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Alzheimer’s disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors. Quantitative examination of superior and inferior temporal retinas from mild cognitive impairment (MCI) and AD patients compared to those with normal cognition (NC) revealed significant increases in amyloid β-protein (Aβ42) forms and novel intraneuronal Aβ oligomers (AβOi), which were closely associated with exacerbated retinal macrogliosis, microgliosis, and tissue atrophy. These pathologies were unevenly distributed across retinal layers and geometrical areas, with the inner layers and peripheral subregions exhibiting most pronounced accumulations in the MCI and AD versus NC retinas. While microgliosis was increased in the retina of these patients, the proportion of microglial cells engaging in Aβ uptake was reduced. Female AD patients exhibited higher levels of retinal microgliosis than males. Notably, retinal Aβ42, S100 calcium-binding protein B+ macrogliosis, and atrophy correlated with severity of brain Aβ pathology, tauopathy, and atrophy, and most retinal pathologies reflected Braak staging. All retinal biomarkers correlated with the cognitive scores, with retinal Aβ42, far-peripheral AβOi and microgliosis displaying the strongest correlations. Proteomic analysis of AD retinas revealed activation of specific inflammatory and neurodegenerative processes and inhibition of oxidative phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps retinopathy in MCI and AD patients, demonstrating the quantitative relationship with brain pathology and cognition, and may lead to reliable retinal biomarkers for noninvasive retinal screening and monitoring of AD.

Alzheimer’s disease (AD) pathologies were discovered in the easily accessible neurosensory retina. Yet, their specific nature, topographical distribution, and relationship with disease status remain undefined. Here, we histologically determined burden and spatial distribution of amyloid β-protein (Aβ42), intraneuronal scFvA13+-Aβ species, macro- and microgliosis, and atrophy in superior- and inferior-temporal retinas of human donors with mild cognitive impairment (MCI) or AD versus normal cognition. AD and MCI patients had enhanced retinopathy, predominantly affecting inner layers and peripheral subregions, which quantitatively correlated with severity of cerebral amyloid, tau, and neurodegeneration, and cognitive scores. In advanced clinical stages AD retinopathy further affected central outer segments. Increased retinal macrogliosis and Aβ-phagocytosing microglia were detected in MCI and AD patients. Further, distinct proteome profiles of AD retinas were identified, displaying greater overlap with the temporal cortices than with hippocampi or cerebella. AD retinas exhibited upregulated inflammatory and neurodegenerative processes and downregulated oxidative-phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps AD retinopathy, demonstrating the quantitative relationship with brain pathology and cognition.

Background Hypertension is considered a major risk factor for the progression of diabetic kidney disease. Type 2 diabetes is associated with increased renal sodium reabsorption and salt-sensitive hypertension. Clinical studies show that men have higher risk than premenopausal women for the development of diabetic kidney disease. However, the renal mechanisms that predispose to salt sensitivity during diabetes and whether sexual dimorphism is associated with these mechanisms remains unknown. Methods Female and male db/db mice exposed to a high-salt diet were used to analyze the progression of diabetic kidney disease and the development of hypertension. Results Male, 34-week-old, db/db mice display hypertension when exposed to a 4-week high-salt treatment, whereas equivalently treated female db/db mice remain normotensive. Salt-sensitive hypertension in male mice was associated with no suppression of the epithelial sodium channel (ENaC) in response to a high-salt diet, despite downregulation of several components of the intrarenal renin-angiotensin system. Male db/db mice show higher levels of proinflammatory cytokines and more immune-cell infiltration in the kidney than do female db/db mice. Blocking inflammation, with either mycophenolate mofetil or by reducing IL-6 levels with a neutralizing anti-IL-6 antibody, prevented the development of salt sensitivity in male db/db mice. Conclusions The inflammatory response observed in male, but not in female, db/db mice induces salt-sensitive hypertension by impairing ENaC downregulation in response to high salt. These data provide a mechanistic explanation for the sexual dimorphism associated with the development of diabetic kidney disease and salt sensitivity.

