Cloud droplet relative dispersion, defined as the standard deviation over the mean cloud droplet size, is of central importance in determining and understanding aerosol indirect effects. In recent ...work, it was found that cloud droplet size distributions become broader as a result of supersaturation variability and that the sensitivity of this effect is inversely related to cloud droplet number density. The subject is investigated in further detail using an extensive dataset from a laboratory cloud chamber capable of producing steady-state turbulence. An extended stochastic theory is found to successfully describe properties of the droplet size distribution, including an analytical expression for the relative dispersion. The latter is found to depend on the cloud droplet removal time, which in turn increases with the cloud droplet number density. The results show that relative dispersion decreases monotonically with increasing droplet number density, consistent with some recent atmospheric observations. Experiments spanning fast to slow microphysics regimes are reported. The observed dispersion is used to estimate time scales for autoconversion, demonstrating the important role of the turbulence-induced broadening effect on precipitation development. An initial effort is made to extend the stochastic theory to an atmospheric context with a steady updraft, for which autoconversion time is the controlling factor for droplet lifetime. As in the cloud chamber, relative dispersion is found to increase with decreasing cloud droplet number density.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Actinic keratoses (AKs) are common premalignant skin lesions triggered by excessive ultraviolet exposure. The majority of AKs regress or persist, but some progress to squamous cell ...carcinomas. Biomarkers associated with their persistence, progression and regression have not been characterized.
Objectives
We performed skin biopsies in patients with extensive actinic damage to identify biomarkers that correlate with clinical progression and regression of AKs.
Methods
This was an observational study of a cohort of patients with extensive actinic damage. AKs were mapped on a clear plastic template in 26 patients at months 3, 6, 9 and 11. Biopsies were taken from randomly selected, predetermined AKs and were evaluated for p53, E‐cadherin, Snail, Slug and Twist. The study is registered at Clinicaltrials.gov: NCT00027976.
Results
p53 exhibited greater expression in clinically apparent AKs (histological score 2·89 ± 1·45) than in regressed AKs (0·75 ± 0·96); P < 0·01. There was also significantly less membrane E‐cadherin, the lack of which is a marker of epithelial–mesenchymal transition, in clinically apparent AKs (1·89 ± 1·81) than in sun‐exposed skin (3·07 ± 1·75); P < 0·005. The E‐cadherin transcription repressors Snail, Slug and Twist were increased in AKs compared with sun‐exposed skin. A limitation of the study is that measurement of histological biomarkers was not a primary end point. In addition, patients were allowed to apply sunscreens.
Conclusions
At the molecular level, loss of E‐cadherin and an increase in p53 are linked to the dynamic interplay between the persistence, progression and regression of AKs.
What's already known about this topic?
Actinic keratoses (AKs) are common dysplastic epidermal lesions that result from chronic and excessive ultraviolet exposure.
Biomarkers associated with progression and regression of AK have not been characterized.
What does this study add?
Decreased E‐cadherin and increased p53, Snail, Slug and Twist (E‐cadherin transcription factors) were associated with progression from AK to nonmelanoma skin cancer.
What is the translational message?
Strategies targeting these molecules may be effective in reversing rising skin cancer rates.
E‐cadherin, p53, Snail, Slug and Twist are potential biomarkers that may be used to assess the efficacy of existing chemopreventive agents.
Linked Comment: O’Shaughnessy. Br J Dermatol 2020; 182:834–835.
Diffusional growth of droplets by stochastic condensation and a resulting broadening of the size distribution has been considered as a mechanism for bridging the cloud droplet growth gap between ...condensation and collision–coalescence. Recent studies have shown that supersaturation fluctuations can lead to a broadening of the droplet size distribution at the condensational stage of droplet growth. However, most studies using stochastic models assume the phase relaxation time of a cloud parcel to be constant. In this paper, two questions are asked: how variability in droplet number concentration and radius influence the phase relaxation time and what effect it has on the droplet size distributions. To answer these questions, steady-state cloud conditions are created in the laboratory and digital inline holography is used to directly observe the variations in local number concentration and droplet size distribution and, thereby, the integral radius. Stochastic equations are also extended to account for fluctuations in integral radius and obtain new terms that are compared with the laboratory observations. It is found that the variability in integral radius is primarily driven by variations in the droplet number concentration and not the droplet radius. This variability does not contribute significantly to the mean droplet growth rate but does contribute significantly to the rate of increase of the size distribution width.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Tildrakizumab is a specific anti‐interleukin‐23p19 monoclonal antibody approved for the treatment of plaque psoriasis.
Objectives
To evaluate the long‐term efficacy and safety of ...tildrakizumab treatment for patients with moderate‐to‐severe psoriasis for up to 148 weeks.
