Significant Regressions Research Articles

Safety and activity of MDX-1106 (ONO-4538), an anti-PD-1 monoclonal antibody, in patients with selected refractory or relapsed malignancies

3006 Background: Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. Objectives of this first in human phase I trial of MDX-1106 (ONO-4538), a fully human IgG4 anti-PD-1 blocking antibody, are to evaluate safety and maximum tolerated dose (MTD). Other objectives include evaluation of pharmacokinetics (PK) and immunological effects. Methods: Patients (pts) had treatment refractory metastatic non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), colon cancer (CC), melanoma (MEL), or prostate cancer (HRPC), and no history of autoimmune disease. Sequential cohorts of 6 pts received a single IV dose of MDX-1106 at 0.3, 1, 3, or 10 mg/kg. Disease status was evaluated at wk 8 by RECIST criteria. Pts with SD or lesional responses could receive additional MDX-1106 at wks 12 and 16, at the original dose. Results: 24 pts, 6 at each dose level (9 CC, 5 NSCLC, 6 MEL, 4 HRPC), were enrolled through 11/07. 23 pts have been assessed for tumor response at 8 wks. All doses were well tolerated and no MDX-1106 related SAEs occurred. Two pts (treated at 3 and 10 mg/kg) developed arthritic symptoms requiring treatment, and 2 pts had an asymptomatic TSH elevation. Objective tumor responses (CR or PR) were not observed within 8 wks. Three pts had significant lesional regressions (1 NSCLC pt at 1 mg/kg, 2 MEL pts at 10 mg/kg). Five pts with SD or lesional regressions received retreatment. Biopsy of a regressing MEL lymph node metastasis showed a moderately increased CD8+ T cell infiltrate post treatment. PK and immunological evaluations are underway. Conclusions: The targeted maximum dose of 10 mg/kg of MDX-1106 was achieved without observing dose-limiting toxicities, and lesional tumor regressions were observed in 3 of 23 pts evaluated. An expansion cohort at 10 mg/kg is enrolling 15 additional pts. Therapy with MDX-1106 to enhance endogenous antitumor immunity, either alone or in combination with other therapeutic modalities, warrants further study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amplimmune, Inc., Medarex Amplimmune, Inc., Bristol-Myers Squibb, Medarex, Inc. Amplimmune, Inc., Medarex Cell Genesys, Inc., Medarex

Abstract 4958: Presence of amphiregulin autocrine-loop predicts sensitivity of EGFR wild type cancers to gefitinib and cetuximab

Abstract Background: Epidermal growth factor receptor (EGFR) is a therapeutic target in non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC). Patients with NSCLC with activating mutations in EGFR typically have significant tumor regressions with gefitinib. However approximately 30% of patients treated with gefitinib develop stable disease even without EGFR mutations. EGFR mutations are rare in HNSCC. As EGFR can be activated by one of its ligands (amphiregulin, EGF, TGFα), we examined the relationship of EGFR ligands and the efficacy of gefitinib and cetuximab using EGFR wild type NSCLC, HNSCC cell lines and in tissue samples from NSCLC pts treated with gefitinib or erlotinib. Methods: Amphiregulin (AR), EGF and TGFα in cell culture media were analyzed with ELISA assays in 18 cell lines, 14 NSCLC (4 EGFR mutant; 10 EGFR wild type) and 4 HNSCC cell lines. The in vitro sensitivity was analyzed using MTS assay. EGFR, HER3, Akt, ERK1/2, Cyclin D1 and phosphorylation of these were analyzed with Western blotting. Cell cycle was analyzed by flow cytometry. Tissue samples from 29 pt with EGFR wild type NSCLC were studied using IHC. These are treated with gefitinib or erlotinib. AR expression was scored (0-400) by multiplying extent (0-100%) and intensity (0-4) of staining. Results: TGFα (range, 0 to 4.8pg/ml) and EGF (0 to 2.2pg/ml) was detected at negligible level in all cell lines except Calu3 (TGF; 116.6pg/ml). The presence of AR varied significantly among the cell lines (range, 4.6 to 1625.8pg/ml). All 4 EGFR mutant cell lines had negligible levels of AR (<50.3pg/ml). Seven cell lines of the 14 cell lines with wild-type EGFR had > 250 pg/ml (718.4 to 1625.8pg/ml) of AR and all were sensitive to gefitinib with an IC50 of < 1 μM (range, 0.10 to 0.33). In addition, they were also sensitive to cetuximab (mean growth inhibition following10ug/ml cetuximab 56.8%, range, 33.1 to 87.1 %). In contrast cell lines producing < 250 pg/ml of AR were resistant to both gefitinib (IC > 1 μM) and cetuximab (mean growth inhibition following 10ug/ml cetuximab 1.0%, range -4.4 to 15.3%). The AR producing cell lines underwent G1/S arrest following either gefitinib or cetuximab. AR producing cell lines exhibited dose dependent decrease in p-EGFR, p-ERK 1/2 and cyclin D1 following gefitinib or cetuximab. AR non-producing cell lines had no effect on these proteins following treatment. IHC of tissue samples showed 9/10 samples from pts, developed stable disease.following gefitinib, had high AR expression (cut off score 100), while only 3/19 samples had high AR expression from pts with progressive disease (p<0.001). Conclusion: Our findings suggest that in EGFR wild type NSCLC and HNSCC cell lines the presence of an AR autocrine loop is a major determinant of in vitro sensitivity to gefitinib and cetuximab. AR expression may be a suitable biomarker to select EGFR wild type NSCLC patients likely to benefit from gefitinib or erlotinib.

NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis

We describe the biological properties of NVP-AUY922, a novel resorcinylic isoxazole amide heat shock protein 90 (HSP90) inhibitor. NVP-AUY922 potently inhibits HSP90 (K(d) = 1.7 nmol/L) and proliferation of human tumor cells with GI(50) values of approximately 2 to 40 nmol/L, inducing G(1)-G(2) arrest and apoptosis. Activity is independent of NQO1/DT-diaphorase, maintained in drug-resistant cells and under hypoxic conditions. The molecular signature of HSP90 inhibition, comprising induced HSP72 and depleted client proteins, was readily demonstrable. NVP-AUY922 was glucuronidated less than previously described isoxazoles, yielding higher drug levels in human cancer cells and xenografts. Daily dosing of NVP-AUY922 (50 mg/kg i.p. or i.v.) to athymic mice generated peak tumor levels at least 100-fold above cellular GI(50). This produced statistically significant growth inhibition and/or regressions in human tumor xenografts with diverse oncogenic profiles: BT474 breast tumor treated/control, 21%; A2780 ovarian, 11%; U87MG glioblastoma, 7%; PC3 prostate, 37%; and WM266.4 melanoma, 31%. Therapeutic effects were concordant with changes in pharmacodynamic markers, including induction of HSP72 and depletion of ERBB2, CRAF, cyclin-dependent kinase 4, phospho-AKT/total AKT, and hypoxia-inducible factor-1alpha, determined by Western blot, electrochemiluminescent immunoassay, or immunohistochemistry. NVP-AUY922 also significantly inhibited tumor cell chemotaxis/invasion in vitro, WM266.4 melanoma lung metastases, and lymphatic metastases from orthotopically implanted PC3LN3 prostate carcinoma. NVP-AUY922 inhibited proliferation, chemomigration, and tubular differentiation of human endothelial cells and antiangiogenic activity was reflected in reduced microvessel density in tumor xenografts. Collectively, the data show that NVP-AUY922 is a potent, novel inhibitor of HSP90, acting via several processes (cytostasis, apoptosis, invasion, and angiogenesis) to inhibit tumor growth and metastasis. NVP-AUY922 has entered phase I clinical trials.

Convergence in the relationship of CO2 and N2O exchanges between soil and atmosphere within terrestrial ecosystems

AbstractEcosystem CO2 and N2O exchanges between soils and the atmosphere play an important role in climate warming and global carbon and nitrogen cycling; however, it is still not clear whether the fluxes of these two greenhouse gases are correlated at the ecosystem scale. We collected 143 pairs of ecosystem CO2 and N2O exchanges between soils and the atmosphere measured simultaneously in eight ecosystems around the world and developed relationships between soil CO2 and N2O fluxes. Significant linear regressions of soil CO2 and N2O fluxes were found for all eight ecosystems; the highest slope occurred in rice paddies and the lowest in temperate grasslands. We also found the dominant role of growing season on the relationship of annual CO2 and N2O fluxes. No significant relationship between soil CO2 and N2O fluxes was found across all eight ecosystem types. The estimated annual global N2O emission based on our findings is 13.31 Tg N yr−1 with a range of 8.19–18.43 Tg N yr−1 for 1980–2000, of which cropland contributes nearly 30%. Our findings demonstrated that stoichiometric relationships may work on ecological functions at the ecosystem level. The relationship of soil N2O and CO2 fluxes developed here could be helpful in biogeochemical modeling and large‐scale estimations of soil CO2 and N2O fluxes.

