Robust Avoidance of Edge-Localized Modes alongside Gradient Formation in the Negative Triangularity Tokamak Edge.

In a series of high performance diverted discharges on DIII-D, we demonstrate that strong negative triangularity (NT) shaping robustly suppresses all edge-localized mode (ELM) activity over a wide range of plasma conditions: ⟨n⟩=0.1-1.5×10^{20} m^{-3}, P_{aux}=0-15 MW, and |B_{t}|=1-2.2 T, corresponding to P_{loss}/P_{LH08}∼8. The full dataset is consistent with the theoretical prediction that magnetic shear in the NT edge inhibits access to ELMing H-mode regimes; all experimental pressure profiles are found to be at or below the infinite-n ballooning stability limit. Our present dataset also features edge pressure gradients in strong NT that are closer to an H-mode than a typical L-mode plasma, supporting the consideration of NT for reactor design.

Fatigue as a key factor for testing knee stability with single leg drop landing for injury prevention and return to play tests.

Objectives: Fatigue can decrease knee stability and increase the injury risk. However, fatigue is rarely being applied throughout movement analysis. The aim of this study was to investigate if the knee stability throughout SLDLs differ between cyclic and acyclic sports, before and after fatigue in general, and between the dominant and non-dominant leg of soccer players. Methods: A total of 43 active male (n = 34) and female (n = 9) athletes (age: 26.5 ± 7.2) participated in this study with a pre-post-design. Subjects performed a single leg drop landing (SLDL) from a plyobox. For each leg, the two-dimensional frontal plane projection angle (FPPA) was analyzed. After pretesting the shuttle run test was performed until exhaustion, before repeating the measurements. Results: ANOVA with repeated measures was applied and identified no significance difference for the FPPA between cyclic and acyclic sports (F = 0.98, p = 0.33), a significant difference before and after fatigue (F = 12.49, p = 0.002) and no significant difference between the dominant and non dominant leg of soccer players (F = 4.35, p = 0.26). Discussion: Fatigue seems to be able to have a significant influence on knee stability in the frontal axis. Therefore, fatigue should be included in motion analysis for injury prevention and return to play tests because during this physical state most injuries happen.

Turbulence characteristics and flow dynamics impacts on the H-mode transition in favourable magnetic geometry with lower power threshold.

The L-H transition power threshold (PLH) in favourable magnetic geometry (ion ∇B drift pointing towards X-point) is much lower than in the unfavourable magnetic geometry (ion ∇B drift pointing away from X-point) on multiple tokamaks. In a systematic experiment on DIII-D, the ion ∇B drift direction was changed continuously from the unfavourable to favourable configuration during plasma discharges. During such process, the input neutral beam power was kept constant at a value that was above PLH for favourable configuration, but lower than PLH for unfavourable configuration. Toroidal field and plasma current were also kept constant and there was little change in the edge electron density ne and electron temperature Te profiles. The density fluctuation amplitude was reduced approaching the transition, while a large increase of turbulence Reynolds stress and flow shear were simultaneously observed. The turbulence decorrelation rate was found to increase as the ion ∇B drift direction was moving towards the favourable configuration, but the flow shear also increased and exceeded the turbulence decorrelation rate. These measurements demonstrate an important correlation between turbulence and turbulence-driven flow and a lowering of PLH, provide insights into the underlyingphysics behind the hidden parameters and inform a more complete physics-based model of the L-H transition power threshold. This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.

Pretreatment with ablative fractional carbon dioxide laser improves treatment efficacy in a synergistic PDT protocol for actinic keratoses on the head.

