Focal cone high harmonic generation driven by a 400 TW laser.

The generation of self-focusing beams of extreme ultraviolet (XUV) radiation using the focal cone high harmonic generation (FCHHG) technique is examined for high energy lasers. The FCHHG geometry is created by passing a focusing laser beam through a gas sheet prior to reaching focus and thus creating a converging beam of high harmonic radiation. This leads to a larger interaction area that increases the total area of XUV emission while not exceeding the saturation intensity of the target atoms or increasing the density of the atoms. Such a method allows for scaling of HHG to any incident laser power. An experiment was conducted demonstrating such scaling to incident 400 TW pulses, showing both the expected spectral signature of HHG and the converging cone of XUV radiation. It was found that this technique is very sensitive to spatial non-uniformity in the driving laser, which has become more prevalent in high energy laser systems.

Kilotesla plasmoid formation by a trapped relativistic laser beam.

A strong quasistationary magnetic field is generated in hollow targets with curved internal surface under the action of a relativistically intense picosecond laser pulse. Experimental data evidence the formation of quasistationary strongly magnetized plasma structures decaying on a hundred picoseconds timescale, with the magnetic field strength of the kilotesla scale. Numerical simulations unravel the importance of transient processes during the magnetic field generation and suggest the existence of fast and slow regimes of plasmoid evolution depending on the interaction parameters. The proposed setup is suited for perspective highly magnetized plasma application and fundamental studies.

Cylindrical implosion platform for the study of highly magnetized plasmas at Laser MegaJoule.

Investigating the potential benefits of the use of magnetic fields in inertial confinement fusion experiments has given rise to experimental platforms like the Magnetized Liner Inertial Fusion approach at the Z-machine (Sandia National Laboratories) or its laser-driven equivalent at OMEGA (Laboratory for Laser Energetics). Implementing these platforms at MegaJoule-scale laser facilities, such as the Laser MegaJoule (LMJ) or the National Ignition Facility (NIF), is crucial to reaching self-sustained nuclear fusion and enlarges the level of magnetization that can be achieved through a higher compression. In this paper, we present a complete design of an experimental platform for magnetized implosions using cylindrical targets at LMJ. A seed magnetic field is generated along the axis of the cylinder using laser-driven coil targets, minimizing debris and increasing diagnostic access compared with pulsed power field generators. We present a comprehensive simulation study of the initial B field generated with these coil targets, as well as two-dimensional extended magnetohydrodynamics simulations showing that a 5 T initial B field is compressed up to 25 kT during the implosion. Under these circumstances, the electrons become magnetized, which severely modifies the plasma conditions at stagnation. In particular, in the hot spot the electron temperature is increased (from 1 keV to 5 keV) while the density is reduced (from 40g/cm^{3} to 7g/cm^{3}). We discuss how these changes can be diagnosed using x-ray imaging and spectroscopy, and particle diagnostics. We propose the simultaneous use of two dopants in the fuel (Ar and Kr) to act as spectroscopic tracers. We show that this introduces an effective spatial resolution in the plasma which permits an unambiguous observation of the B-field effects. Additionally, we present a plan for future experiments of this kind at LMJ.

Neural network analysis of quasistationary magnetic fields in microcoils driven by short laser pulses.

Optical generation of kilo-tesla scale magnetic fields enables prospective technologies and fundamental studies with unprecedentedly high magnetic field energy density. A question is the optimal configuration of proposed setups, where plenty of physical phenomena accompany the generation and complicate both theoretical studies and experimental realizations. Short laser drivers seem more suitable in many applications, though the process is tangled by an intrinsic transient nature. In this work, an artificial neural network is engaged for unravelling main features of the magnetic field excited with a picosecond laser pulse. The trained neural network acquires an ability to read the magnetic field values from experimental data, extremely facilitating interpretation of the experimental results. The conclusion is that the short sub-picosecond laser pulse may generate a quasi-stationary magnetic field structure living on a hundred picosecond time scale, when the induced current forms a closed circuit.

