Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and ...survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000–2014. Patients diagnosed in 1997–2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5‐year relative survival (RS). During 2000–2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person‐years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5‐year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% 2002–2007 vs. 13.0% 2008–2013, p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020–2030 in Western countries.
What's new?
Certain cancer types that originate from the epithelial or mesothelial tissues of the thoracic cavity are exceedingly rare. As a consequence, little is known about their incidence and survival. Here, utilizing national databases, the authors estimated incidence and survival of malignant mesothelioma (MM) and other rare thoracic cancers in Germany and the United States. Analyses show that between 2000 and 2014, MM incidence declined in both countries, although only MM survival improved in Germany. No improvements were observed in either country for survival of epithelial tumors of the trachea and thymus, highlighting a need for preventive and therapeutic advances.
The Genomic Landscape of Male Breast Cancers Piscuoglio, Salvatore; Ng, Charlotte K Y; Murray, Melissa P ...
Clinical cancer research,
08/2016, Volume:
22, Issue:
16
Journal Article
The speed-robust scheduling problem is a two-stage problem where, given
m
machines, jobs must be grouped into at most
m
bags while the processing speeds of the machines are unknown. After the speeds ...are revealed, the grouped jobs must be assigned to the machines without being separated. To evaluate the performance of algorithms, we determine upper bounds on the worst-case ratio of the algorithm’s makespan and the optimal makespan given full information. We refer to this ratio as the robustness factor. We give an algorithm with a robustness factor
2
-
1
m
for the most general setting and improve this to 1.8 for equal-size jobs. For the special case of infinitesimal jobs, we give an algorithm with an optimal robustness factor equal to
e
e
-
1
≈
1.58
. The particular machine environment in which all machines have either speed 0 or 1 was studied before by Stein and Zhong (ACM Trans Algorithms 16(1):1-20, 2020.
https://doi.org/10.1145/3340320
). For this setting, we provide an algorithm for scheduling infinitesimal jobs with an optimal robustness factor of
1
+
2
2
≈
1.207
. It lays the foundation for an algorithm matching the lower bound of
4
3
for equal-size jobs.
Recognition and elimination of nonsense mRNA Mühlemann, Oliver; Eberle, Andrea B.; Stalder, Lukas ...
Biochimica et biophysica acta,
09/2008, Volume:
1779, Issue:
9
Journal Article
Peer reviewed
Among the different cellular surveillance mechanisms in charge to prevent production of faulty gene products, nonsense-mediated mRNA decay (NMD) represents a translation-dependent posttranscriptional ...process that selectively recognizes and degrades mRNAs whose open reading frame (ORF) is truncated by a premature translation termination codon (PTC, also called “nonsense codon”). In doing so, NMD protects the cell from accumulating C-terminally truncated proteins with potentially deleterious functions. Transcriptome profiling of NMD-deficient yeast,
Drosophila, and human cells revealed that 3–10% of all mRNA levels are regulated (directly or indirectly) by NMD, indicating an important role of NMD in gene regulation that extends beyond quality control J. Rehwinkel, J. Raes, E. Izaurralde, Nonsense-mediated mRNA decay: Target genes and functional diversification of effectors, Trends Biochem. Sci. 31 (2006) 639-646.
1. In this review, we focus on recent results from different model organisms that indicate an evolutionarily conserved mechanism for PTC identification.
Objectives
This study aimed to investigate the recovery of limb function following a single intra‐articular injection of platelet‐rich plasma or hyaluronic acid in dogs with cranial cruciate ligament ...rupture treated with tibial plateau levelling osteotomy compared to dogs receiving no injection intraoperatively.