BACKGROUND: A recently proposed synergistic photodynamic therapy protocol (s-PDT) combining advantages of both conventional- and daylight-PDT proved to be an effective and almost painless treatment for patients with actinic keratoses (AKs). This study investigated the safety and efficacy of an additional ablative fractional CO2-laser (AFXL) pretreatment. METHODS: 28 patients with AKs on the head received s-PDT using 5-aminolevulinic acid. AFXL pretreatment was conducted using the following parameters: pulse energy 8 mJ, spot density 50 spots/cm2, power 30 W, beam size 4-18 mm. Outcome was assessed by AK area and severity index (AKASI) and lesion count (LC) before and 3 months after treatment. Safety was monitored by blood pressure and pulse measurements. Intensity of pain was determined by use of a visual analog scale (VAS). RESULTS: Most patients (96.4 %) showed a significant AKASI reduction (P < 0.0001) 3 months after PDT (median AKASI 1.6 [0-2.4]) compared to baseline (5.3 [4-7.75]). Median reduction rate was 75.5 % (61.3 %-100 %). Eleven patients (39.3 %) achieved AKASI 100, three (10.7 %) AKASI 75 and ten (35.7 %) AKASI 50. Blood pressure and pulse did not change significantly throughout treatment. Median VAS for pain during irradiation was 0 (0-0), 0 (0-2) and 0 (0-2) at the beginning, in the meantime and at the end, respectively. Compared to data without AFXL pretreatment, this study showed significantly higher AKASI and LC reduction rates (75.5 % vs. 63.7 % [P = 0.023] and 91.3 % vs. 80.4 % [P = 0.043]). CONCLUSIONS: S-PDT with AFXL pretreatment represents a safe and almost painless treatment for patients with AKs on the head and improves treatment efficacy.

Chemical peelings for the treatment of actinic keratosis: a systematic review and meta-analysis.

BACKGROUND: Actinic keratosis (AK) is a common precancerous lesion of the skin that may be treated with chemical peelings. Despite their long-standing usage and clinical experience, no evidence-based recommendation regarding the efficacy and safety of chemical peelings for AK exists. OBJECTIVES: To systematically review and synthesize the current knowledge on chemically exfoliative peelings as interventions for AK. METHODS: We performed a systematic literature research in Medline, Embase and CENTRAL and hand-searched pertinent trial registers for eligible records until 5 August 2019. Results from individual studies were pooled using a random-effects model or described in a qualitative synthesis. The risk of bias was estimated with the tools provided by the Cochrane Collaboration (randomized and non-randomized trials) and the Evidence Project (single-arm trials). RESULTS: Four randomized controlled trials, two non-randomized controlled trials and two single-arm studies with a total sample size of n = 170 patients were included. Trichloroacetic acid (TCA) plus Jessner's solution showed significantly lower participant complete clearance (RR 0.36, 95% CI: 0.14-0.90, two studies, I2  = 0%, P = 0.03) and lower lesion clearance (RR 0.92, 95% CI: 0.85-0.99, one study, P = 0.03) compared to 5-fluorouracil (5-FU) 5% cream. TCA as monotherapy showed lower lesion complete clearance (RR 0.75, 95% CI: 0.69-0.82, two studies, I2  = 7%, P < 0.001) and lower mean lesion reduction per patient compared to conventional photodynamic therapy (cPDT) (MD -20.48, 95% CI: -31.55 to -9.41, two studies, I2  = 43%, P = 0.0003). Pain was more pronounced in patients treated with cPDT in comparison with TCA (MD -1.71 95% CI: -3.02 to -0.41, two studies, I2  = 55%, P = 0.01). In the single-arm studies, 5-FU plus glycolic acid showed 92% lesion clearance and phenol peeling 90.6% participant complete clearance. All studies showed a high risk for bias. CONCLUSIONS: Future high-quality studies and a standardization of peeling protocols are warranted to determine the value of chemical peelings in the treatment of AK.

Histological classification of cutaneous squamous cell carcinomas with different severity.

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer. Histology represents the gold standard to confirm the diagnosis of cSCC and is mandatory to determine important findings for tumour grading, such as tumour thickness, depth of invasion, degree of differentiation and histological subtype, perineural and vascular invasion, and assessing tumour margins. In daily clinical practice, the combination of clinical and histological features should be considered when grading the tumours and treating the patients, accordingly. This article aims to provide a structured overview of the most common histological findings of in situ and invasive cSCCs, namely those relevant to their severity, and should facilitate the understanding and evaluation of these results.

