200 Jahre sächsischer Orgelbau Jehmlich - Aus der Geschichte des ältesten Orgelbaubetriebs in Deutschland

Vielleicht ist es kein Zufall, dass gleich zwei Orgelbauer der Firma Jehnlich mit Bibliothekarinnen der SLUB Dresden verheiratet sind. Wer Orgeln baut und alte Orgeln restauriert, muss sich in der Geschichte des Instrumentenbaus gut auskennen – oder wissen, wie man schnell an Informationen kommt

Felix Draeseke zum 100. Todestag: Vom jugendlichen Wagner-Verehrer zum Urheber des „Christus“

Ein anderes Jubiläum lenkt die Aufmerksamkeit auf einen Komponisten, der Richard Wagner verehrte und als ausgebildeter Musiker in den besten Jahren nach Dresden zog, um dort für 37 Jahre bis zum seinem Lebensende erfolgreich zu wirken. Die Sächsische Landesbibliothek – Staats- und Universitätsbibliothek Dresen (SLUB) führt in ihren Beständen nicht nur Wissen; sie verfügt auch über ein ausgezeichnetes Gedächtnis. Seit 1953 erinnert der Nachlass Felix Draesekes in der SLUB an den spätromantischen Komponisten, Musikpädagogen und Musikschriftsteller, der sonst wohl völlig zu Unrecht in Vergessenheit geraten wäre

Efficacy of Revefenacin in treatment of moderate-to-very-severe Chronic Obstructive Pulmonary Disease: a systematic review and meta-analysis

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a major global health issue responsible for 5% of global deaths each year, and novel treatments are at a premium. Long acting-muscarinic antagonists are a standard treatment for COPD, and the recent approval of Revefenacin, a novel, once-daily, nebulized LAMA, prompts a need for a systematic review and meta-analysis of results. OBJECTIVES: To assess the efficacy of Revefenacin, a novel, once-daily, nebulized LAMA in the treatment of moderate to very severe COPD. DATA SOURCES: MEDLINE (OVID), EMBASE, and CINAHL databases, as well as grey literature sources Clinicaltrials.gov and the International Clinical Trials Registry Portal. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: No age, geographical, contextual or other restrictions were imposed on populations. All human subjects diagnosed with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) were eligible. Intervention: a novel bronchodilator (Revefenacin). Comparator: Placebo. Outcomes: the efficacy of Revefenacin, measured as the endpoint change in trough FEV1 from baseline. Study design: Randomised Controlled Trials (RCTs). Only studies written in English were considered. STUDY APPRAISAL AND SYNTHESIS METHODS: 1571 records were initially screened, with 27 being eligible for full text review. Eventually, 12 articles for 7 trials were included. A random-effects meta-analysis was conducted with the primary outcome of difference in means for change in trough FEV1 from baseline to study endpoint. RESULTS: 1472 patients were analysed, and the overall difference in means was an increase of 119.073 mL in change in trough FEV1 from baseline to study endpoint for the Revefenacin group compared to the placebo. This result was statistically significant, with a 95% confidence interval of 102.254 mL to 135.893 mL. LIMITATIONS: Limitations of the study include possible risk of publication bias and placebo as the only comparator, relatively few trials (7), and a low generalizability of findings due to the specific nature of RCT populations excluding multi-morbid, and other complicated patients. CONCLUSIONS: Revefenacin is an efficacious intervention when compared to placebo in the treatment of moderate to very severe COPD. Further research is needed in order to assess its efficacy compared to current standard of care, through RCTs or network meta-analysis. What is known: - Existing COPD treatments aim to relief symptoms and improve quality of life. - Revefenacin a novel bronchodilator, was approved in 2018 by the US FDA. - Mong-acting muscarinic antagonists are often used in the management of COPD symptoms. What this study adds: - Revefenacin is a novel drug and no systematic review has been conducted on its efficacy. - The meta-analysis utilised a novel method which accounts for the unit-of-analysis error, when comparing multi- arms studies to a single placebo group (technique of exact adjustment