[Ocular surface and outdoor air pollution: A systematic review]. / Surface oculaire et pollution environnementale extérieure : revue systématisée de la littérature.

INTRODUCTION: Air pollution has steadily increased for several decades, with widely studied effects on human health, including increased mortality, incidence of stroke, respiratory and allergic disease. However, the effects of pollution on the ocular surface, in direct contact with the outside world, have been less precisely studied. MATERIALS AND METHODS: We conducted a literature review of articles on the subject published from 1966 to October 2020. Among the 661 articles identified, 33 were retained. Ocular surface disease associated with pollution included non-specific conjunctivitis, dry eye disease, blepharitis, and allergic conjunctivitis. The studied pollutants were particulate matter less than 2.5µm and 10µm (PM2.5, PM10), ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO) and sulfur dioxide (SO2). Certain air quality parameters such as temperature and relative humidity were also studied. RESULTS: Among the markers of air pollution possibly associated with ophthalmic disease, NO2 and SO2 appear to be the most frequent and highly correlated. High temperatures and low humidity levels also appear to be aggravating factors for the ocular surface. However, due to the heterogeneity of the studies, the results must be interpreted with caution. Indeed, the methodology and the results of the various studies are sometimes contradictory. The inclusion of patients, the analysis of environmental data, and the correlation between these two elements indeed raise numerous methodological questions. CONCLUSION: Air pollution control would appear essential, as well as the development of new studies based on reliable methods of studying the environmental and its clinical effects.

The use of digital dermoscopy in the surveillance of melanocytic skin lesions: A real-life retrospective study comparing university hospital and private practices.

BACKGROUND: Few studies have evaluated the role of digital dermoscopy (DD) in the surveillance of pigmented lesions in real-life practice. PATIENTS AND METHODS: Patients followed with DD by 4 hospital dermatologists (group 1) and 4 private dermatologists (group 2) were retrospectively included if they had had at least 2 DD examinations for a minimum of 4 pigmented lesions. Their characteristics, risk factors, history of excision of benign nevi and melanomas prior to and during the DD follow-up, and characteristics of detected melanomas, were recorded. RESULTS: One hundred and ninety-six patients were included in group 1 and 205 in groups 2. A family history of melanoma (25% vs. 12%, p<0.01), a personal history of melanoma before DD follow-up (47% vs. 15%, p<0.01), and a family (3% vs. 0%, p=0.01) and personal (8% vs. 1%, p<0.01) germline CDKN2a mutation were more frequent in group 1 than in group 2. In both groups, the number of excisions of benign lesions was higher before DD follow-up (380 and 347, respectively) than during DD follow-up (194 and 132). During follow-up, 29 melanomas were detected in group 1, with a median Breslow thickness of 0.4mm, versus 1.3mm for melanomas diagnosed before DD follow-up (p<0.02). In group 2, 4 melanoma and 5 superficial atypical melanocytic proliferations of unknown significance were detected. The median Breslow thickness of newly diagnosed melanomas was 0.35mm vs. 0.6mm before DD follow-up (p=0.1). CONCLUSION: In both populations in real-life practice, DD seemed to allow the detection of thin melanomas and to decrease the rate of "futile" resections.

Parkinsonian gait in elderly people: Significance of the threshold value of two and more falls per year.

OBJECTIVES: Parkinsonism in the elderly presents a major risk factor for recurrent falls (2 and more falls per year), which is associated with increased morbidity. The main objective was to investigate explanatory variables relating to the risk of being recurrent fallers (RF) in persons with parkinsonian gait. METHODS: Seventy-nine among 172 eligible persons were enrolled in this prospective study, the findings of which were analyzed at 12 months. Motor and non-motor features, as well as follow-up interviews to identify falls, loss of ability to walk, fluctuating cognition, traumatic falls, all-cause hospitalizations and deaths were collated and results compared between non RF (zero and one fall per year) and RF. Bayesian model averaging was used to predict the probability of patients being RF from their medical history as well as from cognitive assessment, gait velocity, vision and posture. RESULTS: N=79, 0.58 men, 50% had Parkinson's disease, 14% other neurodegenerative parkinsonian syndrome, 23% vascular parkinsonism and 13% Lewy body disease, 58% were RF. Median age 81.2 years and median MMSE 25/30. A history of falls and of hallucinations, median odds ratio respectively 9.06 (CI 2.34-38.22), 4.21 (CI 1.04-18.67) were associated with the highest odds ratios along with fluctuating cognition and abnormal posture. Two or more falls a year was a relevant threshold to distinguish a population with a high risk of comorbidity. CONCLUSION: The whole history of falls, hallucinations and fluctuating cognition can be considered predictive of recurrent falls in elderly people with parkinsonian gait and provide a tracking tool for patient management.

