Actinic keratoses show variable histological basal growth patterns - a proposed classification adjustment

Background: Common histological classification schemes of actinic keratoses (AK) do not evaluate growth patterns at basal epidermal aspects of AK. Until now, the importance of basal epidermal growth patterns of AK has not been studied. Objective: To investigate the extent of atypical keratinocytes throughout the epidermis and variation in basal growth patterns of AK. Methods: AK lesions occurring on the head/face from patients seen in routine practice were assessed histologically. We determined histological grade (AK I-III), basal growth patterns of atypical keratinocytes (crowding, budding, papillary sprouting) and accompanying parameters. Results: Of the 246 lesions included, 28.0% were histologically classified as AK I, 46.7% as AK II, and 25.2% as AK III. 26.4% of the basal growth patterns were classified as crowding (pro I), 49.6% as budding (pro II), 17.9% as papillary sprouting (pro III) and 6.1% without basal directed growth. No significant correlation of the histological AK I-III grading and underlying growth patterns was observed (P= 0.4666). However, adnexal structure involvement (OR= 2.37; 95%CI 1.21-4.65), infiltration (OR= 2.53; 95%CI 1.31-4.90) and increased number of vessels (OR= 2.56; 95%CI 1.42-4.65) were independent positive predictive markers for pro II and pro III basal growth patterns. Conclusions: Basal growth patterns (pro I-III) in AK do not correlate with the established AK I-III histological grading system. Besides the degree of upward extension, varying degrees of downward extension exist. Histological classification should consider both, upwards and downward growth patterns when assessing AK

Prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection : a retrospective study

Objective: To assess the prevalence of prenatal screening and of adverse outcome in high-risk pregnancies due to maternal HIV infection. Study design: The prevalence of prenatal screening in 330 pregnancies of HIV-positive women attending the department for prenatal screening and/or during labour between January 1, 2002 and December 31, 2012, was recorded. Screening results were compared with the postnatal outcome and maternal morbidity, and mother-to-child transmission (MTCT) was evaluated. Results: One hundred of 330 women (30.5%) had an early anomaly scan, 252 (74.5%) had a detailed scan at 20–22 weeks, 18 (5.5%) had a detailed scan prior to birth, and three (0.9%) had an amniocentesis. In seven cases (2.12%), a fetal anomaly was detected prenatally and confirmed postnatally, while in eight (2.42%) an anomaly was only detected postnatally, even though a prenatal scan was performed. There were no anomalies in the unscreened group. MTCT occurred in three cases (0.9%) and seven fetal and neonatal deaths (2.1%) were reported. Conclusion: The overall prevalence of prenatal ultrasound screening in our cohort is 74.5%, but often the opportunity for prenatal ultrasonography in the first trimester is missed. In general, the aim should be to offer prenatal ultrasonography in the first trimester in all pregnancies. This allows early reassurance or if fetal disease is suspected, further steps can be taken

The complexity of the dark matter sheet

One of the most important open questions of modern physics is: What is dark matter? Astrophysical approaches to learn more about the nature of dark matter rely upon the numerical modelling of the dark matter fluid in cosmological simulations. In this thesis we develop new mathematical tools and numerical simulation techniques to understand and predict the evolution of the dark matter fluid and its phase space distribution. Dark matter has an unknown, but small primordial velocity dispersion. Therefore the dark matter fluid effectively occupies a three dimensional Lagrangian submanifold in the six dimensional phase space - also know as the dark matter sheet. This has many implications for fine-grained features in the density field, the formation of structures and numerical simulation possibilities. We develop new tools to identify and understand different largescale structures types (single-stream regions, pancakes, filaments and haloes) from a phase space perspective. Further, we develop an excursion set approach for single-stream regions which is used to answer the question “what is the median density of the universe?” and to investigate whether single-stream regions form a connected percolating complex or distinct isolated regions. Further we introduce a “sheet + release” simulation approach to make reliable cosmological warm dark matter simulations possible. This combines a sheet-based phase space interpolation scheme (Hahn & Angulo, 2016) which is used in low density regions (like single-stream regions, pancakes and filaments) with a combined N-body + geodesic deviation equation simulation approach in complex high-density regions (like haloes). Thereby this overcomes problems in pure sheet-schemes (which become untraceably complex inside haloes) and N-body simulations (which tend to fragment in low-density regions). Further, we introduce a novel scheme for calculating forces from an oct-tree of cubes, which makes it possible to use the sheet + release scheme at high force resolution. Thereby we present the first scheme which makes possible warm dark matter simulations that are reliable from low-density regions up to the very dense and complex centers of haloes – and this while following a lot of fine-grained phase space information. As a first test case we apply this simulation scheme in a “zoom-in” simulation of a small warm dark matter halo. The simulation shows no artificial structures and the radial density structure of the halo converges well. The density profile seems to be consistent with an NFW-profile and does not differ significantly from an N-body simulation (which shows artificial fragments in the density field). In a final part of this thesis we discuss the possibility of following warm and hot phase space distributions by reconstructing the phase space locally around cold sheets in phase space. This could allow to simulate warm dark matter while explicitly modelling the thermal smoothing due to the primordial velocity dispersion. Further, it might be used to simulate the cosmic neutrino background with a relatively small number of required resolution elements

