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Aerosol mass and the absorbing fraction are important variables, needed to constrain the role of atmospheric particles in the Earth radiation budget, both directly and indirectly through CCN activation. In particular, their monitoring in remote areas and mountain sites is essential for determining source regions, elucidating the mechanisms of long range transport of anthropogenic pollutants, and validating regional and global models. Since March 2006, aerosol mass and black carbon concentration have been monitored at the Nepal Climate Observatory-Pyramid, a permanent high-altitude research station located in the Khumbu valley at 5079 m a.s.l. below Mt. Everest. The first two-year averages of PM1 and PM1−10 mass were 1.94 μg m−3 and 1.88 μg m−3, with standard deviations of 3.90 μg m−3 and 4.45 μg m−3, respectively, while the black carbon concentration average is 160.5 ng m−3, with a standard deviation of 296.1 ng m−3. Both aerosol mass and black carbon show well defined annual cycles, with a maximum during the pre-monsoon season and a minimum during the monsoon. They also display a typical diurnal cycle during all the seasons, with the lowest particle concentration recorded during the night, and a considerable increase during the afternoon, revealing the major role played by thermal winds in influencing the behaviour of atmospheric compounds over the high Himalayas. The aerosol concentration is subject to high variability: in fact, as well as frequent \"background conditions\" (55% of the time) when BC concentrations are mainly below 100 ng m−3, concentrations up to 5 μg m−3 are reached during some episodes (a few days every year) in the pre-monsoon seasons. The variability of PM and BC is the result of both short-term changes due to thermal wind development in the valley, and long-range transport/synoptic circulation. At NCO-P, higher concentrations of PM1 and BC are mostly associated with regional circulation and westerly air masses from the Middle East, while the strongest contributions of mineral dust arrive from the Middle East and regional circulation, with a special contribution from North Africa and South-West Arabian Peninsula in post-monsoon and winter season.

This paper provides a detailed description of the atmospheric conditions characterizing the high Himalayas, thanks to continuous observations begun in March 2006 at the Nepal Climate Observatory-Pyramid (NCO-P) located at 5079 m a.s.l. on the southern foothills of Mt. Everest, in the framework of ABC-UNEP and SHARE-Ev-K2-CNR projects. The work presents a characterization of meteorological conditions and air-mass circulation at NCO-P during the first two years of activity. The mean values of atmospheric pressure, temperature and wind speed recorded at the site were: 551 hPa, −3.0 °C, 4.7 m s−1, respectively. The highest seasonal values of temperature (1.7 °C) and relative humidity (94%) were registered during the monsoon season, which was also characterized by thick clouds, present in about 80% of the afternoon hours, and by a frequency of cloud-free sky of less than 10%. The lowest temperature and relative humidity seasonal values were registered during winter, −6.3 °C and 22%, respectively, the season being characterised by mainly cloud-free sky conditions and rare thick clouds. The summer monsoon influenced rain precipitation (seasonal mean: 237 mm), while wind was dominated by flows from the bottom of the valley (S–SW) and upper mountain (N–NE). The atmospheric composition at NCO-P has been studied thanks to measurements of black carbon (BC), aerosol scattering coefficient, PM1, coarse particles and ozone. The annual behaviour of the measured parameters shows the highest seasonal values during the pre-monsoon (BC: 316.9 ng m−3, PM1: 3.9 μg m−3, scattering coefficient: 11.9 Mm−1, coarse particles: 0.37 cm−3 and O3: 60.9 ppbv), while the lowest concentrations occurred during the monsoon (BC: 49.6 ng m−3, PM1: 0.6 μg m−3, scattering coefficient: 2.2 Mm−1, and O3: 38.9 ppbv) and, for coarse particles, during the post-monsoon (0.07 cm−3. At NCO-P, the synoptic-scale circulation regimes present three principal contributions: Westerly, South-Westerly and Regional, as shown by the analysis of in-situ meteorological parameters and 5-day LAGRANTO back-trajectories. The influence of the brown cloud (AOD>0.4) extending over Indo–Gangetic Plains up to the Himalayan foothills has been evaluated by analysing the in-situ concentrations of the ABC constituents. This analysis revealed that brown cloud hot spots mainly influence the South Himalayas during the pre-monsoon, in the presence of very high levels of atmospheric compounds (BC: 1974.1 ng m−3, PM1: 23.5 μg m−3, scattering coefficient: 57.7 Mm−1, coarse particles: 0.64 cm−3, O3: 69.2 ppbv, respectively). During this season 20% of the days were characterised by a strong brown cloud influence during the afternoon, leading to a 5-fold increased in the BC and PM1 values, in comparison with seasonal means. Our investigations provide clear evidence that, especially during the pre-monsoon, the southern side of the high Himalayan valleys represent a \"direct channel\" able to transport brown cloud pollutants up to 5000 m a.s.l., where the pristine atmospheric composition can be strongly influenced.