[Interest of environmental exposure chambers in the evaluation of allergic conjunctivitis]. / Intérêt des chambres d'exposition environnementale dans l'évaluation des conjonctivites allergiques.

Allergic conjunctivitis affects 15 to 20% of the general population. It is currently evaluated by the Conjunctival Provocation Test (CPT), which is considered as the gold standard. In the investigation of allergic rhinitis and asthma, environmental exposure chambers (EEC) are increasingly utilised. For allergic conjunctivitis, EEC might be a valid alternative to the CPT. However, evaluation of the allergen response in individual provocation tests or in EECs is still in discussion due to the multiplicity of symptom scores. Indeed, there are many scores used to evaluate allergic conjunctivitis. The main criteria used were described by Abelson in 1990 and include redness, itching, tearing, and swelling. In clinical studies, the specifically ocular score most used is the Total Ocular Symptom Score (TOSS). Few treatments have been evaluated by EEC, including cold compresses, epinastine and N-acetyl aspartyl glutamic acid. Moreover, early data shows good correlation between ocular symptoms induced in an EEC and those assessed during natural exposure. EEC might be a valid alternative to CPT and correlate with natural seasonal allergen exposure. Finally, EEC might be useful in other fields as well, such as in the study of dry eye disease.

Relativistic magnetic reconnection in laser laboratory for testing an emission mechanism of hard-state black hole system.

Magnetic reconnection in a relativistic electron magnetization regime was observed in a laboratory plasma produced by a high-intensity, large energy, picoseconds laser pulse. Magnetic reconnection conditions realized with a laser-driven several kilotesla magnetic field is comparable to that in the accretion disk corona of black hole systems, i.e., Cygnus X-1. We observed particle energy distributions of reconnection outflow jets, which possess a power-law component in a high-energy range. The hardness of the observed spectra could explain the hard-state x-ray emission from accreting black hole systems.

Efficacy and safety of panitumumab alone or in association with radiotherapy in unresectable cutaneous squamous cell carcinoma.

BACKGROUND: The prognosis of unresectable cutaneous squamous cell carcinomas is very poor. OBJECTIVE: To evaluate the efficacy and safety of panitumumab alone or in association with radiotherapy in the treatment of unresectable cutaneous squamous cell carcinoma. METHODS: This was a monocentre retrospective study of all consecutive patients having received at least two courses of panitumumab, alone or in association with radiotherapy, between 2016 and 2019. The primary endpoint was the rate of best overall response, evaluated according to the RECIST 1.1 criteria. The secondary endpoints were the response and disease control rates at 6 weeks and 6 months, progression-free survival, overall survival and safety. RESULTS: A total of 25 patients were included; their median age was 86 years, and 17 (86%) had a WHO performance status over 2. The best overall response rate was 52%, including four complete responses (16%) and nine partial responses (36%). All patients with complete response and five out of nine patients with partial response had received concurrent radiotherapy, in most cases in moderate to low doses (<40 Gray, 67%). The response rates at 6 weeks and 6 months were 12% and 28%, respectively. The control rates at 6 weeks and 6 months were 84% and 32%, respectively. Median progression-free survival was 6.9 months, and median overall survival was 10.5 months. Grade 3 side-effects, mostly dermatological, occurred in 16 patients (64%). CONCLUSION: These results suggest that panitumumab remains pertinent in the treatment of unresectable cutaneous squamous cell carcinoma, in particular in association with radiotherapy, despite recent advances with anti-PD-1 antibodies. It presents several advantages: it can be used in very elderly or feeble patients, it does not provoke anaphylactic or other irreversible or life-threatening side-effects, and our study observed some long-term responses. Further prospective investigation of anti-EGFR antibodies, in association with anti-PD-1 antibodies and/or chemotherapy, should be conducted.

