Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall

Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.

The effect of Gaussian noise on the threshold, dynamic range, and loudness of analogue cochlear implant stimuli

The deliberate addition of Gaussian noise to cochlear implant signals has previously been proposed to enhance the time coding of signals by the cochlear nerve. Potentially, the addition of an inaudible level of noise could also have secondary benefits: it could lower the threshold to the information-bearing signal, and by desynchronization of nerve discharges, it could increase the level at which the information-bearing signal becomes uncomfortable. Both these effects would lead to an increased dynamic range, which might be expected to enhance speech comprehension and make the choice of cochlear implant compression parameters less critical (as with a wider dynamic range, small changes in the parameters would have less effect on loudness). The hypothesized secondary effects were investigated with eight users of the Clarion cochlear implant; the stimulation was analogue and monopolar. For presentations in noise, noise at 95% of the threshold level was applied simultaneously and independently to all the electrodes. The noise was found in two-alternative forced-choice (2AFC) experiments to decrease the threshold to sinusoidal stimuli (100 Hz, 1 kHz, 5 kHz) by about 2.0 dB and increase the dynamic range by 0.7 dB. Furthermore, in 2AFC loudness balance experiments, noise was found to decrease the loudness of moderate to intense stimuli. This suggests that loudness is partially coded by the degree of phase-locking of cochlear nerve fibers. The overall gain in dynamic range was modest, and more complex noise strategies, for example, using inhibition between the noise sources, may be required to get a clinically useful benefit. © 2006 Association for Research in Otolaryngology.

Sensor and software use for the glycaemic management of insulin-treated type 1 and type 2 diabetes patients

Lowering glucose levels, while avoiding hypoglycaemia, can be challenging in insulin-treated patients with diabetes. We evaluated the role of ambulatory glucose profile in optimising glycaemic control in this population. Insulin-treated patients with type 1 and type 2 diabetes were recruited into a prospective, multicentre, 100-day study and randomised to control (n = 28) or intervention (n = 59) groups. The intervention group used ambulatory glucose profile, generated by continuous glucose monitoring, to assess daily glucose levels, whereas the controls relied on capillary glucose testing. Patients were reviewed at days 30 and 45 by the health care professional to adjust insulin therapy. Comparing first and last 2 weeks of the study, ambulatory glucose profile-monitored type 2 diabetes patients (n = 28) showed increased time in euglycaemia (mean ± standard deviation) by 1.4 ± 3.5 h/day (p = 0.0427) associated with reduction in HbA1c from 77 ± 15 to 67 ± 13 mmol/mol (p = 0.0002) without increased hypoglycaemia. Type 1 diabetes patients (n = 25) showed reduction in hypoglycaemia from 1.4 ± 1.7 to 0.8 ± 0.8 h/day (p = 0.0472) associated with a marginal HbA1c decrease from 75 ± 10 to 72 ± 8 mmol/mol (p = 0.0508). Largely similar findings were observed comparing intervention and control groups at end of study. In conclusion, ambulatory glucose profile helps glycaemic management in insulin-treated diabetes patients by increasing time spent in euglycaemia and decreasing HbA1c in type 2 diabetes patients, while reducing hypoglycaemia in type 1 diabetes patients.

Database of the GLAMAP project

A uniform chronology for foraminifera-based sea surface temperature records has been established in more than 120 sediment cores obtained from the equatorial and eastern Atlantic up to the Arctic Ocean. The chronostratigraphy of the last 30,000 years is mainly based on published d18O records and 14C ages from accelerator mass spectrometry, converted into calendar-year ages. The high-precision age control provides the database necessary for the uniform reconstruction of the climate interval of the Last Glacial Maximum within the GLAMAP-2000 project.

