On developing an unambiguous peatland classification using fusion of IKONOS and LiDAR DEM terrain derivatives – Victor Project, James Bay Lowlands

Bogs and fens, which comprise > 90% of the landscape near the De Beers Victor diamond mine, 90 km west of Attawapiskat, ON, provide different hydrological functions in connecting water flow pathways to the regional drainage network. It is essential to define their distribution, area and arrangement to understand the impact of mine dewatering, which is expected to increase groundwater recharge. Classification was achieved by developing a technique that uses IKONOS satellite imagery coupled with LiDAR-derived DEM derivatives to identify peatland classes. A supervised maximum likelihood classification was performed on the 1 m resolution IKONOS Red/Green/Blue without the infrared (RGB) and with the infrared (IR_RGB) band to determine the overall accuracy prior to inclusion of the DEM derivatives. Confusion matrices indicated 62.9% and 65.8% overall accuracy for the RGB and IR_RGB, respectively. Terrain derivatives were computed from the DEM including slope, vertical distance to channel network (VDCN), deviation from mean elevation (DME), percentile (PER) and difference from mean elevation (DiME). These derivatives were computed at a local (15-cell grid size) and meso (250-cell grid size) scale to capture terrain morphology. The mesoscale 250-cell grid analysis produced the most accurate classifications for all derivatives. However, spectral confusion still occurred (regardless of scale) most frequently in the Fen Dense Conifer vs. Bog Dense Conifer classes and also in the Bog Lichen vs. Bog Lichen Conifer. Despite this confusion, by combining the larger scale LiDAR DEM derivatives and the IKONOS imagery it was found that the overall classification accuracy could be improved by 13%. Specifically, the DiME derivative combined with the multispectral IKONOS (IR_RGB) produced an overall accuracy of 76.5%, and increased to 83.7% when Bog Lichen and Bog Lichen Conifer were combined during a post hoc analysis. This classification revealed the landscape composition of the North Granny Creek subwatershed, which is divided into north and south. The north portion comprises 67.4% bog, 13.6% fen and 18.9% water class, while the south is 63.7% bog, 15.2% fen and 21.1% water class. These proportions provide insight into the hydrology of the landscape and are indicative of the storage and conveyance properties of the subwatershed based on the percentage of bog, fen, or open water

Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study.

BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study. MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated. RESULTS: The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1-59.9) weeks for skin sTRAEs to 47.6 (47.1-48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1-123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1-79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab. CONCLUSION: Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment. IMPLICATIONS FOR PRACTICE: Nivolumab is a viable treatment option for patients with previously treated advanced hepatocellular carcinoma as it has demonstrated durable tumor responses and promising survival. Nivolumab has a manageable safety profile. The most common select treatment-related adverse events (sTRAEs) in this analysis were skin related (35%). Gastrointestinal and hepatic sTRAEs were observed in approximately 14% of patients. The majority of sTRAEs resolved (68%). Safety events are easier to manage if addressed early. Patient education on signs and symptoms to watch out for and the importance of early reporting and consultation should be emphasized

Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study

Background. CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study. Materials and Methods. Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated. Results. The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1–59.9) weeks for skin sTRAEs to 47.6 (47.1–48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1–123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1–79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab. Conclusion. Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment

Omeprazole and ultrastructural modifications occurring in reflux esophagitis [1]

Dilated intercellular spaces are a sign of esophageal epithelial damage in acid-perfused rabbits. This alteration can be identified only by transmission electron microscopy (TEM).1,2 The same changes have also been demonstrated in reflux esophagitis in humans, occurring in patients with either erosive or nonerosive esophagitis.3 As yet, we do not know if successful medical therapy induces a regression of these ultrastructural changes. We observed a case of hematemesis and melena occurring in an 11-month-old child. Upper gastrointestinal endoscopy revealed a hemorrhagic erosive esophagitis (stage IV of Savary-Miller modified classification). Eight endoscopic biopsies were taken 5 cm above the Z line. Of these, 4 were stained with H&E, to assess general pathology, and 4 were selected for processing by TEM.4 The latter biopsies showed mean intercellular space diameters of $3.04 mm (mean normal values reported in humans, 0.46 6 0.06 mm SD)3 (Figure 1A). After 6 months of treatment with ranitidine (10 mg z kg21 z d syrup) upper GI endoscopy showed a stage II esophagitis. TEM demonstrated mean intercellular space diameters of$2.5 mm (Figure 1B). As a consequence, the patient was treated with omeprazole 10 mg/day for 18 months (the half granular content of the capsule of 20 mg was administrated in a few milliliters of orange juice, 30 minutes before breakfast). During this period, the patient was asymptomatic, growth was normal, and no side effects were recorded. Upper GI endoscopy at the end of therapy showed a normal esophageal mucosa both endoscopically and histologically. TEM also demonstrated the complete recovery of the ultrastructural changes (Figure 1C) with the mean intercellular space diameters being #0.40. This is the first demonstration that omeprazole is effective not only in inducing the regression of symptoms and macroscopic lesions but in the restoration of normal intercellular space dimensions, whose dilatation must be considered the first alteration of reflux esophagitis. Nevertheless, to date we do not know if such an outcome is achieved in every patient considered clinically and endoscopically cured, nor do we know details of the treatment time interval required to achieve complete ultrastructural recovery

