Albuminuria and the risk of cancer:the Stockholm CREAtinine Measurements (SCREAM) project

Background:Studies investigating the association of chronic kidney disease and cancer have focused on estimated glomerular filtration (eGFR) rather than on albuminuria. This study aimed to examine whether albuminuria is associated with cancer incidence, and whether this association is independent of eGFR. Methods:We included subjects of the Stockholm Creatinine Measurements (SCREAM) project without a history of cancer—250 768 subjects with at least one urine albumin–creatinine ratio (ACR) test (primary cohort) and 433 850 subjects with at least one dipstick albuminuria test (secondary cohort). Albuminuria was quantified as KDIGO albuminuria stages. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidence rates. Multivariable Cox proportional hazards regression models adjusted for confounders including eGFR to calculate hazard ratios and 95% confidence intervals (HRs, 95% CIs). Results:During a median follow-up of 4.3 (interquartile range 2.0–8.2) years, 21 901 subjects of the ACR cohort developed de novo cancer. In multivariable analyses, adjusting among others for eGFR, subjects with an ACR of 30–299 mg/g or ≥300 mg/g had a 23% (HR 1.23; 95% CI 1.19–1.28) and 40% (HR 1.40; 95% CI 1.31–1.50) higher risk of developing cancer, respectively, when compared with subjects with an ACR &lt;30 mg/g. This graded, independent association was also observed for urinary tract, gastrointestinal tract, lung and hematological cancer incidence (all P &lt; .05). Results were similar in the dipstick albuminuria cohort. Conclusions:Albuminuria was associated with the risk of cancer independent of eGFR. This association was primarily driven by a higher risk of urinary tract, gastrointestinal tract, lung and hematological cancers.</p

Cyclin E expression is associated with high levels of replication stress in triple-negative breast cancer

Replication stress entails the improper progression of DNA replication. In cancer cells, including breast cancer cells, an important cause of replication stress is oncogene activation. Importantly, tumors with high levels of replication stress may have different clinical behavior, and high levels of replication stress appear to be a vulnerability of cancer cells, which may be therapeutically targeted by novel molecularly targeted agents. Unfortunately, data on replication stress is largely based on experimental models. Further investigation of replication stress in clinical samples is required to optimally implement novel therapeutics. To uncover the relation between oncogene expression, replication stress, and clinical features of breast cancer subgroups, we immunohistochemically analyzed the expression of a panel of oncogenes (Cyclin E, c-Myc, and Cdc25A,) and markers of replication stress (phospho-Ser33-RPA32 and γ-H2AX) in breast tumor tissues prior to treatment (n = 384). Triple-negative breast cancers (TNBCs) exhibited the highest levels of phospho-Ser33-RPA32 (P < 0.001 for all tests) and γ-H2AX (P < 0.05 for all tests). Moreover, expression levels of Cyclin E (P < 0.001 for all tests) and c-Myc (P < 0.001 for all tests) were highest in TNBCs. Expression of Cyclin E positively correlated with phospho-RPA32 (Spearman correlation r = 0.37, P < 0.001) and γ-H2AX (Spearman correlation r = 0.63, P < 0.001). Combined, these data indicate that, among breast cancers, replication stress is predominantly observed in TNBCs, and is associated with expression levels of Cyclin E. These results indicate that Cyclin E overexpression may be used as a biomarker for patient selection in the clinical evaluation of drugs that target the DNA replication stress response

An improved design of an inductive fault current limiter based on a superconducting cylinder

The paper deals with basic designs of a fault current limiter of the transformer type which differ each other by the mutual location of a primary winding and a superconducting short-circuited cylinder. Theoretical study of the main parameters of the different designs is performed in the framework of the critical state model and shows that the most effective is a design in which the primary winding is divided to two sections with equal turn numbers. The sections are placed inside and outside of the cylinder and connected in series. Such arrangement of the windings leads to a substantial reduction of AC losses in the superconducting cylinder, an increase of the activation current and a decrease of the inductive reactance in the normal regime of a protected circuit. The experimental results obtained on the laboratory model with a BSSCO cylinder confirm the theoretical predictions.Comment: 17 pages, 9 figure

Interleukin‐6 initiates muscle‐ and adipose tissue wasting in a novel C57BL/6 model of cancer‐associated cachexia