[Generalized granuloma annulare: A clinicopathological study]. / Granulome annulaire généralisé : étude anatomoclinique.

BACKGROUND: Granuloma annulare (GA) is a benign granulomatous skin disorder that is generalized (GGA) in 15 % of cases. Although many case reports describe a relationship between GGA and systemic diseases, few large series have been published, and their association is debated. We present herein a series of GGA in order to describe their clinical and histological features. PATIENTS AND METHODS: We included all biopsy-proven cases of GA presenting at the dermatopathology laboratory of Strasbourg where generalized (i.e. over 10 lesions). Clinical features were obtained from patients' medical files. RESULTS: We included 35 GGA, with a sex ratio of 0.5. The mean age was 54 years. Lesions were annular or non-annular in equal measure and were symptomatic in 25 % of cases. Most patients (77 %) had an associated disease, already known in 60 % of cases, including dyslipidemia (27 %), diabetes mellitus (20 %), immunosuppressive drugs (17 %), atopy (17 %), auto-immune disease (17 %), hematological disease (14 %), and cancer (9 %). Histological analysis revealed the predominant pattern to be interstitial (54 %) rather than palisading (20 %), having no correlation with clinical type. Eosinophils were frequent (46 %) in GA but were not correlated with systemic disease or drug taking. Among the 40 % of patients treated, 50 % had a successful outcome on topical corticosteroids, doxycycline, antimalarial drugs or phototherapy. DISCUSSION: GGA differs from localized GA, which is mostly associated with an already known systemic disease, whether metabolic, infectious or neoplastic, uncorrelated with clinical or histological features, and screening is necessary.

Development of gas jet targets for laser-plasma experiments at near-critical density.

Computational fluid dynamics simulations are performed to design gas nozzles, associated with a 1000 bars backing pressure system, capable of generating supersonic gas jet targets with densities close to the critical density for 1053 nm laser radiation (1021 cm-3). Such targets should be suitable for laser-driven ion acceleration at a high repetition rate. The simulation results are compared to the density profiles measured by interferometry, and characterization of the gas jet dynamics is performed using strioscopy. Proton beams with maximum energies up to 2 MeV have been produced from diatomic hydrogen gas jet targets in a first experiment.

[Rapidly growing squamous cell carcinoma after ingenol mebutate treatment]. / Carcinome épidermoïde de croissance rapide après traitement par mébutate d'ingénol.

INTRODUCTION: Ingenol mebutate is an actinic keratosis treatment, which has a dual action mechanism. It allows a rapid cellular death and a severe inflammation. OBSERVATION: We report the case of a 75 years old patient with a rapidly growing tumor 5 weeks after application of ingenol mebutate on typical actinic keratosis. Histological analysis after surgical excision showed an invasive squamous cell carcinoma (SCC); with aggressiveness signs: perineural infiltration and vascular permeation. DISCUSSION: Ingenol mebutate's common side effects are benign and regressive within 2 to 4 weeks. There are erythema, edema, crusts, and ulcerations/erosions. Squamous cell carcinoma development was rarely reported. We have tried to collect other cases in the literature and in pharmacovigilance centres: three similar cases were recently published in the literature, 21 cases were notified to the European Medicines Agency and we asked French pharmacovigilance centres and found 5 cases of SCC after ingenol mebutate application. The role of the molecule in SCC development is currently unknown. Induced inflammation could take part in the development of these tumors. We compare this case with other situations of inflammation, such skin graft donor site or surgical incision, complicated of rapidly growing SCC. Our case, literature's and pharmacovigilance's cases encourage us to follow ingenol mebutate's side effects. Careful follow-up and registration of such cases are important to gain further insight on this topic.

