To better understand experimental conditions and performances of its experiment, the LHCb collaboration executes tens of thousands of looselycoupled and CPU-intensive Monte Carlo simulation workflows ...per hour. To meet the increasing LHC computing needs, funding agencies encourage the collaboration to exploit High-Performance Computing resources, and more specifically supercomputers, which offer a significant additional amount of computing resources but also come with higher integration challenges. This state-ofpractice paper outlines years of integration of LHCb simulation workflows on several supercomputers. The main contributions of this paper are: (i) an extensive description of the gap to address to run High-Energy Physics Monte Carlo simulation workflows on supercomputers; (ii) various methods and proposals to maximize the use of allocated CPU resources; (iii) a comprehensive analysis of LHCb production workflows running on diverse supercomputers.
Abstract Objective Physical therapy strategies have recently proved their efficacy in the field of Parkinson's disease management. The purpose of this paper was to access the efficacy and the limits ...of aerobic training and strength training included in physical rehabilitation programs and to define practical modalities. Method A comprehensive search on Pubmed and Cochrane databases was made. Results Five literature revues and thirty one randomised trials have been selected. Exercise training improves aerobic capacities, muscle strength, walking, posture and balance parameters. Rehabilitation programs should begin as soon as possible, last several weeks and be repeated. They should include aerobic training on bicycle or treadmill and a muscle strengthening program. Conclusion There is evidence that aerobic and strength training improve physical habilities of patients suffering from Parkinson's Disease. Rehabilitation programs should be discussed with the patient, taking in account his difficulties and his physical capacities. Two questions are debatable: exercise intensity and phase ON / phase OFF timing.
The aim of this study was to investigate how body thermal resistance between sexes evolves over time in the recovery period after a WBC session and to show how this parameter should be considered as ...a key parameter in WBC protocols. Eighteen healthy participants volunteered for the study (10 males and 8 females). Temperature (core and skin) were recorded pre- and post (immediately and every 5 min until 35 min post) exposure to a single bout of WBC (30 s at −60 °C, 150 s at −110 °C). From both core and skin temperatures a bio-heat transfer model was applied which led to the analytical formulation of the body thermal resistance. An unsteady behavior presenting a similar time-evolution trend in the body insulative response is shown for both females and males, possibly due to the vasodilatation process following an intense peripheral vasoconstriction during the extreme cold. Females present a 37% higher inner thermal resistance than males when reaching an asymptotical thermal state at rest due to a higher concentration of body fat percentage. Adiposity of tissues inherent in fat mass percentage appears to be a key parameter in the body thermal resistance to be taken into account in the definition of appropriate protocols for males and females. The conclusions of this preliminary study suggest that in order to achieve the same skin effects on temperature and consequently to cool efficiency tissues in the same way, the duration of cryotherapy protocols should be shorter when considering female compared to male.
Abstract This article establishes the basics of a theoretical model for the constitutive law that describes the skin temperature and thermolysis heat losses undergone by a subject during a session of ...whole-body cryotherapy (WBC). This study focuses on the few minutes during which the human body is subjected to a thermal shock. The relationship between skin temperature and thermolysis heat losses during this period is still unknown and have not yet been studied in the context of the whole human body. The analytical approach here is based on the hypothesis that the skin thermal shock during a WBC session can be thermally modelled by the sum of both radiative and free convective heat transfer functions. The validation of this scientific approach and the derivation of temporal evolution thermal laws, both on skin temperature and dissipated thermal power during the thermal shock open many avenues of large scale studies with the aim of proposing individualized cryotherapy protocols as well as protocols intended for target populations. Furthermore, this study shows quantitatively the substantial imbalance between human metabolism and thermolysis during WBC, the explanation of which remains an open question.
Pdx1 (IPF-1 in humans, which is altered in MODY-4) is essential for pancreas development and mature beta-cell function. Pdx1 is expressed dynamically within the developing foregut, but how its ...expression characteristics are linked to the various steps of organ specification, differentiation, and function is unknown. Deletion of a conserved enhancer region (Area I-II-III) from Pdx1 produced a hypomorphic allele (Pdx1(DeltaI-II-III)) with altered timing and level of expression, which was studied in combination with wild-type and protein-null alleles. Lineage labeling in homozygous Area I-II-III deletion mutants (Pdx1(DeltaI-II-III/DeltaI-II-III)) revealed lack of ventral pancreatic bud specification and early-onset hypoplasia in the dorsal bud. Acinar tissue formed in the hypoplastic dorsal bud, but endocrine maturation was greatly impaired. While Pdx1(-/-) (protein-null) mice have nonpancreatic abnormalities (e.g., distorted pylorus, absent Brunner's glands), these structures formed normally in Pdx1(DeltaI-II-III/DeltaI-II-III) and Pdx1(DeltaI-II-III/-) mice. Surprisingly, heterozygous (Pdx1(+/DeltaI-II-III)) mice had abnormal islets and a more severe prediabetic condition than Pdx1(+/-) mice. These findings provide in vivo evidence of the differential requirements for the level of Pdx1 gene activity in the specification and differentiation of the various organs of the posterior foregut, as well as in pancreas and gut endocrine cell differentiation.
