First Results from the DEAP-3600 Dark Matter Search with Argon at SNOLAB.

This Letter reports the first results of a direct dark matter search with the DEAP-3600 single-phase liquid argon (LAr) detector. The experiment was performed 2 km underground at SNOLAB (Sudbury, Canada) utilizing a large target mass, with the LAr target contained in a spherical acrylic vessel of 3600 kg capacity. The LAr is viewed by an array of PMTs, which would register scintillation light produced by rare nuclear recoil signals induced by dark matter particle scattering. An analysis of 4.44 live days (fiducial exposure of 9.87 ton day) of data taken during the initial filling phase demonstrates the best electronic recoil rejection using pulse-shape discrimination in argon, with leakage <1.2×10^{-7} (90% C.L.) between 15 and 31 keV_{ee}. No candidate signal events are observed, which results in the leading limit on weakly interacting massive particle (WIMP)-nucleon spin-independent cross section on argon, <1.2×10^{-44} cm^{2} for a 100 GeV/c^{2} WIMP mass (90% C.L.).

Chemical, biological, and DNA markers for tracing slaughterhouse effluent.

Agricultural practices, if not managed correctly, can have a negative impact on receiving environments via waste disposal and discharge. In this study, a chicken slaughter facility on the rural outskirts of Sydney, Australia, has been identified as a possible source of persistent effluent discharge into a peri-urban catchment. Questions surrounding the facility's environmental management practices go back more than four decades. Despite there having never been a definitive determination of the facility's impact on local stream water quality, the New South Wales Environment Protection Authority (NSW EPA) has implemented numerous pollution reduction requirements to manage noise and water pollution at the slaughter facility. However, assessment of compliance remains complicated by potential additional sources of pollution in the catchment. To unravel this long-standing conundrum related to water pollution we apply a forensic, multiple lines of evidence approach to delineate the origin of the likely pollution source(s). Water samples collected between 2014 and 2016 from irrigation pipes and a watercourse exiting the slaughter facility had elevated concentrations of ammonia (max: 63,000µg/L), nitrogen (max: 67,000µg/L) and phosphorus (max: 39,000µg/L), which were significantly higher than samples from adjacent streams that did not receive direct runoff from the facility. Arsenic, sometimes utilised in growth promoting compounds, was detected in water discharging from the facility up to ~4 times (max 3.84µg/L) local background values (<0.5µg/L), with inorganic As(∑V+III) being the dominant species. The spatial association of elevated water pollution to the facility could not unequivocally distinguish a source and consequently DNA analysis of a suspected pollution discharge event was undertaken. Analysis of catchment runoff from several local streams showed that only water sampled at the downstream boundary of the facility tested positive for chicken DNA, with traces of duck DNA being absent, which was a potential confounder given that wild ducks are present in the area. Further, PCR analysis showed that only the discharge water emanating from the slaughter facility tested positive for a generalized marker of anthropogenic pollution, the clinical class 1 integron-integrase gene. The environmental data collected over a three-year period demonstrates that the slaughter facility is indisputably the primary source of water-borne pollution in the catchment. Moreover, application of DNA and PCR for confirming pollution sources demonstrates its potential for application by regulators in fingerprinting pollution sources.

Geochemical sources, forms and phases of soil contamination in an industrial city.

This study examines current soil contamination in an Australian industrial city, Newcastle. Public (roadside verges and parks) and private (homes) surface soils (n=170) contained metal(loid)s elevated above their respective Australian Health Investigation Levels (HIL). Lead (Pb), the most common contaminant in the city, exceeds the HIL for residential soils (HIL-A, 300mg/kg) in 88% of private soils (median: 1140mg/kg). In-vitro Pb bio-accessibility analysis of selected soils (n=11) using simulated gastric fluid showed a high affinity for Pb solubilisation (maximum Pb concentration: 5190mg/kg, equating to 45% Pb bio-accessibility). Highly soluble Pb-laden Fe- and Mn-oxides likely contribute to the bio-accessibility of the Pb. Public and private space surface soils contain substantially less radiogenic Pb (range: 208Pb/207Pb: 2.345-2.411, 206Pb/207Pb: 1.068-1.312) than local background soil (208Pb/207Pb: 2.489, 206Pb/207Pb: 1.198), indicating anthropogenic contamination from the less radiogenic Broken Hill type Pb ores (208Pb/207Pb: 2.319, 206Pb/207Pb: 1.044). Source apportionment using Pb isotopic ratio quantification and soil mineralogy indicate the city's historic copper and steel industries contributed the majority of the soil contaminants through atmospheric deposition and use of slag waste as fill material. High-temperature silicates and oxides combined with rounded particles in the soil are characteristic of smelter dust emissions. Additionally, a preliminary investigation of polycyclic aromatic hydrocarbons in soils, sometimes associated with ferrous metal smelting, coal processing or burning of fossil fuels, shows that these too pose a health exposure risk (calculated in comparison to benzo(a)pyrene: n=12, max: 13.5mg/kg, HIL: 3mg/kg).

