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.

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.

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.

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).

Radical intermediates in veratryl alcohol oxidation by ligninase. NMR evidence.

Proton nuclear magnetic resonance (NMR) spectra of veratryl alcohol (3,4-dimethoxybenzyl alcohol) were obtained during its oxidation by ligninase. It was observed that a substantial increase in the linewidths of the resonances occurred only in the presence of both the enzyme and hydrogen peroxide. Quenching the reaction by the addition of alkali immediately restored the normal linewidths of the resonances. Furthermore, inversion-recovery experiments showed a decrease in the longitudinal relaxation time of the substrate when the enzyme was actively turning over. Changes in both these NMR parameters are consistent with the generation of radical intermediates during the ligninase-catalysed oxidation of veratryl alcohol.

Pre-steady-state kinetic study on the formation of compound I and II of ligninase.

The reaction between ligninase and hydrogen peroxide yielding Compound I has been investigated using a stopped-flow rapid-scan spectrophotometer. The optical absorption spectrum of Compound I appears different to that reported by Andrawis, A. et al. (1987) and Renganathan, V. and Gold, M.H. (1986), in that the Soret-maximum is at 401 nm rather than 408 nm. The second-order rate constant (4.2.10(5) M-1.s-1) for the formation of Compound I was independent of pH (pH 3.0-6.0). In the absence of external electron donors, Compound I decayed to Compound II with a half-life of 5-10 s at pH 3.1. The rate of this reaction was not affected by the H2O2 concentration used. In the presence of either veratryl alcohol or ferrocyanide, Compound II was rapidly generated. With ferrocyanide, the second-order rate constant increased from 1.9.10(4) M-1.s-1 to 6.8.10(6) M-1.s-1 when the pH was lowered from 6.0 to 3.1. With veratryl alcohol as an electron donor, the second-order rate constant for the formation of Compound II increased from 7.0.10(3) M-1.s-1 at pH 6.0 to 1.0.10(5) M-1.s-1 at pH 4.5. At lower pH values the rate of Compound II formation no longer followed an exponential relationship and the steady-state spectral properties differed to those recorded in the presence of ferrocyanide. Our data support a model of enzyme catalysis in which veratryl alcohol is oxidized in one-electron steps and strengthen the view that veratryl alcohol oxidation involves a substrate-modified Compound II intermediate which is rapidly reduced to the native enzyme.

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.

The effects of different types and doses of oestrogen replacement therapy on clinic and ambulatory blood pressure and the renin-angiotensin system in normotensive postmenopausal women.

OBJECTIVE: The effect on blood pressure of oral replacement' doses of exogenous oestrogen may depend on the type and dose of oestrogen administered. This study was designed to compare with placebo the effect of once daily treatment with a 'natural' oestrogen, piperazine oestrone sulphate, in two different doses and a semisynthetic oestrogen, ethinyloestradiol, on clinic and ambulatory blood pressure and the renin-angiotensin system in postmenopausal women. DESIGN AND METHODS: Twenty-four normotensive postmenopausal women (median age 54 years, range 47-60 years) participated in the study which used a double-blind crossover design. For each subject there were four randomized treatment phases, each lasting 4 weeks. The separate treatments administered once daily were 0.625 mg oestrone sulphate, 2.5 mg oestrone sulphate, 0.02 mg ethinyloestradiol and matching placebo. Clinic blood pressure, heart rate and weight were measured weekly with the mean values of weeks three and four of each phase used for analysis. Ambulatory blood pressure and biochemical measurements were performed in the final week of each phase. RESULTS: Twenty-four subjects entered and 22 completed the randomized phases of the study. Compared with the placebo phase, end-of-phase mean clinic diastolic blood pressure was reduced in subjects taking the semisynthetic oestrogen (P < 0.01) but was unchanged in those taking the 'low' and 'high' dose natural oestrogen. Mean clinic systolic blood pressure was also unchanged by any of the oestrogen treatments. Ambulatory night-time systolic, diastolic and mean arterial blood pressures were reduced with the low-dose natural and semisynthetic oestrogen treatments compared with placebo (P < 0.01), whereas there was no significant effect of the oestrogen treatments on ambulatory daytime blood pressures. A reduction in clinic and ambulatory heart rate was observed with the high-dose oestrone and semisynthetic oestrogen treatments. There was a dose-dependent increase in plasma renin substrate and decrease in plasma renin concentration with all active treatments; however, there was no change in plasma renin activity or plasma aldosterone concentration. CONCLUSION: In normotensive postmenopausal women, replacement doses of natural and semisynthetic oestrogen reduce night-time ambulatory blood pressure with either no change or a small reduction in clinic blood pressure. Reduction in blood pressure is not explained by reduced activity of the renin-angiotensin system but could have a component of reduced central sympathetic drive consistent with the decreased heart rate.