Infrequent Occurrence of Peach Skin Streaking and the Role of Rainwater Attributes on Symptom Development.

Streaks lacking pigmentation have impacted red blush cultivars of peaches in many East Coast production areas, but the underlying cause is still unclear. Some evidence suggests that streaking may be caused by reactive agents in rainwater. Peach skin streaking was monitored over two consecutive years at a commercial farm with a history of streaking problems located near Ridge Spring, SC. Six cultivars (two early season, two midseason, and two late season) were evaluated, each in two locations (LocA and LocB). Among those 12 experimental block cultivars, streaking occurred only in 2017 in cv. Scarletprince of LocA with an incidence of 6%. That same year two nearby nonexperimental blocks with 'Scarletprince' revealed 11 and 25% streaking. Streaking was also monitored at the Musser Fruit Research Center (MFRC) in Seneca, SC. At that location, a high incidence of streaking was observed, with 50 and 64% in 'Julyprince' (2017) and 'Carored' (2018), respectively. Rainwater pH taken from each of the 12 experimental blocks ranged from 3.03 to 7.4, ozone (O3) levels ranged from <0.02 to 0.37 mg/liter, and chlorine (Cl2) and chlorine dioxide (ClO2) levels were either just above or under the detection limit of 0.01 mg/liter and 0.02 mg/liter, respectively. Although the electrical conductivity (EC) was below 100 µS/cm on average, we did measure EC values as high as 1,500 µS/cm. For all samples, the oxidation-reduction potential (ORP) ranged from 90 to 302 mV, indicating oxidizing conditions. Fruit harvested 1 or 2 weeks prior to commercial maturity and treated with solutions of high (10) or low (3) pH, ozone >0.37 mg/liter, and EC values of up to 3,000 µS/cm did not produce symptoms. However, streaking was reproduced with collected rainwater, but the remaining sample volume did not allow further analyses. Using 0.05% ClO2 to induce streaking, we show that fruit of different cultivars varied in susceptibility when treated 1 week prior to commercial maturity, with 'Juneflame' being the most susceptible and 'August Lady' being the least susceptible. Our study shows that multiple factors determine the occurrence of streaking in peach orchards, including cultivar susceptibility, ripening stage, and the presence of rainwater with sufficient amounts of a yet unknown reactive agent or agent combination.

PDT with PPIX absorption peaks adjusted wavelengths: Safety and efficacy of a new irradiation procedure for actinic keratoses on the head.

BACKGROUND: Daylight photodynamic therapy (dl-PDT) is an effective and almost painless treatment for patients with actinic keratoses (AKs) but carries important limitations due to seasonal conditions. PDT with Protoporphyrin IX (PPIX) peaks adjusted wavelengths might overcome these shortcomings. The aim of this study was to determine safety and efficacy of ALA-PDT with a new irradiation procedure. METHODS: Patients with AKs on the head received ALA-PDT with a new irradiation device. Emitted wavelengths are adjusted to PPIX absorption peaks (457 nm, 523 nm, 593 nm, 631 nm; 20.000 lx). PDT protocol was adapted for both 1 h of incubation and irradiation time. Outcome was assessed by AK area and severity index (AKASI) and lesion count (LC) prior to and 3 months after treatment. Safety was monitored by blood pressure and pulse measurements throughout treatment. Pain was determined by use of a visual analog scale (VAS). RESULTS: Overall, 39 patients were included and showed a significant AKASI reduction (P < 0.0001) 3 months after PDT (mean AKASI of 2 ±â€¯1.6) compared to baseline (5.2 ±â€¯1.9). Mean reduction rate was 63.7% ±24.2%, accordingly. Eight patients (20.5%) achieved AKASI 100, eleven (28.2%) AKASI 75 and thirty (76.9%) AKASI 50, respectively. There were no significant changes in blood pressure and pulse throughout treatment. Median VAS for pain during irradiation was 0 (0-1), 1 (0-1) and 0 (0-1) at the beginning, in the meantime and at the end, respectively. CONCLUSIONS: ALA-PDT with a new irradiation procedure is a safe, effective and almost painless treatment option for patients with AKs on the head.

