Pulse-shape discrimination against low-energy Ar-39 beta decays in liquid argon with 4.5 tonne-years of DEAP-3600 data.

The DEAP-3600 detector searches for the scintillation signal from dark matter particles scattering on a 3.3 tonne liquid argon target. The largest background comes from 39 Ar beta decays and is suppressed using pulse-shape discrimination (PSD). We use two types of PSD estimator: the prompt-fraction, which considers the fraction of the scintillation signal in a narrow and a wide time window around the event peak, and the log-likelihood-ratio, which compares the observed photon arrival times to a signal and a background model. We furthermore use two algorithms to determine the number of photons detected at a given time: (1) simply dividing the charge of each PMT pulse by the mean single-photoelectron charge, and (2) a likelihood analysis that considers the probability to detect a certain number of photons at a given time, based on a model for the scintillation pulse shape and for afterpulsing in the light detectors. The prompt-fraction performs approximately as well as the log-likelihood-ratio PSD algorithm if the photon detection times are not biased by detector effects. We explain this result using a model for the information carried by scintillation photons as a function of the time when they are detected.

Phase partitioning during fragmentation revealed by QEMSCAN Particle Mineralogical Analysis of volcanic ash.

Volcanic ash particle properties depend upon their genetic fragmentation processes. Here, we introduce QEMSCAN Particle Mineralogical Analysis (PMA) to quantify the phase distribution in ash samples collected during activity at Santiaguito, Guatemala and assess the fragmentation mechanisms. Volcanic ash from a vulcanian explosion and from a pyroclastic density current resulting from a dome collapse were selected. The ash particles resulting from both fragmentation modes are dense and blocky, typical of open-vent dome volcanoes and have a componentry consistent with their andesitic composition. We use image analysis to compare the fraction of each phase at particle boundaries compared to the total particle fraction. Our results show that the explosion-derived ash has an even distribution of plagioclase and glass, but boundaries enriched in pyroxene and amphibole. In contrast, the ash generated during dome collapse has an increased fraction of glass and decreased fraction of plagioclase at particle boundaries, suggesting that fractures preferentially propagate through glass during abrasion and milling in pyroclastic flows. This study presents QEMSCAN PMA as a new resource to identify generation mechanisms of volcanic ash, which is pertinent to volcanology, aviation, respiratory health and environmental hazards, and highlights the need for further experimental constraints on the fragmentation mechanism fingerprint.

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.).

An international consensus statement on the management of postoperative anaemia after major surgical procedures.

Despite numerous guidelines on the management of anaemia in surgical patients, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in the postoperative period. A number of experienced researchers and clinicians took part in a two-day expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the postoperative period. These statements include: a diagnostic approach to iron deficiency and anaemia in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up that is easy to implement. Available data allow the fulfilment of the requirements of Pillar 1 of Patient Blood Management. We urge national and international research funding bodies to take note of these recommendations, particularly in terms of funding large-scale prospective, randomised clinical trials that can most effectively address the important clinical questions and this clearly unmet medical need.

Cornerstones of patient blood management in surgery.

Pre-operative anaemia and perioperative red blood cell transfusion carry significant consequence when it comes to surgical outcomes. The establishment of patient-centred clinical pathways has been designed to harness and endorse good transfusion practice, termed the three pillars of patient blood management (PBM). These focus on the timely and appropriate management of anaemia, prevention of blood loss and restrictive transfusion where appropriate. This article reviews the current evidence and ongoing research in the field of PBM in surgery. Strategies to implement PBM have shown significant benefits in appropriate transfusion practice, reduced costs and improved length of hospital stay. Recently published national quality standards have recognised the features of the PBM blueprint such as the consideration of alternatives to red blood cell transfusion, the active measures to reduce perioperative blood loss and the appropriate management of post-operative anaemia. Adopting PBM in surgical patients should be paramount to reduce the risks posed by perioperative anaemia and blood transfusions. The principles of PBM help structure the interventions and decisions relating to anaemia and blood transfusion, but, more importantly, represent a paradigm shift towards a more considered approach to blood transfusion, acknowledging its risks, preventatives and alternatives.

The nitrate time bomb: a numerical way to investigate nitrate storage and lag time in the unsaturated zone.