The Influence of Wind Speed on Heat Island Phenomena in Athens, Greece

The present study is focused on the relation between wind speed and air temperature during the summer period over the greater Athens area. Specifically, hourly air temperature data, recorded at 27 stations, were studied for June, July, August and September between 1996 and 1998. These data were related to the corresponding mean hourly values of wind speed, which were measured by the National Observatory of Athens. A small increase in air temperature in relation to increasing wind speed was found for daytime and night-time periods. This relation was derived from statistically significant regressions of hyperbolic or exponential functions. The relationship between the wind speed and the air temperature difference between the measurement point and a reference station, and its spatial distribution over the greater Athens area was examined.

Influência da abertura de trilhas antrópicas e clareiras naturais na fenologia reprodutiva de Gymnanthes concolor (Spreng.) Müll. Arg. (Euphorbiaceae)

In the interior of a seasonal semideciduous forest at Santa Maria, RS, Brazil, we investigated whether a wide and lighter trail differed from a narrow and darker path (darker trail) concerning the reproductive phenology of G. concolor. We also examined whether the creation of natural gaps in 2002 affected the incident light and phenology of G. concolor in 2003, answering the questions: (a) Do the trails differ regarding the incident light on the tree canopy and the number of male inflorescences, female flowers, fruits and fruit size (phenological variables)? (b) Is there a relationship between incident light on the tree canopy and the phenological variables? (c) In each trail, do individuals adjacent to gaps differ from individuals far away from gaps regarding the interannual variation in the incident light and phenological variables? In 2002, the incident light was significantly higher on lighter trail than darker trail trees, but trails did not differ in respect to phenological variables. In 2003, incident light and phenological variables did not differ significantly between trees in lighter trail and darker trail. Therefore, the light incidence on lighter trail did not promote a significantly phenological change. The result is supported by the low number of significant regressions between light incidence and phenological variables. Trees adjacent to gaps presented a light incidence variation significantly higher than those trees far away from gaps, but did not differ in respect to interannual variation in phenological variables. Hence, the higher light incidence after the creation of gaps did not affect significantly the phenology of G. concolor as well, which may need even higher amounts of light to respond to gaps or open trails. Our results may give some insight to the design of ecological trails or other open spaces on natural reserves, to reduce its impact on flowering and fruiting production of the species nearby.

Detection of a resistance gradient to Passion fruit woodiness virus and selection of ‘yellow’ passion fruit plants under field conditions

Productivity of 'yellow' passion fruit (Passiflora edulis Sims. f. flavicarpa O. Deg.) is reduced by infection with Cowpea aphid-borne mosaic virus (CABMV). We examined resistance in 72 yellow passion fruit plants grown from open-pollinated commercial seed. Plants were mechanically inoculated with CABMV virus and maintained in the field in order to select contrasting genotypes for resistance. Isolates were obtained from symptomatic leaves of yellow passion fruit plants from field production in Livramento de Nossa Senhora, Bahia state and were characterized by sequencing the viral coat protein gene. Severity of leaf symptoms of the disease, evaluated through a global leaf disease index, was measured during the eighth month of growth. Morpho-agronomic variables of fruit were evaluated from months 10 to 12. Significant linear regressions between the quantification of the leaf symptoms and the morpho-agronomic characteristics related to productivity were detected (5.17% <or= R(2) <or= 11%; 0.002 <or= p <or= 0.028). Based on evaluations of fruit productivity, severity of leaf symptoms of the disease, and the application of a selection index of 10%, four contrasting groups of 'yellow' passion fruit plants considered as "resistant", "mildly resistant", "susceptible" and "extremely susceptible" in their reaction to CABMV (0.0001 < p < 0.024) were selected. These plants could be useful for genetic studies and for breeding yellow passion fruit plants resistant to this disease.