The complexity of the dark matter sheet

One of the most important open questions of modern physics is: What is dark matter? Astrophysical approaches to learn more about the nature of dark matter rely upon the numerical modelling of the dark matter fluid in cosmological simulations. In this thesis we develop new mathematical tools and numerical simulation techniques to understand and predict the evolution of the dark matter fluid and its phase space distribution. Dark matter has an unknown, but small primordial velocity dispersion. Therefore the dark matter fluid effectively occupies a three dimensional Lagrangian submanifold in the six dimensional phase space - also know as the dark matter sheet. This has many implications for fine-grained features in the density field, the formation of structures and numerical simulation possibilities. We develop new tools to identify and understand different largescale structures types (single-stream regions, pancakes, filaments and haloes) from a phase space perspective. Further, we develop an excursion set approach for single-stream regions which is used to answer the question “what is the median density of the universe?” and to investigate whether single-stream regions form a connected percolating complex or distinct isolated regions. Further we introduce a “sheet + release” simulation approach to make reliable cosmological warm dark matter simulations possible. This combines a sheet-based phase space interpolation scheme (Hahn & Angulo, 2016) which is used in low density regions (like single-stream regions, pancakes and filaments) with a combined N-body + geodesic deviation equation simulation approach in complex high-density regions (like haloes). Thereby this overcomes problems in pure sheet-schemes (which become untraceably complex inside haloes) and N-body simulations (which tend to fragment in low-density regions). Further, we introduce a novel scheme for calculating forces from an oct-tree of cubes, which makes it possible to use the sheet + release scheme at high force resolution. Thereby we present the first scheme which makes possible warm dark matter simulations that are reliable from low-density regions up to the very dense and complex centers of haloes – and this while following a lot of fine-grained phase space information. As a first test case we apply this simulation scheme in a “zoom-in” simulation of a small warm dark matter halo. The simulation shows no artificial structures and the radial density structure of the halo converges well. The density profile seems to be consistent with an NFW-profile and does not differ significantly from an N-body simulation (which shows artificial fragments in the density field). In a final part of this thesis we discuss the possibility of following warm and hot phase space distributions by reconstructing the phase space locally around cold sheets in phase space. This could allow to simulate warm dark matter while explicitly modelling the thermal smoothing due to the primordial velocity dispersion. Further, it might be used to simulate the cosmic neutrino background with a relatively small number of required resolution elements

Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma

Background: Actinic keratoses (AKs) are commonly diagnosed clinically. Actinic keratosis area and severity index (AKASI) is a new easy-to-use tool to assess the severity of AK on the head. Objective: To determine the association between chronically UV-induced tumours such as basal cell carcinomas (BCC) or squamous cell carcinomas (SCC) and AKASI. Methods: We performed a retrospective analysis of patients who had undergone oncological surgery due to UV-induced tumours and who were assessed for AKASI and Physician's Global Assessment (PGA) prior to surgery. Statistical analysis was performed to evaluate correlation between AKASI, PGA and invasive carcinomas. Results: Of the 210 patients included, 26 patients had histologically diagnosed SCCs and presented with a median (range) AKASI of 6.9 (0 – 13.0) and PGA of 2 (0 - 4). In contrast, the 82 patients with BCCs showed a median (range) AKASI of 3.3 (0 -15.2) and PGA of 1 (0 - 4). The Mann-Whitney U test showed significant differences (p= 0.0018) between AKASI of patients with SCC and BCC. In addition, we found a significantly higher AKASI in patients with SCC compared to patients with non-invasive lesions like AK and Bowen disease (BD) (p= 0.0275). Spearman's coefficient of rank correlation between AKASI and PGA indicates that these measures of AK severity were strongly correlated (p< 0.0001; r = 0.90; 95%CI 0,865 to 0,920). Conclusions: Patients with SCC show significantly higher AKASI than patients with BCC or patients without invasive tumours. Hence, AKASI may be used to stratify risk for developing invasive SCC

