Patterns and mechanisms of fluvial sediment flux and accumulation in two subarctic fjords: Nachvak and Saglek Fjords, Nunatsiavut, Canada

Recent marine sedimentary deposits and river discharge in two subarctic fjords in Nunatsiavut (Northern Labrador, Canada) have been studied to elucidate patterns and mechanisms of fluvial sediment transfer and accumulation in the fjords, to further our understanding of the longer-term sedimentary record. Multibeam and sub-bottom acoustic data and sediment cores were collected in Nachvak and Saglek fjords, within Canada\u27s Torngat Mountains National Park, as part of the most extensive study of the park\u27s marine resources to date. Cores were subsampled for X-radiography, grain size, and 210Pb/ 137Cs geochronology. Muddy basin sediments within each fjord are bioturbated, indicating circulation of oxygenated bottom water. Depositional fluxes and inventories of 210Pb indicate efficient marine scavenging of 210Pb by fine suspended sediments. In Nachvak Fjord, with small rivers and steep, presently glaciated catchments, postglacial and recent sediment accumulation rates are similar, implying relatively constant sedimentation over time. In Saglek Fjord, fed by larger rivers with more extensive catchments that lack glaciers, recent sediment accumulation is more rapid than that averaged over postglacial time. Present mass accumulation rates for the Nachvak Fjord basin are on average 39 000 t·year -1 for the entire basin, and for Saglek 43 000 t·year -1 for the entire basin, with sediment-gravity flows being one likely mechanism for sediment delivery to deep basins. Results collectively suggest that both marine basins are excellent natural sediment traps. Comparison of accumulation rates from 137Cs and 210Pb suggest that sediment fluxes to Nachvak Fjord may have decreased slightly over the past ~130 years

Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma

Immuno-oncological therapy with checkpoint inhibition (CI) has become a new standard treatment in metastatic renal cell carcinoma (RCC), but the prognostic value of the expression of CI therapy target molecules is still controversial. 342 unselected consecutive RCC tumor samples were analyzed regarding their PD-1, PD-L1, and CTLA-4 expression by immunohistochemistry (IHC). The prognostic values for cancer-specific survival (CSS) and overall survival (OS) were analyzed for those not exposed to CI therapy. The expression of PD-1 in tumor-infiltrating mononuclear cells (TIMC) and PD-L1 in tumor cells was detected in 9.4% and 12.3%, respectively (Immune reactive score (IRS) > 0). Furthermore, PD-L1 expression in TIMC (IRS > 0) and CTLA-4 expression in TIMC (>1% positive cells) was detected in 4.8% and 6.3%. PD-1 expression and CTLA-4 expression were significantly associated with a worse OS and CSS in log rank survival analysis and univariate Cox regression analysis. CTLA-4 expression is a prognostic marker that is independently associated with a worse outcome in multivariate Cox regression analysis in the whole cohort (OS: p = 0.013; CSS: p = 0.048) as well as in a non-metastatic subgroup analysis (OS: p = 0.028; CSS: p = 0.022). Patients with combined CTLA-4 expression and PD-1-expression are at highest risk in OS and CSS. In RCC patients, PD-1 expression in TIMC and CTLA-4 expression in TIMC are associated with a worse OS and CSS. The combination of PD-1 expression in TIMC and CTLA-4 expression in TIMC might identify high risk patients. This is, to our knowledge, the first description of CTLA-4 expression to be a prognostic marker in RCC

Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis

PURPOSE:Genome-wide analyses revealed basal and luminal subtypes of urothelial carcinomas of the bladder. It is unknown if this subtyping can also be applied to upper tract urothelial carcinomas. MATERIALS AND METHODS:Tumor samples from 222 patients with upper tract urothelial carcinomas who were treated with radical nephroureterectomy were analyzed for the expression of seven basal/luminal immunohistochemical markers (CK5, EGFR, CD44, CK20, p63, GATA3, FOXA1). RESULTS:Hierarchical clustering revealed a basal-like subtype (enrichment of CK5, EGFR and CD44) in 23.9% and a luminal-like subtype (enrichment of CK20, GATA3, p63 and FOXA1) in 13.1% of the patients. In 60.8%, little to no markers were expressed, whereas markers of both subtypes were expressed in 2.2%. By using CK5 and CK20 as surrogate markers for the basal and luminal subtypes, we defined four subtypes of upper tract urothelial carcinomas: (i) exclusively CK20 positive and CK5 negative (CK20+/CK5-), (ii) exclusively CK5 positive and CK20 negative (CK20-/ CK5+), (iii) both markers positive (CK20+/CK5+) and (iv) both markers negative (CK20-/CK5-). A receiver-operator analysis provided the optimal cut-off values for this discrimination. An immunoreactive score >1 for CK5 and >6 for CK20 were defined as positive. In multivariate Cox's regression analysis, the CK20+/CK5- subtype was an independent negative prognostic marker with a 3.83-fold increased risk of cancer-specific death (p = 0.02) compared to the other three subtypes. CONCLUSIONS:Immunohistochemical subgrouping of upper tract urothelial carcinomas by analyzing CK5 and CK20 expression can be performed in a routine setting and can identify tumors with a significantly worse cancer-specific survival prognosis

Effects of whole-body electromyostimulation combined with individualized nutritional support on body composition in patients with advanced cancer: a controlled pilot trial

Abstract Background Physical exercise and nutritional treatment are promising measures to prevent muscle wasting that is frequently observed in advanced-stage cancer patients. However, conventional exercise is not always suitable for these patients due to physical weakness and therapeutic side effects. In this pilot study, we examined the effect of a combined approach of the novel training method whole-body electromyostimulation (WB-EMS) and individualized nutritional support on body composition with primary focus on skeletal muscle mass in advanced cancer patients under oncological treatment. Methods In a non-randomized controlled trial design patients (56.5% male; 59.9 ± 12.7 years) with advanced solid tumors (UICC III/IV, N = 131) undergoing anti-cancer therapy were allocated to a usual care control group (n = 35) receiving individualized nutritional support or to an intervention group (n = 96) that additionally performed a supervised physical exercise program in form of 20 min WB-EMS sessions (bipolar, 85 Hz) 2×/week for 12 weeks. The primary outcome of skeletal muscle mass and secondary outcomes of body composition, body weight and hand grip strength were measured at baseline, in weeks 4, 8 and 12 by bioelectrical impedance analysis and hand dynamometer. Effects of WB-EMS were estimated by linear mixed models. Secondary outcomes of physical function, hematological and blood chemistry parameters, quality of life and fatigue were assessed at baseline and week 12. Changes were analyzed by t-tests, Wilcoxon signed-rank or Mann-Whitney-U-tests. Results Twenty-four patients of the control and 58 of the WB-EMS group completed the 12-week trial. Patients of the WB-EMS group had a significantly higher skeletal muscle mass (0.53 kg [0.08, 0.98]; p = 0.022) and body weight (1.02 kg [0.05, 1.98]; p = 0.039) compared to controls at the end of intervention. WB-EMS also significantly improved physical function and performance status (p < 0.05). No significant differences of changes in quality of life, fatigue and blood parameters were detected between the study groups after 12 weeks. Conclusions Supervised WB-EMS training is a safe strength training method and combined with nutritional support it shows promising effects against muscle wasting and on physical function in advanced-stage cancer patients undergoing treatment. Trial registration ClinicalTrials.gov NCT02293239 (Date: November 18, 2014)

Distribution of subtypes of UTUC.

<p>Distribution of subtypes of UTUC.</p

Heatmap and cluster dendrogram demonstrating the expression patterns of CK5 and CK20 in UTUC.

<p>Using CK5 and CK20 as surrogate markers for the subtypes, hierarchical clustering again found four subtypes: a basal-like subtype with high CK5 expression (green cluster), a luminal-like subtype with high CK20 expression (red cluster); a subtype with expression of CK5 and CK20 (blue cluster); a cluster without a predominant expression of CK5 nor CK20 (black cluster).</p

Cancer-specific survival depending on subtype of UTUC defined by CK5 and CK20 expression using IRS cut-off values determined by ROC analysis.

<p>Using ROC analysis the optimal IRS cut-off values for CK5 and CK20 were defined. IRS scores >1 for CK5 and >6 for CK20 were defined as high expression. Using these cut-off values to define the four subgroups, the CK20+/CK5- subtype showed a significantly worse cancer-specific survival when compared to the other subtypes.</p