Relationship between streamflow and nutrient and sediment losses from an oak-beech forest watershed during an 18-year long monitoring study in Turkey

The objectives of this study were to quantify the amount of the stream discharge, nutrient fluxes, suspended sediment loss, and to define the relationship between streamflow and these parameters in a forest-covered watershed. The study was carried out in an experimental watershed, which has been monitored since 1979 in the Belgrad forest in Istanbul. Significant linear regressions were obtained between streamflow and discharge of selected water quality parameters. Mean monthly losses were 10.01 kg/ha for HCO3 −, 5.92 kg/ha for CI−, 0.07 kg/ha for total N, 1.29 kg/ha for Mg2+, 3.59 kg/ha for Ca2+, 2.59 kg/ha for Na+, 1.82 kg/ha for K+, 0.0113 kg/ha for P-PO4 3−, and 35.82 kg/ha for suspended sediments. Among the monitored water quality parameters, HCO3 −, CI−, and Ca2+ had greater losses than the rest of the chemical parameters studied in the watershed. Net gains (influx exceeded outflux) calculated for total N, Mg2+, K+, and P-PO4 3− in the annual basis can be considered as an addition to the ecosystem’s organic nutrient pool. In contrast, net losses occurred for HCO3 −, CI−, Ca2+, and Na+.

Breeding Bird Communities Across an Upland Disturbance Gradient in the Western Lake Superior Region

Upland breeding bird communities were sampled from 225 points in 15 survey routes in the coastal region of western Lake Superior to examine relationships to human land use. Eighty-four species were detected and 50 were abundant enough to be included in data analysis. Monotonic quadratic regression models were constructed for these 50 species by using species counts as the dependent variable and the proportion of human conversion of the landscape (residential, agriculture, and commercial/industrial land uses) within each study area as the independent variable. Twenty-seven bird species had significant regressions (P < 0.05), 18 of which generally avoided areas developed by humans and 9 of which were attracted to development. Detrended correspondence analysis using counts of these 27 bird species was used to investigate multivariate, community responses to development. The first DCA axis was interpreted as a gradient from urban avoiding to urban exploiting bird species and was strongly correlated with land cover variables related to human development. Our results advance the idea that breeding bird communities can be used as indicators of ecological condition and can diagnose potential causes for changes in these conditions. Further, our study points out the usefulness of bird monitoring data in regional planning efforts that incorporate goals for maintaining native biological diversity.

SPRING ARRIVAL DATES OF MIGRATORY BREEDING BIRDS IN MAINE: SENSITIVITY TO CLIMATE CHANGE

I analyzed the relationship between spring temperature and arrival date for 105 species using over 32,000 arrival records of migratory breeding birds in Maine collected by a volunteer network between 1994 and 2005. I used quantile regression analysis, testing three different quantiles (0.1, 0.25, 0.5). Only 69 of 315 regressions yielded a significant negative relationship. Five species showed significant regressions for all three quantiles and 15 showed significant regressions for two quantiles. Quantile regressions of arrival date with a hemispheric measure of climate variability, the North Atlantic Oscillation index, produced only 63 statistically significant regressions for the three quantiles. Seven species and 12 species had significant regressions with three and two quantiles, respectively. Overall, 60 species had at least one significant relationship with a climatic variable. These results indicate the arrival dates of most migratory breeding birds in Maine show a modest relationship with the significant temperature variability seen over the 12-year study period. The data suggest the response of migratory birds in Maine to global warming impacts will be a gradual process.

The effect of dietary protein content on calcium and phosphorus retention in the growing Iberian pig

The effects of dietary protein content (DPC) from excessive (192 g/kg DM) to marginally deficient (101 g/kg DM) upon whole-body retention of Ca and P was studied in 25 purebred Iberian pigs growing from 15 to 50 kg BW by means of a comparative slaughter experiment which included a digestibility trial. Ca and P retention related to intake remained unaffected at 0.228 ± 0.0072 and 0.184 ± 0.0052, reaching 3.64 ± 0.119 and 2.00 ± 0.057 g Ca and P per day respectively. Pigs fed on diets containing protein levels in excess of requirements had significantly higher concentrations of Ca and P ( P < 0.05) in their bodies (14.41–14.99 and 7.88–8.08 g Ca and P/kg fat-free empty-body gain respectively) than those given adequate or marginally deficient amounts of dietary protein (11.80–12.72 and 6.61–7.01 g Ca and P/kg fat-free empty-body gain respectively). In a second experiment, made with 25 Iberian pigs of 21 kg initial weight, daily intakes of Ca and P to maintain zero retention were determined using five experimental diets in which the concentrations of Ca and P were varied by the addition of graded levels of Ca carbonate and inorganic phosphate to a basal diet balanced in protein-to-energy ratio (131 g CP; 13.8–14.4 MJ ME/kg DM). Growth rate and protein deposition were unaffected by the level of Ca and P in the diet and reached average values of 485 ± 15.4 and 103 ± 1.2 g/d. Increasing the dietary Ca and P levels increased the absolute amounts of Ca and P retained daily from 0.69 to 5.77 and 1.12 to 3.70 g respectively ( P < 0.001). Highly significant ( P < 0.001) curvilinear regressions were obtained when relating Ca and P absorption or retention (g/d) with Ca and P intake (g/d). From these equations, daily maintenance requirements of 105 and 72 mg/kg BW for Ca and P respectively were obtained. Average total net requirements of Ca and P for the Iberian pig at this stage of growth were estimated to be 5.25 and 3.10 g/d respectively, considerably lower than those reported for conventional and high-performance pig genotypes.