Materials and Methods
Sixty‐two dogs with cranial cruciate ligament rupture, body weights of 20 to 40 kg, and no other orthopaedic conditions were enrolled in this prospective, randomised, double‐blind, controlled study at the small animal clinic at LMU Munich. All dogs underwent tibial plateau levelling osteotomy. Based on random allocation, they received either a single intra‐articular injection of platelet‐rich plasma, hyaluronic acid or no injection intraoperatively. Gait analysis, clinical examinations, radiography of the stifle joint for osteoarthritis progression and two validated owner questionnaires were compared among groups at three timepoints postoperatively (6 weeks, 3 and 6 months). Limb function was primarily assessed by measuring the ground reaction forces.
Results
At all times postoperatively, no differences were observed among groups regarding clinical examinations, osteoarthritis score values, ground reaction forces or owner questionnaires. All dogs showed significant improvement in limb function clinically, in all ground reaction forces and in the validated questionnaires. Osteoarthritis progressed minimally during rechecks in all dogs regardless of the additional injection or not.
Clinical Significance
All dogs treated with tibial plateau levelling osteotomy for cranial cruciate ligament rupture showed improvements in limb function. No additive effect on faster recovery was demonstrated with the additional intra‐articular injection of platelet‐rich plasma or hyaluronic acid. Addition of platelet‐rich plasma/hyaluronic acid injections during tibial plateau levelling osteotomy is unnecessary considering the lack of benefit observed up to 6 months postoperatively.
Background
Bullous pemphigoid (BP) is the most common autoimmune blistering disease of the skin requiring skin and serum tests for a precise diagnosis.
Objectives
We analysed the sensitivity and ...specificity of BP-relevant parameters and the value of autoantibody titres during follow-up of BP patients.
Materials & methods
In a retrospective single-centre study, we included 200 consecutive patients with BP and 400 non-BP patients, and evaluated the test results of patients’ serum and skin. In addition, we followed patients’ autoantibody titres and clinical characteristics.
Results
BP180-ELISA revealed the highest sensitivity (85.0%; specificity: 93.9%), while BP230-ELISA demonstrated the lowest sensitivity (55.5%; specificity: 92.9%). Direct and indirect immunofluorescence showed comparable results for sensitivity (77.2%/72.7%) and specificity (94.9%/93.7%). The sensitivity for skin histology was 76.3% (specificity: 81.3%). Longitudinal analysis showed significant changes in autoantibody titres.
Conclusions
BP diagnostics should include serum tests for BP autoantibodies and skin immunofluorescence. Skin histology is supportive for diagnosis. Autoantibody titres are markers for disease activity.
Eukaryotic cells have developed surveillance mechanisms to prevent the expression of aberrant transcripts. An early surveillance checkpoint acts at the transcription site and prevents the release of ...mRNAs that carry processing defects. The exosome subunit Rrp6 is required for this checkpoint in Saccharomyces cerevisiae, but it is not known whether Rrp6 also plays a role in mRNA surveillance in higher eukaryotes.
We have developed an in vivo system to study nuclear mRNA surveillance in Drosophila melanogaster. We have produced S2 cells that express a human beta-globin gene with mutated splice sites in intron 2 (mut beta-globin). The transcripts encoded by the mut beta-globin gene are normally spliced at intron 1 but retain intron 2. The levels of the mut beta-globin transcripts are much lower than those of wild type (wt) ss-globin mRNAs transcribed from the same promoter. We have compared the expression of the mut and wt beta-globin genes to investigate the mechanisms that down-regulate the production of defective mRNAs. Both wt and mut beta-globin transcripts are processed at the 3', but the mut beta-globin transcripts are less efficiently cleaved than the wt transcripts. Moreover, the mut beta-globin transcripts are less efficiently released from the transcription site, as shown by FISH, and this defect is restored by depletion of Rrp6 by RNAi. Furthermore, transcription of the mut beta-globin gene is significantly impaired as revealed by ChIP experiments that measure the association of the RNA polymerase II with the transcribed genes. We have also shown that the mut beta-globin gene shows reduced levels of H3K4me3.