BACKGROUND: Cancer‐associated cachexia (CAC) is a wasting syndrome drastically reducing efficacy of chemotherapy and life expectancy of patients. CAC affects up to 80% of cancer patients, yet the mechanisms underlying the disease are not well understood and no approved disease‐specific medication exists. As a multiorgan disorder, CAC can only be studied on an organismal level. To cover the diverse aetiologies of CAC, researchers rely on the availability of a multifaceted pool of cancer models with varying degrees of cachexia symptoms. So far, no tumour model syngeneic to C57BL/6 mice exists that allows direct comparison between cachexigenic‐ and non‐cachexigenic tumours. METHODS: MCA207 and CHX207 fibrosarcoma cells were intramuscularly implanted into male or female, 10–11‐week‐old C57BL/6J mice. Tumour tissues were subjected to magnetic resonance imaging, immunohistochemical‐, and transcriptomic analysis. Mice were analysed for tumour growth, body weight and ‐composition, food‐ and water intake, locomotor activity, O(2) consumption, CO(2) production, circulating blood cells, metabolites, and tumourkines. Mice were sacrificed with same tumour weights in all groups. Adipose tissues were examined using high‐resolution respirometry, lipolysis measurements in vitro and ex vivo, and radioactive tracer studies in vivo. Gene expression was determined in adipose‐ and muscle tissues by quantitative PCR and Western blotting analyses. Muscles and cultured myotubes were analysed histologically and by immunofluorescence microscopy for myofibre cross sectional area and myofibre diameter, respectively. Interleukin‐6 (Il‐6) was deleted from cancer cells using CRISPR/Cas9 mediated gene editing. RESULTS: CHX207, but not MCA207‐tumour‐bearing mice exhibited major clinical features of CAC, including systemic inflammation, increased plasma IL‐6 concentrations (190 pg/mL, P ≤ 0.0001), increased energy expenditure (+28%, P ≤ 0.01), adipose tissue loss (−47%, P ≤ 0.0001), skeletal muscle wasting (−18%, P ≤ 0.001), and body weight reduction (−13%, P ≤ 0.01) 13 days after cancer cell inoculation. Adipose tissue loss resulted from reduced lipid uptake and ‐synthesis combined with increased lipolysis but was not associated with elevated beta‐adrenergic signalling or adipose tissue browning. Muscle atrophy was evident by reduced myofibre cross sectional area (−21.8%, P ≤ 0.001), increased catabolic‐ and reduced anabolic signalling. Deletion of IL‐6 from CHX207 cancer cells completely protected CHX207(IL6KO)‐tumour‐bearing mice from CAC. CONCLUSIONS: In this study, we present CHX207 fibrosarcoma cells as a novel tool to investigate the mediators and metabolic consequences of CAC in C57BL/6 mice in comparison to non‐cachectic MCA207‐tumour‐bearing mice. IL‐6 represents an essential trigger for CAC development in CHX207‐tumour‐bearing mice

Agrarische ondernemers over de mestwetgeving : beleving van het mestbeleid: draagvlak, knelpunten en oplossingen

Akkerbouwers, melkveehouders en varkenshouders vinden het goed dat er een mestbeleid is en hebben de intentie om hier nauwkeurig aan te blijven voldoen, ook als het verder wordt aangescherpt. Het draagvlak voor het huidige mestbeleid, ofwel de mate waarin ondernemers achter het beleid staan, is echter gering bij agrarische ondernemers en andere belanghebbenden. Dit is een belangrijke conclusie uit het onderzoek naar de beleving van het mestbeleid door agrarische ondernemers en andere belanghebbenden dat is uitgevoerd in het kader van de evaluatie van de mestwetgeving in 2016

Association of Cardiometabolic Disease With Cancer in the Community

BACKGROUND: Obesity and cardiometabolic dysfunction have been associated with cancer risk and severity. Underlying mechanisms remain unclear. OBJECTIVES: The aim of this study was to examine associations of obesity and related cardiometabolic traits with incident cancer. METHODS: FHS (Framingham Heart Study) and PREVEND (Prevention of Renal and Vascular End-Stage Disease) study participants without prevalent cancer were studied, examining associations of obesity, body mass index (BMI), waist circumference, visceral adipose tissue (VAT) and subcutaneous adipose tissue depots, and C-reactive protein (CRP) with future cancer in Cox models. RESULTS: Among 20,667 participants (mean age 50 years, 53% women), 2,619 cancer events were observed over a median follow-up duration of 15 years. Obesity was associated with increased risk for future gastrointestinal (HR: 1.30; 95% CI: 1.05-1.60), gynecologic (HR: 1.62; 95% CI: 1.08-2.45), and breast (HR: 1.32; 95% CI: 1.05-1.66) cancer and lower risk for lung cancer (HR: 0.62; 95% CI: 0.44-0.87). Similarly, waist circumference was associated with increased risk for overall, gastrointestinal, and gynecologic but not lung cancer. VAT but not subcutaneous adipose tissue was associated with risk for overall cancer (HR: 1.22; 95% CI: 1.05-1.43), lung cancer (HR: 1.92; 95% CI: 1.01-3.66), and melanoma (HR: 1.56; 95% CI: 1.02-2.38) independent of BMI. Last, higher CRP levels were associated with higher risk for overall, colorectal, and lung cancer (P < 0.05 for all). CONCLUSIONS: Obesity and abdominal adiposity are associated with future risk for specific cancers (eg, gastrointestinal, gynecologic). Although obesity was associated with lower risk for lung cancer, greater VAT and CRP were associated with higher lung cancer risk after adjusting for BMI

Stopping power and collective flow of nuclear matter in the reaction Ar+Pb at 0.8 GeV/u

Charged-particle exclusive data for Ar+Pb collisions at 0.772 GeV/u are analyzed in terms of collective variables for the event shapes in momentum space. Semicentral collisions lead to sidewards flow whereas nearly head-on collisions have spherical shapes in the c.m. frame, resulting from complete stopping of projectile motion. The hydrodynamical model predictions agree qualitatively with the data whereas the standard cascade model disagrees, lacking in stopping power and collective flow