Allometric basis of enrofloxacin scaling in green iguanas

When body size varies greatly, drug disposition can best be described as an allometric function of body weight. Therefore, the allometry of standard metabolic rate (SMR; 3/4 power) and body surface area (BSA; 2/3 power) have been advocated as surrogate markers for the prediction of key pharmacokinetic parameters. The goal of the present study was to examine the allometric basis of pharmacokinetic scaling within a species, green iguanas. Enrofloxacin was administered intravenously to 20 green iguanas (322-3824 g), and noncompartmental analysis was used to calculate standard pharmacokinetic parameters, which were log(10) transformed and regressed against log(10) body weight. The slopes of significant regressions were compared with the values of unity, 3/4, and 2/3. The slope of enrofloxacin total body clearance (Cl) was also compared with the slopes relating SMR and renal Cl of (99m)Tc-diethylenetriamine penta-acetic acid ((99m)DTPA) to body weight in iguanas. Enrofloxacin Cl depended allometrically on body weight with the power of 0.32. The slope of enrofloxacin Cl was significantly less than those of SMR, Cl of (99m)DTPA, and the 2/3 value. Therefore, the relationship between enrofloxacin Cl and body weight does not directly depend on the allometry of BSA, SMR, or renal Cl of (99m)DTPA in iguanas.

Der Gestationsdiabetes unter klinischen Bedingungen bei angestrebter Normoglykämie: Korrelationsuntersuchungen zwischen maternalen Blutzuckertagesprofilen und fetometrischen Ultraschallparametern

One of the therapeutic aims in gestational diabetes (GDM) is to prevent the development of fetal hypertrophy by adaptation of maternal glycemic control. Relating to this context, maternal blood glucose daily profiles and fetal biometry ultrasound parameters were analysed for a possible correlation. A special focus was given to the question as to whether a latency period exists for this possible connection. 152 pregnancies affected by GDM, without fetal malformations or aneuploidies, were enrolled. Altogether, 746 ultrasound examinations consisting of 7 fetometric parameters each and 1 288 blood glucose daily profiles originating from the 20 (th) to 40 (th) gestational week were systematically investigated for interrelation by correlation and multiple regression analysis. No robust, constant correlation between the analysed parameters could be observed. However, marked differences between latency periods were noticed. Blood glucose parameters, which revealed significant regressions with fetal abdominal circumference, had an average time lag of 6.2 +/- 2.5 weeks, whereas the latency period for head circumference averaged 2.4 +/- 1.2 weeks. The overall small-for-gestational-age (SGA) rate was 20 %, pregnant women with a body mass index > 30 kg / m (2) revealed the highest rate of 28 %. Therapeutic intervention depending on sonographically detected hypertrophy must be considered as being delayed. The currently valid therapeutic criteria including intended normoglycemia and regular fetometric ultrasound controls cannot prevent markedly high SGA rates, especially among obese women, in adequately treated GDM.

