Deriving probabilistic short-range forecasts from a deterministic high-resolution model

In order to take full advantage of short-range forecasts from deterministic high-resolution NWP models, the direct model output must be addressed in a probabilistic framework. A promising approach is mesoscale ensemble prediction. However, its operational use is still hampered by conceptual deficiencies and large computational costs. This study tackles two relevant issues: (1) the representation of model-related forecast uncertainty in mesoscale ensemble prediction systems and (2) the development of post-processing procedures that retrieve additional probabilistic information from a single model simulation. Special emphasis is laid on mesoscale forecast uncertainty of summer precipitation and 2m-temperature in Europe. Source of forecast guidance is the deterministic high-resolution model Lokal-Modell (LM) of the German Weather Service. This study gains more insight into the effect and usefulness of stochastic parametrisation schemes in the representation of short-range forecast uncertainty. A stochastic parametrisation scheme is implemented into the LM in an attempt to simulate the stochastic effect of sub-grid scale processes. Experimental ensembles show that the scheme has a substantial effect on the forecast of precipitation amount. However, objective verification reveals that the ensemble does not attain better forecast goodness than a single LM simulation. Urgent issues for future research are identified. In the context of statistical post-processing, two schemes are designed: the neighbourhood method and wavelet smoothing. Both approaches fall under the framework of estimating a large array of statistical parameters on the basis of a single realisation on each parameter. The neighbourhood method is based on the notion of spatio-temporal ergodicity including explicit corrections for enhanced predictability from topographic forcing. The neighbourhood method derives estimates of quantiles, exceedance probabilities and expected values at each grid point of the LM. If the post-processed precipitation forecast is formulated in terms of probabilities or quantiles, it attains clear superiority in comparison to the raw model output. Wavelet smoothing originates from the field of image denoising and includes concepts of multiresolution analysis and non-parametric regression. In this study, the method is used to produce estimates of the expected value, but it may be easily extended to the additional estimation of exceedance probabilities. Wavelet smoothing is not only computationally more efficient than the neighbourhood method, but automatically adapts the amount of spatial smoothing to local properties of the underlying data. The method apparently detects deterministically predictable temperature patterns on the basis of statistical guidance only

Detailed expression profile of the six Glypicans and their modifying enzyme, Notum during chick limb and feather development

The development of vertebrate appendages, especially the limb and feather buds are orchestrated by numerous secreted signalling molecules including Sonic Hedgehog, Bone Morphogenetic Proteins, Fibroblast Growth Factors and Wnts. These proteins coordinate the growth and patterning of ectodermal and mesenchymal cells. The influence of signalling molecules is affected over large distances by their concentration (morphogen activity) but also at local levels by the presence of proteins that either attenuate or promote their activity. Glypicans are cell surface molecules that regulate the activity of the major secreted signalling molecules expressed in the limb and feather bud. Here we investigated the expression of all Glypicans during chick limb and feather development. In addition we profiled the expression of Notum, an enzyme that regulates Glypican activity. We show that five of the six Glypicans and Notum are expressed in a dynamic manner during the development of limbs and feathers. We also investigated the expression of key Glypicans and show that they are controlled by signalling molecules highlighting the presence of feedback loops. Lastly we show that Glypicans and Notum are expressed in a tissue specific manner in adult chicken tissues. Our results strongly suggest that the Glypicans and Notum have many as yet undiscovered roles to play during the development of vertebrate appendage

Generation of scenarios from calibrated ensemble forecasts with a dual ensemble copula coupling approach

Probabilistic forecasts in the form of ensemble of scenarios are required for complex decision making processes. Ensemble forecasting systems provide such products but the spatio-temporal structures of the forecast uncertainty is lost when statistical calibration of the ensemble forecasts is applied for each lead time and location independently. Non-parametric approaches allow the reconstruction of spatio-temporal joint probability distributions at a low computational cost. For example, the ensemble copula coupling (ECC) method rebuilds the multivariate aspect of the forecast from the original ensemble forecasts. Based on the assumption of error stationarity, parametric methods aim to fully describe the forecast dependence structures. In this study, the concept of ECC is combined with past data statistics in order to account for the autocorrelation of the forecast error. The new approach, called d-ECC, is applied to wind forecasts from the high resolution ensemble system COSMO-DE-EPS run operationally at the German weather service. Scenarios generated by ECC and d-ECC are compared and assessed in the form of time series by means of multivariate verification tools and in a product oriented framework. Verification results over a 3 month period show that the innovative method d-ECC outperforms or performs as well as ECC in all investigated aspects