Background Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is used increasingly when performing a prophylactic mastectomy. Few prospective studies have reported on complication rates. This complementary trial to the French prospective multicentre MAPAM trial aimed to evaluate the nipple–areola complex (NAC) necrosis rate in prophylactic NSM with IBR. Methods Patient characteristics and surgical data were recorded. Morbidity after prophylactic NSM with a focus on NAC necrosis was analysed. Results Among 59 women undergoing prophylactic NSM, 19 (32 per cent) of the incisions were partly on the NAC. Reconstructions were performed with 46 definitive implants and 13 expanders. The crude rate of postoperative complications was 25 per cent (15 patients). Complete NAC necrosis was reported in two women (3 per cent) and partial or total necrosis in nine (15 per cent). No NAC resection was necessary. Median BMI was lower in women with total or partial NAC necrosis compared with the others (20.0 versus 21.3 kg/m2 respectively; P = 0.034). Conclusion Results of this prospective study confirm that prophylactic NSM with IBR is associated with a low risk of total NAC necrosis.

In most scenarios where detonations in fuel–air mixtures can present a hazard, such as in industrial accidents, or where they can be used for practical purposes, like detonative propulsion applications, the mixture is essentially non-uniform. For industrial accidents, it is important to understand what fraction of the mixture can detonate in order to limit the consequences of an explosion event by ensuring proper separation distances to critical facilities and personnel. For propulsion applications, mixture non-uniformities directly affect the performance of the device by limiting the detonable portion of the mixture. While it is known that detonation limits depend on mixture composition, geometry, and concentration gradients, these limits have only been defined for either uniform mixtures, or for detonation propagation in the direction of a smooth concentration gradient. In this study, a model is developed to generalize these classic detonation limits to consider arbitrary concentration distributions and is compared with experimental data for detonation propagation in non-uniform mixtures. The model is then applied to representative concentration distributions corresponding to two practical examples, a high-pressure hydrogen jet and a large-scale vapor cloud explosion (VCE). For both distributions, the model illustrates how a non-uniform mixture composition significantly limits the detonable portion of the flammable mixture created by a realistic release.

Les douleurs neuropathiques (DN) restent très difficiles à soulager. Plusieurs recommandations ont été proposées au cours de ces dernières années, mais aucune n’a pris en compte à ce jour l’ensemble des approches thérapeutiques disponibles. Nous avons réalisé une revue systématique portant sur toutes les études concernant le traitement des DN périphériques et centrales de l’adulte et de l’enfant, publiées jusqu’en janvier 2018 et avons évalué la qualité des études et le niveau de preuve des traitements au moyen du système GRADE. Les principaux critères d’inclusion étaient l’existence d’une DN chronique (≥ 3 mois), une méthodologie contrôlée et randomisée, un suivi supérieur ou égal à trois semaines, un nombre de patients supérieur ou égal à dix par groupe et une évaluation en double insu pour les traitements pharmacologiques. Sur la base du GRADE, nous recommandons en première intention les antidépresseurs inhibiteurs mixtes de recapture des monoamines (duloxétine et venlafaxine), les antidépresseurs tricycliques, la gabapentine pour toute DN, et les emplâtres de lidocaïne 5 % et la stimulation électrique transcutanée pour les DN périphériques localisées. Nous recommandons en deuxième intention la prégabaline, le tramadol (avec les précautions d’emploi afférentes aux opioïdes) et certaines associations pharmacologiques (antidépresseurs et gabapentine ou prégabaline) pour toute DN, et les patchs de haute concentration de capsaïcine (8 %) et la toxine botulique de type A (en milieu spécialisé) pour les DN périphériques localisées. Nous recommandons en troisième intention la stimulation magnétique transcrânienne répétitive à haute fréquence du cortex moteur (en milieu spécialisé) et les opioïdes forts (en l’absence d’alternative et en respectant les précautions d’emploi afférentes aux opioïdes) pour toute douleur neuropathique, et la stimulation médullaire pour les douleurs radiculaires chroniques postchirurgicales et la polyneuropathie diabétique douloureuse. La psychothérapie (thérapie cognitivocomportementale et thérapie de pleine conscience) peut être recommandée en deuxième intention en association avec les traitements précédents.

