validated the performance of the activity monitors and processing methodologies in a clinical population showing profile of intermittent walking due to functional limitations during outdoor walking sessions., Results: In study 1, GS1s, scapula, QS1s, scapula/wrist speed, and AG0.033s, hip VM raw data provided the highest bout detection rates (>96.7%) and the lowest root mean square errors in speed (≤0.4 km·h-1) and distance (<18 m) estimation. Using SW3s, ankle steps, the root mean square error for walking/stopping duration estimation reached 13.6 min using proprietary software and 0.98 min using our algorithm (total recording duration, 282 min). In study 2, using AG0.033s, hip VM raw data, the bout detection rate (95% confidence interval) reached 100% (99%-100%), and the mean (SD) absolute percentage errors in speed and distance estimation were 9% (6.6%) and 12.5% (7.9%), respectively., Conclusions: GPS receivers and AG demonstrated high performance in assessing intermittent outdoor walking in both healthy and clinical populations., (Copyright © 2021 by the American College of Sports Medicine.)

Background: Arterial Doppler Ultrasound waveform (DW) analysis allows the detection and evaluation of lower extremity peripheral artery disease. The high heterogeneity of the reported description of DW is reduced by the use of classification. However, the reliability of these classifications is either unknown or low to moderate and practices of vascular caregivers regarding the use of these classifications remain unknown. Aims: This study aims to assess the inter-observer reliability of the Saint-Bonnet classification, a 13-category DW classification. The secondary objective was to determine the utilization rate of the most common classifications and the ability of these classifications to describe DW. Methods: A national survey was conducted among all vascular physicians of French society of vascular medicine. They were invited by email to describe on a website 20 DW without and with the display of the Saint-Bonnet classification. The reliability of this classification was estimated by Fleiss' Kappa expressed with [95% confidence interval]. A semantic analysis allowed us to classify the physicians' responses according to the terms used. Finally we have evaluated for each classification the rate of misuse, i.e., the addition of a complementary term to the defined categories. Results: One hundred and ten physicians participated and only 5% of these were familiar with Saint-Bonnet classification. Fifty-four percent of vascular physicians used no classification at all. Vascular physicians used the Spronk (four-category), Descotes (five-category) and Saint-Bonnet (13-category) classifications for respectively, 31, 10, and 5%. Kappa coefficient of Fleiss (κ) was 0.546 [0.544-0.547] ( p < 0.001). Reliability by category ranges from κ of 0.075 to 0.864. In multivariate analysis, the use of a classification was associated with fewer years of experience and was dependent on geographic location. Misuse rate by classification was 88, 82, and 5% using Spronk, Descotes and Saint-Bonnet classifications respectively. Conclusion: The reliability of Saint-Bonnet classification is weak to moderate by vascular physicians who are not familiar with its use. However, unlike the other classifications, it seems to be sufficiently precise so that the user does not need to complete its description. There is a significant heterogeneity in the use of arterial Doppler classifications in France., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lanéelle, Guillaumat, Trihan, Pottier, Omarjee, Mahé and SFMV PAD Study Group.)

Objective: Arterial Doppler waveform recordings are commonly used to assess lower extremity arterial disease (LEAD) severity. However, little is known about the relationship between arterial Doppler waveform profiles and patients' walking capacity. The purpose of this study was to assess whether arterial Doppler waveforms are independently associated with maximal walking distance (MWD) in patients experiencing exertional limb symptoms. Materials and Methods: This cross-sectional study included suspected LEAD patients experiencing exertional limb symptoms. In both lower extremities, arterial Doppler waveforms and ankle-brachial index (ABI) values were obtained from the pedis and tibial posterior arteries. Each arterial flow measurement was ranked using the Saint-Bonnet classification system. Treadmill stress testing (3.2 km/h, 10% slope) coupled with exercise oximetry (Exercise-TcPO2) were used to determine MWD. Delta from rest oxygen pressure (DROP) was calculated. Following treadmill stress testing, post-exercise ABI values were recorded. Univariate and multivariate analyses were used to determine the clinical variables associated with MWD. Results: 186 patients experiencing exertional limb symptoms (62 ± 12 years and 26.8 ± 4.5 kg/m 2 ) were included between May 2016 and June 2019. Median [25th; 75th] treadmill MWD was 235 [125;500]m. Better arterial Doppler waveforms were associated with better walking distance ( p = 0.0012). Whereas, median MWD was 524 [185;525]m in the group that yielded the best Doppler waveforms, it was 182 [125,305]m in the group with the poorest Doppler waveforms ( p = 0.0012). MWD was significantly better ( p = 0.006) in the patients with the best ABIs. However, arterial Doppler waveforms alone were significantly associated with MWD ( p = 0.0009) in the multivariate model. When exercise variables (post-exercise ABI or DROP) were incorporated into the multivariate model, these were the only variables to be associated with MWD. Conclusion: Of the various clinical parameters at rest, Doppler flow waveform profiles were associated with MWD in suspected LEAD patients. A stronger link was however found between exercise variables and MWD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miossec, Tollenaere, Lanéelle, Guilcher, Métairie, Le Pabic, Carel, Le Faucheur and Mahé.)