Closely related sympatric species commonly develop different ecological strategies to avoid competition. Ctenomys minutus and C. flamarioni are subterranean rodents parapatrically distributed in the ...southern Brazilian coastal plain, showing a narrow sympatric zone. To gain understanding on food preferences and possible competition for food resources, we evaluated their diet composition performing DNA metabarcoding analyzes of 67 C. minutus and 100 C. flamarioni scat samples, collected along the species geographical ranges. Thirteen plant families, mainly represented by Poaceae, Araliaceae, Asteraceae and Fabaceae, were identified in the diet of C. minutus. For C. flamarioni, 10 families were recovered, with a predominance of Poaceae, Araliaceae and Asteraceae. A significant correlation between diet composition and geographical distance was detected in C. minutus, whereas the diet of C. flamarioni was quite homogeneous throughout its geographical distribution. No significant differences were observed between males and females of each species. However, differences in diet composition between species were evident according to multivariate analysis. Our results suggest some level of diet partitioning between C. flamarioni and C. minutus in the sympatric region. While the first species is more specialized on few plant items, the second showed a more varied and heterogeneous diet pattern among individuals. These differences might have been developed to avoid competition in the region of co-occurrence. Resource availability in the environment also seems to influence food choices. Our data indicate that C. minutus and C. flamarioni are generalist species, but that some preference for Poaceae, Asteraceae and Araliaceae families can be suggested for both rodents.
Botulinum toxin (BTX) injection alone is not sufficient to treat spasticity in children, notably those with cerebral palsy; thus, there is an emerging trend for adjunct therapies to offer greater ...outcomes than BTX alone.
The aim of this systematic review was to evaluate the general effectiveness of adjunct therapies regardless of their nature in children with spasticity.
Medline, Cochrane and Embase databases were searched from January 1980 to March 15, 2018 for reports of parallel-group trials (randomized controlled trials RCTs and non-RCTs) assessing adjunct therapies after BTX injection for treating spasticity in children. Two independent reviewers extracted data and assessed the risk of bias by using the PEDro scale for RCTs and Downs and Black scale (D&B) for non-RCTs.
Overall, 20 articles involving 662 participants met the inclusion criteria. The average quality was good for the 16 RCTs (mean PEDro score 7.4 SD 1.6) and poor to moderate for the 4 non-RCTs (D&B score 9 to 17). Adjunct therapies consisted of casting/posture, electrical stimulation, resistance training and rehabilitation programmes. Casting associated with BTX injection improved the range of passive and active motion and reduced spasticity better than did BTX alone (9 studies), with a follow-up of 1 year. Resistance training enhanced the quality and performance of muscles without increasing spasticity. Only 3 rehabilitation programmes were studied, with encouraging results for activities.
Lower-limb posture with casting in children has a high level of evidence, but the long-term efficacy of short-leg casting needs to be evaluated. A comparison between the different modalities of casting is missing, and studies specifically devoted to testing the different kinds of casting are needed. Moreover, the delay to casting after BTX injection is not clear. Data on electrical stimulation are not conclusive. Despite the small number of studies, resistance training could be an interesting adjunct therapy notably to avoid loss of strength after BTX injection. Rehabilitation programmes after BTX injection still need to be evaluated.
Sunlight induces actinic keratosis, skin cancers and photoaging. Photoprotection is thus a major issue in public health to prevent the harmful effects of solar ultraviolet (UV) radiations. Recent ...data have shown that the visible (VIS) and infrared (IR) radiations can lead to skin damage by oxidative stress, suggesting that a balanced protection across the entire spectrum of sunlight is necessary to prevent cutaneous alterations. In this context, we developed a new generation of sunfilter called Phenylene Bis-Diphenyltriazine or TriAsorB (CAS N°55514-22-2). The aim of the present study was to assess the photoprotective efficacy of TriAsorB from UV to IR light. Spectrophotometric assays were performed to measure absorption and reflectance of TriAsorB in the different spectral ranges of sunlight: UV, VIS including blue light or high energy visible (HEV) and IR. DNA damage was evaluated using reconstructed human epidermis (RHE): 8-hydroxy-2'-deoxyguanosine (8OHdG) in response to HEV exposure, pyrimidine dimers (CPDs) and (6-4) photoproducts following solar-simulated radiation (SSR). TriAsorB is a broad spectrum UVB + UVA filter including long UVA. Interestingly, it also absorbs VIS radiations, especially in the HEV region. These radiations are also reflected. Protection in the IR spectral range is weak. Furthermore, the sunfilter specifically protects the skin against the oxidative lesions 8OHdG induced by HEV and prevents SSR-induced DNA damage. Thus, TriAsorB is an innovative sunfilter that might be used in sun care products for skin photoprotection from UV to VIS radiations. Finally, it prevents sunlight genotoxicity and protected the skin against solar radiations, especially blue light.
Pompe disease (PD) is caused by a deficiency of lysosomal acid α-glucosidase resulting from mutations in the
GAA
gene. The clinical spectrum ranges from a rapidly fatal multisystemic disorder ...(classic PD, onset < 1 year) to a milder adult onset myopathy. The aims of this study were to characterize the
GAA
mutations, to establish the disease epidemiology, and to identify potential genotype-phenotype correlations in French late-onset PD patients (onset ≥ 2 years) diagnosed since the 1970s. Data were collected from the two main laboratories involved in PD diagnosis and from the French Pompe registry. Two hundred forty-six patients (130 females and 116 males) were included, with a mean age at diagnosis of 43 years. Eighty-three different mutations were identified in the
GAA
gene, among which 28 were novel. These variants were spread all over the sequence and included 42 missense (one affecting start codon), 8 nonsense, 15 frameshift, 14 splice mutations, 3 small in-frame deletions, and one large deletion. The common c.-32-13T>G mutation was detected in 151/170 index cases. Other frequent mutations included the exon 18 deletion, the c.525del, and the missense mutations c.1927G>A (p.Gly643Arg) and c.655G>A (p.Gly219Arg). Patients carrying the c.-32-13T>G mutation had an older mean age at onset than patients non-exhibiting this mutation (36 versus 25 years). Patients with the same genotype had a highly variable age at onset. We estimated the frequency of late-onset PD in France around 1/69,927 newborns. In conclusion, we characterized the French cohort of late-onset PD patients through a nationwide study covering more than 40 years.
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