Archaeological otoliths as environmental recorders: high resolution sampling of pacific cod (Gadus macrocephalus) otoliths from Kiska Island, Alaska

Archaeological fish otoliths have the potential to serve as proxies for both season of site occupation and palaeoclimate conditions. By sampling along the distinctive sub-annual seasonal bands of the otolith and completing a stable isotope (δ¹⁸O, δ¹³C) analysis, variations within the fish’s environment can be identified. Through the analysis of cod otoliths from two archaeological sites on Kiska Island, Gertrude Cove (KIS-010) and Witchcraft Point (KIS-005), this research evaluates a micromilling methodological approach to extracting climatic data from archaeological cod otoliths. In addition, δ¹⁸Ootolith data and radiocarbon dates frame a discussion of Pacific cod harvesting, site occupation, and changing climatic conditions on Kiska Island. To aid in the interpretation of the archaeological Pacific cod results, archaeological and modern Atlantic cod otoliths were also analyzed as a component of this study to develop. The Atlantic cod otoliths provided the methodological and interpretative framework for the study, and also served to assess the efficacy of this sampling strategy for archaeological materials and to add time-depth to existing datasets. The δ¹⁸Ootolith values successfully illustrate relative variation in ambient water temperature. The Pacific cod δ¹⁸O values demonstrate a weak seasonal signal identifiable up to year 3, followed by relatively stable values until year 6/7 when values continuously increase. Based on the δ¹⁸O values, the Pacific cod were exposed to the coldest water temperatures immediately prior to capture. The lack of a clear cycle of seasonal variation and the continued increase in values towards the otolith edge obscures the season of capture, and indicates that other behavioural, environmental, or methodological factors influenced the otolith δ¹⁸O values. It is suggested that Pacific cod would have been harvested throughout the year, and the presence of cod remains in Aleutian archaeological sites cannot be used as a reliable indicator of summer occupation. In addition, when the δ¹⁸O otolith values are integrated with radiocarbon dates and known climatic regimes, it is demonstrated that climatic conditions play an integral role in the pattern of occupation at Gertrude Cove. Initial site occupation coincides with the end of a neoglacial cooling period, and the most recent and continuous occupation coincides with the end of a localized warming period and the onset of the Little Ice Age (LIA).

(Table 2) Radiocarbon dates from lakes on Fildes Peninsula, King George Island

Precise relative sea level (RSL) data are important for inferring regional ice sheet histories, as well as helping to validate numerical models of ice sheet evolution and glacial isostatic adjustment. Here we develop a new RSL curve for Fildes Peninsula, South Shetland Islands (SSIs), a sub-Antarctic archipelago peripheral to the northern Antarctic Peninsula ice sheet, by integrating sedimentary evidence from isolation basins with geomorphological evidence from raised beaches. This combined approach yields not only a Holocene RSL curve, but also the spatial pattern of how RSL change varied across the archipelago. The curve shows a mid-Holocene RSL highstand on Fildes Peninsula at 15.5 m above mean sea level between 8000 and 7000 cal a BP. Subsequently RSL gradually fell as a consequence of isostatic uplift in response to regional deglaciation. We propose that isostatic uplift occurred at a non-steady rate, with a temporary pause in ice retreat ca. 7200 cal a BP, leading to a short-lived RSL rise of ~1 m and forming a second peak to the mid-Holocene highstand. Two independent approaches were taken to constrain the long-term tectonic uplift rate of the SSIs at 0.22-0.48 m/ka, placing the tectonic contribution to the reconstructed RSL highstand between 1.4 and 2.9 m. Finally, we make comparisons to predictions from three global sea level models.

Stable carbon and oxygen isotope ratios of benthic foraminifera

Carbon isotopic measurements on the benthic foraminiferal genus Cibicidoides document that mean deep ocean delta13C values were 0.46 per mil lower during the last glacial maximum than during the Late Holocene. The geographic distribution of delta13C was altered by changes in the production rate of nutrient-depleted deep water in the North Atlantic. During the Late Holocene, North Atlantic Deep Water, with high delta13C values and low nutrient values, can be found throughout the Atlantic Ocean, and its effects can be traced into the southern ocean where it mixes with recirculated Pacific deep water. During the glaciation, decreased production of North Atlantic Deep Water allowed southern ocean deep water to penetrate farther into the North Atlantic and across low-latitude fracture zones into the eastern Atlantic. Mean southern ocean delta13C values during the glaciation are lower than both North Atlantic and Pacific delta13C values, suggesting that production of nutrient-depleted water occurred in both oceans during the glaciation. Enriched 13C values in shallow cores within the Atlantic Ocean indicate the existence of a nutrient-depleted water mass above 2000 m in this ocean.