Prenatal Growth and Development in the Angolan Free-tailed Bat, Mops condylurus (Chiroptera: Molossidae)

We present data on prenatal growth, development, and skeletal ossification for the Angolan free-tailed bat (Mops condylurus), a species distributed throughout sub-Saharan Africa. Specimens were measured for crown‐rump length (CRL), greatest length of the skull (GLS), forearm length, mass, and wing area. We cleared and differentially stained specimens for cartilage and bone to quantify pattern of skeletogenesis. Significant regressions for general growth trajectories were generated by plotting CRL and fetal mass against GLS. We quantified growth of the forearm, which showed a positive relationship with growth of the skull. Curiously, wing area was highly positively related to fetal mass, suggesting an ecomorphological relationship of wing loading and flight ability being established early in development in this species. Patterns of ossification in this species were more similar to those of phyllostomid and pteropodid bats than they were to vespertilionid bats, to which M. condylurus is apparently more closely related. In this paper, we provide the 1st published account of prenatal growth, development, and skeletal ossification for the Angolan free-tailed bat, Mops condylurus (Chiroptera: Molossidae). Understanding developmental patterns provides key insights into the evolution of form and function as well as the origins of key evolutionary innovations (Jablonka and Lamb 1998). Indeed, heterochronic shifts in developmental timing are in large part responsible for the evolutionary diversity of the vertebrate limb (Smith 2003).

The development of a Biotic Pollution Index for the River Nile in Egypt

This article describes the development of a Nile Biotic Pollution Index (NBPI) for the River Nile in Egypt. Chemical data were collected from 30 locations along the Nile from Aswan to Cairo and 21 sites within the river delta, incorporating a range of conditions from unpolluted to grossly polluted. Seven chemical variables were used to calculate a Nile Chemical Pollution Index (NCPI) for each site. Biological data were collected primarily using Artificial Substrate Samplers (ASS). The UK developed, Biological Monitoring Working Party (BMWP) biotic index and the BMWP-ASPT were applied to the data. A Nile Biotic Pollution Index (NBPI) and the NBPI-ASPT were obtained by incorporating more of the Nile taxa. There were highly significant regressions (P < 0.001) for both the UK and the Nile Pollution Index scores with the NCPI for the whole river. The modification of the UK indices improved the Nile Indices increasing the number of taxa recorded from 29 to 43 and the total number of recorded taxon occurrences from 377 to 490. The Nile Indices provided better discrimination at both ends of the pollution spectrum. The NBPI-ASPT was best for the river as a whole, and particularly for the river from Aswan to Cairo. The NBPI was much better in the delta than from Aswan to Cairo. These differences in performance were attributed to the fact that the NBPI-ASPT excludes information on taxon diversity. In clean waters there was a wide range of NBPI score suggesting that the biodiversity of taxa is dependent on other aspects of habitat quality. Conversely in the polluted delta the high score of an individual taxon is critical for the NBPI-ASPT as it may have a distorting effect. As the NBPI-ASPT was the most consistent biotic index it is recommended as the regular biological assessment and regulatory tool for Egypt to meet the requirements of the Convention for Biodiversity.

Landscape indicators of wetland condition in the Nanticoke River watershed, Maryland and Delaware, USA

We developed relationships for estimating wetland condition from remotely sensed data and digital maps. Assessment methods relying on maps rather than field sampling (level 1 assessment) are often expert systems summarizing the best professional judgments of wetland scientists. We instead developed level 1 assessment relationships by statistically analyzing results from field sampling. The field campaign applied the hydrogeomorphic (HGM) functional assessment approach to sample 143 freshwater flat and riverine wetlands in the Nanticoke River watershed, Maryland and Delaware, USA. Functional condition index (FCI) scores for five wetland functions were calculated from the field observations. We used geographic information system (GIS) analysis of digital maps to derive candidate landscape indicators for the sampled points. We tested which indicators correlated strongly with the field condition scores, and then we used stepwise multiple regression and regression tree analysis to identify the most effective combinations of landscape metrics for predicting the condition measurements. The best multiple regressions combined information from land-cover, road, and stream maps, especially a stream map resolving natural stream reaches from channelized or ditched reaches. For riverine wetlands, we obtained statistically significant regressions explaining 63%–85% of the variance of measured FCI scores for all five HGM functions (hydrology, biogeochemistry, habitat, plant community, and landscape). Comparable models for flat wetlands were also statistically significant but explained less (48%–54%) of the variance. Regression tree analysis produced more parsimonious models than did stepwise multiple regression. A tree model explained the same amount of variability as the multiple regression model for two flat and two riverine functions, but the tree model explained less variability for two flat and three riverine functions. Our level 1 relationships can be applied to estimate condition scores for unsampled wetlands and to provide confidence limits for those estimates. The uncertainty in predicting a condition scores for individual assessment points is high for most HGM functions, but the models can still help prioritize field visits to select sites for management action. Confidence limits are narrower for predicting mean scores across many wetlands, so the relationships are more powerful for predicting average wetland condition across an assessment area, such as a watershed.