Widespread copper and lead contamination of household drinking water, New South Wales, Australia.

This study examines arsenic, copper, lead and manganese drinking water contamination at the domestic consumer's kitchen tap in homes of New South Wales, Australia. Analysis of 212 first draw drinking water samples shows that almost 100% and 56% of samples contain detectable concentrations of copper and lead, respectively. Of these detectable concentrations, copper exceeds Australian Drinking Water Guidelines (ADWG) in 5% of samples and lead in 8%. By contrast, no samples contained arsenic and manganese water concentrations in excess of the ADWG. Analysis of household plumbing fittings (taps and connecting pipework) show that these are a significant source of drinking water lead contamination. Water lead concentrations derived for plumbing components range from 108µg/L to 1440µg/L (n=28, mean - 328µg/L, median - 225µg/L). Analysis of kitchen tap fittings demonstrates these are a primary source of drinking water lead contamination (n=9, mean - 63.4µg/L, median - 59.0µg/L). The results of this study demonstrate that along with other potential sources of contamination in households, plumbing products that contain detectable lead up to 2.84% are contributing to contamination of household drinking water. Given that both copper and lead are known to cause significant health detriments, products for use in contact with drinking water should be manufactured free from copper and lead.

Evaluation and assessment of the efficacy of an abatement strategy in a former lead smelter community, Boolaroo, Australia.

This study examines the recent soil Lead Abatement Strategy (LAS) in Boolaroo, New South Wales, Australia, that was designed to "achieve a reduction in human exposure to lead dust contamination in surface soils". The abatement programme addressed legacy contamination of residential areas following closure of lead smelting operations in 2003 at the Pasminco Cockle Creek Smelter (PCCS). The principal objective of the LAS was to "cap and cover" lead-contaminated soils within the urban environment surrounding the PCCS. Soil lead concentrations of 2500-5000 mg/kg were scheduled for removal and replacement, while concentrations between 1500 and 2500 mg/kg were replaced only under limited circumstances. To date, there has been no industry, government or independent assessment of the clean-up programme that involved >2000 homes in the township of Boolaroo. Thus, by measuring post-abatement soil lead concentrations in Boolaroo, this study addresses this knowledge gap and evaluates the effectiveness of the LAS for reducing the potential for lead exposure. Soil lead concentrations above the Australian residential soil health investigation level value for residential soils (300 mg/kg) were identified at all but one of the residential properties examined (n = 19). Vacuum dust samples (n = 17) from the same homes had a mean lead concentration of 495 mg/kg (median 380 mg/kg). Bio-accessibility testing revealed that lead in household vacuum dust was readily accessible (% bio-accessible) (mean = 92 %, median = 90 %), demonstrating that the risk of exposure via this pathway remains. Assessment of a limited number of properties (n = 8) where pre-abatement soil lead levels were available for comparison showed they were not statistically different to post-abatement. Although the LAS did not include treatment of non-residential properties, sampling of community areas including public sports fields, playgrounds and schools (n = 32) was undertaken to determine the contamination legacy in these areas. Elevated mean soil lead concentrations were found across public lands: sports fields = 5130 mg/kg (median = 1275 mg/kg), playgrounds and schools = 812 mg/kg (median = 920 mg/kg) and open space = 778 mg/kg (median = 620 mg/kg). Overall, the study results show that the LAS programme that was dominated by a "cap and cover" approach to address widespread lead contamination was inadequate for mitigating current and future risk of lead exposures.

Benefits and risks of antihypertensive medications in the elderly.

