No Survival Differences among Germ-Cell Cancer Patients from Urban and Rural Areas

INTRODUCTION Germ-cell cancer (GCC) is curable in the majority of men. However, previous reports have described inferior outcomes in men living in rural as compared to urban residential areas. METHODS We identified all GCC patients treated at two large university hospitals in Zürich and Bern, both in Switzerland, between 2010 and 2020 by retrospective chart review. In 400 patients from Zürich and 274 patients from Bern, details on presentation, diagnosis, treatment, and outcomes were abstracted from medical records. For follow-up, we contacted referring centers or private physicians. Residential region was allocated according to the Federal Statistical Office of Switzerland. RESULTS We found no differences in initial presentation (clinical stage I [CSI] versus de novo metastatic), relapse rate in CSI patients, response in metastatic patients (favorable vs. unfavorable), progression-free survival (PFS) or overall survival (OS) between patients from urban as compared to suburban or rural residential areas. PFS at 3 years for CSI patients was 78% (95% confidence interval 72-82%) and OS at 5 years was 98% (95% confidence interval 96-99%). PFS at 3 years for de novo metastatic patients was 74% (95% confidence interval 68-79%) and OS at 5 years was 86% (95% confidence interval 80-90%). CONCLUSION Treatment outcomes in GCC patients were excellent and comparable to international standards at both centers irrespective of the residential area of patients documenting equal access to high-level oncological care at both centers

No Survival Differences among Germ-Cell Cancer Patients from Urban and Rural Areas.

INTRODUCTION Germ-cell cancer (GCC) is curable in the majority of men. However, previous reports have described inferior outcomes in men living in rural as compared to urban residential areas. METHODS We identified all GCC patients treated at two large university hospitals in Zürich and Bern, both in Switzerland, between 2010 and 2020 by retrospective chart review. In 400 patients from Zürich and 274 patients from Bern, details on presentation, diagnosis, treatment, and outcomes were abstracted from medical records. For follow-up, we contacted referring centers or private physicians. Residential region was allocated according to the Federal Statistical Office of Switzerland. RESULTS We found no differences in initial presentation (clinical stage I [CSI] versus de novo metastatic), relapse rate in CSI patients, response in metastatic patients (favorable vs. unfavorable), progression-free survival (PFS) or overall survival (OS) between patients from urban as compared to suburban or rural residential areas. PFS at 3 years for CSI patients was 78% (95% confidence interval 72-82%) and OS at 5 years was 98% (95% confidence interval 96-99%). PFS at 3 years for de novo metastatic patients was 74% (95% confidence interval 68-79%) and OS at 5 years was 86% (95% confidence interval 80-90%). CONCLUSION Treatment outcomes in GCC patients were excellent and comparable to international standards at both centers irrespective of the residential area of patients documenting equal access to high-level oncological care at both centers

Perioperative complications and oncological outcomes of post-chemotherapy retroperitoneal lymph node dissection in patients with germ cell cancer at two high-volume university centres in Switzerland - a retrospective chart review

BACKGROUND: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is an integral part of the management of patients with metastatic non-seminoma and residual masses >1 cm after chemotherapy. AIMS: To assess perioperative complications and oncological outcomes at two major referral centres in Switzerland. METHODS: This was a retrospective chart review of 136 patients with non-seminoma who underwent PC-RPLND between 2010 and 2020 at the university hospitals of Bern and Zürich. Patient, treatment and tumour characteristics as well as the types and frequencies of intra- and postoperative complications were registered and compared using the chi-square test. Oncological outcomes consisted of the time and location of relapses as well as progression-free and overall survival, which were compared using the log-rank test. RESULTS: Overall, 70 patients from Bern and 66 patients from Zürich were included; 5 patients had a previous retroperitoneal lymph node dissection (RPLND) (2 Bern, 3 Zürich). Vascular injuries were the most frequent intraoperative complication, occurring in 27/136 (19.9%) patients. Postoperative complications were observed in 42/136 (30.9%) patients, ileus being the most common. Perioperative mortality was 2.2%. A retroperitoneal mass ≥50 mm was significantly associated with intraoperative complications (p = 0.004) and increased resource demands (p = 0.021). Postoperative morbidity was higher according to age at post-chemotherapy retroperitoneal lymph node dissection ≥40 years (p = 0.028) and retroperitoneal mass ≥20 mm (p = 0.005). The median follow-up time was 37 months (interquartile range [IQR] 18-64 months). The median progression-free survival at 5 years was 76% (95% confidence interval [CI]: 64-85%) in Bern and 69% (95% CI: 54-80%) in Zürich (p = 0.464). The median overall survival at 5 years was 88% (95% CI: 76-94%) in Bern and 77% (95% CI: 60-87%) in Zürich (p = 0.335). Patients with progressive disease or a tumour marker increase before retroperitoneal lymph node dissection had significantly inferior progression-free and overall survival compared to non-progressing patients. The presence of teratoma in resected specimens did not confer inferior survival probabilities compared to necrosis only, whereas the presence of vital undifferentiated tumour conferred inferior progression-free and overall survival. Patients with a previous retroperitoneal lymph node dissection and patients operated for late relapses >2 years after chemotherapy also had significantly inferior progression-free and overall survival. CONCLUSIONS: We found a relevant rate of severe perioperative complications at PC-RPLND at even experienced high-volume centres. The oncological outcomes at two major university urological centres in Switzerland were similar and determined by preoperative risk factors and intraoperative histology