Lacidipine, hydrochlorothiazide and their combination in systolic hypertension in the elderly.

OBJECTIVE: To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension. DESIGN AND METHODS: Nineteen elderly subjects (five men and 14 women, median age 71 years, range 62-79 years) participated in the study, which had a randomized double-blind crossover design. For each subject there were four treatment phases, each of duration 4 weeks. The initial treatments in each phase were 2 mg lacidipine once a day and 25 mg hydrochlorothiazide once a day, separately and in combination, and placebo. Doses of each agent could be doubled after 2 weeks in each phase if the patient's goal systolic blood pressure had not been achieved. The numbers of subjects administered the higher dose of each treatment were 13 for placebo, 14 for lacidipine, 11 for hydrochlorothiazide and eight for lacidipine plus hydrochlorothiazide. RESULTS: End-of-phase mean clinic blood pressures were 164/85 mmHg with placebo, 159/82 mmHg with lacidipine, 157/84 mmHg with hydrochlorothiazide and 152/82 mmHg with lacidipine plus hydrochlorothiazide. Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases. There was no difference between sitting and standing blood pressure for any phase. Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered. Ambulatory blood pressure monitoring confirmed the pattern of the responses of blood pressure and showed that administration of hydrochlorothiazide had a significantly greater effect on systolic blood pressure and a longer duration of action than did administration of lacidipine. There was no difference in the frequency of adverse effects among any of the phases. CONCLUSIONS: In treating elderly systolic hypertensives the diuretic hydrochlorothiazide is a more effective antihypertensive agent with a longer duration of action than is the calcium channel antagonist lacidipine. In combination the effects of these two drugs on blood pressure are additive.

Duplication 5q(5q22----5q33): from an intrachromosomal insertion.

We report on an infant with an as yet undescribed partial duplication 5q(q22----5q33). He had a number of the already recorded manifestations of partial trisomy 5q, namely microcephaly, growth retardation, brachydactyly, long flat philtrum, thin upper lip vermilion and downturned angles of mouth and apparently low set ears. He survived only 6 months. He inherited his duplication from a maternal intrachromosomal insertion; thus he represents a pure dup(5)(q22----5q33).

Respiratory pathways and oxygen toxicity in Phanerochaete chrysosporium.

Phanerochaete chrysosporium maintained on glucose as the carbon source contained severely impaired mitochondria that were characterised by the loss of both succinate dehydrogenase and cytochrome oxidase activities. These cells maintained a constant value for energy charge using anaerobic metabolism. Cells with these properties express lignin peroxidase when supplied with a pure oxygen atmosphere, which may reflect a response to accumulating reactive oxygen species. Cells maintained on cellulose retained fully functional mitochondria, but expressed lignin peroxidase without being exposed to a pure oxygen atmosphere. In the cells maintained on cellulose, mitochondrial function may be limited by the supply of glucose, leading to the accumulation of reactive oxygen species.

Metabolism of cellulose by Phanerochaete chrysosporium in continuously agitated culture is associated with enhanced production of lignin peroxidase.