Guiding of relativistic electron beams in dense matter by laser-driven magnetostatic fields.

Intense lasers interacting with dense targets accelerate relativistic electron beams, which transport part of the laser energy into the target depth. However, the overall laser-to-target energy coupling efficiency is impaired by the large divergence of the electron beam, intrinsic to the laser-plasma interaction. Here we demonstrate that an efficient guiding of MeV electrons with about 30 MA current in solid matter is obtained by imposing a laser-driven longitudinal magnetostatic field of 600 T. In the magnetized conditions the transported energy density and the peak background electron temperature at the 60-µm-thick target's rear surface rise by about a factor of five, as unfolded from benchmarked simulations. Such an improvement of energy-density flux through dense matter paves the ground for advances in laser-driven intense sources of energetic particles and radiation, driving matter to extreme temperatures, reaching states relevant for planetary or stellar science as yet inaccessible at the laboratory scale and achieving high-gain laser-driven thermonuclear fusion.

Experimental discrimination of ion stopping models near the Bragg peak in highly ionized matter.

The energy deposition of ions in dense plasmas is a key process in inertial confinement fusion that determines the α-particle heating expected to trigger a burn wave in the hydrogen pellet and resulting in high thermonuclear gain. However, measurements of ion stopping in plasmas are scarce and mostly restricted to high ion velocities where theory agrees with the data. Here, we report experimental data at low projectile velocities near the Bragg peak, where the stopping force reaches its maximum. This parameter range features the largest theoretical uncertainties and conclusive data are missing until today. The precision of our measurements, combined with a reliable knowledge of the plasma parameters, allows to disprove several standard models for the stopping power for beam velocities typically encountered in inertial fusion. On the other hand, our data support theories that include a detailed treatment of strong ion-electron collisions.

Prevention of interferon-alpha-associated depression with antidepressant medications in patients with hepatitis C virus: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis evaluating the efficacy and safety of antidepressant medications for the prevention of interferon-alpha (INF-α)-associated depression in patients with chronic hepatitis C virus (HCV). DATA SOURCES: Medline, Cochrane Central and PsycInfo from inception to September 2012, without limitations using terms describing hepatitis C and the individual drug names. STUDY SELECTION: We reviewed 132 citations for inclusion using the following criteria: randomised controlled trials in patients with chronic HCV initiating INF-α comparing prophylactic use of an antidepressant vs. placebo and reporting at least one outcome of interest [depression, completion of antiviral therapy, sustained virologic response (SVR), and serious adverse events and bleeding]. DATA EXTRACTION: Trial characteristics, assessment of risk of bias and data needed for analyses were extracted by two independent investigators using a standard extraction form. Disagreements were reviewed by a third investigator. RESULTS: A DerSimonian and Laird random-effects model was used for analysis. Heterogeneity and publication bias were evaluated where applicable. Of the seven included trials, the risk of bias was low in four and unclear in the remaining three. All trials evaluated selective serotonin reuptake inhibitors (SSRIs). Prophylactic use of a SSRI significantly reduced the risk of depression by 41% compared with placebo [RR, relative risk 0.59 (0.37-0.93)]. The impact of SSRIs on completion of antiviral therapy, SVR and serious adverse events was not found to be significant. CONCLUSIONS: SSRIs prevent depression in patients with HCV treated with INF-α therapy. The impact of SSRIs on completion of antiviral therapy or on the development of adverse events is less clear.

Psychotropic medication adherence in correctional facilities: a review of the literature.

Despite the high percentage of incarcerated persons with mental illness, surprisingly little is known about effective ways to increase psychotropic medication adherence in prison and upon release. Currently, there are limited definitive data regarding psychotropic medication adherence patterns among incarcerated persons, and the data that exist often miss specific information on changes in behaviour, symptom management and adherence patterns over the length of a person's sentence, which has implications for post-release ability to live in the community. This paper presents the current literature regarding psychotropic medication adherence among mentally ill persons who are incarcerated. The factors identified in support of medication adherence, future clinical research and care strategies are provided.

Venlafaxine induces P-glycoprotein in human Caco-2 cells.