Methods
Pooled analysis from two double‐blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50–75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4‐week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all‐patients‐as‐treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).
Results
At week 148 (NRI), 72·6%, 53·8% and 28·9% of tildrakizumab 100‐mg responders and 80·2%, 59·9% and 32·6% of tildrakizumab 200‐mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events tildrakizumab 100 mg: 1·7 per 100 patient‐years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs and exposure‐adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 per 100 PYs) were low.
Conclusions
Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab.
What's already known about this topic?
Tildrakizumab 100 mg and 200 mg are efficacious and well tolerated with short‐term use in the treatment of patients with moderate‐to‐severe plaque psoriasis.
What does this study add?
High levels of efficacy are maintained for up to 3 years of psoriasis treatment with tildrakizumab.
There is a favourable long‐term safety profile with both tildrakizumab 100 mg and 200 mg, with a low incidence of adverse events of special interest through 3 years.
Plain language summary available online
Respond to this article
What concentration of ice‐nucleating particles is required to completely glaciate a typical atmospheric supercooled liquid cloud? This seemingly esoteric question has far reaching implications, as ...the ratio of liquid to ice in these clouds governs, for example, their influence on Earth's radiation budget and their precipitation efficiency. Microphysical properties of steady‐state mixed‐phase clouds formed in a laboratory convection chamber are observed using digital holography. It is observed that the ratio of ice to total water content of steady‐state mixed‐phase clouds is determined by the concentration of ice‐nucleating aerosol particles. Existing theory is adapted to show such clouds result from a balance between the thermodynamic forcing (i.e., the source of excess water vapor that is condensing to liquid and ice) and the number and size of particles that become ice (i.e., the ice integral radius). The measurements quantitatively support the Korolev‐Mazin conditions for existence of mixed‐phase clouds.
Key Points
Holographic measurements of steady‐state mixed‐phase clouds are made in a laboratory cloud‐convection chamber
The ice fraction in the cloud is determined by varying the ice‐nucleating particle concentration while holding CCN concentration constant
Measurements are in agreement with an extension of Korolev‐Mazin theory for critical forcing needed for mixed‐phase conditions
Cloud optical properties are determined not only by the number density nd and mean radius
r̄ of cloud droplets but also by the shape of the droplet size distribution. The change in cloud optical ...depth with changing nd, due to the change in distribution shape, is known as the dispersion effect. Droplet relative dispersion is defined as
d=σr/r̄. For the first time, a commonly used effective radius parameterization is tested in a controlled laboratory environment by creating a turbulent cloud. Stochastic condensation growth suggests d independent of nd for a nonprecipitating cloud, hence nearly zero albedo susceptibility due to the dispersion effect. However, for size‐dependent removal, such as in a laboratory cloud or highly clean atmospheric conditions, stochastic condensation produces a weak dispersion effect. The albedo susceptibility due to turbulence broadening has the same sign as the Twomey effect and augments it by order 10%.
Plain Language Summary
Clouds cover a large fraction of the Earth and play an important role in determining Earth's climate. Their optical properties, such as how much sunlight they reflect back to space, are determined in part by the number of aerosol particles in the atmosphere. In addition to the mean cloud droplet size, the range of droplet sizes influences cloud optical properties, and that influence is called the dispersion effect. A positive dispersion effect means that an increase in cloud droplet number leads to a more reflective (brighter) cloud. We have carried out experiments in a laboratory cloud chamber to observe how the average size and the range of droplet sizes changes as aerosol concentration is varied. The laboratory chamber creates a turbulent environment. The results show that the the dispersion effect is positive, but small in magnitude. Cloud droplet activation, condensation growth in turbulence, and sedimentation are enough to reproduce stratocumulus observations.
Key Points
A commonly used, empirical effective radius parameterization is observed under controlled laboratory conditions
Cloud droplet activation, condensation growth in turbulence, and sedimentation are enough to reproduce stratocumulus observations
Stochastic condensation growth produces relative size dispersion nearly independent of aerosol concentration for a nonprecipitating cloud
Prior observations have documented the process of cloud cleansing, through which cloudy, polluted air from a continent is slowly transformed into cloudy, clean air typical of a maritime environment. ...During that process, cloud albedo changes gradually, followed by a sudden reduction in cloud fraction and albedo as drizzle forms and convection changes from closed to open cellular. Experiments in a cloud chamber that generates a turbulent environment show a similar cloud cleansing process followed by rapid cloud collapse. Observations of (1) cloud droplet size distribution, (2) interstitial aerosol size distribution, (3) cloud droplet residual size distribution, and (4) water vapor supersaturation are all consistent with the hypothesis that turbulent fluctuations of supersaturation accelerate the cloud cleansing process and eventual cloud collapse. Decay of the interstitial aerosol concentration occurs slowly at first then more rapidly. The accelerated cleansing occurs when the cloud phase relaxation time exceeds the turbulence correlation time.