The dynamics of granular mixtures, involved in several geophysical phenomena like rock avalanches and debris flows, is far from being completely understood. Several features of their motion, such as non-local and boundary effects, still represent open problems. An extensive experimental study on free-surface channelized granular flows is here presented, where the effects of the fixed boundaries are systematically investigated. The entire experimental data set is obtained by using a homogenous acetal-polymeric granular material and three different basal surfaces, allowing different kinematic boundary conditions. Velocity profiles at both the sidewall and the free surface are obtained by using high-speed cameras and the open-source particle image velocimetry code, PIVlab. Significantly, different sidewall velocity profiles are observed by varying the basal roughness and the flow depth. Owing to sidewall friction and non-local effects, such profiles exhibit a clear rheological stratification for high enough flow depths and they can be well described by recurring to composite functions, variously formed of linear, Bagnold and exponential scalings. Moreover, it has been discovered that transitions from one velocity profile to another are also possible on the same basal surface by merely varying the flow depth. This shape transition is due partly to the sidewall resistances, the basal boundary condition and, in particular, the occurrence/inhibition of basal grain rolling. In most of the experiments, the normal-to-bed velocity profiles and the velocity measurements at the free surface strongly suggest the occurrence of a secondary circulating flow, made possible by a chiefly collisional regime beneath the free surface.

A Hygroscopicity Tandem Differential Mobility Analyser (HTDMA) was used to evaluate the hygroscopic properties of aerosol particles measured at the Puy de Dôme research station in central France, periodically from September 2008 to January 2010, and almost continuously from October 2010 to December 2012. This high-altitude site is ideally situated to allow for both the upper part of the planetary boundary layer and the lower free troposphere to be sampled. The aim of the study is to investigate both the influence of year-to-year, seasonal and diurnal cycles, as well as the influence of air mass type on particle hygroscopicity and mixing state. Results show that particle hygroscopicity increases with particle size and depends both on air mass type and on season. Average growth factor values, GFs, are lowest in winter (1.21 ± 0.13, 1.23 ± 0.18 and 1.38 ± 0.25 for 25, 50 and 165 nm particles, respectively) and highest in autumn (1.27 ± 0.11, 1.32 ± 0.12 and 1.49 ± 0.15 for 25, 50 and 165 nm particles, respectively). Particles are generally more hygroscopic at night than during the day. The seasonal and diurnal variations are likely to be strongly influenced by boundary layer dynamics. Furthermore, particles originating from oceanic and continental regions tend to be more hygroscopic than those measured in African and local air masses. The high hygroscopicity of oceanic aerosol can be explained by large proportions of inorganic aerosol and sea salts. Aerosols measured at the Puy de Dôme display a high degree of external mixing, and hygroscopic growth spectra can be divided into three different hygroscopic modes: a less-hygroscopic mode (GF < 1.3), a hygroscopic mode (GF~1.3–1.7) and a more-hygroscopic mode (GF > 1.7). The majority of particles measured can be classified as being in either the less-hygroscopic mode or the hygroscopic mode, and only few of them have more-hygroscopic properties. The degree of external mixing, evaluated as the fraction of time when the aerosol is found with two or more aerosol populations with different hygroscopic properties, increases with particle size (average yearly values are 20, 28 and 45 % for 25, 50, and 165 nm particles, respectively). The degree of external mixing is more sensitive to season than to air mass type, and it is higher in the cold seasons than in the warm seasons. With more than two years of nearly continuous measurements, this study gathers the results from one of the longest data sets of hygroscopic growth factor measurements to date, allowing a statistically relevant hygroscopic growth parameterization to be determined as a function of both air mass type and season.