Low Drosha protein expression in cutaneous T-cell lymphoma is associated with worse disease outcome.

BACKGROUND: Dysregulation of microRNAs (miRNAs) key regulators may contribute to the pathogenesis of malignancies. miRNA machinery genes such Dicer and Drosha have been reported to be biomarkers in different cancer types. OBJECTIVES: We aimed to evaluate Drosha and Dicer protein expression in cutaneous T-cell lymphoma (CTCL). METHODS: We performed Drosha and Dicer immunohistochemistry in 45 patients with mycosis fungoides and subtypes. Drosha and Dicer expression scores were correlated with clinical parameters including disease-specific death (DSD), stage of disease and different laboratory data. Uni- and multivariate statistics were performed. RESULTS: On univariate analysis, elevated serum LDH and low Drosha expression were significantly associated with advanced stage (P = 0.032 and 0.0062, respectively) and lymphoma-specific death (LSD; P = 0.017 and P = 0.005, respectively). Moreover, elevated circulating CD4+/CD26- lymphocytes were significantly associated with advanced stage (P = 0.032) and DSD (P = 0.0098). On multivariate analysis, low Drosha expression remained in the logistic regression model as significant independent predictor for advanced disease stages [P = 0.013; odds ratio: 5 (confidence interval) CI 1.3-19.3]. Moreover, low Drosha expression (P = 0.026) and elevated LDH (P = 0.025) remained as significant independent predictors for DSD with odds ratios of 13.5 (CI 1.3-134.4 and 8.7 CI 1.3-57.2, respectively). CONCLUSIONS: Low Drosha expression is an independent predictor for advanced stage as well as LSD in CTCL patients indicating a tumour suppressor gene function of Drosha in this disorder.

Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma.

BACKGROUND: Mutations in kinetochore gene KNSTRN accelerate the development of cutaneous squamous cell carcinoma (SCC) and may correlate with different histological classifications of actinic keratosis (AKs). OBJECTIVE: To determine KNSTRN gene mutation frequency in healthy skin (HS), actinically damaged skin (ADS), in AKs with different histomorphological gradings and invasive SCCs. METHODS: All samples were histologically evaluated. AK lesions were additionally classified according to their upwards (AK I-III) and downwards (PRO I-III) directed growth pattern. Mutation analyses of all samples were performed using the Sanger method. RESULTS: With one exception, all detected mutations in KNSTRN gene showed an alanine-to-glutamate substitution at codon 40 (p.Ala40Glu). p.Ala40Glu mutation was found in 6.9% (2/29) of HS, in 16.1% (5/31) of ADS, in 18.3% (20/109) of AKs and in 30.0% (9/30) of invasive SCCs. Further stratification of AKs using the common AK classification of Röwert-Huber revealed the p.Ala40Glu mutation in 14.7% (5/43), 13.3% (4/30) and 24.4% (11/45) (AK I, II and III). In contrast, the new PRO classification showed a distribution of 3.6% (1/28) in PRO I, 21.7% (13/60) in PRO II and 28.6% (6/21) in PRO III. Mutation frequency in HS showed significant differences compared to AKs classified as PRO III and invasive SCCs (P < 0.05). In contrast, there were no statistically significant differences between HS and AKs when classified according to Röwert-Huber. CONCLUSIONS: Recurrent somatic mutation p.Ala40Glu in KNSTRN gene is associated with basal proliferating AKs in accordance with invasive SCCs. This supports the impact of basal proliferative pattern in terms of progression.

Evaluation of two histological classifications for actinic keratoses - PRO classification scored highest inter-rater reliability.