PURPOSE: The objective of this study was to evaluate the effect of a treatment with venlafaxine on the expression of multidrug resistance-associated protein (MRP) gene and multidrug resistance-related proteins (MDR) in human colon carcinoma cells (Caco-2) compared to a known P-glycoprotein (PGY1) inducer, rifampine. METHODS: Caco-2 cells were treated with venlafaxine (50 microM, 100 microM, 250 microM, and 500 microM) and rifampin (25 microM and 50 microM) to test the possible induction of MRP and MDR expression. The treatment times used were 1.5, 3, 6, 12, 24, 48, and 72 h. RNA was isolated from the cells, and MDR and MRP genes were amplified using PCR. RESULTS: Both venlafaxine and rifampine had the most dramatic effect at the 50 microM concentration. There was an increase in MDR and MRP expression in Caco-2 cells after the acute treatment (1.5, 3, and 6 h) with venlafaxine. These results were similar to those with rifampine. CONCLUSIONS: PGY1 contributes to renal and biliary elimination of drugs by transporting the drug out of the cell and back into the intestinal lumen, where drugs may be further metabolized by intestinal enzymes such as Cytochrome P (CYP)-450 3A4. Its function is to limit the bioavailability of orally administered compounds. Due to the increase in MDR and MRP gene expression seen after the acute treatment with venlafaxine, there could be a potential drug-drug interaction with other medications that are metabolized via CYP450-3A4 when coadministered with venlafaxine.

Ultrastructural analysis of tryptophan hydroxylase immunoreactive nerve terminals in the rat cerebral cortex and hippocampus: their associations with local blood vessels.

Physiological evidence has indicated that serotonin (5-hydroxytryptamine) could be a regulator of cerebral blood flow in various regions of the brain. In the present study, tryptophan hydroxylase immunocytochemistry was used to characterize, both at the light and electron microscopic levels, serotonergic nerve terminals and primarily their relationships with intraparenchymal microarterioles and capillaries in the rat frontoparietal cortex, entorhinal cortex and hippocampus. Irrespective of the brain area, serotonergic varicosities were primarily apposed to either dendrites or nerve terminals, were on average 0.37 micron2 in surface area (0.69 micron calculated diameter) and 12-22% of them engaged in synaptic junctions, mostly with dendritic elements. Perivascular terminals (defined as immunolabelled varicosities located within a 3 micron perimeter around the vessel basal lamina) in the frontoparietal cortex represented 8-11% of all immunoreactive terminals counted, as determined by light and electron microscopy, respectively. In the entorhinal cortex and hippocampus, the proportion of perivascular terminals was only determined at the ultrastructural level and corresponded to 10% and 4%, respectively. In the frontoparietal cortex, serotonergic varicosities were located significantly closer (n = 250, 0.98 +/- 0.05 micron; P < 0.001) to the blood vessels than those of the entorhinal cortex (n = 116, 1.41 +/- 0.08 microns) or hippocampus (n = 105, 1.31 +/- 0.08 microns). Of all perivascular serotonergic terminals in the frontoparietal cortex, 26% were in the immediate vicinity (0-0.25 micron) of the vessel wall, with 2.8% directly abutting on the basement membrane, while 11.6% were separated from it only by a thin astrocytic leaflet. This situation contrasts with that observed in the entorhinal cortex and hippocampus, where no immunoreactive varicosity was ever seen directly contacting the vessel basal lamina and with only 10-13% of the terminals being within 0.25 micron from the vessels. The surface area of perivascular serotonergic terminals was comparable in all regions studied and corresponded to 0.22 micron2; these virtually never engaged in synaptic contacts with adjacent neuronal structures. Our results indicate that tryptophan hydroxylase-immunolabelled terminals are identical to previously characterized serotonin-containing varicosities. Furthermore, the present data show intimate associations between serotonergic terminals and microvessels in the three regions examined. However, perivascular terminals in the frontoparietal cortex were more frequent and/or located much closer to local microvessels than those in the other regions, and might be more directly involved in neurogenic control of local cerebral blood flow.