Hypertension is highly prevalent in older age and accounts for a large proportion of cardiovascular (CV) morbidity and mortality worldwide. Isolated systolic hypertension is more common in the elderly than younger adults and associated with poor outcomes such as cerebrovascular disease and acute coronary events. International guidelines are inconsistent in providing recommendations on optimal blood pressure targets in hypertensive elderly patients as a result of the limited evidence in this population. Evidence from clinical trials supports the use of antihypertensive drugs in hypertensive elderly patients due to benefits in reducing CV disease and mortality. However, elderly participants in these trials may not be typical of elderly patients seen in routine clinical practice, and the potential risks associated with use of antihypertensive drugs in the elderly are not as well studied as younger participants. Therefore, the purpose of this review was to provide a comprehensive summary of the benefits and risks of the use of antihypertensive drugs in elderly patients (aged ≥65 years), highlighting landmark clinical trials and observational studies. We will focus on specific outcomes relating to the benefits and risks of these medications in hypertensive elderly patients, such as CV disease, cognitive decline, dementia, orthostatic hypotension, falls, fractures, cancer and diabetes, in order to provide an update of the most relevant and current evidence to help inform clinical decision-making.

Identification of the sources of metal (lead) contamination in drinking waters in north-eastern Tasmania using lead isotopic compositions.

This study utilises a range of scientific approaches, including lead isotopic compositions, to differentiate unknown sources of ongoing lead contamination of a drinking water supply in north-eastern Tasmania, Australia. Drinking water lead concentrations are elevated above the Australian Drinking Water Guideline (10 µg/L), reaching 540 µg/L in the supply network. Water lead isotopic compositions from the town of Pioneer ((208)Pb/(207)Pb 2.406, (206)Pb/(207)Pb 1.144 to (208)Pb/(207)Pb 2.360, (206)Pb/(207)Pb 1.094) and Ringarooma ((208)Pb/(207)Pb 2.398, (206)Pb/(207)Pb 1.117) are markedly different from the local bedrock ((208)Pb/(207)Pb 2.496, (206)Pb/(207)Pb 1.237). The data show that the lead in the local waters is sourced from a combination of dilapidated drinking water infrastructure, including lead jointed pipelines, end-of-life polyvinyl chloride pipes and household plumbing. Drinking water is being inadvertently contaminated by aging infrastructure, and it is an issue that warrants investigation to limit the burden of disease from lead exposure.

Behavioural modification of the cholinergic anti-inflammatory response to C-reactive protein in patients with hypertension.

OBJECTIVES: A central hypothesis of the cholinergic anti-inflammatory reflex model is that innate immune activity is inhibited by the efferent vagus. We evaluated whether changes in markers of tonic or reflex vagal heart rate modulation following behavioural intervention were associated inversely with changes in high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). DESIGN: Subjects diagnosed with hypertension (n = 45, age 35-64 years, 53% women) were randomized to an 8-week protocol of behavioural neurocardiac training (with heart rate variability biofeedback) or autogenic relaxation. Assessments before and after intervention included pro-inflammatory factors (hsCRP, IL-6), markers of vagal heart rate modulation [RR high-frequency (HF) power within 0.15-0.40 Hz, baroreflex sensitivity and RR interval], conventional measures of lipoprotein cholesterol and 24-h ambulatory systolic and diastolic blood pressure. RESULTS: Changes in hsCRP and IL-6 were not associated with changes in lipoprotein cholesterol or blood pressure. After adjusting for anti-inflammatory drugs and confounding factors, changes in hsCRP related inversely to changes in HF power (ß = -0.25±0.1, P = 0.02), baroreflex sensitivity (ß = -0.33±0.7, P = 0.04) and RR interval (ß = -0.001 ± 0.0004, P = 0.02). Statistically significant relationships were not observed for IL-6. CONCLUSIONS: Changes in hsCRP were consistent with the inhibitory effect of increased vagal efferent activity on pro-inflammatory factors predicted by the cholinergic anti-inflammatory reflex model. Clinical trials for patients with cardiovascular dysfunction are warranted to assess whether behavioural interventions can contribute independently to the chronic regulation of inflammatory activity and to improved clinical outcomes.

Serotonin facilitates a persistent calcium current in motoneurons of rats with and without chronic spinal cord injury.