Neuropathic pain remains a significant unmet medical need. Several recommendations have recently been proposed concerning pharmacotherapy, neurostimulation techniques and interventional management, but no comprehensive guideline encompassing all these treatments has yet been issued. We performed a systematic review of pharmacotherapy, neurostimulation, surgery, psychotherapies and other types of therapy for peripheral or central neuropathic pain, based on studies published in peer-reviewed journals before January 2018. The main inclusion criteria were chronic neuropathic pain for at least three months, a randomized controlled methodology, at least three weeks of follow-up, at least 10 patients per group, and a double-blind design for drug therapy. Based on the GRADE system, we provide weak-to-strong recommendations for use and proposal as a first-line treatment for SNRIs (duloxetine and venlafaxine), gabapentin and tricyclic antidepressants and, for topical lidocaine and transcutaneous electrical nerve stimulation specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a second-line treatment for pregabalin, tramadol, combination therapy (antidepressant combined with gabapentinoids), and for high-concentration capsaicin patches and botulinum toxin A specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a third-line treatment for high-frequency rTMS of the motor cortex, spinal cord stimulation (failed back surgery syndrome and painful diabetic polyneuropathy) and strong opioids (in the absence of an alternative). Psychotherapy (cognitive behavioral therapy and mindfulness) is recommended as a second-line therapy, as an add-on to other therapies. An algorithm encompassing all the recommended treatments is proposed.

Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ40 and Aβ42 burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased vascular amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy. Electronic supplementary material The online version of this article (10.1007/s00401-020-02134-w) contains supplementary material, which is available to authorized users.

Rendos, NK, Harriell, K, Qazi, S, Regis, RC, Alipio, TC, and Signorile, JF. Variations in verbal encouragement modify isokinetic performance. J Strength Cond Res 33(3): 708-716, 2019-Verbal instruction and encouragement are common in exercise testing; however, the verbiage used during exercise testing is rarely controlled despite the likelihood it may affect the participant's performance. Although variations in verbal cuing based on rate and intensity have been examined during isometric contractions, they have not been examined during isokinetic testing, which is a standardized assessment of muscle performance in athletic, rehabilitation, and research settings. This study examined the effects of 4 variations in verbal encouragement during isokinetic knee flexion and extension exercises. Twenty-three healthy participants (aged 19-34 years) completed 4 isokinetic testing sessions on a Biodex isokinetic dynamometer. Each session consisted of 5, 10, and 15 repetitions at 1.05 rad·s (60°·s), 3.14 rad·s (180°·s), and 5.24 rad·s (300°·s), respectively, separated by 5-minute passive recoveries. The variations in verbal encouragement randomized during each testing session used the following statements: (a) "as fast as you can" (FAST); (b) "as hard as you can" (HARD); (c) "as hard and as fast as you can" (BOTH); and (d) no verbal encouragement (NO CUE). Repeated-measures analyses of variance with a Bonferroni post hoc analysis revealed that the FAST and BOTH verbal cues produced greater work, peak torque, and power at all 3 speeds of isokinetic testing. These findings indicate the verbal cues "as fast as you can" and "as hard and as fast as you can" should be used to maximize performance during isokinetic testing.

Accurate models to predict large-scale flame propagation are crucial to assessing the consequences of accidental explosions. A freely expanding spherical flame can experience significant acceleration due to the growth of the Darrieus–Landau instability, increasing the severity of the explosion hazard, and must be accounted for when modeling large-scale flames. Recent large-scale experiments have demonstrated an oscillatory rate of flame acceleration, consistent with self-similar flame propagation and the formation and growth of cells with discrete length scales. In this work, an analytical model describing the growth of multiple generations of cells on a flame surface is developed. Each generation is treated independently with a criteria for cell splitting based on a critical stretch rate. Superposition of the length scales is used to determine the global flame surface wrinkling and propagation velocity of the flame. The model is compared with experimental results and the effect of upstream flow disturbances on the development of the instability is also discussed. It is found that the model reproduces a number of features observed in the experiments, including the overall rate of flame acceleration and the frequency of oscillation. The model also captures the correct trends of flame behavior for the effect of elevated initial turbulence and the transition from positive to negative Markstein length. These results support the self-similar argument of spherical-flame acceleration and can be used in future studies to develop new models describing the behavior of large-scale flames.

