Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research

This randomized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate (ORR) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil (ECF) as first-line advanced gastric cancer therapy.

Effect of 6-month supervised exercise on low-density lipoprotein apolipoprotein B kinetics in patients with type 2 diabetes mellitus

Although low-density lipoprotein (LDL) cholesterol is often normal in patients with type 2 diabetes mellitus, there is evidence for a reduced fractional catabolic rate and consequently an increased mean residence time (MRT), which can increase atherogenic risk. The dyslipidemia and insulin resistance of type 2 diabetes mellitus can be improved by aerobic exercise, but effects on LDL kinetics are unknown. The effect of 6-month supervised exercise on LDL apolipoprotein B kinetics was studied in a group of 17 patients with type 2 diabetes mellitus (mean age, 56.8 years; range, 38-68 years). Patients were randomized into a supervised group, who had a weekly training session, and an unsupervised group. LDL kinetics were measured with an infusion of 1-(13)C leucine at baseline in all groups and after 6 months of exercise in the patients. Eight body mass index-matched nondiabetic controls (mean age, 50.3 years; range, 40-67 years) were also studied at baseline only. At baseline, LDL MRT was significantly longer in the diabetic patients, whereas LDL production rate and fractional clearance rates were significantly lower than in controls. Percentage of glycated hemoglobin A(1c), body mass index, insulin sensitivity measured by the homeostasis model assessment, and very low-density lipoprotein triglyceride decreased (P < .02) in the supervised group, with no change in the unsupervised group. After 6 months, LDL cholesterol did not change in either the supervised or unsupervised group; but there was a significant change in LDL MRT between groups (P < .05) that correlated positively with very low-density lipoprotein triglyceride (r = 0.51, P < .04) and negatively with maximal oxygen uptake, a measure of fitness (r = -0.51, P = .035), in all patients. The LDL production and clearance rates did not change in either group. This study suggests that a supervised exercise program can reduce deleterious changes in LDL MRT.

A 700-year paleoecological record of boreal ecosystem responses to climatic variation from Alaska

Recent observations and model simulations have highlighted the sensitivity of the forest - tundra ecotone to climatic forcing. In contrast, paleoecological studies have not provided evidence of tree-line fluctuations in response to Holocene climatic changes in Alaska, suggesting that the forest - tundra boundary in certain areas may be relatively stable at multicentennial to millennial time scales. We conducted a multiproxy study of sediment cores from an Alaskan lake near the altitudinal limits of key boreal-forest species. Paleoecological data were compared with independent climatic reconstructions to assess ecosystem responses of the forest - tundra boundary to Little Ice Age (LIA) climatic. uctuations. Pollen, diatom, charcoal, macrofossil, and magnetic analyses provide the first continuous record of vegetation -. re - climate interactions at decadal to centennial time scales during the past 700 years from southern Alaska. Boreal-forest diebacks characterized by declines of Picea mariana, P. glauca, and tree Betula occurred during the LIA ( AD 1500 - 1800), whereas shrubs ( Alnus viridis, Betula glandulosa/nana) and herbaceous taxa (Epilobium, Aconitum) expanded. Marked increases in charcoal abundance and changes in magnetic properties suggest increases in. re importance and soil erosion during the same period. In addition, the conspicuous reduction or disappearance of certain aquatic ( e. g., Isoetes, Nuphar, Pediastrum) and wetland ( Sphagnum) plants and major shifts in diatom assemblages suggest pronounced lake-level. uctuations and rapid ecosystem reorganization in response to LIA climatic deterioration. Our results imply that temperature shifts of 1 - 2 degrees C, when accompanied by major changes in moisture balance, can greatly alter high-altitudinal terrestrial, wetland, and aquatic ecosystems, including conversion between boreal-forest tree line and tundra. The climatic and ecosystem variations in our study area appear to be coherent with changes in solar irradiance, suggesting that changes in solar activity contributed to the environmental instability of the past 700 years.

Infra-Population and -Community Dynamics of the Parasites Nosema apis and Nosema ceranae, and Consequences for Honey Bee (Apis mellifera) Hosts

Nosema spp. fungal gut parasites are among myriad possible explanations for contemporary increased mortality of western honey bees (Apis mellifera, hereafter honey bee) in many regions of the world. Invasive Nosema ceranae is particularly worrisome because some evidence suggests it has greater virulence than its congener N. apis. N. ceranae appears to have recently switched hosts from Asian honey bees (Apis cerana) and now has a nearly global distribution in honey bees, apparently displacing N. apis. We examined parasite reproduction and effects of N. apis, N. ceranae, and mixed Nosema infections on honey bee hosts in laboratory experiments. Both infection intensity and honey bee mortality were significantly greater for N. ceranae than for N. apis or mixed infections; mixed infection resulted in mortality similar to N. apis parasitism and reduced spore intensity, possibly due to inter-specific competition. This is the first long-term laboratory study to demonstrate lethal consequences of N. apis and N. ceranae and mixed Nosema parasitism in honey bees, and suggests that differences in reproduction and intra-host competition may explain apparent heterogeneous exclusion of the historic parasite by the invasive species