In the months after spinal cord transection, motoneurons in the rat spinal cord develop large persistent inward currents (PICs) that are responsible for muscle spasticity. These PICs are mediated by low-threshold TTX-sensitive sodium currents (Na PIC) and L-type calcium currents (Ca PIC). Recently, the Na PIC was shown to become supersensitive to serotonin (5-HT) after chronic injury. In the present paper, a similar change in the sensitivity of the Ca PIC to 5-HT was investigated after injury. The whole sacrocaudal spinal cord from acute spinal rats and spastic chronic spinal rats (S2 level transection 2 mo previously) was studied in vitro. Intracellular recordings were made from motoneurons and slow voltages ramps were applied to measure PICs. TTX was used to block the Na PIC. For motoneurons of chronic spinal rats, a low dose of 5-HT (1 microM) significantly lowered the threshold of the Ca PIC from -56.7 +/- 6.0 to -63.1 +/- 7.1 mV and increased the amplitude of the Ca PIC from 2.4 +/- 1.0 to 3.0 +/- 0.73 nA. Higher doses of 5-HT acted similarly. For motoneurons of acute spinal rats, low doses of 5-HT had no significant effects, whereas a high dose (about 30 microM) significantly lowered the threshold of the L-Ca PIC from -58.5 +/- 14.8 to -62.5 +/- 3.6 mV and increased the amplitude of the Ca PIC from 0.69 +/- 1.05 to 1.27 +/- 1.1 nA. Thus Ca PICs in motoneurons are about 30-fold supersensitive to 5-HT in chronic spinal rats. The 5-HT-induced facilitation of the Ca PIC was blocked by nimodipine, not by the I(h) current blocker Cs(+) (3 mM) or the SK current blocker apamin (0.15 microM), and it lasted for hours after the removal of 5-HT from the nCSF, even increasing initially after removing 5-HT. The effects of 5-HT make motoneurons more excitable and ultimately lead to larger, more easily activated plateaus and self-sustained firing. The supersensitivity to 5-HT suggests the small amounts of endogenous 5-HT below the injury in a chronic spinal rat may act on supersensitive receptors to produce large Ca PICs and ultimately enable muscle spasms.

Endogenous monoamine receptor activation is essential for enabling persistent sodium currents and repetitive firing in rat spinal motoneurons.

The spinal cord and spinal motoneurons are densely innervated by terminals of serotonin (5-HT) and norepinephrine (NE) neurons arising mostly from the brain stem, but also from intrinsic spinal neurons. Even after long-term spinal transection (chronic spinal), significant amounts (10%) of 5-HT and NE (monoamines) remain caudal to the injury. To determine the role of such endogenous monoamines, we blocked their action with monoamine receptor antagonists and measured changes in the sodium currents and firing in motoneurons. We focused on persistent sodium currents (Na PIC) and sodium spike properties because they are critical for enabling repetitive firing in motoneurons and are facilitated by monoamines. Intracellular recordings were made from motoneurons in the sacrocaudal spinal cord of normal and chronic spinal rats (2 mo postsacral transection) with the whole sacrocaudal cord acutely removed and maintained in vitro (cords from normal rats termed acute spinal). Acute and chronic spinal rats had TTX-sensitive Na PICs that were respectively 0.62 +/- 0.76 and 1.60 +/- 1.04 nA, with mean onset voltages of -63.0 +/- 5.6 and -64.1 +/- 5.4 mV, measured with slow voltage ramps. Application of 5-HT2A, 5-HT2C, and alpha1-NE receptor antagonists (ketanserin, RS 102221, and WB 4101, respectively) significantly reduced the Na PICs, and a combined application of these three monoamine antagonists completely eliminated the Na PIC, in both acute and chronic spinal rats. Likewise, reduction of presynaptic transmitter release (including 5-HT and NE) with long-term application of cadmium also eliminated the Na PIC. Associated with the elimination of the Na PIC in monoamine antagonists, the motoneurons lost their ability to fire during slow current ramps. At this point, the spike evoked by antidromic stimulation was not affected, suggesting that activation of the transient sodium current was not impaired. However, the spike evoked after a slow ramp depolarization was slightly reduced in height and rate-of-rise, suggesting decreased sodium channel availability as a result of increased channel inactivation. These results suggest that endogenous monoamine receptor activation is critical for enabling the Na PIC and decreasing sodium channel inactivation, ultimately enabling steady repetitive firing in both normal and chronic spinal rats.

5-HT2 receptor activation facilitates a persistent sodium current and repetitive firing in spinal motoneurons of rats with and without chronic spinal cord injury.

