Ecological and social effects on reproduction and local recruitment in the red-backed shrike

Numerous hypotheses have been proposed to explain variation in reproductive performance and local recruitment of animals. While most studies have examined the influence of one or a few social and ecological factors on fitness traits, comprehensive analyses jointly testing the relative importance of each of many factors are rare. We investigated how a multitude of environmental and social conditions simultaneously affected reproductive performance and local recruitment of the red-backed shrike Lanius collurio (L.). Specifically, we tested hypotheses relating to timing of breeding, parental quality, nest predation, nest site selection, territory quality, intraspecific density and weather. Using model selection procedures, predictions of each hypothesis were first analysed separately, before a full model was constructed including variables selected in the single-hypothesis tests. From 1988 to 1992, 50% of 332 first clutches produced at least one fledgling, while 38.7% of 111 replacement clutches were successful. Timing of breeding, nest site selection, predation pressure, territory quality and intraspecific density influenced nest success in the single-hypothesis tests. The full model revealed that nest success was negatively associated with laying date, intraspecific density, and year, while nest success increased with nest concealment. Number of fledglings per successful nest was only influenced by nest concealment: better-camouflaged nests produced more fledglings. Probability of local recruitment was related to timing of breeding, parental quality and territory quality in the single-hypothesis tests. The full models confirmed the important role of territory quality for recruitment probability. Our results suggest that reproductive performance, and particularly nest success, of the red-backed shrike is primarily affected by timing of breeding, nest site selection, and intraspecific density. This study highlights the importance of considering many factors at the same time, when trying to evaluate their relative contributions to fitness and life history evolutio

Description of a clinical decision support tool with integrated dose calculator for paediatrics

Medication errors, especially dosing errors are a leading cause of preventable harm in paediatric patients. The paediatric patient population is particularly vulnerable to dosing errors due to immaturity of metabolising organs and developmental changes. Moreover, the lack of clinical trial data or suitable drug forms, and the need for weight-based dosing, does not simplify drug dosing in paediatric or neonatal patients. Consequently, paediatric pharmacotherapy often requires unlicensed and off-label use including manipulation of adult dosage forms. In practice, this results in the need to calculate individual dosages which in turn increases the likelihood of dosing errors. In the age of digitalisation, clinical decision support (CDS) tools can support healthcare professionals in their daily work. CDS tools are currently amongst the gold standards in reducing preventable errors. In this publication, we describe the development and core functionalities of the CDS tool PEDeDose, a Class IIa medical device software certified according to the European Medical Device Regulation. The CDS tool provides a drug dosing formulary with an integrated calculator to determine individual dosages for paediatric, neonatal, and preterm patients. Even a technical interface is part of the CDS tool to facilitate integration into primary systems. This enables the support of the paediatrician directly during the prescribing process without changing the user interface. Conclusion: PEDeDose is a state-of-the-art CDS tool for individualised paediatric drug dosing that includes a certified calculator

Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BK-beta-1-subunit leads to progressive hearing loss

The large conductance voltage- and Ca2+-activated potassium (BK) channel has been suggested to play an important role in the signal transduction process of cochlear inner hair cells. BK channels have been shown to be composed of the pore-forming alpha-subunit coexpressed with the auxiliary beta-1-subunit. Analyzing the hearing function and cochlear phenotype of BK channel alpha-(BKalpha–/–) and beta-1-subunit (BKbeta-1–/–) knockout mice, we demonstrate normal hearing function and cochlear structure of BKbeta-1–/– mice. During the first 4 postnatal weeks also, BKalpha–/– mice most surprisingly did not show any obvious hearing deficits. High-frequency hearing loss developed in BKalpha–/– mice only from ca. 8 weeks postnatally onward and was accompanied by a lack of distortion product otoacoustic emissions, suggesting outer hair cell (OHC) dysfunction. Hearing loss was linked to a loss of the KCNQ4 potassium channel in membranes of OHCs in the basal and midbasal cochlear turn, preceding hair cell degeneration and leading to a similar phenotype as elicited by pharmacologic blockade of KCNQ4 channels. Although the actual link between BK gene deletion, loss of KCNQ4 in OHCs, and OHC degeneration requires further investigation, data already suggest human BK-coding slo1 gene mutation as a susceptibility factor for progressive deafness, similar to KCNQ4 potassium channel mutations. © 2004, The National Academy of Sciences. Freely available online through the PNAS open access option

Toward Clinically Compatible Phase-Contrast Mammography

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom

Toward Clinically Compatible Phase-Contrast Mammography

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom

Planning target volume as a predictor of disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition

BACKGROUND The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). METHOD AND PATIENTS Prospective data of thirty-three consecutive patients with inoperable stage III NSCLC treated with CRT and sequential durvalumab (67%, 22 patients) or concurrent and sequential nivolumab (33%, 11 patients) were analyzed. Different PTV cut offs and PTV as a continuous variable were evaluated for their association with progression-free (PFS), local-regional progression-free (LRPFS), extracranial distant metastasis-free (eMFS) and brain-metastasis free-survival (BMFS). RESULTS All patients were treated with conventionally fractionated thoracic radiotherapy (TRT); 93% to a total dose of at least 60~Gy, 97% of patients received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 19.9 (range: 6.0-42.4) months; median overall survival (OS), LRFS, BMFS and eMFS were not reached. Median PFS was 22.8 (95% CI: 10.7-34.8) months. Patients with PTV ≥ 900ccm had a significantly shorter PFS (6.9 vs 22.8~months, p = 0.020) and eMFS (8.1~months vs. not reached, p = 0.003). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (UICC-TNM Classification 8th Edition) achieved a very poor outcome with a median PFS and eMFS of 3.6 vs 22.8~months (p < 0.001) and 3.6~months vs. not reached (p = 0.001), respectively. PTV as a continuous variable also had a significant impact on eMFS (p = 0.048). However, no significant association of different PTV cut-offs or PTV as a continuous variable with LRPFS and BMFS could be shown. The multivariate analysis that was performed for PTV ≥ 900ccm and age (≥ 65~years), gender (male), histology (non-ACC) as well as T- and N-stage (T4, N3) as covariates also revealed PTV ≥ 900ccm as the only factor that had a significant correlation with PFS (HR: 5.383 (95% CI:1.263-22.942, p = 0.023)). CONCLUSION In this prospective analysis of inoperable stage III NSCLC patients treated with definitive CRT combined with concurrent and/or sequential CPI, significantly shorter PFS and eMFS were observed in patients with initial PTV ≥ 900ccm