Countermanding in rats as a practical model for investigation of adaptive control of behaviour, lifespan changes in behavioural control and neurotransmitter function

The countermanding paradigm was designed to investigate the ability to cancel a prepotent response when a stop signal is presented and allows estimation of the stop signal response time (SSRT), an otherwise unobservable behaviour. Humans exhibit adaptive control of behaviour in the countermanding task, proactively lengthening response time (RT) in expectation of stopping and reactively lengthening RT following stop trials or errors. Human performance changes throughout the lifespan, with longer RT, SSRT and greater emphasis on post-error slowing reported for older compared to younger adults. Inhibition in the task has generally been improved by drugs that increase extracellular norepinephrine. The current thesis examined a novel choice response countermanding task in rats to explore whether rodent countermanding performance is a suitable model for the study of adaptive control of behaviour, lifespan changes in behavioural control and the role of neurotransmitters in these behaviours. Rats reactively adjusted RT in the countermanding task, shortening RT after consecutive correct go trials and lengthening RT following non-cancelled, but not cancelled stop trials, in sessions with a 10 s, but not a 1 s post-error timeout interval. Rats proactively lengthened RT in countermanding task sessions compared to go trial-only sessions. Together, these findings suggest that rats strategically lengthened RT in the countermanding task to improve accuracy and avoid longer, unrewarded timeout intervals. Next, rats exhibited longer RT and relatively conserved post-error slowing, but no significant change in SSRT when tested at 12, compared to 7 months of age, suggesting that rats exhibit changes in countermanding task performance with aging similar to those observed in humans. Finally, acute administration of yohimbine (1.25, 2.5 mg/kg) and d-amphetamine (0.25, 0.5 mg/kg), which putatively increase extracellular norepinephrine and dopamine respectively, resulted in RT shortening, baseline-dependent effects on SSRT, and attenuated adaptive RT adjustments in rats in the case of d-amphetamine. These findings suggest that dopamine and norepinephrine encouraged motivated, reward-seeking behaviour and supported inhibitory control in an inverted-U-like fashion. Taken together, these observations validate the rat countermanding task for further study of the neural correlates and neurotransmitters mediating adaptive control of behaviour and lifespan changes in behavioural control.

Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: A multicentre double-blind, placebo-controlled phase II study - AIO SUP-0108

PURPOSE: Malignant ascites is debilitating for patients with advanced cancer. As shown previously, tumour cell production of vascular endothelial growth factor might be a major cause of the formation of malignant ascites. Intraperitoneal bevacizumab could therefore be an option for symptom control in refractory ascites. PATIENTS AND METHODS: Patients with advanced gastrointestinal cancer and malignant ascites who had undergone paracentesis at least twice within the past 4 weeks were randomly assigned in a 2:1 ratio to intraperitoneal bevacizumab (400 mg absolute) or placebo after paracentesis. During the 8-week treatment period, a minimum interval of 14 d was kept between the applications of the study drug. Primary end-point was paracentesis-free survival (ParFS). RESULTS: Fifty-three patients (median age 63 years) were randomised. Forty-nine patients received at least one study drug application and qualified for the main analysis. The proportion of patients with at least one common toxicity criteria grade III-V event was similar with 20/33 (61%) on bevacizumab and 11/16 (69%) on placebo. Median ParFS was 14 d (95% confidence interval [CI]: 11-17) in the bevacizumab arm and 10.5 d (95% CI: 7-21) on placebo (hazard ratio 0.74, 95% CI: 0.40-1.37; P = 0.16). The longest paracentesis-free period was 19 d on bevacizumab (range 6-66 d) and 17.5 d in the placebo arm (range 4-42) (P = 0.85). Median overall survival was 64 d (95% CI: 45-103) on bevacizumab compared to 31.5 d (95% CI: 20-117) on placebo (P = 0.31). CONCLUSION: Intraperitoneal bevacizumab was well tolerated. Overall, treatment did not result in a significantly better symptom control of malignant ascites. However, patients defined by specific immune characteristics may benefit.

Lake-effect snow as the dominant control of mesic-forest distribution in Michigan, USA

1Recent studies demonstrated the sensitivity of northern forest ecosystems to changes in the amount and duration of snow cover at annual to decadal time scales. However, the consequences of snowfall variability remain uncertain for ecological variables operating at longer time scales, especially the distributions of forest communities. 2The Great Lakes region of North America offers a unique setting to examine the long-term effects of variable snowfall on forest communities. Lake-effect snow produces a three-fold gradient in annual snowfall over tens of kilometres, and dramatic edaphic variations occur among landform types resulting from Quaternary glaciations. We tested the hypothesis that these factors interact to control the distributions of mesic (dominated by Acer saccharum, Tsuga canadensis and Fagus grandifolia) and xeric forests (dominated by Pinus and Quercus spp.) in northern Lower Michigan. 3We compiled pre-European-settlement vegetation data and overlaid these data with records of climate, water balance and soil, onto Landtype Association polygons in a geographical information system. We then used multivariate adaptive regression splines to model the abundance of mesic vegetation in relation to environmental controls. 4Snowfall is the most predictive among five variables retained by our model, and it affects model performance 29% more than soil texture, the second most important variable. The abundance of mesic trees is high on fine-textured soils regardless of snowfall, but it increases with snowfall on coarse-textured substrates. Lake-effect snowfall also determines the species composition within mesic forests. The weighted importance of A. saccharum is significantly greater than of T. canadensis or F. grandifolia within the lake-effect snowbelt, whereas T. canadensis is more plentiful outside the snowbelt. These patterns are probably driven by the influence of snowfall on soil moisture, nutrient availability and fire return intervals. 5Our results imply that a key factor dictating the spatio-temporal patterns of forest communities in the vast region around the Great Lakes is how the lake-effect snowfall regime responds to global change. Snowfall reductions will probably cause a major decrease in the abundance of ecologically and economically important species, such as A. saccharum.