Plain Language Summary
Initially, polluted clouds can slowly transform into clean clouds when there is no significant source of aerosol particles. The rate at which this aerosol removal occurs, which can be thought of as cloud cleansing, undergoes a sudden acceleration when a cloud becomes sufficiently clean. Cloud chamber experiments show that random, turbulent fluctuations become large when a cloud becomes sufficiently clean, and these large fluctuations in temperature and the concentration of water vapor cause rapid activation of aerosol particles and rapid growth of cloud droplets. In the atmosphere these large droplets would be expected to aid in initiating the formation of precipitation by collisions and coalescence of droplets.
Key Points
Cloud cleansing of aerosols is simulated in a cloud chamber with steady state turbulence
Turbulent fluctuations in supersaturation become more pronounced as cloud is cleansed
Aerosol removal process is accelerated, leading to cloud collapse during the cleansing process
Summary
Background
The phase III reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti‐interleukin‐23p19 monoclonal antibody tildrakizumab (TIL) for psoriasis treatment are ...complete.
Objectives
We present 5‐year pooled data from reSURFACE 1 and reSURFACE 2.
Methods
reSURFACE 1 and reSURFACE 2 were double‐blind, randomized, controlled studies with optional long‐term extensions. Adults with moderate‐to‐severe chronic plaque psoriasis were randomized 2 : 2 : 1 to TIL 100 mg (TIL 100) or 200 mg (TIL 200) or placebo at weeks 0 and 4, and every 12 weeks thereafter reSURFACE 2 included an etanercept (ETN) arm. Efficacy outcomes included proportions of patients achieving absolute and relative improvement from baseline Psoriasis Area and Severity Index (PASI) score through week 244 in TIL responders (≥ 75% improvement from baseline PASI; PASI 75 response) continuously receiving the same dose and ETN partial responders and nonresponders (PASI < 75 response) switched to TIL 200 at week 28. Safety was assessed from adverse events (AEs) in all patients as treated.
Results
Efficacy analyses included 329 and 227 week 28 responders to TIL 100 and TIL 200, respectively, and 121 ETN partial responders/nonresponders switched to TIL 200 at week 28. Of TIL 100 or TIL 200 responders and ETN partial responders/nonresponders entering the extensions, 235/302, 176/213 and 85/107, respectively, were evaluated at week 244, and 88·7%, 92·5% and 81·3%, respectively, achieved PASI 75 response. Exposure‐adjusted rates of serious AEs were 6·3 and 6·0 patients with events per 100 patient‐years of TIL 100 and TIL 200, respectively.
Conclusions
TIL treatment provided sustained disease control over 5 years in week 28 TIL responders and ETN partial responders/nonresponders, with a reassuring safety profile.
What’s already known about this topic?
Tildrakizumab (TIL) is approved for treatment of moderate‐to‐severe psoriasis, and 3‐year data have been previously published.
Long‐term efficacy and safety data of biological therapies is crucial to inform clinical practice.
What does this study add?
TIL is the first anti‐interleukin‐23p19 treatment for which 5‐year efficacy and safety data are reported from two phase III studies, reSURFACE 1 and reSURFACE 2.
These data provide evidence of sustained efficacy in TIL responders and in patients switched from etanercept to TIL at week 28, and a favourable long‐term safety profile with total TIL exposure of over 5400 patient‐years.
Linked Comment: C.G. Purvis et al. Br J Dermatol 2021; 185:242–243.
Plain language summary available online
Prison Meditation Movements and Mass Incarceration Lyons, Thomas; Cantrell, W. Dustin
International journal of offender therapy and comparative criminology,
09/2016, Letnik:
60, Številka:
12
Journal Article
Recenzirano
Odprti dostop
By some estimates, more than half of inmates held in jails and prisons in the United States have a substance use disorder. Treatments involving the teaching of meditation and other contemplative ...practices have been developed for a variety of physical and mental disorders, including drug and alcohol addiction. At the same time, an expanding volunteer movement across the country has been bringing meditation and yoga into jails and prisons. This review first examines the experimental research on one such approach—mindfulness meditation as a treatment for drug and alcohol addiction, as well as the research on mindfulness in incarcerated settings. We argue that to make a substantial impact on recidivism, such programs must mirror volunteer programs which emphasize interdependency and non-duality between the “helper” and the “helped,” and the building of meditation communities both inside and outside of prison.
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