Detailed expression profile of all six Glypicans and their modifying enzyme Notum during chick embryogenesis and their role in dorsal-ventral patterning of the neural tube

Vertebrate development is orchestrated by secreted signalling molecules that regulate cell behaviour and cell fate decisions during early embryogenesis. The activity of key signalling molecules including members of Hedgehog, Bone Morphogenetic Proteins and Wnt families are regulated by Glypicans, a family of GPI linked polypeptides. Glypicans either promote or inhibit the action of signalling molecules and add a layer of complexity that needs to be understood in order to fully decipher the processes that regulate early vertebrate development. Here we pres-ent a detailed expression profile of all six Glypicans and their modifying enzyme Notum during chick embryogen-esis. Our results strongly suggest that these proteins have many as yet undiscovered roles to play during early embryogenesis. Finally, we have taken an experimental approach to investigate their role during the patterning of a key embryonic structure - the neural tube. In particular, we show that over-expression of Notum leads to the dorsalisation of this structure

Progestogens for endometrial protection in combined menopausal hormone therapy: A systematic review.

Menopausal women with an intact uterus choosing estrogens for menopausal symptom relief require a progestogen for endometrial protection. The aim of this systematic review was to evaluate the risks of endometrial hyperplasia resp. malignancy with different progestogens used in combined MHT. Overall, 84 RCTs were included. We found that 1) most studies were done with NETA, followed by MPA, MP and DYD and LNG, 2) most progestogens were only available as oral formulations, 3) the most frequently studied progestogens (oral MP, DYD, MPA, oral and transdermal NETA, transdermal LNG) were assessed in continuously as well as in sequentially combined MHT regimens, 4) FDA endometrial safety criteria were only fulfilled for some progestogen formulations, 5) most studies demonstrated endometrial protection for the progestogen dose and time period examined. However, 6) study quality varied which should be taken into account, when choosing a combined MHT, especially if off-label-use is chosen

Factors Associated with Increased Analgesic Use in German Women with Endometriosis during the COVID-19 Pandemic

(1) Background: Endometriosis is a frequent chronic pain condition in women of fertile age. Pain management with analgesics is frequently used by women with endometriosis. During the COVID-19 pandemic, access to health services was temporarily restricted in various countries for persons without serious conditions, resulting in increased physical and mental health issues. The present study was conducted in order to assess the risk factors predicting increased analgesic intake by women with endometriosis during the COVID-19 pandemic. (2) Methods: The increased intake of over-the-counter (OTC) and prescription-only (PO) analgesics was assessed with an anonymous online questionnaire, along with demographic, pandemic-specific, disease-specific, and mental health characteristics. Anxiety and depression were assessed with the Generalized Anxiety Disorder Scale (GAD-2) and the Patient Health Questionnaire for Depression (PHQ-2), respectively. Pain-induced disability was assessed with the pain-induced disability index (PDI). (3) Results: A high educational level (OR 2.719; 95% CI 1.137–6.501; p = 0.025) and being at higher risk for depressive disorders, as measured by PHQ-2 ≥ 3 (OR 2.398; 95% CI 1.055–5.450; p = 0.037), were independent risk factors for an increased intake of OTC analgesics. Current global pain-induced disability (OR 1.030; 95% CI 1.007–1.054; p = 0.010) was identified as a risk factor for an increased intake of PO pain medication. The degree of reduction in social support and in social networks were independent predictors of an increased intake of PO analgesics in a univariate logistic regression analysis, but lost significance when adjusted for additional possible influencing factors. (4) Conclusions: In this population, an increased intake of OTC analgesics was related to a higher educational level and having a depressive disorder, while a higher pain-induced disability was an independent risk factor for an increased intake of PO analgesics. Pandemic-specific factors did not significantly and independently influence an increased intake of analgesics in women with endometriosis during the first wave of the COVID19 pandemic in Germany. Healthcare providers should be aware of the possible factors related to increased analgesic use in women with endometriosis in order to identify persons at risk for the misuse of pain medication and to prevent potential adverse effects

