Environmental Controls on Nitrogen and Sulfur Cycles in Surficial Aquatic Sediments

Enhanced anthropogenic inputs of nitrogen (N) and sulfur (S) have disturbed their biogeochemical cycling in aquatic and terrestrial ecosystems. The N and S cycles interact with one another through competition for labile forms of organic carbon between nitrate-reducing and sulfate-reducing bacteria. Furthermore, the N and S cycles could interact through nitrate (NO3-) reduction coupled to S oxidation, consuming NO3-, and producing sulfate (SO42-). The research questions of this study were: (1) what are the environmental factors explaining variability in N and S biogeochemical reaction rates in a wide range of surficial aquatic sediments when NO3- and SO42- are present separately or simultaneously, (2) how the N and S cycles could interact through S oxidation coupled to NO3- reduction, and (3) what is the extent of sulfate reduction inhibition by nitrate, and vice versa. The N and S biogeochemical reaction rates were measured on intact surface sediment slices using flow-through reactors. The two terminal electron acceptors NO3- and SO42- were added either separately or simultaneously and NO3- and SO42- reduction rates as well as NO3- reduction linked to S oxidation were determined. We used redundancy analysis, to assess how environmental variables were related to these rates. Our analysis showed that overlying water pH and salinity were two dominant environmental factors that explain 58% of the variance in the N and S biogeochemical reaction rates when NO3- and SO42- were both present. When NO3- and SO42- were added separately, however, sediment N content in addition to pH and salinity accounted for 62% of total variance of the biogeochemical reaction rates. The SO42- addition had little effect on NO3- reduction; neither did the NO3- addition inhibit SO42- reduction. The presence of NO3- led to SO42- production most likely due to the oxidation of sulfur. Our observations suggest that metal-bound S, instead of free sulfide produced by SO42- reduction, was responsible for the S oxidation

Mass-dependent Selenium Isotopic Fractionation during Microbial Reduction of Seleno-oxyanions by Phylogenetically Diverse Bacteria

Selenium (Se) isotope fractionation has been widely used for constraining redox conditions and microbial processes in both modern and ancient environments, but our knowledge of the controls on fractionation during microbial reduction of Se-oxyanions is based on a limited number of studies. Here we complement and expand the currently available pure culture data for Se isotope fractionation by investigating for the first time six phylogenetically and physiologically non-respiring bacterial strains that reduce Se-oxyanions to elemental Se [Se(0)]. Experiments were performed with either selenate [Se(VI)] or selenite [Se(IV)] at lower, more environmentally-relevant concentrations (9 to 47 μM) than previously investigated. Enterobacter cloacae SLD1a-1, Desulfitobacterium chlororespirans Co23 and Desulfitobacterium sp. Viet-1 were incubated with Se(VI) and Se(IV). Geobacter sulfurreducens PCA, Anaeromyxobacter dehalogenans FRC-W and Shewanella sp. (NR) were examined for their ability reducing Se(IV) to Se(0). Our data confirm that microbial reduction of both Se-oxyanions is accompanied by large kinetic isotopic fractionation (reported as 82/76ε =1000*(82/76α-1) ‰). Under our experimental conditions, microbial reduction of Se(VI) shows consistently greater isotope fractionation (ε= -9.2‰ to -11.8‰) than reduction of Se(IV) (ε= -6.2 to -7.8‰) confirming the difference in metabolic pathways for the reduction of the two Se-oxyanions. For Se(VI), the inverse relationship between normalized cell specific reduction rate (cSRR) and Se isotope fractionation suggests that the kinetic isotope effect for Se(VI) reduction is governed by an enzymatically-specific pathway related to the bacterial strain-specific physiology. In contrast, the lack of correlation between normalized cSRR and isotope fractionation for Se(IV) reduction indicates a non-enzyme specific pathway which is dominantly extracellular. Our study highlights the importance to understand microbially-mediated Se isotope fractionation depending on Se species, and cell-specific reduction rates before Se isotope ratios can become a fully applicable tool to interpret Se isotopic changes in modern and ancient environments

Expression of Bcl-2 in node-negative breast cancer is associated with various prognostic factors, but does not predict response to one course of perioperative chemotherapy.

The aim of this study was to assess relationships between Bcl-2 expression, response to chemotherapy and a number of pathological and biological tumour parameters in premenopausal, lymph node-negative breast cancer patients. Expression of Bcl-2 was determined using immunohistochemistry on paraffin-embedded sections in a series of 441 premenopausal, lymph node-negative breast cancers of patients randomised to receive perioperative chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) or no perioperative chemotherapy. Immunohistochemistry of Bcl-2 was evaluated by scoring both staining intensity (0-3) and number of positive cells (0-2). Using these scores tumours were grouped into categories 0-6. It was found that 9.2% of the tumours were completely negative (0), 17.2% weakly (1 + 2), 41.6% moderately (3 + 4) and 31.9% strongly positive (5 + 6) for Bcl-2. A positive correlation was found between high Bcl-2 expression and oestrogen (P < 0.001) and progesterone receptor positivity (P < 0.001) and low tumour grade (P < 0.001), whereas high Bcl-2 expression was negatively correlated with p53 (P < 0.001) and c-erb-B-2 positively (P < 0.001), high Ki-67 index (P < 0.001), mitotic index (P < 0.001) and large tumour size (P = 0.006). Patients with tumours expressing high levels of Bcl-2 (overall score 3-6) had a significantly better disease-free (P = 0.004) and overall (P = 0.009) survival. However, in a multivariate model this association no longer remained significant. There was a trend for an effect of adjuvant chemotherapy on disease-free survival both for patients with Bcl-2-positive (HR-0.61, 95% CI 0.35-1.06, P = 0.07) and negative (HR = 0.55, 95% CI 0.27-1.12, P = 0.09) breast tumours at a median follow-up of 49 months. The level of Bcl-2 expression does not seem to predict response to perioperative chemotherapy in premenopausal, lymph node-negative breast cancer patients. High levels of Bcl-2 are preferentially expressed in well-differentiated tumours and are associated with favourable prognosis. However, Bcl-2 expression is not an independent prognostic factor in this patient series

Chemotherapy and diffuse low-grade gliomas: a survey within the European Low-Grade Glioma Network.

Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial. An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients. The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression. The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues

A generative approach for image-based modeling of tumor growth

22nd International Conference, IPMI 2011, Kloster Irsee, Germany, July 3-8, 2011. ProceedingsExtensive imaging is routinely used in brain tumor patients to monitor the state of the disease and to evaluate therapeutic options. A large number of multi-modal and multi-temporal image volumes is acquired in standard clinical cases, requiring new approaches for comprehensive integration of information from different image sources and different time points. In this work we propose a joint generative model of tumor growth and of image observation that naturally handles multi-modal and longitudinal data. We use the model for analyzing imaging data in patients with glioma. The tumor growth model is based on a reaction-diffusion framework. Model personalization relies only on a forward model for the growth process and on image likelihood. We take advantage of an adaptive sparse grid approximation for efficient inference via Markov Chain Monte Carlo sampling. The approach can be used for integrating information from different multi-modal imaging protocols and can easily be adapted to other tumor growth models.German Academy of Sciences Leopoldina (Fellowship Programme LPDS 2009-10)Academy of Finland (133611)National Institutes of Health (U.S.) (NIBIB NAMIC U54-EB005149)National Institutes of Health (U.S.) (NCRR NAC P41- RR13218)National Institutes of Health (U.S.) (NINDS R01-NS051826)National Institutes of Health (U.S.) (NIH R01-NS052585)National Institutes of Health (U.S.) (NIH R01-EB006758)National Institutes of Health (U.S.) (NIH R01-EB009051)National Institutes of Health (U.S.) (NIH P41-RR014075)National Science Foundation (U.S.) (CAREER Award 0642971

Impaired set-shifting from dorsal stream disconnection: Insights from a european series of right parietal lower-grade glioma resection

Awake surgery with cognitive monitoring has increasingly been implemented to preserve brain networks and functionality. More recently, not only surgery in the left but also in the right hemisphere, i.c., the parietal lobe, was associated with potential risk for deficits in cognitive functions, such as cognitive flexibility. In this explorative pilot study, we compare cognitive performance more than three months after surgery with baseline measurements and explore the association between cognitive decline and subcortical tracts that may have been severed during surgery in the right hemisphere. Twenty-two patients who underwent surgery for a right parietal low-grade glioma were assessed pre-and postoperatively using the Trail Making Test and the Stroop task to administer set-shifting abilities and inhibition. Volume measurements and lesion–symptom mapping analyses were performed on postoperative MRI scans. Careful interpretation of the results shows a change in TMT performance and not on the Stroop Task when the lateral part of the arcuate fasciculus is damaged, indicating that disconnection of the lateral part of the dorsal stream might be correlated specifically with impaired set-shifting and not with inhibition. More importantly, this study underlines the need for international concertation to allow larger studies to increase power and perform more detailed analyses

Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging

Objective: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. Methods: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. Results: A total of 128 fully completed surveys were received and analyzed. Most centers (n=96, 75%) were academic and half of the centers (n=64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI.ConclusionA minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of 3mm. No common standard could be obtained regarding advanced MRI protocols and PET. Importance of the study: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed minimal core of imaging in clinical routine will facilitate future cooperative studies

Predictive value of S100-B and copeptin for outcomes following seizure: the BISTRO International Cohort Study.

OBJECTIVE: To evaluate the performance of S100-B protein and copeptin, in addition to clinical variables, in predicting outcomes of patients attending the emergency department (ED) following a seizure. METHODS: We prospectively included adult patients presented with an acute seizure, in four EDs in France and the United Kingdom. Participants were followed up for 28 days. The primary endpoint was a composite of seizure recurrence, all-cause mortality, hospitalization or rehospitalisation, or return visit in the ED within seven days. RESULTS: Among the 389 participants included in the analysis, 156 (40%) experienced the primary endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B (0.11 μg/l [95% CI 0.07-0.20] vs 0.09 μg/l [0.07-0.14]) and copeptin (23 pmol/l [9-104] vs 17 pmol/l [8-43]) were higher in participants meeting the primary endpoint. However, both biomarkers were poorly predictive of the primary outcome with a respective area under the receiving operator characteristic curve of 0.57 [0.51-0.64] and 0.59 [0.54-0.64]. Multivariable logistic regression analysis identified higher age (odds ratio [OR] 1.3 per decade [1.1-1.5]), provoked seizure (OR 4.93 [2.5-9.8]), complex partial seizure (OR 4.09 [1.8-9.1]) and first seizure (OR 1.83 [1.1-3.0]) as independent predictors of the primary outcome. A second regression analysis including the biomarkers showed no additional predictive benefit (S100-B OR 3.89 [0.80-18.9] copeptin OR 1 [1.00-1.00]). CONCLUSION: The plasma biomarkers S100-B and copeptin did not improve prediction of poor outcome following seizure. Higher age, a first seizure, a provoked seizure and a partial complex seizure are independently associated with adverse outcomes