Despite growing evidence for the characteristic signs of Alzheimer's disease (AD) in the neurosensory retina, our understanding of retina–brain relationships, especially at advanced disease stages and in response to therapy, is lacking. In transgenic models of AD (APPSWE/PS1∆E9; ADtg mice), glatiramer acetate (GA) immunomodulation alleviates disease progression in pre‐ and early‐symptomatic disease stages. Here, we explored the link between retinal and cerebral AD‐related biomarkers, including response to GA immunization, in cohorts of old, late‐stage ADtg mice. This aged model is considered more clinically relevant to the age‐dependent disease. Levels of synaptotoxic amyloid β‐protein (Aβ)1–42, angiopathic Aβ1–40, non‐amyloidogenic Aβ1–38, and Aβ42/Aβ40 ratios tightly correlated between paired retinas derived from oculus sinister (OS) and oculus dexter (OD) eyes, and between left and right posterior brain hemispheres. We identified lateralization of Aβ burden, with one‐side dominance within paired retinal and brain tissues. Importantly, OS and OD retinal Aβ levels correlated with their cerebral counterparts, with stronger contralateral correlations and following GA immunization. Moreover, immunomodulation in old ADtg mice brought about reductions in cerebral vascular and parenchymal Aβ deposits, especially of large, dense‐core plaques, and alleviation of microgliosis and astrocytosis. Immunization further enhanced cerebral recruitment of peripheral myeloid cells and synaptic preservation. Mass spectrometry analysis identified new parallels in retino‐cerebral AD‐related pathology and response to GA immunization, including restoration of homeostatic glutamine synthetase expression. Overall, our results illustrate the viability of immunomodulation‐guided CNS repair in old AD model mice, while shedding light onto similar retino‐cerebral responses to intervention, providing incentives to explore retinal AD biomarkers., In this study, Doustar et al. revealed that retinal Abeta burden predicts its brain levels in old, late‐stage murine models of Alzheimer's disease and further in response to immunotherapy. Substantial therapeutic effects are detected even at such advanced disease stage; immunomodulation effectively mitigates vascular and parenchymal amyloid‐beta deposition, diminishes neuroinflammation, as well as restores synaptic density and retino‐cerebral glutamine synthetase levels.

Targeted overexpression of angiotensin-converting enzyme (ACE), an amyloid-β protein degrading enzyme, to brain resident microglia and peripheral myelomonocytes (ACE10 model) substantially diminished Alzheimer’s-like disease in double-transgenic APPSWE/PS1ΔE9 (AD+) mice. In this study, we explored the impact of selective and transient angiotensin-converting enzyme overexpression on macrophage behaviour and the relative contribution of bone marrow-derived ACE10 macrophages, but not microglia, in attenuating disease progression. To this end, two in vivo approaches were applied in AD+ mice: (i) ACE10/GFP+ bone marrow transplantation with head shielding; and (ii) adoptive transfer of CD115+-ACE10/GFP+ monocytes to the peripheral blood. Extensive in vitro studies were further undertaken to establish the unique ACE10-macrophage phenotype(s) in response to amyloid-β1-42 fibrils and oligomers. The combined in vivo approaches showed that increased cerebral infiltration of ACE10 as compared to wild-type monocytes (∼3-fold increase; P < 0.05) led to reductions in cerebral soluble amyloid-β1-42, vascular and parenchymal amyloid-β deposits, and astrocytosis (31%, 47–80%, and 33%, respectively; P < 0.05–0.0001). ACE10 macrophages surrounded brain and retinal amyloid-β plaques and expressed 3.2-fold higher insulin-like growth factor-1 (P < 0.01) and ∼60% lower tumour necrosis factor-α (P < 0.05). Importantly, blood enrichment with CD115+-ACE10 monocytes in symptomatic AD+ mice resulted in pronounced synaptic and cognitive preservation (P < 0.05–0.001). In vitro analysis of macrophage response to well-defined amyloid-β1-42 conformers (fibrils, prion rod-like structures, and stabilized soluble oligomers) revealed extensive resistance to amyloid-β1-42 species by ACE10 macrophages. They exhibited 2–5-fold increased surface binding to amyloid-β conformers as well as substantially more effective amyloid-β1-42 uptake, at least 8-fold higher than those of wild-type macrophages (P < 0.0001), which were associated with enhanced expression of surface scavenger receptors (i.e. CD36, scavenger receptor class A member 1, triggering receptor expressed on myeloid cells 2, CD163; P < 0.05–0.0001), endosomal processing (P < 0.05–0.0001), and ∼80% increased extracellular degradation of amyloid-β1-42 (P < 0.001). Beneficial ACE10 phenotype was reversed by the angiotensin-converting enzyme inhibitor (lisinopril) and thus was dependent on angiotensin-converting enzyme catalytic activity. Further, ACE10 macrophages presented distinct anti-inflammatory (low inducible nitric oxide synthase and lower tumour necrosis factor-α), pro-healing immune profiles (high insulin-like growth factor-1, elongated cell morphology), even following exposure to Alzheimer’s-related amyloid-β1-42 oligomers. Overall, we provide the first evidence for therapeutic roles of angiotensin-converting enzyme-overexpressing macrophages in preserving synapses and cognition, attenuating neuropathology and neuroinflammation, and enhancing resistance to defined pathognomonic amyloid-β forms.