HCV INFECTION AND CHRONIC ACTIVE HEPATITIS IN ALCOHOLICS

Histological signs of chronic active hepatitis were found in 11/41 (27%) patients with chronic alcoholic liver disease. All these 11 patients tested positive for antibodies to HCV and no other causes of chronic hepatitis were found

Neural precursors (NPCs) from adult L967Q mice display early commitment to "in vitro" neuronal differentiation and hyperexcitability

The pathogenic factors leading to selective degeneration of motoneurons in ALS are not yet understood. However, altered functionality of voltage-dependent Na+ channels may play a role since cortical hyperexcitability was described in ALS patients and riluzole, the only drug approved to treat ALS, seems to decrease glutamate release via blockade or inactivation of voltage-dependent Na+ channels. The wobbler mouse, a murine model of motoneuron degeneration, shares some of the clinical features of human ALS. At early stages of the wobbler disease, increased cortical hyperexcitability was observed. Moreover, riluzole reduced motoneuron loss and muscular atrophy in treated wobbler mice. Here, we focussed our attention on specific electrophysiological properties, like voltage-activated Na+ currents and underlying regenerative electrical activity, as readouts of the neuronal maturation process of neural stem/progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of adult early symptomatic wobbler mice. In self-renewal conditions, the rate of wobbler NPC proliferation “in vitro” was 30% lower than that of healthy mice. Conversely, the number of wobbler NPCs displaying early neuronal commitment and action potentials was significantly higher. Upon switching from proliferative to differentiative conditions, NPCs underwent significant changes in the key properties of voltage gated Na+ currents. The most notable finding, in cells with neuronal morphology, was an increase in Na+ current density that strictly correlated with an increased probability to generate action potentials. This feature was remarkably more pronounced in neurons differentiated from wobbler NPCs that upon sustained stimulation, displayed short trains of pathological facilitation. In agreement with this result, an increase in the number of c-Fos positive cells, a surrogate marker of neuronal network activation, was observed in the mesial cortex of the wobbler mice “in situ”. Thus these findings, all together, suggest that a state of early neuronal hyperexcitability may be a major contributor of motoneuron vulnerability

RECTAL CELL-PROLIFERATION AND COLON CANCER RISK IN ULCERATIVE-COLITIS

Cell proliferation kinetics of 30 patients affected by extensive ulcerative colitis in remission have been studied with autoradiography of rectal biopsies incubated with tritiated thymidine. The results have been compared with those of 20 control subjects without evidence of colonic diseases, and of 16 patients with multiple nonfamilial colonic adenomas. The labeling index was similar in the three groups (P = NS). On the contrary, the labeling frequency (SEM) in the upper 40% of the crypt (phi h value) was 0.04 +/- 0.01 in controls, 0.16 +/- 0.02 in ulcerative colitis, and 0.10 +/- 0.01 in adenoma patients (P less than 0.001 ulcerative colitis versus controls, P less than 0.01 adenomas versus controls, P = NS ulcerative colitis versus adenomas). The distribution of phi h values in ulcerative colitis showed a bimodal trend with 22 patients having mean phi h values similar to adenoma patients (0.10 +/- 0.01) and 8 with higher values (0.30 +/- 0.02). No relationship was found between phi h values and duration of colitis, age of patients, or age at onset of symptoms. These data show that cell kinetics studies can detect patients at particularly high risk of colon cancer, and that additional factors should determine colon cancer risk level in ulcerative colitis