Laboratory tests with Lepidoptera to assess non-target effects of Bt maize pollen: analysis of current studies and recommendations for a standardised design

Background and approach Common standards for laboratory studies of non-target organisms are recognised as prerequisite to assist the risk assessments regarding the evaluation of environmental effects of transgenic crops. Here, we provide specific recommendations significant for experimental procedures of laboratory studies to test potential adverse effects of Bt maize on larvae of non-target Lepidoptera. We searched and analysed both ecotoxicological test protocols for pesticides in the EU as well as the non-target tests with Lepidoptera applied in unpublished industry studies submitted officially by agro-companies for the GMO authorisation in Europe. Results The classical ecotoxicology protocols applied for testing pesticides could serve as general guidelines, but do not completely fit the specific and differing requirements for assessing non-target effects of transgenic crops. The analysis of the non-target studies submitted for the application of the cultivation of Bt maize in Europe revealed critical limitations, thus corroborating the urgent need for common quality criteria. Based on our evaluations, we identified several issues requiring harmonisation or standardisation of the experimental conditions and approach, e.g., the application of Bt maize pollen, synthetic toxins, the provided diet for larvae, experimental controls, magnitude and duration of exposure to Bt, relevant variables to be recorded, and sufficient statistical power. Conclusions Our recommendations should stimulate the development of precise guidance for the authorities, and support the operationalisation of the required laboratory tests for the evaluation of non-target effects of Bt maize pollen on non-target Lepidoptera, also contributing to standards of other ecotoxicity tests with Lepidoptera larvae, e.g., for pesticides.This article has been prepared as an outcome of the BfN research project “Basisdaten zur Effektbewertung verschiedener Bt-Toxine auf Schmetterlingslarven” (FKZ 3515890100)

Predicting melatonin suppression by light in humans:Unifying photoreceptor-based equivalent daylight illuminances, spectral composition, timing and duration of light exposure

Light‐induced melatonin suppression data from 29 peer‐reviewed publications was analysed by means of a machine‐learning approach to establish which light exposure characteristics (ie photopic illuminance, five α‐opic equivalent daylight illuminances [EDIs], duration and timing of the light exposure, and the dichotomous variables pharmacological pupil dilation and narrowband light source) are the main determinants of melatonin suppression. Melatonin suppression in the data set was dominated by four light exposure characteristics: (1) melanopic EDI, (2) light exposure duration, (3) pupil dilation and (4) S‐cone‐opic EDI. A logistic model was used to evaluate the influence of each of these parameters on the melatonin suppression response. The final logistic model was only based on the first three parameters, since melanopic EDI was the best single (photoreceptor) predictor that was only outperformed by S‐cone‐opic EDI for (photopic) illuminances below 21 lux. This confirms and extends findings on the importance of the metric melanopic EDI for predicting biological effects of light in integrative (human‐centric) lighting applications. The model provides initial and general guidance to lighting practitioners on how to combine spectrum, duration and amount of light exposure when controlling non‐visual responses to light, especially melatonin suppression. The model is a starting tool for developing hypotheses on photoreceptors’ contributions to light's non‐visual responses and helps identifying areas where more data are needed, like on the S‐cone contribution at low illuminances

ATR maintains chromosomal integrity during postnatal cerebellar neurogenesis and is required for medulloblastoma formation

Microcephaly and medulloblastoma may both result from mutations that compromise genomic stability. We report that ATR, which is mutated in the microcephalic disorder Seckel syndrome, sustains cerebellar growth by maintaining chromosomal integrity during postnatal neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis and cerebellar hypoplasia in mice. Co-deletions of either p53 or Bax and Bak prevented apoptosis in Atr-deleted CGNPs, but failed to fully rescue cerebellar growth. ATR-deficient CGNPs had impaired cell cycle checkpoint function and continued to proliferate, accumulating chromosomal abnormalities. RNA-Seq demonstrated that the transcriptional response to ATR-deficient proliferation was highly p53 dependent and markedly attenuated by p53 co-deletion. Acute ATR inhibition in vivo by nanoparticle-formulated VE-822 reproduced the developmental disruptions seen with Atr deletion. Genetic deletion of Atr blocked tumorigenesis in medulloblastoma-prone SmoM2 mice. Our data show that p53-driven apoptosis and cell cycle arrest – and, in the absence of p53, non-apoptotic cell death – redundantly limit growth in ATR-deficient progenitors. These mechanisms may be exploited for treatment of CGNP-derived medulloblastoma using ATR inhibition

Does universal newborn hearing screening impact the timing of deafness treatment?