Collection of Human Genomic DNA From Buccal Cells for Genetics Studies: Comparison Between Cytobrush, Mouthwash, and Treated Card

Alternative sources such as buccal cells have already been tested for genetic studies and epidemiological investigations. Thirty-seven volunteers participated in this study to compare cytology brushes, mouthwash, and treated cards for DNA collection. Quantity and quality of DNA and cost and feasibility were assessed. The mean DNA yield at 260 nm was found to be 3.5, 4, and 2.6 μg for cytobrushes, mouthwashes, and treated cards, respectively. A second quantification technique by fluorescence showed differences in the DNA yield with 1.1 and 5.2 μg for cytobrushes and mouthwash, respectively. All buccal samples allowed isolation of DNA suitable for polymerase chain reaction. According to the procedure of sample collection, the yield and purity of collected DNA, and storage conditions, the use of cytobrush appears to be the more appropriate method for DNA collection. This protocol has been validated and is currently applied in three large-scale multicentric studies including adults or children

The effect of stellar encounters on the dark matter annihilation signal from prompt cusps

Prompt cusps are the densest quasi-equilibrium dark matter objects; one forms at the instant of collapse within every isolated peak of the initial cosmological density field. They have power-law density profiles, $\rho \propto r^{-1.5}$ with central phase-space density set by the primordial velocity dispersion of the dark matter. At late times they account for $\sim 1\%$ of the dark matter mass but for $>90\%$ of its annihilation luminosity in all but the densest regions, where they are tidally disrupted. Here we demonstrate that individual stellar encounters, rather than the mean galactic tide, are the dominant disruptors of prompt cusps within galaxies. Their cumulative effect is fully (though stochastically) characterised by an impulsive shock strength $B_* = 2\pi G\int\rho_*({\bf x}(t))\, \mathrm{d}t$ where $\rho_*$, the total mass density in stars, is integrated over a cusp's entire post-formation trajectory. Stellar encounters and mean tides have only a small effect on the halo annihilation luminosity seen by distant observers, but this is not true for the Galactic halo because of the Sun's position. For a 100 GeV WIMP, Earth-mass prompt cusps are predicted, and stellar encounters suppress their mean annihilation luminosity by a factor of two already at 20 kpc, so that their annihilation emission is predicted to appear almost uniform over the sky. The Galactic Center $\gamma$-ray Excess is thus unaffected by cusps. If it is indeed dark matter annihilation radiation, then prompt cusps in the outer Galactic halo and beyond must account for 20-80% of the observed isotropic $\gamma$-ray background in the 1 to 10 GeV range.Comment: 22 pages, 23 figures, for a video and code see https://github.com/jstuecker/cusp-encounter

Primary merkel cell carcinoma clinically presenting as deep oedematous mass of the groin

Merkel cell carcinoma (MCC) is a relatively rare, polyomavirus associated, primary neuroendocrine carcinoma of the skin which is usually arising from dermal skin layers. However, the origin of MCC in the subcutaneous tissue is debatable. We report a 58-yearold female patient with an oedematous mass on her left groin that was firm in consistency and had no discoloration or other visible abnormality of the overlying skin. On histology and immunohistology the tumour was consistent with the diagnosis of MCC showing a predominant subcutanous growth pattern. Pelvic magnetic resonance tomography revealed a tumour conglomerate reaching from the subcutis of the left groin to the left paraaortal and parailiacal region indicating widespread lymphogenic metastisation. Despite complete medical work-up no other MCC primary could be detected. In conclusion, predominant subcutaneous growth pattern as well as tumour localization in the groin are uncommon features of MCC. MCC showing the aforementioned features may be associated with significant delay of diagnosis and therefore represents an unfavourable prognostic factor