We examined the modulation of persistent inward currents (PICs) by serotonin (5-HT) in spinal motoneurons of normal and chronic spinal rats. PICs are composed of both a TTX-sensitive persistent sodium current (Na PIC) and a nimodipine-sensitive persistent calcium current (Ca PIC), and we focused on quantifying the Na PIC (and its action on the total PIC), which is known to be critical in enabling repetitive firing. Intracellular recordings were made from motoneurons of the whole sacrocaudal spinal cord of normal adult rats after the cord was acutely transected at the S2 spinal level (acute spinal rat condition), removed from the animal, and then maintained in vitro. In vitro motoneuron recordings were likewise made from rats that had a sacral spinal transection 2 mo previously (chronic spinal rats). In motoneurons from acute spinal rats, moderately high doses of 5-HT (> or = 10 microM), or the 5-HT2 receptor agonist DOI (> or = 30 microM), significantly increased the total PIC, hyperpolarized the PIC onset voltage, and hyperpolarized the spike threshold, whereas lower doses had no effect. Both 5-HT and DOI specifically increased the Na PIC portion of the total PIC (tested with nimodipine blocking the Ca PIC). Additionally, 5-HT, but not DOI, depolarized the resting membrane potential (Vm) and increased the input resistance (Rm) in a dose-dependent manner. Therefore 5-HT2 receptor activation facilitated the Na PIC, whereas other 5-HT receptors modulated Vm and Rm. Motoneurons of chronic spinal rats responded to 5-HT and DOI in the same way, but with larger responses and at much lower doses (0.3-1 microM), thus exhibiting a 30-fold supersensitivity to 5-HT. Specifically the Na PIC was supersensitive to 5-HT2 receptor activation with DOI. Also, Rm and Vm were supersensitive to 5-HT. Consistent with the known critical role of the Na PIC in repetitive firing, enhancement of the Na PIC by DOI or 5-HT facilitated the repetitive firing evoked by steady current injection and enabled repetitive firing in a subpopulation of motoneurons of acute spinal rats that were initially unable to produce sustained repetitive firing. We suggest that after spinal transection, residual endogenous spinal sources of 5-HT help facilitate the Na PIC and repetitive firing. With chronic injury, the developed 5-HT supersensitivity more than compensates for lost brain stem 5-HT, so that the Na PIC is large and motoneurons are very excitable, thus contributing to spasticity.

Persistent sodium currents and repetitive firing in motoneurons of the sacrocaudal spinal cord of adult rats.

Months after sacral spinal transection in rats (chronic spinal rats), motoneurons below the injury exhibit large, low-threshold persistent inward currents (PICs), composed of persistent sodium currents (Na PICs) and persistent calcium currents (Ca PICs). Here, we studied whether motoneurons of normal adult rats also exhibited Na and Ca PICs when the spinal cord was acutely transected at the sacral level (acute spinal rats) and examined the role of the Na PIC in firing behavior. Intracellular recordings were obtained from motoneurons of acute and chronic spinal rats while the whole sacrocaudal spinal cord was maintained in vitro. Compared with chronic spinal rats, motoneurons of acute spinal rats were more difficult to activate because the input resistance was 22% lower and resting membrane potential was hyperpolarized 4.1 mV further below firing threshold (-50.9 +/- 6.2 mV). In acute spinal rats, during a slow voltage ramp, a PIC was activated subthreshold to the spike (at -57.2 +/- 5.0 mV) and reached a peak current of 1.11 +/- 1.21 nA. This PIC was less than one-half the size of that in chronic spinal rats (2.79 +/- 0.94 nA) and usually was not large enough to produce bistable behavior (plateau potentials and self-sustained firing not present), unlike in chronic spinal rats. The PIC was composed of two components: a TTX-sensitive Na PIC (0.44 +/- 0.36 nA) and a nimodipine-sensitive Ca PIC (0.78 +/- 0.82 nA). Both were smaller than in chronic spinal rats (but with similar Na/Ca ratio). The presence of the Na PIC was critical for normal repetitive firing, because no detectable Na PIC was found in the few motoneurons that could not fire repetitively during a slow ramp current injection and motoneurons that had large Na PICs more readily produced repetitive firing and had lower minimum firing rates compared with neurons with small Na PICs. Furthermore, when the Na PIC was selectively blocked with riluzole, steady repetitive firing was eliminated, even though transient firing could be evoked on a rapid current step and the spike itself was unaffected. In summary, only small Ca and Na PICs occur in acute spinal motoneurons, but the Na PIC is essential for steady repetitive firing. We discuss how availability of monoamines may explain the variability in Na PICs and firing in the normal and spinal animals.