Intense anthropogenic emissions over the Indian sub-continent lead to the formation of layers of particulate pollution that can be transported to the high altitude regions of the Himalaya-Hindu-Kush (HKH). Aerosol particles contain a substantial fraction of strongly absorbing material, including black carbon (BC), organic compounds (OC), and dust all of which can contribute to atmospheric warming, in addition to greenhouse gases. Using a 3-year record of continuous measurements of aerosol optical properties, we present a time series of key climate relevant aerosol properties including the aerosol absorption (σap) and scattering (σsp) coefficients as well as the single-scattering albedo (w0). Results of this investigation show substantial seasonal variability of these properties, with long range transport during the pre- and post-monsoon seasons and efficient precipitation scavenging of aerosol particles during the monsoon season. The monthly averaged scattering coefficients range from 0.1 Mm−1 (monsoon) to 20 Mm−1 while the average absorption coefficients range from 0.5 Mm−1 to 3.5 Mm−1. Both have their maximum values during the pre-monsoon period (April) and reach a minimum during Monsoon (July–August). This leads to dry w0 values from 0.86 (pre-monsoon) to 0.79 (monsoon) seasons. Significant diurnal variability due to valley wind circulation is also reported. Using aerosol optical depth (AOD) measurements, we calculated the resulting direct local radiative forcing due to aerosols for selected air mass cases. We found that the presence of absorbing particulate material can locally induce an additional top of the atmosphere (TOA) forcing of 10 to 20 W m−2 for the first atmospheric layer (500 m above surface). The TOA positive forcing depends on the presence of snow at the surface, and takes place preferentially during episodes of regional pollution occurring on a very regular basis in the Himalayan valleys. Warming of the first atmospheric layer is paralleled by a substantial decrease of the amount of radiation reaching the surface. The surface forcing is estimated to range from −4 to −20 W m−2 for small-scale regional pollution events and large-scale pollution events, respectively. The calculated surface forcing is also very dependent on surface albedo, with maximum values occurring over a snow-covered surface. Overall, this work presents the first estimates of aerosol direct radiative forcing over the high Himalaya based on in-situ aerosol measurements, and results suggest a TOA forcing significantly greater than the IPCC reported values for green house gases.

Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials. SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries. Patients aged 18 years old or older with the capacity to provide written informed consent and with moderate-to-severe hidradenitis suppurativa (defined as a total of ≥5 inflammatory lesions affecting ≥2 distinct anatomical areas) for at least 1 year were eligible for inclusion. Included patients also agreed to daily use of topical over-the-counter antiseptics on the areas affected by hidradenitis suppurativa lesions while on study treatment. Patients were excluded if they had 20 or more fistulae at baseline, had ongoing active conditions requiring treatment with prohibited medication (eg, systemic biological immunomodulating treatment, live vaccines, or other investigational treatments), or met other exclusion criteria. In both trials, patients were randomly assigned (1:1:1) by means of interactive response technology to receive subcutaneous secukinumab 300 mg every 2 weeks, subcutaneous secukinumab 300 mg every 4 weeks, or subcutaneous placebo all via a 2 mL prefilled syringe in a double-dummy method as per treatment assignment. The primary endpoint was the proportion of patients with a hidradenitis suppurativa clinical response, defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or in the number of draining fistulae compared with baseline, at week 16, assessed in the overall population. Hidradenitis suppurativa clinical response was calculated based on the number of abscesses, inflammatory nodules, draining fistulae, total fistulae, and other lesions in the hidradenitis suppurativa affected areas. Safety was assessed by evaluating the presence of adverse events and serious adverse events according to common terminology criteria for adverse events, which were coded using Medical Dictionary for Regulatory Activities terminology. Both the SUNSHINE, NCT03713619, and SUNRISE, NCT03713632, trials are registered with ClinicalTrials.gov. Between Jan 31, 2019, and June 7, 2021, 676 patients were screened for inclusion in the SUNSHINE trial, of whom 541 (80%; 304 [56%] women and 237 [44%] men; mean age 36·1 years [SD 11·7]) were included in the analysis (181 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 180 [33%] in the placebo group). Between the same recruitment dates, 687 patients were screened for inclusion in the SUNRISE trial, of whom 543 (79%; 306 [56%] women and 237 [44%] men; mean age 36·3 [11·4] years) were included in the analysis (180 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 183 [34%] in the placebo group). In the SUNSHINE trial, significantly more patients in the secukinumab every 2 weeks group had a hidradenitis suppurativa clinical response (rounded average number of patients with response in 100 imputations, 81·5 [45%] of 181 patients) compared with the placebo group (60·7 [34%] of 180 patients; odds ratio 1·8 [95% CI 1·1–2·7]; p=0·0070). However, there was no significant difference between the number of patients in the secukinumab every 4 weeks group (75·2 [42%] of 180 patients) and the placebo group (1·5 [1·0–2·3]; p=0·042). Compared with the placebo group (57·1 [31%] of 183 patients), significantly more patients in the secukinumab every 2 weeks group (76·2 [42%] of 180 patients; 1·6 [1·1–2·6]; p=0·015) and the secukinumab every 4 weeks group (83·1 [46%] of 180 patients; 1·9 [1·2–3·0]; p=0·0022) had a hidradenitis suppurativa clinical response in the SUNRISE trial. Patient responses were sustained up to the end of the trials at week 52. The most common adverse event by preferred term up to week 16 was headache in both the SUNSHINE (17 [9%] patients in the secukinumab every 2 weeks group, 20 [11%] in the secukinumab every 4 weeks group, and 14 [8%] in the placebo group) and SUNRISE (21 [12%] patients in the secukinumab every 2 weeks group, 17 [9%] in the secukinumab every 4 weeks group, and 15 [8%] in the placebo group) trials. No study-related deaths were reported up to week 16. The safety profile of secukinumab in both trials was consistent with that previously reported, with no new or unexpected safety findings detected. When given every 2 weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment. Novartis Pharma.

Sarcopenia is a muscle disease defined by a loss of muscle strength associated to a decrease in skeletal muscle mass. In addition to aging, many factors may contribute to sarcopenia as cancer and/or androgen deprivation therapy (ADT). The aims of this study are to describe the prevalence of sarcopenia in older prostate cancer patients before initiation of treatment with ADT and radiotherapy, and to evaluate the impact of ADT on the occurrence or aggravation of sarcopenia in this population. Longitudinal study. Sarcopenia was prospectively evaluated in 31 consecutive patients aged 70 to 88 years, referred in one hospital unit of south eastern France, for a comprehensive geriatric assessment (CGA) before cancer treatment initiation. CGA, measures of muscle strength and physical performances were performed at baseline (T0) and at the end of cancer treatment (T1). Appendicular skeletal muscle mass was measured by Dual-energy X-ray absorptiometry (DXA) at the end of treatment. At T0, 8 patients (among 31) had a probable sarcopenia according to European consensus, and 18 had altered physical performance. At T1, 15 patients (among 19) had abnormal one leg balance test. Finally, only one patient had a sarcopenia confirmed by DXA. This preliminary study showed a high prevalence of muscle disorders before initiation of ADT in a population of elderly cancer prostate patients with intermediate frailty status, and an increased risk of falls at the end of ADT. This highlighted the importance of screening for sarcopenia before treatment initiation, to prevent the occurrence or aggravation of sarcopenia by possible adjustment of treatment, and implementation of appropriate exercise and nutrition interventions.