Several international guidelines concerning lower extremity arterial disease (LEAD) have been published recently, in particular, by the American Heart Association the European Society of Cardiology/European Society for Vascular Surgery, the European Society for Vascular Medicine and the Society for Vascular Surgery. These guidelines differ in some respects and certain issues are not addressed. The objective of this consensus driven by the French Societies of vascular Medicine and surgery was to analyze the disparities between the different guidelines, as well as certain issues not covered, and develop proposals with regard to these points. The following fields of LEAD have been explored: 1) classifications, 2) clinical evaluation, 3) diagnostic criteria, 4) quantification of arterial stenosis using duplex ultrasound, 5) detection of asymptomatic multisite lesions, 6) screening for LEAD in the context of cardiac disease, 7) medical treatment, 8) supervised exercise therapy, 9) revascularization and revascularization of the internal artery stenosis, 10) management of chronic limb ischemia, 11) longitudinal follow-up, and 12) diet., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The arid coasts of North Africa, extending over 4633 km from the Gulf of Tunis to the Nile Delta, are undergoing pronounced shoreline retreats and coastal floodings that are reported as a consequence of the ongoing sea level rise resulting from global warming. Of particular interest are the abnormal shoreline dynamics for deltaic and sandy beaches, which are severely impacted by abrupt decadal variabilities in both climatic and anthropogenic drivers resulting in their increased vulnerability to disturbances from coastal hazards. Unfortunately, the evolution, distribution and impacts of these drivers remain largely unquantified, let alone understood, for these extensive arid coasts that harbor the major portion of North Africa's population as well as unique and fragile marine ecosystems. To address this deficiency, we use GIS-based multi-criteria approaches combined with analytic hierarchy process to map the Coastal Vulnerability Index and the Socioeconomic Vulnerability Index along these coasts to investigate the amplitude and extent of shoreline deterioration resulting from sudden fluctuations in sediment transport to the coastline. We use the western bay of the Gulf of Tunis, the coasts of Tripoli and the Nile Delta as three validation sites for our vulnerability assessment. The statistical Integrated Coastal Vulnerability Index map reveals that 47% of arid North African coasts are characterized by high to very high vulnerability. In particular, we observe that the densely populated deltaic coasts in both Tunisia and Egypt are 70% more vulnerable than any others coast in the eastern Mediterranean Basin. These abnormally high-vulnerability extensive areas are also correlated with significant deterioration of coastal aquifers and hence in crop production, compromising local food security and resulting in increasing outflow migration trends. Both Tunisia and Egypt observed dramatic increases in the net population outflow migration by respectively 62% and 248% between 2000 and 2016, mostly from coastal areas. Our source analysis of the amplitude and extent of these high coastal vulnerabilities suggests that they result from the anthropogenic drivers of damming and rapid urban growth over the last few decades rather than the effects of global warming.

Background: Characterisation of arterial Doppler waveforms is a persistent problem and a source of confusion in clinical practice. Classifications have been proposed to address the problem but their efficacy in clinical practice is unknown. The aim of the present study was to compare the efficacy of the categorisation rate of Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications., Methods: This is a multicentre prospective study where 130 patients attending a vascular arterial ultrasound were enrolled and Doppler waveform acquisition was performed at the common femoral, the popliteal, and the distal arteries at both sides. Experienced vascular specialists categorized these waveforms according to the three classifications., Results: of 1033 Doppler waveforms, 793 (76.8%), 943 (91.3%) and 1014 (98.2%) waveforms could be categorized using Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications, respectively. Differences in categorisation between classifications were significant (Chi squared test, p < 0.0001). Of 19 waveforms uncategorized using the simplified Saint-Bonnet classification, 58% and 84% were not categorized using the Spronk et al. and Descotes and Cathignol classifications, respectively., Conclusions: The results of the present study suggest that the simplified Saint-Bonnet classification provides a superior categorisation rate when compared with Spronk et al. and Descotes and Cathignol classifications.