Effects of baclofen on spinal reflexes and persistent inward currents in motoneurons of chronic spinal rats with spasticity.

In the months after spinal cord injury, motoneurons develop large voltage-dependent persistent inward currents (PICs) that cause sustained reflexes and associated muscle spasms. These muscle spasms are triggered by any excitatory postsynaptic potential (EPSP) that is long enough to activate the PICs, which take > 100 ms to activate. The PICs are composed of a persistent sodium current (Na PIC) and a persistent calcium current (Ca PIC). Considering that Ca PICs have been shown in other neurons to be inhibited by baclofen, we tested whether part of the antispastic action of baclofen was to reduce the motoneuron PICs as opposed to EPSPs. The whole sacrocaudal spinal cord from acute spinal rats and spastic chronic spinal rats (with sacral spinal transection 2 mo previously) was studied in vitro. Ventral root reflexes were recorded in response to dorsal root stimulation. Intracellular recordings were made from motoneurons, and slow voltage ramps were used to measure PICs. Chronic spinal rats exhibited large monosynaptic and long-lasting polysynaptic ventral root reflexes, and motoneurons had associated large EPSPs and PICs. Baclofen inhibited these reflexes at very low doses with a 50% inhibition (EC50) of the mono- and polysynaptic reflexes at 0.26 +/- 0.07 and 0.25 +/- 0.09 (SD) microM, respectively. Baclofen inhibited the monosynaptic reflex in acute spinal rats at even lower doses (EC50 = 0.18 +/- 0.02 microM). In chronic (and acute) spinal rats, all reflexes and EPSPs were eliminated with 1 microM baclofen with little change in motoneuron properties (PICs, input resistance, etc), suggesting that baclofen's antispastic action is presynaptic to the motoneuron. Unexpectedly, in chronic spinal rats higher doses of baclofen (20-30 microM) significantly increased the total motoneuron PIC by 31.6 +/- 12.4%. However, the Ca PIC component (measured in TTX to block the Na PIC) was significantly reduced by baclofen. Thus baclofen increased the Na PIC and decreased the Ca PIC with a net increase in total PIC. By contrast, when a PIC was induced by 5-HT (10-30 microM) in motoneurons of acute spinal rats, baclofen (20-30 microM) significantly decreased the PIC by 38.8 +/- 25.8%, primarily due to a reduction in the Ca PIC (measured in TTX), which dominated the total PIC in these acute spinal neurons. In summary, baclofen does not exert its antispastic action postsynaptically at clinically achievable doses (< 1 microM), and at higher doses (10-30 microM), baclofen unexpectedly increases motoneuron excitability (Na PIC) in chronic spinal rats.

Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations.

Our objective was to compare brachial artery endothelium dependent and independent vasodilation in lupus patients and healthy females, by means of high-resolution noninvasive brachial artery ultrasound. Endothelially mediated vasodilation was estimated noninvasively by examination of brachial artery responses to postischemic reactive hyperemia and endothelial independent vasodilation from response to sublingual glycerlynitrate (GTN) using high-resolution external vascular ultrasound. Five patients with known coronary artery disease (CAD), five with subclinical CAD, five with no CAD and five control subjects were assessed. Endothelium dependent vasodilation was significantly blunted in lupus patients with CAD as compared with healthy female controls (0.11 versus 11.1%, P = 0.018). Corresponding values for lupus patients with subclinical CAD and no CAD were 11 and 9.6%, respectively. For each subject, endothelium dependent vasodilation (EDV) was related to endothelium independent vasodilation (EIV) to adjust for varying vascular smooth muscle responses to GTN in individual subjects. This ratio was markedly depressed in lupus patients with CAD as compared with control subjects (0.12 versus 1.15). The corresponding EDV/EIV ratios for patients with subclinical CAD and no CAD were similar at 0.69 and 0.65, respectively. The conclusion was that flow mediated vasodilation in lupus patients with coronary artery disease is markedly depressed as compared to healthy subjects.