Explosion isolation systems provide critical protection for interconnected vessels and work areas, preventing the spread of explosions through interconnecting pipes and ducts. These systems not only prevent propagating events, but also mitigate the elevated explosion hazards of interconnected vessels, related to pressure piling and enhanced turbulence. Explosion isolation systems can, however, fail catastrophically when they are not properly designed for a use case. Evaluating the performance of explosion isolation systems includes assessing their pressure resistance, flame-barrier efficacy, and determining appropriate installation distances, which typically requires extensive testing. To predict the performance of a system for use cases outside the tested conditions, models are needed to reliably predict both the explosion dynamics and the isolation system response. In this study, a physics-based model for explosion dynamics in vented vessel-pipe systems is developed and validated. An extensive series of large-scale validation experiments were conducted, including tests using an 8 m3 vessel with attached pipes, varying the pipe dimensions, ignition location, and mixture reactivity. The model accurately captures the effects of experimental parameters and predicts the time available for isolation systems to form a flame barrier. This model can help to predict installation distances and reduce the number of tests needed to comprehensively evaluate explosion isolation systems and their use cases.

In this work, the development of the Darrieus–Landau instability is examined at large scale using atmospheric-pressure methane-air flames in the presence of weak initial turbulence, as well as in quiescent conditions. In the absence of initial turbulence, the critical flame radius for the onset of instability is found to be on the order of 20–35 cm, increasing with methane concentration. In addition, an oscillatory flame acceleration is observed that is directly analogous to the behavior of propane-air mixtures seen in a previous study. Weakly-turbulent initial conditions lead to an earlier onset of flame instability that eliminates the rapid acceleration that occurs during global cell formation along with the oscillatory flame acceleration. It is also shown that weak initial turbulence does not significantly affect the burning velocity during the initial, laminar, flame propagation. Instead, initial turbulence triggers both an earlier onset of instability as well as an increase in the rate of flame acceleration. As a result, significant increases in overall flame velocity is observed in the presence of weak initial turbulence, and this difference increases with flame radius.

Background Mechanical ventilation is strongly associated with cognitive decline after critical illness. This finding is particularly evident among older individuals who have pre-existing cognitive impairment, most commonly characterized by varying degrees of cerebral amyloid-β accumulation, neuroinflammation, and blood-brain barrier dysfunction. We sought to test the hypothesis that short-term mechanical ventilation contributes to the neuropathology of cognitive impairment by (i) increasing cerebral amyloid-β accumulation in mice with pre-existing Alzheimer’s disease pathology, (ii) increasing neurologic and systemic inflammation in wild-type mice and mice with pre-existing Alzheimer’s disease pathology, and (iii) increasing hippocampal blood-brain barrier permeability in wild-type mice and mice with pre-existing Alzheimer’s disease pathology. Methods We subjected double transgenic Alzheimer’s disease (APP/PSEN1) and wild-type mice to mechanical ventilation for 4 h and compared to non-mechanically ventilated Alzheimer’s disease model and wild-type mice. Cerebral soluble/insoluble amyloid-β1–40/amyloid-β1–42 and neurological and systemic markers of inflammation were quantified. Hippocampal blood-brain barrier permeability was quantified using a novel methodology that enabled assessment of small and large molecule permeability across the blood-brain barrier. Results Mechanical ventilation resulted in (i) a significant increase in cerebral soluble amyloid-β1–40 (p = 0.007) and (ii) significant increases in neuroinflammatory cytokines in both wild-type and Alzheimer’s disease mice which, in most cases, were not reflected in the plasma. There were (i) direct correlations between polymorphonuclear cells in the bronchoalveolar fluid and cerebral soluble amyloid-β1–40 (p = 0.0033), and several Alzheimer’s disease-relevant neuroinflammatory biomarkers including cerebral TNF-α and IL-6; (iii) significant decreases in blood-brain barrier permeability in mechanically ventilated Alzheimer’s disease mice and a trend towards increased blood-brain barrier permeability in mechanically ventilated wild-type mice. Conclusions These results provide the first evidence that short-term mechanical ventilation independently promotes the neuropathology of Alzheimer’s disease in subjects with and without pre-existing cerebral Alzheimer’s disease pathology. Future studies are needed to further clarify the specific mechanisms by which this occurs and to develop neuroprotective mechanical ventilation strategies that mitigate the risk of cognitive decline after critical illness. Electronic supplementary material The online version of this article (10.1186/s13054-019-2356-2) contains supplementary material, which is available to authorized users.