BACKGROUND: Actinic keratoses (AKs) can histologically be classified by the extent of atypical keratinocytes throughout the epidermis or their pattern of basal proliferation. Currently, no data on the inter-rater reliability of both scores is available. OBJECTIVE: To evaluate the inter-rater reliability of the two classification schemes; histological grade (AK I-III) and basal proliferation (PRO I-III). METHODS: Histological images of 54 AKs were classified by 21 independent dermatopathologists with regard to basal proliferation (PRO I-III), histological grade (AK I-III) and assumed risk of progression into invasive carcinoma. RESULTS: Overall, of the 54 AKs 16.7% (9/54) were classified as AK I, 66.7% (36/54) as AK II, and 16.7% (9/54) as AK III. With regards to basal growth pattern, 25.9% (14/54) were classified as PRO I, 42.6% (23/54) as PRO II, and 31.5% (17/54) as PRO III. We observed a highly significant inter-rater reliability for PRO-grading (P < 0.001) which was higher than for AK-grading (Kendall's W coefficient: AK = 0.488 vs. PRO = 0.793). We found substantial agreement for assumed progression risk for AKs with worsening basal proliferation (k = 0.759) compared to moderate agreement (k = 0.563) for different AK-gradings. CONCLUSIONS: Histological classification of basal growth pattern (PRO) showed higher inter-rater reliability compared to the established classification of atypical keratinocytes throughout epidermal layers. Moreover, experienced dermatopathologists considered basal proliferation to be more important in terms of progression risk than upwards directed growth patterns. It should be considered to classify AKs according to their basal proliferation pattern (PRO I-III).

[Violence in the emergency department of a maximum care hospital]. / Gewalt in der Notaufnahme eines Maximalversorgers.

INTRODUCTION: The emergency department of hospitals is known as a violent place, nevertheless the true incidence of violent acts in emergency departments in the German-speaking area has been little studied. The goal of this study was to record the occurrence of violence in a university hospital located in the inner city and to evaluate parameters, such as type of violence and accumulation in certain patient groups. MATERIAL AND METHODS: Cases of violence in the emergency department were documented by the personnel over the time frame of 1 year (March 2017 to February 2018) and retrospectively evaluated. RESULTS: An increase of violence during the evening hours (10.3% vs. 67.8%) could be shown. Intoxicated patients were responsible for the highest proportion of acts of violence. In addition, intoxicated patients were shown to be significantly more frequently aggressive than sober patients (63.72% vs. 31.65%). Non-intoxicated patients were as a rule only verbally aggressive. De-escalation by emergency room personnel was shown to be successful in 62.5% of the cases. In the rest of the cases help from outside, such as security personnel or the police was necessary, especially for intoxicated patients. DISCUSSION: Violence occurs with high regularity in emergency departments. The average incidence of acts of violence of every 0.7 days shows the need for safety precautions for hospital personnel.

Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses.

BACKGROUND: In addition to the extent of atypical keratinocytes throughout the epidermis, actinic keratoses (AKs) are histologically characterized by downward-directed basal-layer expansion. It is not known whether this growth pattern correlates with the risk of developing invasive squamous cell carcinoma (iSCC). OBJECTIVES: To characterize the prevalence of downward-directed basal-layer expansion of AKs adjacent to iSCC. METHODS: The epidermis overlying and adjacent to iSCCs was assessed histologically. We determined the histological grade (AK I-III), basal growth pattern (PRO I-III) and accompanying parameters such as adnexal involvement. RESULTS: Among 307 lesions, 52·4% of AKs were histologically classified as AK grade I, 38·1% as AK II and 6·8% as AK III (χ2 -test, P < 0·001). Only 2·6% of adjacent epidermal samples did not show any atypical keratinocytes. The epidermis adjacent to iSCCs was classified as having a PRO I basal growth pattern in 25·7%, PRO II in 31·9% and PROIII in 39·4% of cases. Only 2·9% of AKs showed no basal growth (χ2 -test, P < 0·001). In total 118 AKs (48·8%) showed extension into adnexal structures. These AKs were graded as PRO I in 18·6% of cases, PRO II in 30·5% and PRO III in 50·8%. The epidermis above iSCCs could be assessed only for upwards-directed growth and showed no significant differences in the three AK grades (P = 0·42). CONCLUSIONS: Basal proliferative AKs, as well as atypical keratinocytes restricted to the lower third of the epidermis, are most commonly seen adjacent to iSCC, with less evidence for full-thickness epidermal dysplasia. Our study supports the important role of dysplastic keratinocytes in the epidermal basal layer and their potential association with iSCC.