Objective To evaluate the impact of the Universal Neonatal Hearing Screening (UNHS) on the age at diagnosis, beginning of treatment, and first cochlear implant surgery. Methods A retrospective cohort study with children up to 12 years old with bilateral hearing loss were divided into two groups: patients who underwent UNHS and the ones who didn't. The groups were compared according to their age at the beginning of the evaluation at a specialized center, at the beginning of the intervention, and, for the ones who had indication, at the cochlear implant surgery. The group who underwent UNHS was divided between the ones who passed the screening test and the ones who didn't. They were compared according to their ages at the same moments as the first two groups. Results 135 patients were included. The median age at the first appointment in a specialized center was 1.42 (0.50 and 2.50) years, at the beginning of treatment 2.00 (1.00 and 3.52) years, and the cochlear implant surgery 2.83 (1.83 and 4.66) years. Children who underwent UNHS were younger than those who didn't, at the three evaluated moments (p < 0.001). In a subanalysis, children who passed the UNHS but were later diagnosed with hearing loss reached the first appointment with a specialist and started treatment older than those who failed the tests. Conclusion Performing UNHS interfered with the timing of deafness diagnosis and treatment. However, children who passed the screening but were later diagnosed with hearing loss were the category with the most important delay

Ferramentas da web 2.0 como elemento de flexibilização do ensino e aprendizagem de química

Os avanços tecnológicos vem modificando as relações dos indivíduos e oacesso a informação, nesse sentido, o ensino mediado por tecnologias tem despertado o interesse de muitos pesquisadores. Assim, o presente trabalho relata a experiência do uso das tecnologias como elemento de mediação e flexibilização do aprendizado de química. O estudo foi realizado com 66 alunos ingressantes do Curso de Agronomia de uma instituição pública. Como ambiente de mediação virtual para expansão da sala de aula foi escolhido o Facebook, visto que todos os estudantes possuíam perfil na rede social. Semanalmente eram postados recursos educacionais que fomentassem a construção do conhecimento. Os resultados obtidos confirmam que o uso das ferramentas da Web 2.0 contribuem para o ensino-aprendizagem, desde que problematizadas e utilizadas como elemento de mediação do processo. Os estudantes corroboram a ideia dos pesquisadores indicando a importância da tecnologias para a construção de saberes

Isolated Cervical Dystonia: Diagnosis and Classification

This document presents a consensus on the diagnosis and classification of isolated cervical dystonia (iCD) with a review of proposed terminology. The International Parkinson and Movement Disorder Society Dystonia Study Group convened a panel of experts to review the main clinical and diagnostic issues related to iCD and to arrive at a consensus on diagnostic criteria and classification. These criteria are intended for use in clinical research, but also may be used to guide clinical practice. The benchmark is expert clinical observation and evaluation. The criteria aim to systematize the use of terminology as well as the diagnostic process, to make it reproducible across centers and applicable by expert and non-expert clinicians. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations, which are incorporated into the current criteria. Three iCD presentations are described in some detail: idiopathic (focal or segmental) iCD, genetic iCD, and acquired iCD. The relationship between iCD and isolated head tremor is also reviewed. Recognition of idiopathic iCD has two levels of certainty, definite or probable, supported by specific diagnostic criteria. Although a probable diagnosis is appropriate for clinical practice, a higher diagnostic level may be required for specific research studies. The consensus retains elements proven valuable in previous criteria and omits aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of iCD expands, these criteria will need continuous revision to accommodate new advances. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society