Production of the extracellular heme protein lignin peroxidase (LiP) by Phanerochaete chrysosporium is currently associated with a number of requirements, namely exposure of the cultures to oxygen; limiting nutrient nitrogen or carbon and static or semi-static culture conditions. To obtain LiP activity in continuously agitated liquid culture requires the inclusion of a surfactant. However, using cellulose as the carbon source, we obtained high titres (0.2-0.4 U ml(-1)) of LiP in submerged liquid cultures under conditions of continuous agitation, without substrate limitation or the need to add oxygen or surfactant. Comparison of the morphological and physiological traits of hyphae maintained on either cellulose or free glucose supports observations that the synthesis of extracellular polysaccharide in the cultures grown on glucose, restricts oxygen diffusion into the hyphae, which is necessary for LiP induction. They also suggest that isozymes of LiP synthesised under these conditions may be triggered in response to oxidant stress.

Dose response effect of cyclical medroxyprogesterone on blood pressure in postmenopausal women.

OBJECTIVE: This study was designed to compare with placebo the dose-response effect of cyclical doses of the C21 progestogen, medroxyprogesterone acetate (MPA) on blood pressure (BP) when administered to normotensive postmenopausal women receiving a fixed mid-range daily dose of conjugated equine oestrogen (CEE). MATERIALS AND METHODS: Twenty normotensive postmenopausal women (median age 53 years) participated in the study which used a double-blind crossover design. There were four randomised treatment phases, each of 4 weeks duration. The four blinded treatments were MPA 2.5 mg, MPA 5 mg, MPA 10 mg and matching placebo, taken for the last 14 days of each 28 day treatment cycle. CEE 0.625 mg was also administered once daily as open labelled tablets to all subjects throughout the study. Clinic BP was measured weekly with the mean values of weeks 3 and 4 of each phase used for analysis. Ambulatory BP was performed in the final week of each phase. RESULTS: Compared with the placebo phase, end of phase clinic BP was unchanged by any of the progestogen treatments. There was a dose-dependent decrease in ambulatory daytime diastolic and mean arterial BP with the progestogen treatments compared with placebo (P < 0.05). CONCLUSION: In a regimen of postmenopausal hormone replacement therapy with a fixed mid-range daily dose of CEE combined with a cyclical regimen of a C21 progestogen spanning the current clinical dose range, the progestogen has either no effect or a small dose-dependent reduction in clinic and ambulatory BPs over one treatment cycle.

Signal-to-noise ratios for attenuation correction in PET imaging.

Attenuation correction is an important part of accurate image reconstruction in positron tomography. The usual correction method involves direct measurement of attenuation correction factors (ACFs). A reconstruct-reproject method, which has been suggested as providing superior noise properties, is sometimes employed; an attenuation image is first reconstructed from the measurement and then ACFs are obtained by reprojection through this image. Here the authors present a model which follows the signal-to-noise ratio (SNR) through the attenuation correction by both the direct and reconstruct-reproject methods. This model is applicable to both 2D and 3D imaging geometry, but applies to the central elements of emission and transmission objects with circular symmetry and constant amplitude. For this simplified geometry, the model predicts that the SNR of the emission image following attenuation correction is the same for both direct and reconstruct-reproject methods, although the SNRs of the ACFs are themselves substantially different. The authors also present the measured SNR at the various steps of attenuation correction for both the direct and reconstruct-reproject methods using simulated transmission and emission data. The measured SNRs agree with the model; no significant difference between the direct and reconstruct-reproject SNRs was observed.

A deconvolution scatter correction for a 3-D PET system.

A method to remove the scattered background from a reconstructed image by deconvolution with a point response function which includes the scatter contribution is presented. The amplitude of the scattered response function is obtained by constraining a region of the corrected image to zero average amplitude. This method assumes that the shape of scatter distribution is shift invariant and independent of the shape of the scattering object and the distribution of the positron activity. The validity of these approximations for the QPET geometry was tested using simulations. An average scatter response function for the system was obtained from these simulations and compared with results from measurements. The method was tested using experimental data from an irregularly shaped acrylic phantom. It was simple to implement and resulted in a satisfactory correction of the scattered background for a small-volume system.