International audience

A series of large-scale field trials to better understand the explosion characteristics of silane–air was conducted by the G-13 Silane Task Group under the direction of the Compressed Gas Association (CGA) and its guidelines. Silane was released from a high-pressure source into the open atmosphere, and overpressure measurements of unconfined silane–air explosions were taken at different locations away from the explosion centre. It was found that significant blast effects can result from relatively small releases of silane (around 0.1 kg). It is possible to achieve these small releases during an accidental discharge from a “pigtail” connection (a small-diameter coiled tube that connects a silane tube trailer to a process). Therefore, accidental silane explosions should be recognized as significant and possible events when handling silane. These results were also used in the proposed revision of ANSI/CGA G-13 Storage and Handling of Silane and Silane Mixtures.

In early 2011, the G-13 Silane Modeling Task Force of the Compressed Gas Association (CGA) proposed a series of tests to better define pyrophoric behavior during unintentional, large-scale releases of silane. The tests were conducted in two phases under the direction of CGA and its guidelines. Phase I took place from June 27 to June 30, 2011, focusing primarily on thermal radiation and the heat transfer from flame impingement due to silane release from a fully open pressure relief device (PRD) on a tonner. Phase II took place on June 19 and 20, 2012, focusing on thermal radiation and explosion overpressure. The results were subsequently utilized to revise CGA G-13 guidelines on the safe handling of silane. In the present two-part papers, the results from the tests are summarized in order to highlight the key findings. The first part of summary described the results of the flame impingement and thermal radiation tests. Three different test series were conducted, including shakedown tests using nitrogen instead of silane, silane flame-impingement tests onto an adjacent target tonner, and heat-flux tests. For comparison with known values in the published literature, thermal radiation of ethylene flame jets was also measured. In addition, metallurgical analyses of the target tonner indicated that the metallurgical properties of the cylinder material were not altered by the flame impingement. The steel surface temperature at the point of impingement was estimated to be below 853.15 K and definitely did not exceed 950.15 K. Thus, the combination of internal pressure and vessel metal temperature was unlikely to exceed the rupture pressure of the ton cylinder.

In the present investigation, laminar burning velocities (LBVs) were measured for several different silane fuels (i.e., trichlorosilane, trimethylchlorosilane, methyldichlorosilane, dimethylchlorosilane, and tetramethylsilane) in order to evaluate their potential for vapour cloud explosions (VCEs). Laminar burning velocities were determined from constant-volume explosions in a closed vessel; the pressure rise of the initial portion of flame propagation was used to calculate the laminar burning velocity. The LBVs for the different silane compounds were found to be in the range of 43 cm/s (for dimethylchlorosilane) to 124 cm/s (for trichlorosilane). These values were then used to estimate blast effects of VCEs resulting from a 25,000 kg release of each fuel. In particular, the VCE severity of trichlorosilane was compared to that of propane and ethylene for a given release mass. It was found that a trichlorosilane VCE would produce greater overpressures than propane and ethylene in the near field but the pressure would decay more rapidly with increasing distance from the explosion centre. Moreover, the impulse from a trichlorosilane VCE would be considerably lower than that of propane and ethylene.

Large-scale experiments examining spherical-flame propagation of propane–air flames up to a diameter of 1.2 m were performed. Throughout these experiments, the growth of the Darrieus–Landau instability was directly observed and detailed measurements show that the increase of flame velocity follows a pattern of self-similar oscillatory growth that has not been previously reported. These oscillations are found to be the result of periodic growth and saturation of a narrow range of length scales that follows each generation of cell formation. Based on these observations, a new method to estimate the fractal-acceleration exponent is proposed based on the amplitude and frequency of these oscillations. Comparisons between the fractal exponents derived by this method and a direct power law fit show reasonable agreement with one another, as well as with values reported by previous studies.