SummarySignificant dropout rates have been observed throughout Fracture Liaison Service (FLS) programs, especially for elderly patients. In an FLS program set up specifically for patients over 70, the non-initiation of osteoporosis treatment was the only factor associated with poor adherence to the program. Neither age nor frailty factors affected adherence.IntroductionFLS programs are considered the most effective interventions for secondary prevention of osteoporotic fractures. Our objective was to identify risk factors for non-adherence to an FLS program set up specifically for patients over 70.MethodsOur multifaceted, intensive program included five appointments over a 2-year period. One hundred sixty-seven patients (mean age 83.5 years) who presented with a recent fragility fracture were enrolled. Multivariable analysis was conducted to determine whether the demographic, clinical, frailty, and osteoporotic risk factors of the patients influenced their adherence to the program.ResultsAbout half of the patients did not attend the follow-up visits. According to the regression analysis, non-initiation of osteoporosis treatment was associated with poor adherence to the program (aHR 3.66). Demographic, clinical, dwelling, frailty factors, osteoporotic risk factors, fracture type, or densitometric scores were not associated with adherence. The first self-reported reason for withdrawal was the difficulty of attending several follow-up visits, and the second was the feeling of not being concerned.ConclusionWe observed that non-initiation of osteoporosis treatment was the only factor correlated with non-adherence to an FLS program. Thus, neither age nor frailty factors should result in patients not being included in FLS. Beyond the necessity of the osteoporosis treatment, good patient understanding of the relevance of all the interventions included in the program is the key.

Background Inappropriate drug prescribing causes preventable drug-related adverse events that result in increased morbidity and mortality, additional costs and diminished quality of life. Numerous initiatives have been launched to improve the quality of drug prescribing and safeguard the security of drug administration processes in nursing homes. Against the backdrop of implementation of telemedicine services, the focus of the present work is to evaluate the impact of a telemedication review carried out by a hospital physician and pharmacist as part of the telemedicine offer. Methods The present study is a randomized controlled clinical trial. A total of 364 patients will be randomized into two groups: (1) an experimental group (182 patients) benefiting from a telemedication review using tele-expertise and (2) a control group (182 patients) receiving standard care. The primary endpoint will be rate of all-cause unplanned hospital admissions occurring within 3 months of randomization. The secondary endpoints will be rate of unplanned admissions at 6 months, patient quality of life, incidence of behavioral disturbances, number of falls, number of residents prescribed at least one inappropriate medication, nursing staff satisfaction, proposed medication reviews and their acceptability rate, characteristics of patients whose general practitioners have taken account of tele-expertise, efficacy of tele-expertise as compared to standard prescription and acceptability and satisfaction surveys of participating caregivers. Discussion In the literature, various studies have investigated the utility of structured medication review processes, but outcome measures are heterogeneous, and results vary widely. Medication review can detect medication-related problems in many patients, but evidence of clinical impact is scant. Incremental cost-effectiveness ratios will be used to compare the cost and effectiveness of the experimental strategy and that of standard care. Our approach, involving the combination of an acceptability survey and a mixed-method (qualitative and quantitative) satisfaction survey, is particularly innovative. The results of this randomized trial are expected to confirm that medication review using tele-expertise has potential as a worthwhile care management strategy for nursing home residents. Trial registration Clinicaltrials.gov NCT03640845 ; registered August 21, 2018 (Clinicaltrials.gov NCT03640845 ).

Background: Data on the therapeutic management and healthcare cost of moderate to severe psoriasis in France are scarce.Objective: To assess the therapeutic management and economic burden of patients with moderate to severe psoriasis.Setting: This is a retrospective observational study on the Generalist Beneficiaries Sample of the National Health Data System.Patients and outcome measures:Adults with moderate to severe psoriasis (with a topical vitamin D derivative followed by systemic treatment or hospitalization for psoriasis) were included and followed-up from 1 January 2009 to 31 December 2018. Patients were matched to controls without psoriasis. Patients’ characteristics and healthcare cost from the National Health Insurance’s (NHI) perspective were described.Results: Overall, 1,848 and 5,544 adults were included in the psoriatic and control cohorts, respectively. The most frequent treatments were methotrexate (18.5% to 21.4% of patients by year), phototherapy (29.9% in 2010 down to 6.2% in 2018), and acitretin (25.9% in 2010 down to 8.6% in 2018). Overall, 19% of patients used biotherapies. The mean healthcare costs reimbursed by NHI was €5,365/psoriatic patient (including €2,685 potentially attributable to psoriasis), which was twice as high as in controls. In both cohorts, healthcare costs increased over time.Conclusion: Moderate to severe psoriasis healthcare costs are high.