Determinants of Pain-Induced Disability in German Women with Endometriosis during the COVID-19 Pandemic

(1) Background: The main aim of this research was to examine the factors leading to pain induced disability by assessing the impact of demographic, endometriosis-specific, pandemic-specific, and mental health factors. (2) Methods: Women with endometriosis who attended online support groups were invited to respond to an online survey during the first wave of the COVID-19 pandemic in Germany. The Pain Disability Index (PDI) was employed to assess disability-related daily functioning. Independent predictors of pain-induced disability were determined using univariate and multivariate logistic regression analyses. (3) Results: The mean PDI score of the study population was 31.61 (SD = 15.82), which was significantly higher (p < 0.001) than that reported in a previously published normative study of the German population. In the present study, a high level of pain-induced disability, as defined by scores equal to or higher than the median of the study population, older age (OR 1.063, 95% CI 1.010–1.120, p = 0.020), dysmenorrhea (OR 1.015, 95% CI 1.005–1.026, p = 0.005), dysuria (OR 1.014; 95% CI 1.001–1.027, p = 0.029), lower back pain (OR 1.018, 95% CI 1.007–1.029, p = 0.001), and impaired mental health (OR 1.271, 95% CI 1.134–1.425, p < 0.001) were found to be independent risk factors. Pandemic-specific factors did not significantly influence the pain-induced disability of the participants in this study. (4) Conclusions: The level of pain-induced disability was significantly higher among the women with endometriosis than among women in the normative German validation study. Our findings identified risk factors for experiencing a high level of pain induced disability, such as demographic and specific pain characteristics. Pandemic-specific factors did not significantly and independently influence the pain-induced disability during the first wave of the COVID-19 pandemic in Germany. Impaired mental health negatively influenced functioning during daily activities. Thus, women with endometriosis should be managed by a multidisciplinary team of healthcare professionals to prevent negative effects of pain-induced disability on their quality of life

Optimization of transcription factor binding map accuracy utilizing knockout-mouse models

Genome-wide assessment of protein-DNA interaction by chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) is a key technology for studying transcription factor (TF) localization and regulation of gene expression. Signal-to-noise-ratio and signal specificity in ChIP-seq studies depend on many variables, including antibody affinity and specificity. Thus far, efforts to improve antibody reagents for ChIP-seq experiments have focused mainly on generating higher quality antibodies. Here we introduce KOIN (knockout implemented normalization) as a novel strategy to increase signal specificity and reduce noise by using TF knockout mice as a critical control for ChIP-seq data experiments. Additionally, KOIN can identify \u27hyper ChIPable regions\u27 as another source of false-positive signals. As the use of the KOIN algorithm reduces false-positive results and thereby prevents misinterpretation of ChIP-seq data, it should be considered as the gold standard for future ChIP-seq analyses, particularly when developing ChIP-assays with novel antibody reagents

Alternative elektronische Tierkennzeichnung

Das neue Tieridentifikationssystem Agro SAW IDENT wurde gemeinsam mit Industriepartnern entwickelt. Den Kern bilden piezoelektrische Kristalle mit aufgedampften Metallstrukturen, die den internationalen Tiercode darstellen. Zum Auslesen des Tiercodes werden akustische Oberflächenwellen (Surface Acoustic Wave = SAW) ohne jegliche Energiequelle genutzt. Die SAW-Codierung und der Charakter der Funkübertragung im Mikrowellenbereich um 2,4 GHz unterscheiden sich grundlegend von der üblichen Tieridentifikation im Niederfrequenzbereich bei 134 kHz. Die Vorteile der passiven SAW-Identifikation liegen in der höheren Lesereichweite bis zu 10 m und der sehr kurzen Identifikationsdauer unter 10 ms bei hoher Erkennungssicherheit. In vier Betrieben wurde an 1.652 Milchkühen die Funktionssicherheit untersucht