Late-Holocene climate variability and ecosystem responses in Alaska inferred from high-resolution multiproxy sediment analyses at Grizzly Lake

The late-Holocene shift from Picea glauca (white spruce) to Picea mariana (black spruce) forests marked the establishment of modern boreal forests in Alaska. To understand the patterns and drivers of this vegetational change and the associated late-Holocene environmental dynamics, we analyzed radiocarbon-dated sediments from Grizzly Lake for chironomids, diatoms, pollen, macrofossils, charcoal, element composition, particle size, and magnetic properties for the period 4100–1800 cal BP. Chironomid assemblages reveal two episodes of decreased July temperature, at ca. 3300–3150 (ca −1 °C) and 2900–2550 cal BP (ca −2 °C). These episodes coincided with climate change elsewhere in the Northern Hemisphere, atmospheric reorganization, and low solar activity. Diatom-inferred lake levels dropped by ca. 5 m at 3200 cal BP, suggesting dry conditions during the period 3200–1800 cal BP. P. glauca declined and P. mariana expanded at ca. 3200 cal BP; this vegetational change was linked to diatom-inferred low lake levels and thus decreased moisture availability. Forest cover declined at 3300–3100, 2800–2500 and 2300–2100 cal BP and soil erosion as inferred from increased values of Al, K, Si, Ti, and Ca intensified, when solar irradiance was low. Plant taxa adapted to disturbance and cold climate (e.g. Alnus viridis, shrub Betula, Epilobium) expanded during these periods of reduced forest cover. This open vegetation type was associated with high fire activity that peaked at 2800 cal BP, when climatic conditions were particularly cold and dry. Forest recovery lagged behind subsequent climate warming (≤+3 °C) by ca. 75–225 years. Our multiproxy data set suggests that P. glauca was dominant under warm-moist climatic conditions, whereas P. mariana prevailed under cold-dry and warm-dry conditions. This pattern implies that climatic warming, as anticipated for this century, may promote P. glauca expansions, if moisture availability will be sufficiently high, while P. mariana may expand under dry conditions, possibly exacerbating climate impacts on the fire regime.

Pollen and charcoal in lake sediments compared with historically documented forest fires in southern Switzerland since AD 1920

Charcoal in unlaminated sediments dated by 210Pb was analysed by the pollen-slide and thin-section methods. The results were compared with the number and area of forest fires on different spatial scales in the area around Lago di Origlio as listed in the wildfire database of southern Switzerland since AD 1920. The influx of the number of charcoal particles > 75 µm2 in pollen slides correlates well with the number of annual forest fires recorded within a distance of 20-50 km from the coring site. Hence a size-class distinction or an area measurement by image analysis may not be absolutely necessary for the reconstruction of regional fire history. A regression equation was computed and tested against an independent data set. Its use makes it possible to estimate the charcoal area influx (or concentration) from the particle number influx (or concentration). Local fires within a radius of 2 km around the coring site correlate well with the area influx of charcoal particles estimated by the thin-section method measuring the area of charcoal particles larger than 20 000 µm2 or longer than 50 µm. Pollen percentages and influx values suggest that intensive agriculture and Castanea sativa cultivation were reduced 30-40 years ago, followed by an increase of forest area and a development to more natural woodlands. The traditional Castanea sativa cultivation was characterized by a complete use of the biomass produced, so abandonment of chestnut led to an increasing accumulation of dead biomass, thereby raising the fire risk. On the other hand, the pollen record of the regional vegetation does not show any clear response to the increase of fire frequency during the last three decades in this area.

Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic stem cell disorder resulting from mutations in an X-linked gene, PIG-A, that encodes an enzyme required for the first step in the biosynthesis of glycosylphosphatidylinositol (GPI) anchors. PIG-A mutations result in absent or decreased cell surface expression of all GPI-anchored proteins. Although many of the clinical manifestations (e.g., hemolytic anemia) of the disease can be explained by a deficiency of GPI-anchored complement regulatory proteins such as CD59 and CD55, it is unclear why the PNH clone dominates hematopoiesis and why it is prone to evolve into acute leukemia. We found that PIG-A mutations confer a survival advantage by making cells relatively resistant to apoptotic death. When placed in serum-free medium, granulocytes and affected CD34+ (CD59−) cells from PNH patients survived longer than their normal counterparts. PNH cells were also relatively resistant to apoptosis induced by ionizing irradiation. Replacement of the normal PIG-A gene in PNH cell lines reversed the cellular resistance to apoptosis. Inhibited apoptosis resulting from PIG-A mutations appears to be the principle mechanism by which PNH cells maintain a growth advantage over normal progenitors and could play a role in the propensity of this disease to transform into more aggressive hematologic disorders. These data also suggest that GPI anchors are important in regulating apoptosis.

Notes of proceedings and cases determined in the high court of errors and appeals, the court of chancery, and the orphans court of the state of Delaware, 1792-1832

Contains summaries of cases heard by the Delaware Supreme Court and the Delaware Appeals Court in the counties of Sussex, Kent, and Newcastle covering a variety of legal topics. Supposedly based on Wilson's Red Book.