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Background: For prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany.
Methods/design: This German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3–5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients.
Discussion: The HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials.
Study status: The study is ongoing and currently recruiting patients.
Trial registration: Registration number: NCT02635256 (clinicaltrials.gov). Registered 8 December 2015
Sample-based longitudinal discrete choice experiments: preferences for electric vehicles over time
(2021)
Discrete choice experiments have emerged as the state-of-the-art method for measuring preferences, but they are mostly used in cross-sectional studies. In seeking to make them applicable for longitudinal studies, our study addresses two common challenges: working with different respondents and handling altering attributes. We propose a sample-based longitudinal discrete choice experiment in combination with a covariate-extended hierarchical Bayes logit estimator that allows one to test the statistical significance of changes. We showcase this method’s use in studies about preferences for electric vehicles over six years and empirically observe that preferences develop in an unpredictable, non-monotonous way. We also find that inspecting only the absolute differences in preferences between samples may result in misleading inferences. Moreover, surveying a new sample produced similar results as asking the same sample of respondents over time. Finally, we experimentally test how adding or removing an attribute affects preferences for the other attributes.
Device-to-device (D2D) communication is an innovative solution for improving wireless network performance to efficiently handle the ever-increasing mobile data traffic. Communication takes place directly between two devices that are in each other’s transmission range. So far, research has focused on the technical challenges of implementing this technology and assumes a user’s general willingness to participate as forwarder in this technology. However, this simplifying assumption is not realistic, as willingness to participate in D2D communication can vary depending on the user. In this work, we consider the scenario that a user can act as a forwarder for a receiver who is not directly or insufficiently reached by the base station and accordingly has no or poor Internet connection. We take a user-centric approach and investigate the willingness to provide an Internet connection as a forwarder. We are the first to investigate user preferences for D2D communication using a choice-based conjoint analysis. Our results, based on a representative sample of potential users (N=181), show that the social relationship between the potential forwarder and the receiver has the greatest impact on the potential forwarder’s decision to provide an Internet connection to the receiver, accepting sacrifices in terms of additional battery consumption and reduced own service performance. In a detailed segment analysis, we observe significant preference differences depending on smartphone usage behavior and user age. Taking the corresponding preferences into account when matching forwarders and receivers can further increase technology adoption.
The firefly species described by Carl Linnaeus in 1758 and 1767 (Coleoptera: Lampyridae) were checked to determine the actual dates of publication. Nine out of twelve species were originally described in 1758 and not in 1767 as published in the majority of firefly literature. Lampyris hespera Linnaeus, 1767 as a junior synonym of Aspisoma lampyris (Linnaeus, 1758) is established.
ZooBank registration. urn:lsid:zoobank.org:pub:C04B88B3-DDBF-4878-B43E-71642AFC8AAA
We propose several nomenclatural changes for taxa in the lampyrid subfamilies Ototretinae, Photurinae, and Psilocladinae (Coleoptera: Lampyridae). Evidence for the correct year of description of Drilaster albicornis lateobscura (Pic, 1921) is presented. Spellings are corrected for Drilaster debilis holzi (Pic, 1914), Drilaster impustulata fukienensis (Pic, 1955), Drilaster moutoni (Pic, 1911), Drilaster pendleburyi (Pic, 1943) and Pyrogaster lunifera (Eschscholtz, 1822). We also explain the validity of the name Photuris flavicollis Fall, 1927. Fifty-eight taxa described as variations or aberrations in the subfamilies Ototretinae, Photurinae, and Psilocladinae by Delkeskamp (1977), McDermott (1966), Wittmer (1944), and Pic (1924c), are evaluated, with their availability determined based on ICZN (1999: Article 45.6).
ZooBank registration. urn:lsid:zoobank.org:pub:65697128-997F-4A52-AC9E-6860B0BF997D
Several nomenclatural changes for taxa in the firefly subfamily Luciolinae (Coleoptera: Lampyridae) are proposed. Evidence is presented to correct the year of description for Luciola dregei Motschulsky 1853 to Motschulsky 1854 when the name was ratified. We correct the authorities and years of descriptions for type species designations for the genera Delopleurus Motschulsky, 1853, and Delopyrus Motschulsky, 1853 to Motschulsky 1854 for both. All remaining taxa described as variations in the subfamily Luciolinae by McDermott (1966), are evaluated to subspecies with their availability determined based on ICZN (1999) Article 45.6.
ZooBank registration. urn:lsid:zoobank.org:pub:618A5442-2644-4E9A-BE70-07C413810DB9
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Background: Alternative polyadenylation (APA) refers to the regulated selection of polyadenylation sites (PASs) in transcripts, which determines the length of their 3′ untranslated regions (3′UTRs). We have recently shown that SRSF3 and SRSF7, two closely related SR proteins, connect APA with mRNA export. The mechanism underlying APA regulation by SRSF3 and SRSF7 remained unknown.
Results: Here we combine iCLIP and 3′-end sequencing and find that SRSF3 and SRSF7 bind upstream of proximal PASs (pPASs), but they exert opposite effects on 3′UTR length. SRSF7 enhances pPAS usage in a concentration-dependent but splicing-independent manner by recruiting the cleavage factor FIP1, generating short 3′UTRs. Protein domains unique to SRSF7, which are absent from SRSF3, contribute to FIP1 recruitment. In contrast, SRSF3 promotes distal PAS (dPAS) usage and hence long 3′UTRs directly by counteracting SRSF7, but also indirectly by maintaining high levels of cleavage factor Im (CFIm) via alternative splicing. Upon SRSF3 depletion, CFIm levels decrease and 3′UTRs are shortened. The indirect SRSF3 targets are particularly sensitive to low CFIm levels, because here CFIm serves a dual function; it enhances dPAS and inhibits pPAS usage by binding immediately downstream and assembling unproductive cleavage complexes, which together promotes long 3′UTRs.
Conclusions; We demonstrate that SRSF3 and SRSF7 are direct modulators of pPAS usage and show how small differences in the domain architecture of SR proteins can confer opposite effects on pPAS regulation.