The Convergence of the Hedgehog/Intein Fold in Different Protein Splicing Mechanisms

Protein splicing catalyzed by inteins utilizes many different combinations of amino-acid types at active sites. Inteins have been classified into three classes based on their characteristic sequences. We investigated the structural basis of the protein splicing mechanism of class 3 inteins by determining crystal structures of variants of a class 3 intein from Mycobacterium chimaera and molecular dynamics simulations, which suggested that the class 3 intein utilizes a different splicing mechanism from that of class 1 and 2 inteins. The class 3 intein uses a bond cleavage strategy reminiscent of proteases but share the same Hedgehog/INTein (HINT) fold of other intein classes. Engineering of class 3 inteins from a class 1 intein indicated that a class 3 intein would unlikely evolve directly from a class 1 or 2 intein. The HINT fold appears as structural and functional solution for trans-peptidyl and trans-esterification reactions commonly exploited by diverse mechanisms using different combinations of amino-acid types for the active-site residues

Influence of household demographic and socio-economic factors on household expenditure on tobacco in six New Independent States

<p>Abstract</p> <p>Background</p> <p>To identify demographic and socio-economic factors that are associated with household expenditure on tobacco in Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Russian Federation, and Tajikistan.</p> <p>Methods</p> <p>Secondary analysis of the data available through the World Bank Living Standards Monitoring Survey conducted in aforementioned countries in 1995–2000. The role of different variables (e.g. mean age of household members, household area of residence, household size, share of adult males, share of members with high education) in determining household expenditure on tobacco (defined as tobacco expenditure share out of total monthly HH consumption) was assessed by using multiple regression analysis.</p> <p>Results</p> <p>Significant differences were found between mean expenditure on tobacco between rich and poor – in absolute terms the rich spend significantly more compared with the poor. Poor households devote significantly higher shares of their monthly HH consumption for tobacco products. Shares of adult males were significantly associated with the share of household consumption devoted for tobacco. There was a significant negative association between shares of persons with tertiary education within the HH and shares of monthly household consumption devoted for tobacco products. The correlation between household expenditures on tobacco and alcohol was found to be positive, rather weak, but statistically significant.</p> <p>Conclusion</p> <p>Given the high levels of poverty and high rates of smoking in the New Independent States, these findings have important policy implications. They indicate that the impact and opportunity costs of smoking on household finances are more significant for the poor than for the rich. Any reductions in smoking prevalence within poor households could have a positive economic impact.</p

The CAT Imaging Telescope for Very-High-Energy Gamma-Ray Astronomy

The CAT (Cherenkov Array at Themis) imaging telescope, equipped with a very-high-definition camera (546 fast phototubes with 0.12 degrees spacing surrounded by 54 larger tubes in two guard rings) started operation in Autumn 1996 on the site of the former solar plant Themis (France). Using the atmospheric Cherenkov technique, it detects and identifies very high energy gamma-rays in the range 250 GeV to a few tens of TeV. The instrument, which has detected three sources (Crab nebula, Mrk 421 and Mrk 501), is described in detail.Comment: 24 pages, 15 figures. submitted to Elsevier Preprin

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al

A formally verified compiler back-end

This article describes the development and formal verification (proof of semantic preservation) of a compiler back-end from Cminor (a simple imperative intermediate language) to PowerPC assembly code, using the Coq proof assistant both for programming the compiler and for proving its correctness. Such a verified compiler is useful in the context of formal methods applied to the certification of critical software: the verification of the compiler guarantees that the safety properties proved on the source code hold for the executable compiled code as well