Our results show that there are at least two surveillance responses that operate cotranscriptionally in insect cells and probably in all metazoans. One response requires Rrp6 and results in the inefficient release of defective mRNAs from the transcription site. The other response acts at the transcription level and reduces the synthesis of the defective transcripts through a mechanism that involves histone modifications.
This essay argues that teaching Landon’s poems in the context of their original volume publication allows for greater understanding of the ways in which all Romantic-era poets deploy multiple voices ...in their collected works. It focuses upon strategies for teaching Landon’s
(1829) but offers a model for student engagement with Romantic poetry more generally.
Electro-optical imaging sensors are widely distributed and used for many different tasks. Due to technical improvements, their pixel size has been steadily decreasing, resulting in a reduced ...saturation capacity. As a consequence, this progress makes them susceptible to intense point light sources. Developments in laser technology have led to very compact and powerful laser sources of any wavelength in the visible and near infrared spectral region, offered as laser pointers. The manifold of wavelengths makes it difficult to encounter sensor saturation over the complete operating waveband by conventional measures like absorption or interference filters. We present a concept for electro-optical sensors to suppress overexposure in the visible spectral region. The key element of the concept is a spatial light modulator in combination with wavelength multiplexing. This approach allows spectral filtering within a localized area in the field of view of the sensor. The system offers the possibility of automatic reduction of overexposure by monochromatic laser radiation.
Introduction: Cultural factors were shown to be particularly relevant for the development and expression of posttraumatic stress. Recently, the concept of cultural scripts of trauma has been ...introduced, which proposes that trauma sequelae elements may be sequentially linked and specifically associated with cultural factors. Furthermore, a cascade model is proposed, including trauma exposure, demographic characteristics, cultural affiliation, and trauma-related value orientations as influencing factors of posttraumatic development. The purpose of this Network Project is to investigate cultural psychological factors that contribute to the expression of posttraumatic stress.Methods: The present Network Project implements a mixed methods approach and will be conducted in 5 different study sites, including Switzerland, Israel, Georgia, China, and East Africa. In sub-study I, the cultural scripts of traumatic stress inventories (CSTIs) will be developed. These scales provide a pool of trauma sequelae elements for each cultural group. For this purpose, focus groups with trauma survivors and trauma experts will be conducted and analysed using qualitative research methods. Sub-study II implements a validation analysis of the CSTIs and the empirical investigation of a cultural cascade model. This quantitative approach will include a larger sample of individuals who experienced traumatic life events.Discussion: This contribution is timely and enriches the knowledge of trauma and culture. Future publications of this Network Project will address trauma sequelae from a cultural perspective and provide diagnostic and psychotherapeutic implications.Introduction: Cultural factors were shown to be particularly relevant for the development and expression of posttraumatic stress. Recently, the concept of cultural scripts of trauma has been introduced, which proposes that trauma sequelae elements may be sequentially linked and specifically associated with cultural factors. Furthermore, a cascade model is proposed, including trauma exposure, demographic characteristics, cultural affiliation, and trauma-related value orientations as influencing factors of posttraumatic development. The purpose of this Network Project is to investigate cultural psychological factors that contribute to the expression of posttraumatic stress.Methods: The present Network Project implements a mixed methods approach and will be conducted in 5 different study sites, including Switzerland, Israel, Georgia, China, and East Africa. In sub-study I, the cultural scripts of traumatic stress inventories (CSTIs) will be developed. These scales provide a pool of trauma sequelae elements for each cultural group. For this purpose, focus groups with trauma survivors and trauma experts will be conducted and analysed using qualitative research methods. Sub-study II implements a validation analysis of the CSTIs and the empirical investigation of a cultural cascade model. This quantitative approach will include a larger sample of individuals who experienced traumatic life events.Discussion: This contribution is timely and enriches the knowledge of trauma and culture. Future publications of this Network Project will address trauma sequelae from a cultural perspective and provide diagnostic and psychotherapeutic implications.
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