Stable isotope and Cd/Ca ratios of Neogloboquadrina pachyderma in high-latitude sediments

Recent studies have stressed the role of high latitude nutrient levels and productivity in controlling the carbon isotopic composition of the deep sea and the CO2 content of the atmosphere. We undertook a study of the chemical composition of the polar planktonic foraminifer Neogloboquadrina pachyderma (s., sinistral coiling) from 30 late Holocene samples and 49 down core records from the high-latitude North and South Atlantic Oceans to evaluate the history of sea surface chemical change from glacial to interglacial time. Stable isotopic analysis of coretop samples from the Atlantic, Pacific and Southern Oceans shows no significant correlation between the delta13C of N. pachyderma and either delta13C or PO4 in seawater. Conversely, Cd/Ca ratios in planktonic foraminifera are consistent with the PO4 content of surface waters. The level of maximum glaciation (18,000 yr B.P.), identified by CLIMAP and delta18O, was chosen for mapping. Isopleths of delta18O on N. pachyderma (s.) in the North Atlantic reveal a pattern largely influenced by sea surface temperature (S.S.T.) and generally support the S.S.T. reconstruction of CLIMAP. Differences between the two suggest significantly lower salinity in North Atlantic surface waters at high latitudes than in lower latitudes. Down core delta13C records of N. pachyderma confirm that low delta13C values occurred in the northeast Atlantic during the latest glacial maximum (Labeyrie and Duplessy, 1985, doi:10.1016/0031-0182(85)90069-0). However, a map of delta13C for the 18,000 yr B.P. level for a much larger region in the North Atlantic shows that minimum N. pachyderma delta13C occurred in temperate waters. N. pachyderma delta13C decreased toward the southwest, reaching a minimum of -1 per mil at 37°N. Despite the variability seen in delta13C records of N. pachyderma, none of our cores show significant temporal variability in Cd/Ca. From the combined Cd/Ca and delta13C data we can see no evidence for an upwelling gyre in the eastern North Atlantic during the latest glacial maximum, nor evidence that the southern and northern oceans had significantly different levels of preformed nutrients than today.

Compilation of 220 sediment core d13C data from the glacial Atlantic Ocean

We compare a compilation of 220 sediment core d13C data from the glacial Atlantic Ocean with three-dimensional ocean circulation simulations including a marine carbon cycle model. The carbon cycle model employs circulation fields which were derived from previous climate simulations. All sediment data have been thoroughly quality controlled, focusing on epibenthic foraminiferal species (such as Cibicidoides wuellerstorfi or Planulina ariminensis) to improve the comparability of model and sediment core carbon isotopes. The model captures the general d13C pattern indicated by present-day water column data and Late Holocene sediment cores but underestimates intermediate and deep water values in the South Atlantic. The best agreement with glacial reconstructions is obtained for a model scenario with an altered freshwater balance in the Southern Ocean that mimics enhanced northward sea ice export and melting away from the zone of sea ice production. This results in a shoaled and weakened North Atlantic Deep Water flow and intensified Antarctic Bottom Water export, hence confirming previous reconstructions from paleoproxy records. Moreover, the modeled abyssal ocean is very cold and very saline, which is in line with other proxy data evidence.