Lysyl oxidase-like-2 mutations and reduced mRNA and protein expression in mid-dermal elastolysis.

BACKGROUND: Mid-dermal elastolysis (MDE) is a rare skin condition, characterized by selective loss of elastic fibres in the mid dermis. The pathogenesis of MDE is still unclear. AIM: To investigate expression of lysyl oxidase-like 2 (LOXL2) in a reasonable sample of patients with MDE and to search for mutations in LOXL2. METHODS: We investigated archived lesional tissue of 13 patients with MDE and skin tissue samples of 10 sex- and age-matched healthy controls (HCs). Gene and protein expression of LOXL2 was investigated using real-time reverse-transcription PCR and immunohistochemistry. Mutation analysis was performed using the Sanger method. RESULTS: We observed decreased LOXL2 mRNA expression in lesional skin of patients with MDE (0.48 ± 0.16) compared with healthy skin of the same patients (1.5 ± 0.51) and normal skin of HCs (1.9 ± 0.13). Compared with healthy patient skin (epidermis 2.38 ± 1.6, dermis 1.2 ± 1), LOXL2 protein expression in lesional patient skin (epidermis 1.1 ± 0.7, dermis 0.3 ± 0.45) was significantly decreased (P < 0.04 and P = 0.02, respectively). Mutation analysis of the entire LOXL2 gene could be performed for five patients, all of whom were found to have at least one mutation in the LOXL2 gene. Three of these had a mutation in the promoter region (c.967 G>C, c.1022 C>T, and c.1025 G>A, respectively), and one of them also had a mutation in the splice region of intron 11/exon 12 (IVS11-1 G>A). Of the remaining two patients, one had a mutation in exon 3 (T1391), and the other had a mutation in exon 11 (C663Y). CONCLUSIONS: Our present data suggest that decreased elastin renewal due to LOXL2 mutations and consecutive reduced LOXL2 expression contribute to the pathogenesis of MDE.

Combination Doppler backscattering/cross-polarization scattering diagnostic for the C-2W field-reversed configuration.

A versatile combination Doppler backscattering and Cross-Polarization Scattering (CPS) diagnostic for the C-2W beam-driven field-reversed configuration is described. This system is capable of measuring density fluctuations and perpendicular magnetic field fluctuations across a wide wavenumber range (2.5 ≤ k θ ρ s ≤ 50), with typical resolution Δk θ/k θ ≤ 0.4-0.8. Four tunable frequencies (26 GHz ≤ f ≤ 60 GHz corresponding to plasma cut-off densities 0.8 × 1019 ≤ n e ≤ 4.4 × 1019 m-3) are launched via quasi-optical beam combiners/polarizers and an adjustable parabolic focusing mirror selecting the beam incidence angle. GENRAY ray tracing shows that the incident O-mode and backscattered CPS X-mode beam trajectories for C-2W plasma parameters nearly overlap, allowing simultaneous detection of ñ and B̃ r or B̃ θ from essentially the same scattering volume.

Jet outflow and open field line measurements on the C-2W advanced beam-driven field-reversed configuration plasma experiment.

Accurate operation and high performance of the open field line plasma surrounding the field reversed configuration is crucial to achieving the goals of successful temperature ramp up and confinement improvement on C-2W. Knowledge and control of the open field line plasma requires extensive diagnostic efforts. A suite of diagnostics, which consists of microwave interferometry, dispersive spectroscopy, and spatial heterodyne spectroscopy, is being developed to measure electron density, ion temperature, and particle outflow velocity at various locations along the open magnetic field lines. A detailed overview of these diagnostics is presented.