Early Holocene paleoseismic history at the Pakarae locality, eastern North Island, New Zealand, inferred from transgressive marine sequence architecture

Early Holocene transgressive marine deposits infilling the Pakarae River paleovalley are used to extend the paleoseismic history of the Pakarae River locality, East Coast, North Island, New Zealand, back in time prior to eustatic sea level stabilization at ∼7 calibrated (cal) ka B.P. Paleoenvironmental evolution of the Pakarae River paleovalley from 7 to 10 cal ka B.P is reconstructed using sedimentology and biostratigraphy. Two estuarine units display sudden vertical transitions to floodplain sediments implying significant marine regressions and estuary abandonment. These regressions are attributed to coseismic coastal uplift events at ∼9000 and ∼8500 cal years B.P. A third uplift between 8500 and ∼7350 cal years B.P. is inferred from a significant difference between the amount of sediment preserved and the predicted sediment thickness according to the eustatic sea level curve. This study demonstrates the utility of the analysis of transgressive deposits and their paleoenvironmental characteristics for neotectonic investigations on active coasts.

Effect of Timber Harvest on Physical Water Quality Characteristics

The effect of 11% thinning on selected stream water properties in an oak-beech forest ecosystem in the Belgrad Forest of Istanbul, Turkey was studied with a paired catchment experiment. Regression equations for some physical properties of the stream water were developed between control (W-I) and treatment (W-II) watersheds for calibration (with their 95% confidence limits) and treatment periods. The study discovered significant linear regressions between control and treatment watersheds for color, turbidity, air and water temperatures, suspended sediment concentration, pH and electrical conductivity in the calibration period but not turbidity and suspended sediment concentration in the treatment period. The impact of the timber removal was calculated as the difference between measured and predicted values derived from calibration equations. Results showed that timber harvest caused significant decreases in the color, turbidity, temperature, pH, and electrical conductivity values of the stream water and air temperature under the canopy but did not affect the suspended sediment concentration in the stream water.

Fast and Local Assessment of Stilbene Content in Grapevine Leaf by in Vivo Fluorometry

Stilbenes are grapevine phytoalexins. These highly fluorescent molecules are generally analyzed by HPLC. This technique allows accurate assay of different stilbenes, but it is destructive, time-consuming, and neglects their spatial distribution. This is why we have tested a new method based on in vivo fluorescence using commercial spectrofluorometers that allowed fast and local assessment of stilbene content in grapevine leaves. Stilbene synthesis in grapevine Vitis vinifera var. Muscat Ottonel leaves was induced by Plasmopara viticola inoculation or UV-C irradiation. Fluorescence was measured both from the abaxial and adaxial sides of leaves, then stilbene content was analyzed by HPLC. It varied from 0 in control leaves to 15 mg g-1 dry weight in UV-treated leaves. Highly significant regressions were found between HPLC stilbene content and the corresponding leaf UV-induced blue fluorescence. Thus, in vivo fluorescence is a good tool for a rapid study of stilbenes synthesis in grapevine leaves that can potentially be extended to other fluorescent molecules.

Predictors of on-site vocational support for people with schizophrenia in supported employment

This study examined predictors of intensity of vocational specialist support for clients with schizophrenia or schizoaffective disorder in supported employment. Sixty-nine outpatients with schizophrenia or schizoaffective disorder were recruited from a community mental health center for 12 months of vocational and cognitive rehabilitation. Neuropsychological test scores, symptom ratings, illness severity, and employment history were used to predict vocational support intensity, expressed as hours coached in ratio to total hours worked over 12 months for each client. Weekly work hours were inversely correlated with intensity of vocational support. Half of the sample averaged 10 to 40 h of work per week and received significantly lower proportions of on-site job coaching than the lowest quartile, which averaged 2 to 5 h of work per week. Regressions predicting support intensity from neuropsychological composite scores, educational/vocational, and hospitalization history were not significant. Significant regressions included PANSS, SANS, and SAPS subscales, after which individual symptoms responsible for explained variance were isolated. SANS social inattention and PANSS active avoidance together predicted 23% of the variance in support intensity. A one-way ANOVA comparing work participation quartiles on these symptoms revealed significantly higher levels of active avoidance and social inattention for participants working less than 10 h per week. A profile emerged of the high intensity client as a socially inattentive or avoidant individual requiring a limited work schedule. Results suggest that these clients require more specialist contact because of failure to adequately engage natural supports at work.