(Table S1) Age determination of Atlantic Ocean sediment cores

Well-dated benthic foraminifer oxygen isotopic records (d18O) from different water depths and locations within the Atlantic Ocean exhibit distinct patterns and significant differences in timing over the last deglaciation. This has two implications: on the one hand, it confirms that benthic d18O cannot be used as a global correlation tool with millennial-scale precision, but on the other hand, the combination of benthic isotopic records with independent dating provides a wealth of information on past circulation changes. Comparing new South Atlantic benthic isotopic data with published benthic isotopic records, we show that (1) circulation changes first affected benthic d18O in the 1000-2200 m range, with marked decreases in benthic d18O taking place at ~17.5 cal. kyr B.P. (ka) due to the southward propagation of brine waters generated in the Nordic Seas during Heinrich Stadial 1 (HS1) cold period; (2) the arrival of d18O-depleted deglacial meltwater took place later at deeper North Atlantic sites; (3) hydrographic changes recorded in North Atlantic cores below 3000 m during HS1 do not correspond to simple alternations between northern- and southern-sourced water but likely reflect instead the incursion of brine-generated deep water of northern as well as southern origin; and (4) South Atlantic waters at ~44°S and ~3800 m depth remained isolated from better-ventilated northern-sourced water masses until after the resumption of North Atlantic Deep Water (NADW) formation at the onset of the Bølling-Allerod, which led to the propagation of NADW into the South Atlantic.

(Table 2) Age determination of Aegean Sea sediments

The modern Aegean Sea is an important source of deep water for the eastern Mediterranean. Its contribution to deep water ventilation is known to fluctuate in response to climatic variation on a decadal timescale. This study uses marine micropalaeontological and stable isotope data to investigate longer-term variability during the late glacial and Holocene, in particular that associated with the deposition of the early Holocene dysoxic/anoxic sapropel S1. Concentrating on the onset of sapropel-forming conditions, we identify the start of 'seasonal' stratification and highlight a lag in d18O response of the planktonic foraminifer N. pachyderma to termination T1b as identified in the d18O record of G. ruber. By use of a simple model we determine that this offset cannot be a function of bioturbation effects. The lag is of the order of 1 kyr and suggests that isolation of intermediate/deep water preceded the start of sapropel formation by up to 1.5 kyr. Using this discovery, we propose an explanation for the major unresolved problem in sapropel studies, namely, the source of nutrient supply required for export productivity to reach levels needed for sustained sapropel deposition. We suggest that nutrients had been accumulating in a stagnant basin for 1-1.5 kyr and that these accumulated resources were utilized during the deposition of S1. In addition, we provide a first quantitative estimate of the diffusive (1/e) mixing timescale for the eastern Mediterranean in its "stratified" sapropel mode, which is of the order of 450 years.

(Table S1) Age determination of sediment core OCE326-GGC5

The Atlantic meridional overturning circulation is widely believed to affect climate. Changes in ocean circulation have been inferred from records of the deep water chemical composition derived from sedimentary nutrient proxies (Boyle and Keigwin, 1987, doi:10.1038/330035a0), but their impact on climate is difficult to assess because such reconstructions provide insufficient constraints on the rate of overturning (LeGrand and Wunsch, 1995, doi:10.1029/95PA01455). Here we report measurements of 231Pa/230Th, a kinematic proxy for the meridional overturning circulation, in a sediment core from the subtropical North Atlantic Ocean. We find that the meridional overturning was nearly, or completely, eliminated during the coldest deglacial interval in the North Atlantic region, beginning with the catastrophic iceberg discharge Heinrich event H1, 17,500 yr ago, and declined sharply but briefly into the Younger Dryas cold event, about 12,700 yr ago. Following these cold events, the 231Pa/230Th record indicates that rapid accelerations of the meridional overturning circulation were concurrent with the two strongest regional warming events during deglaciation. These results confirm the significance of variations in the rate of the Atlantic meridional overturning circulation for abrupt climate changes.

(Table 1) Age determination of sediment cores HU89038_8 and OCE326-GGC5

Models indicate that a complete shutdown of deep and intermediate water production is a possible consequence of extreme climate conditions in the northern North Atlantic, and the high ratio of 231Pa to 230Th on Bermuda Rise is evidence that this might have happened ?17 ka during Heinrich event 1 (H1). However, new radiocarbon data from bivalves that lived at ?4.6 km on the Bermuda Rise during H1 lead to a different conclusion. The bivalve data do indeed indicate ventilation of the deep western North Atlantic was suppressed during H1 but not as much as it was during the last glacial maximum. We propose that high diatom flux to the Bermuda Rise during H1 is at least in part responsible for increased 231Pa/230Th at that time. Although we cannot say for sure why opal production was so high in a gyre center location at that time, increased leakage of silica rich waters from the Southern Ocean to the North Atlantic is one possibility.