The present study investigates the nature of the spelling-to-sound correspondences taught to enhance phonemic awareness in prereaders. The main assumption in the literature is that learning the alphabetic code through letter-to-phoneme correspondences is the best way to improve phonemic awareness. The alternative syllabic bridge hypothesis, based on the saliency and early availability of syllables, assumes that learning to associate letters to phonological syllables enables phoneme units to be the mirror of the letters and to become accessible, thereby developing phonemic awareness of prereaders. A total of 222 French-speaking prereaders took part in a 4-session learning program based on correspondences either between letters and syllables (letters-to-syllable group) or between letters and phonemes (letter-to-phoneme group), and the fifth last session on coding and decoding. Our results showed a greater increase in phonemic awareness in the letters-to-syllable group than in the letter-to-phoneme group. The present study suggests that teaching prereaders letters-to-syllable correspondences is a key to successful reading.

Background: Non-invasive Doppler waveform (DW) analysis is a widely adopted method for detecting and evaluating lower extremity peripheral artery disease (PAD). Previous investigations have reported that broad heterogeneity in the description of Doppler waveforms is reduced by using a classification method. The reliability of arterial Doppler classification, however, is unknown. Purpose: The purpose of this study is to assess the reliability of a 4-category arterial DW classification method among Chinese sonographers. Methods: During a national ultrasound conference in China attendees were invited to classify thirty arterial Doppler waveforms. After viewing a 4-category (triphasic, biphasic, monophasic, and other) arterial Doppler waveform descriptor presentation, attendees were asked to classify 15 continuous wave (CW) and 15 pulsed wave (PW) Doppler waveforms. Their responses were recorded via mobile phone and the reliability of this 4-category classification was estimated by Fleiss' Kappa inter-rater statistical analysis. Results: One hundred and seventy-eight attendees participated in the analysis. The Kappa coefficient of Fleiss (κ) for all attendees was 0.522 ( p < 0.005) with 95% confidence interval (CI): 0.520-0.523. The reliability of the waveform descriptor triphasic was the highest (κ = 0.621, p < 0.005), and other was the lowest (κ = 0.341, p < 0.005). Conclusion: The inter-rater reliability of a 4-category arterial Doppler waveform classification by Chinese sonographers is considered weak (κ = 0.522, CI95%: 0.520-0.523, p < 0.005). This study reinforces the importance of assessing DW classification reliability and the development of DW descriptors that are more accurately predictive of clinical hemodynamic events., (Copyright © 2020 Zhao, Lanéelle, Gao, Fu, Tong, Scissons, Wen and Mahé.)

Lower extremity peripheral artery disease (PAD) induces an ischemic pain in the lower limbs and leads to walking impairment. Electrical stimulation has been used in patients with PAD, but no systematic review has been proposed to address the efficacy of the technique as a treatment for walking impairment in PAD. A systematic search was performed to identify trials focused on electrical stimulation for the treatment of walking impairment in patients with PAD in the Cochrane Central Register, PubMed, Embase, and the Web of Science. Studies were included where the primary outcomes were pain-free walking distance and/or maximal walking distance. When appropriate, eligible studies were independently assessed for quality using the Cochrane Collaboration's tool for assessing risk of bias. Five studies eligible for inclusion were identified, of which only two were randomized controlled studies. Trial heterogeneity prevented the use of the GRADE system and the implementation of a meta-analysis. Three types of electrical stimulation have been used: neuromuscular electrical stimulation (NMES, n = 3), transcutaneous electrical stimulation ( n = 1), and functional electrical stimulation ( n = 1). The two available randomized controlled studies reported a significant improvement in maximal walking distance (+40 m/+34% and +39 m/+35%, respectively) following a program of NMES. Owing to the low number of eligible studies, small sample size, and the risk of bias, no clear clinical indication can be drawn regarding the efficacy of electrical stimulation for the management of impaired walking function in patients with PAD. Future high-quality studies are required to define objectively the effect of electrical stimulation on walking capacity.