Age control and stratigraphy of a sediment profile from the Lomonosov Ridge, Arctic Ocean

The upper 200 m of the sediments recovered during IODP Leg 302, the Arctic Coring Expedition (ACEX), to the Lomonosov Ridge in the central Arctic Ocean consist almost exclusively of detrital material. The scarcity of biostratigraphic markers severely complicates the establishment of a reliable chronostratigraphic framework for these sediments, which contain the first continuous record of the Neogene environmental and climatic evolution of the Arctic region. Here we present profiles of cosmogenic 10Be together with the seawater-derived fraction of stable 9Be obtained from the ACEX cores. The down-core decrease of 10Be/9Be provides an average sedimentation rate of 14.5 ± 1 m/Ma for the uppermost 151 m of the ACEX record and allows the establishment of a chronostratigraphy for the past 12.3 Ma. The age-corrected 10Be concentrations and 10Be/9Be ratios suggest the existence of an essentially continuous sea ice cover over the past 12.3 Ma.

Latest Cretaceous to Late Paleocene radiolarian biostratigraphy from the New Zealand region

The scarcity of records of Early Paleocene radiolarians has meant that while radiolarian biostratigraphy is firmly established as an important tool for correlation, there has been a long-standing gap between established zonations for the Cretaceous and from latest Paleocene to Recent. It has also led to considerable speculation over the level of faunal change across the Cretaceous/Tertiary (K/T) boundary. Consequently, the discovery of rich and diverse radiolarian assemblages in well-delineated K/T boundary sections within siliceous limestones of the Amuri Limestone Group in eastern Marlborough, New Zealand, is of great significance for biostratigraphy and K/T boundary research. This initial report is restricted to introducing a new latest Cretaceous to mid Late Paleocene zonation based on the radiolarian succession at four of these sections and a re-examination of faunas from coeval sediments at DSDP Site 208 (Lord Howe Rise). Three new Paleocene species are described: Amphisphaera aotea, Amphisphaera kina and Stichomitra wero. Six new interval zones are defined by the first appearances of the nominate species. In ascending order these are: Lithomelissa? hoplites Foreman (Zone RK9, Cretaceous), Amphisphaera aotea n. sp. (Zone RP1, Paleocene), Amphisphaera kina n. sp. (RP2), Stichomitra granulata Petrushevskaya (RP3), Buryellaforemanae petrushevskaya (RP4) and Buryella tetradica (RP5). Good age control from foraminifera and calcareous nannofossils permits close correlation with established microfossil zonations. Where age control is less reliable, radiolarian events are used to substantially improve correlation between the sections. No evidence is found for mass extinction of radiolarians at the end of the Cretaceous. However, the K/T boundary does mark a change from nassellarian to spumellarian dominance, due to a sudden influx of actinommids, which effectively reduces the relative abundance of many Cretaceous survivors. An accompanying influx of diatoms in the basal Paleocene of Marlborough, together with evidence for an increase of total radiolarian abundance, suggests siliceous plankton productivity increased across the K/T boundary. Possible causes for this apparently localised phenomenon are briefly discussed.

(Table 2) Depth-age control points of ODP Site 177-1090

At Ocean Drilling Program (ODP) Site 1090 on the Agulhas Ridge (subantarctic South Atlantic) benthic foraminiferal stable isotope records span the late Oligocene through the early Miocene (25~16 Ma) at a temporal resolution of ?10 kyr. In the same time interval a magnetic polarity stratigraphy can be unequivocally correlated to the geomagnetic polarity timescale (GPTS), thereby providing secure correlation of the isotope record to the GPTS. On the basis of the isotope-magnetostratigraphic correlation we provide refined age calibration of established oxygen isotope events Mi1 through Mi2 as well as several other distinctive isotope events. Our data suggest that the d18O maximum commonly associated with the Oligocene/Miocene (O/M) boundary falls within C6Cn.2r (23.86 Ma). The d13C maximum coincides, within the temporal resolution of our record, with C6Cn.2n/r boundary and hence to the O/M boundary. Comparison of the stable isotope record from ODP Site 1090 to the orbitally tuned stable isotope record from ODP Site 929 across the O/M boundary shows that variability in the two records is very similar and can be correlated at and below the O/M boundary. Site 1090 stable isotope records also provide the first deep Southern Ocean end-member for reconstructions of circulation patterns and late Oligocene to early Miocene climate change. Comparison to previously published records suggests that basin to basin carbon isotope gradients were small or nonexistent and are inconclusive with respect to the direction of deep water flow. Oxygen isotope gradients between sites suggest that the deep Southern Ocean was cold in comparison to the North Atlantic, Indian, and the Pacific Oceans. Dominance of cold Southern Component Deep Water at Site 1090, at least until 17 Ma, suggests that relatively cold circumpolar climatic conditions prevailed during the late Oligocene and early Miocene. We believe that a relatively cold Southern Ocean reflects unrestricted circumpolar flow through the Drake Passage in agreement with bathymetric reconstructions.