International audience; Background: Totally implantable venous access port systems are widely used in oncology, with frequent complications that sometimes necessitate device removal. The aim of this study is to investigate the impact of the time interval between port placement and initiation of chemotherapy and the neutropenia-inducing potential of the chemotherapy administered upon complication-related port removal.Patients and methods: Between January 2010 and December 2013, 4045 consecutive patients were included in this observational, single-center prospective study. The chemotherapy regimens were classified as having a low (20%) risk for inducing neutropenia.Results: The overall removal rate due to complications was 7.2%. Among them, port-related infection (2.5%) and port expulsion (1%) were the most frequent. The interval between port insertion and its first use was shown to be a predictive factor for complication-related removal rates. A cut-off of 6 days was statistically significant (p = 0.008), as the removal rate for complications was 9.4% when this interval was 0-5 days and 5.7% when it was ≥6 days. Another factor associated with port complication rate was the neutropenia-inducing potential of the chemotherapy regimens used, with removal for complications involved in 5.5% of low-risk regimens versus 9.4% for the intermediate- and high-risk regimens (p = 0.003).Conclusion: An interval of 6 days between placement and first use of the port reduces the removal rate from complications. The intermediate- and high-risk for neutropenia chemotherapy regimens are related to higher port removal rates from complications than low-risk regimens.

Signorile, JF, Rendos, NK, Heredia Vargas, HH, Alipio, TC, Regis, RC, Eltoukhy, MM, Nargund, RS, and Romero, MA. Differences in muscle activation and kinematics between cable-based and selectorized weight training. J Strength Cond Res 31(2): 313-322, 2017-Cable resistance training machines are showing resurgent popularity and allow greater number of degrees of freedom than typical selectorized equipment. Given that specific kinetic chains are used during distinct activities of daily living (ADL), cable machines may provide more effective interventions for some ADL, whereas others may be best addressed using selectorized equipment. This study examined differences in activity levels (root mean square of the EMG [rmsEMG]) of 6 major muscles (pectoralis major, PM; anterior deltoid, AD; biceps brachii, BB; rectus abdominis, RA; external obliques, EO; and triceps brachii, TB) and kinematics of multiple joints between a cable and standard selectorized machines during the biceps curl, the chest press, and the overhead press performed at 1.5 seconds per contractile stage. Fifteen individuals (9 men, 6 women; mean age ± SD, 24.33 ± 4.88 years) participated. Machine order was randomized. Significant differences favoring cable training were seen for PM and AD during biceps curl; BB, AD, and EO for chest press; and BB and EO during overhead press (p ≤ 0.05). Greater starting and ending angles were seen for the elbow and shoulder joints during selectorized biceps curl, whereas hip and knee starting and ending angles were greater for cable machine during chest and overhead presses (p < 0.0001). Greater range of motion (ROM) favoring the cable machine was also evident (p < 0.0001). These results indicate that utilization patterns of selected muscles, joint angles, and ROMs can be varied because of machine application even when similar exercises are used, and therefore, these machines can be used selectively in training programs requiring specific motor or biomechanical patterns.

Rendos, NK, Heredia Vargas, HM, Alipio, TC, Regis, RC, Romero, MA, and Signorile, JF. Differences in muscle activity during cable resistance training are influenced by variations in handle types. J Strength Cond Res 30(7): 2001-2009, 2016-There has been a recent resurgence in the use of cable machines for resistance training allowing movements that more effectively simulate daily activities and sports-specific movements. By necessity, these devices require a machine/human interface through some type of handle. Considerable data from material handling, industrial engineering, and exercise training studies indicate that handle qualities, especially size and shape, can significantly influence force production and muscular activity, particularly of the forearm muscles, which affect the critical link in activities that require object manipulation. The purpose for this study was to examine the influence of three different handle conditions: standard handle (StandH), ball handle with the cable between the index and middle fingers (BallIM), and ball handle with the cable between the middle and ring fingers (BallMR), on activity levels (rmsEMG) of the triceps brachii lateral and long heads (TriHLat, TriHLong), brachioradialis (BR), flexor carpi radialis (FCR), extensor carpi ulnaris, and extensor digitorum (ED) during eight repetitions of standing triceps pushdown performed from 90° to 0° elbow flexion at 1.5 s per contractile stage. Handle order was randomized. No significant differences were seen for triceps or BR rmsEMG across handle conditions; however, relative patterns of activation did vary for the forearm muscles by handle condition, with more coordinated activation levels for the FCR and ED during the ball handle conditions. In addition, the rmsEMG for the ED was significantly higher during the BallIM than any other condition and during the BallMR than the StandH. These results indicate that the use of ball handles with the cable passing between different fingers can vary the utilization patterns of selected forearm muscles and may therefore be advantageous for coaches, personal trainers, therapists, or bodybuilders for targeted training or rehabilitation of these muscles.