31P MAS-NMR of human erythrocytes: independence of cell volume from angular velocity.

31P magic angle spinning NMR (MAS-NMR) spectra were obtained from suspensions of human red blood cells (RBCs) that contained the cell-volume-sensitive probe molecule, dimethyl methylphosphonate (DMMP). A mathematical representation of the spectral-peak shape, including the separation and width-at-half-height in the 31P NMR spectra, as a function of rotor speed, enabled us to explore the extent to which a change in cell volume would be reflected in the spectra if it occurred. We concluded that a fractional volume change in excess of 3% would have been detected by our experiments. Thus, the experiments indicated that the mean cell volume did not change by this amount even at the highest spinning rate of 7 kHz. The mean cell volume and intracellular 31P line-width were independent of the packing density of the cells and of the initial cell volume. The relationship of these conclusions to other non-NMR studies of pressure effects on cells is noted.

Measurement of the total active 8B solar neutrino flux at the Sudbury Neutrino Observatory with enhanced neutral current sensitivity.

The Sudbury Neutrino Observatory has precisely determined the total active (nu(x)) 8B solar neutrino flux without assumptions about the energy dependence of the nu(e) survival probability. The measurements were made with dissolved NaCl in heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21 +/- 0.27(stat)+/-0.38(syst) x 10(6) cm(-2) s(-1), in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Deltam(2)=7.1(+1.2)(-0.6) x 10(-5) eV(2) and theta=32.5(+2.4)(-2.3) degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations.

Constraints on nucleon decay via invisible modes from the Sudbury Neutrino Observatory.

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to "invisible" modes, such as n-->3nu. The analysis was based on a search for gamma rays from the deexcitation of the residual nucleus that would result from the disappearance of either a proton or neutron from 16O. A limit of tau(inv)>2 x 10(29) yr is obtained at 90% confidence for either neutron- or proton-decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton-decay modes and 400 times more stringent than similar neutron modes.

Spastic long-lasting reflexes of the chronic spinal rat studied in vitro.

Over the months following sacral spinal cord transection in adult rats, a pronounced spasticity syndrome emerges in the affected tail musculature, where long-lasting muscle spasms can be evoked by low-threshold afferent stimulation (termed long-lasting reflex). To develop an in vitro preparation to examine the neuronal mechanisms underlying spasticity, we removed the whole sacrocaudal spinal cord of these spastic chronic spinal rats (>1 mo after S(2) sacral spinal transection) and maintained it in artificial cerebral spinal fluid in a recording chamber. The ventral roots were mounted on monopolar recording electrodes in grease, and the reflex responses to dorsal root stimulation were recorded and compared with the reflexes seen in the awake chronic spinal rat. When the dorsal roots were stimulated with a single pulse, a long-lasting reflex occurred in the ventral roots, with identical characteristics to the long-lasting reflex in the awake spastic rat tail. The reflex response was low threshold (T), short latency, long duration ( approximately 2 s), and enhanced by repeated stimulation. Brief high-frequency stimulation trains (0.5 s, 100 Hz, 1.5 x T) evoked even longer duration responses (5-10 s), with repeated bursts of activity that were similar to the repeated muscle spasms evoked in awake rats with stimulation trains or manual skin stimulation. Stimulation of a given dorsal root evoked long-lasting reflexes in both the ipsilateral and contralateral ventral roots. Long-lasting reflexes did not occur in the sacrocaudal spinal cord of acute spinal rats (S(2) transection), which is similar to the areflexia seen in awake acute spinal rats. However, long-lasting reflexes could be made to occur in the acute spinal rat by altering K(+) (7 mM) or Mg(2+) (0 mM) concentrations, or by application of high doses of the neuromodulators norepinephrine (NE, >20 microM) or serotonin (5-HT, >20 microM). In chronic spinal rats, much lower doses of these neuromodulators (0.1 microM) enhanced the long-lasting reflexes, suggesting a denervation supersensitivity to 5-HT and NE following injury. Higher doses of NE or 5-HT produced a paradoxical inhibition of the long-lasting reflexes. The high dose inhibition by NE was mimicked by the alpha(2)-adrenergic receptor agonist clonidine but not the alpha(1)-adrenergic receptor agonist methoxamine. In summary, the sacral spinal in vitro preparation offers a new approach to the study of spinal cord injury and analysis of antispastic drugs.