Clay and smectite content in sediment core CRP-3

The Cenozoic sediments of the CRP-3 drill core from the continental shelf of McMurdo Sound in Ross Sea, Pacific sector of the Southern Ocean, have been investigated for their clay mineral assemblages, especially for the smectite abundances, concentrations and crystallinities. The assemblages of CRP-3 are very different from those of the CRP-1 and CRP-2/2A drill cores. Thus, an almost monomineralic assemblage characterizes the sequence below 330 mbsf. This assemblage is made of well-crystallized smectite with probably authigenic origin between 800 mbsf and 625 mbsf. From 625 mbsf to 330 mbsf the assemblage consists of moderately crystallized smectite that, at least in part, seems to be of detrital origin and thus indicates weathering under a relatively warm and wet climate. In the interval 330-145 mbsf, smectite concentrations fluctuate between 50% and 100% and probably document alternating phases of chemical weathering under a warm and wet climate and physical weathering under a relatively cool and dry climate. Above 145 mbsf the smectite decreases dramatically to concentrations of about 20% and becomes poorly crystalline. In contrast, illite and chlorite become more abundant. Such an assemblage is typical for early Oligocene and younger sediments in McMurdo Sound and reflects physical weathering conditions under a cool climate on a glaciated Antarctic continent. Correlations of the changes in the clay mineral spectrum of CRP-3 with other cores from McMurdo Sound and from other parts of the Southern Ocean has to remain speculative at this stage, because of the poor age control.

Distribution of calcareous nannofossils in the Miocene interval of DSDP Hole 94-608 in the north Atlantic (Fig. 1)

DSDP North Atlantic Site 608 yielded an excellent Miocene pelagic section which affords a further opportunity for elucidating the chronology of the calcareous nannofossil succession in the framework of magnetostratigraphic control. Most of the conventional (zonal) markers have been documented for this site and some of the earlier results are confirmed and refined. In addition several unconventional and less known markers have been added. The first two are the highest (last) occurrence of Sphenolithus delphix and Sphenolithus capricornutus at 23.6 Ma, which is immediately above the Oligocene-Miocene boundary as identified by the last occurrence of Reticulofenestra bisecta at 23.7 Ma. The next unconventional datum is the highest (last) occurrence of Ilselithina fusa at 22.8 Ma, which is also the highest (last) occurrence of Helicosphaera recta. Calcidiscus tropicus' lowest (first) occurrence is at 19.5 Ma, which is also the lowest occurrence of Sphenolithus belemnos, and Calcidiscus leptoporus' lowest (first) occurrence coincides with that of Sphenolithus heteromorphus at 18.5 Ma. Sphenolithus dissimilis' highest (last) occurrence is at 18.2 Ma and the Calcidiscus premacintyrei lowest (first) and highest (last) occurrences are, respectively, at 17.7 and 11.7 Ma. Discoaster braarudii occurs from 11.6 to 11.3 Ma and its highest (last) occurrence corresponds to that of Cyclicargolithus floridanus. Minylitha convallis occurs from 9.0 to 6.9 Ma. Within the range of Minylitha, at 8.0 Ma, a major shift occurs in reticulofenestrid placoliths from dominantly large (Reticulofenestra pseudoumbilicus) and medium size (Reticulofenestra minutula) species below to significant numbers of very small species (Dictyococcites productus and Gephyrocapsa) above. This is interpreted to be a major, though perhaps seasonal, change of productivity of the North Atlantic at Site 608. A new genus and species Cryptococcolithus takayamae, is described and a variety, Reticulofenestra pseudoumbilicus var. amplus is identified.

Development of an automated pre-sampling plan for construction projects. Final report.

Mode of access: Internet.

Development and validation of methods for sampling and analysis of workplace toxic substances /

Mode of access: Internet.

Occupational exposure sampling strategy manual /

Includes bibliographical references.

NIOSH manual of sampling data sheets.

Mode of access: Internet.

NIOSH manual of sampling data sheets : supplement to the 1977 edition.

Mode of access: Internet.

Beryllium sampling methods: Comparison of two personal sample collection methods with the AEC sample collection method as used for one year in a beryllium production facility. /

Item 499-F-2

Sampling and evaluating airborne asbestos dust (582).

"June 1988."