Les patients douloureux chroniques qui sont suivis en « structure douleur » sont des patients pour lesquels les voies therapeutiques simples n’ont pas donne de resultats. Le parcours qui les y mene est souvent chaotique. Certains d’entre eux s’installent progressivement dans un nomadisme medical, en quete d’une solution curative aux maux qui les affligent. Malgre les nombreux specialistes consultes et les differents traitements inaugures, leur douleur est malheureusement restee inchangee. C’est alors qu’ils sont orientes vers une structure specialisee dont la vertu principale reste la dimension plurielle des intervenants et des outils permettant de construire une strategie therapeutique que l’on souhaite la plus coherente possible. Pour autant, la pratique clinique aupres de ces patients ne devient pas simple parce qu’ils franchissent les portes de la consultation. Si les intervenants qui ont precede ont ete contraints a l’echec, c’est bien que les tableaux sont d’emblee complexes. En particulier, la question du traumatisme est particulierement epineuse. Au travers d’une prise en charge par hypnoanalgesie, nous souhaitons illustrer ici comment la question du traumatisme a pu etre abordee en consultation infirmiere.

The authors present results of vented explosion tests using stoichiometric propane-air mixtures in a room-size enclosure 63.7 m3 in volume. The tests were focused on the effect of ignition location, vent size, and obstacles on explosion development and pressure buildup. The dependence of the maximum pressure generated on the experimental parameters was analyzed. It was found that the pressure maxima may be caused by pressure transients defined by the interplay of several factors, such as the maximum flame area and burning velocity in the chamber, and the overpressure generated by the external explosion. A simple model was proposed that allowed for the estimation of the maximum pressure for each of the main pressure transients. The model was found to agree with the experimental data within the experimental uncertainty.

Vivipary, referred here as the formation of novel complete plantlets on mature organs, has been reported in many families as an asexual propagation strategy. In K. × houghtonii (Crassulaceae), viviparous plantlets are formed on leaf margin notches in response to a long day photoperiod and their appearance follow a basipetal fashion. To identify genes involved in this process, suppression subtractive hybridisation libraries (SSH) were prepared. Two hundred c-DNA clones were classified and grouped into 14 functional categories according to Goldberg database (http://estdb.biology.ucla.edu/PcEST). Six hundred thirty sequences (200 SSH library, 48 database Kalanchoe genus, 382 other species database genes) were used as probes for microarray analysis according to the CombiMatrix technology and a 4x2K Custom Array ™ was synthesized. RNA was extracted from margin of leaves at 7 stages of development before buds emission (5 to 50 mm) during long-day photoperiod (permissive conditions). Three replications for each sample were prepared. From double strand cDNAs antisense RNAs (a RNA) were synthesized and amino-allil-UTP incorporated and coupled with Alexa Fluor ® 647. Microarray was hybridized according to CombiMatrix protocol. Data were extracted with CombiMatrix Microarray Imager software and exported into Microsoft Excel for computing of mean, median and standard deviation. Person's correlation was computed and data normalized. After background removal, probes were reduced to 484. "Fold change" method (FC=2) was used to compare different levels of gene expression of samples. Significance Analysis of Microarrays Statistic (SAM method) generated 263 significant modulated genes with a False Discovery Rate (FDR) of 5%.

A complete multiple-scale solution is constructed for the one-dimensional problem of an oscillating flame in a tube, ignited at a closed end, with the second end open. The flame front moves into the unburnt mixture at a constant burning velocity relative to the mixture ahead, and the heat release is constant. The solution is based upon the assumption that the propagation speed multiplied by the expansion ratio is small compared with the speed of sound. This approximate solution is compared with a numerical solution for the same physical model, assuming a propagation speed of arbitrary magnitude, and the results are close enough to confirm the validity of the approximate solution. Because ignition takes place at the closed end, the effect of thermal expansion is to push the column of fluid in the tube towards the open end. Acoustics set in motion by the impulsive start of the column of fluid play a crucial role in the oscillation. The analytical solution also captures the subsequent interaction between acoustics and the reaction front, the effect of which does not appear to be as significant as that of the impulsive start, however.