Use of multibeam imaging sonar for observation of marine mammals and fish on a marine renewable energy site.

Environmental data is crucial for planning, permitting, execution and post construction monitoring of marine renewable energy projects. In harsh conditions in which marine renewable energy is harvested, integrated monitoring platforms comprising multibeam imaging sonar systems coupled with other sensors can provide multiparametric data of the marine environment surrounding marine renewable energy installations. The aim of this study was to test the possibilities of observing the occurrence of fish and marine mammals using a multibeam imaging sonar system deployed at a wave power test site. The results obtained from a ten-day data set proved the platform as suitable for long time underwater monitoring and also revealed that the occurrence of fish and marine mammals was distributed across characteristic time and space domains. Large fish [>0.4 m] frequently occurred at night-time and near the benthic zone. Small fish [<0.2 m] frequently occurred during daylight and within the pelagic zone. The occurrence of seals was periodically distributed along a daily cycle, with intervals of 1-2 hours between maxima and minima. In conclusion, the use of multibeam imaging sonar can be a reliable technique for the qualitative and quantitative observations of fish and marine mammals in general and at marine renewable energy sites specifically, including protected and economically important species.

Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN).

Cardiovascular comorbidity is common in small cell lung cancer (SCLC) and may significantly affect treatment tolerability and patient outcome. Still, there are no established biomarkers for objective and dynamic assessment as a tool for improved treatment decisions. We have investigated circulating levels of midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial-natriuretic peptide (MR-proANP), copeptin (surrogate for vasopressin) and suppression-of-tumorigenicity-2 (ST2), all known to correlate with various aspects of cardiovascular function, in a SCLC cohort (N = 252) from a randomized, controlled trial (RASTEN). For all measured biomarkers, protein levels were inversely associated with survival, particularly with ST2 and MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio of 2.40 (95% CI 1.44−3.98; p = 0.001) and 2.18 (95% CI 1.35−3.51; p = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73−6.79; p < 0.001) and 3.49 (95% CI 1.84−6.60; p < 0.001), respectively, in extensive disease patients. A high combined score of MR-proADM and ST2 was associated with a significantly reduced median OS of 7.0 months vs. 14.9 months for patients with a low combined score. We conclude that the cardiovascular biomarkers MR-proADM and ST2 strongly correlate with survival in SCLC, warranting prospective studies on the clinical utility of MR-proADM and ST2 for improved, individualized treatment decisions.

Colonisation of wave power foundations by mobile mega- and macrofauna - a 12 year study.

Environmental impacts from wave energy generators on the local mobile mega- and macrofauna community have been investigated in the Lysekil project by Uppsala University. Offshore renewable energy installations provide hard, artificial substrates, and as such, they could act as artificial reefs. Foundations with manufactured holes served as complex habitats and foundations without served as non-complex. In this long-term study, SCUBA surveys of mobile fauna in the years 2007, 2008 and 2016-2019 were analyzed. The results show a distinct reef effect on the foundations with significant greater species richness, total number of individuals, greater values of the Shannon-Wiener biodiversity index, and greater abundance of specific reef fauna. Complex foundations accommodated a greater abundance of brown crabs than non-complex foundations, other taxa did not show differences between the two foundation types. A successional increase of species richness, numbers of individuals and Shannon-Wiener biodiversity could be revealed from the first to the second survey period. Inter-annual variation was visible throughout all taxa and years.

Palliative short-course hypofractionated radiotherapy followed by chemotherapy in esophageal adenocarcinoma: the phase II PALAESTRA trial.

Background: The majority of patients with incurable esophageal adenocarcinoma suffer from dysphagia. We assessed a novel treatment strategy with initial short-course radiotherapy followed by chemotherapy with the primary aim to achieve long-term relief of dysphagia.Methods: This phase II trial included treatment-naîve patients with dysphagia due to esophageal adenocarcinoma not eligible for curative treatment. External beam radiotherapy with 20 Gy in five fractions to the primary tumor was followed by four cycles of chemotherapy (FOLFOX regimen). Dysphagia was assessed using a five-grade scale.Results: From October 2014 to May 2018 a total of 29 patients were enrolled. The rate of dysphagia improvement was 79%, median duration of improvement 6.7 months (12.2 months for responders) and median overall survival 9.9 months. In the pre-specified per protocol analysis (23 patients) the rate of dysphagia improvement was 91%, median duration of improvement 12.2 months (14.0 months for responders) and median overall survival 16.0 months. The most common grade 3-4 adverse events were neutropenia (29%), infection (25%), anorexia (11%), esophagitis (11%) and fatigue (11%).Conclusion: Initial palliative short-course radiotherapy followed by chemotherapy is a promising treatment strategy that can provide long-lasting relief of dysphagia in patients with esophageal adenocarcinoma.

Vasoactive peptides associate with treatment outcome ofbevacizumab-containing therapy in metastatic colorectal cancer.

BACKGROUND: Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking. In disease associated with hypertension, vasoactive peptides have been linked to cardiovascular pressure load. Here, we have explored potential associations between circulating levels of vasoactive peptides and tumor response during bevacizumab-containing treatment of colorectal cancer. MATERIAL AND METHODS: Metastatic colorectal cancer (mCRC) patients with available best objective response (ORR) and time to tumor progression (TTP) data were included from a randomized clinical trial investigating maintenance therapy after first line chemotherapy plus bevacizumab. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial-natriuretic-peptide (MR-proANP), and C-terminal-prepro-vasopressin (Copeptin) vasoactive peptide concentrations were measured in plasma at baseline and after 6 weeks of chemotherapy and bevacizumab treatment (n = 97). We determined associations among clinical outcome (ORR and TTP), peptide levels, and hypertension (NCI-CTCAE 4.0 criteria), using Spearman's test, multiple linear regression, and Mann-Whitney's test. RESULTS: Increasing levels of vasoactive peptides from baseline and after six weeks of treatment were associated with improved treatment outcome (MR-proADM: ORR, p = .0003; TTP, p = .05; MR-proANP: ORR, p = .05; TTP, p = .03; Copeptin: ORR, p = .10; TTP, p = .02). Patients with increasing levels of all three peptides (n = 28) versus increasing levels of one or two peptides (n = 59) showed a median TTP of 284 and 225 d, respectively (p = .02). CONCLUSIONS: Our results suggest that increasing systemic levels of vasoactive peptides associate with improved tumor response and TTP in mCRC patients treated with a bevacizumab-containing regimen. These findings support the proposed link between the tumor vasculature and the cardiovascular system of the host. This should motivate further studies that investigate the potential role of vasoactive peptides as a novel class of dynamic biomarkers in the treatment of cancer.

Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma.

For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m2 IV, days 1-2 and R 375 mg/m2 IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.