Nitrate pollution in groundwater, which is mainly from agricultural activities, remains an international problem. It threatens the environment, economics and human health. There is a rising trend in nitrate concentrations in many UK groundwater bodies. Research has shown it can take decades for leached nitrate from the soil to discharge into groundwater and surface water due to the 'store' of nitrate and its potentially long travel time in the unsaturated and saturated zones. However, this time lag is rarely considered in current water nitrate management and policy development. The aim of this study was to develop a catchment-scale integrated numerical method to investigate the nitrate lag time in the groundwater system, and the Eden Valley, UK, was selected as a case study area. The method involves three models, namely the nitrate time bomb-a process-based model to simulate the nitrate transport in the unsaturated zone (USZ), GISGroundwater--a GISGroundwater flow model, and N-FM--a model to simulate the nitrate transport in the saturated zone. This study answers the scientific questions of when the nitrate currently in the groundwater was loaded into the unsaturated zones and eventually reached the water table; is the rising groundwater nitrate concentration in the study area caused by historic nitrate load; what caused the uneven distribution of groundwater nitrate concentration in the study area; and whether the historic peak nitrate loading has reached the water table in the area. The groundwater nitrate in the area was mainly from the 1980s to 2000s, whilst the groundwater nitrate in most of the source protection zones leached into the system during 1940s-1970s; the large and spatially variable thickness of the USZ is one of the major reasons for unevenly distributed groundwater nitrate concentrations in the study area; the peak nitrate loading around 1983 has affected most of the study area. For areas around the Bowscar, Beacon Edge, Low Plains, Nord Vue, Dale Springs, Gamblesby, Bankwood Springs, and Cliburn, the peak nitrate loading will arrive at the water table in the next 34 years; statistical analysis shows that 8.7 % of the Penrith Sandstone and 7.3 % of the St Bees Sandstone have not been affected by peak nitrate. This research can improve the scientific understanding of nitrate processes in the groundwater system and support the effective management of groundwater nitrate pollution for the study area. With a limited number of parameters, the method and models developed in this study are readily transferable to other areas.

Survival of bacteria on the ocular surface following double application of povidone-iodine before cataract surgery.

AIMS: This study assessed the effectiveness of one vs two applications of povidone-iodine in decontaminating the eye before cataract surgery. METHODS: This was a prospective, interventional study of 52 patients having elective unilateral phacoemulsification cataract surgery in a tertiary care centre. Each patient had two applications of povidone-iodine before phacoemulsification cataract surgery, separated by 10 min. Conjunctival swabs were taken before and after each application and cultured in 5% CO(2) and anaerobically. Statistical analysis was performed using McNemar's test for correlated proportions. RESULTS: In all, 15 of 52 (29%) patients had positive cultures before the first application and 21 of 52 (40%) patients had positive cultures after it. This was not statistically significant (P=0.239). A total of 25 of 52 (48%) patients were culture positive before the second application. This was not statistically significantly different from 10 min earlier (P=0.423). Six of 52 (12%) patients were positive after the second application (P<0.001). CONCLUSIONS: We conclude that the initial application of povidone-iodine was not effective in decontaminating the eye. Recontamination did not take place between applications. The difference in the proportion of patients with positive results before and after the second application of povidone-iodine was statistically significant. We infer from this that double application of povidone-iodine before cataract surgery is advisable.

Comparison of stool antigen detection kits to PCR for diagnosis of amebiasis.

The present study was conducted to compare two stool antigen detection kits with PCR for the diagnosis of Entamoeba histolytica infections by using fecal specimens submitted to the Department of Microbiology at St. Vincent's Hospital, Sydney, and the Institute of Medical and Veterinary Science, Adelaide, Australia. A total of 279 stool samples containing the E complex (E. histolytica, Entamoeba dispar, and Entamoeba moshkovskii) were included in this study. The stool specimens were tested by using two commercially produced enzyme immunoassays (the Entamoeba CELISA PATH and TechLab E. histolytica II kits) to detect antigens of E. histolytica. DNA was extracted from all of the samples with a Qiagen DNA stool mini kit (Qiagen, Hilden, Germany), and a PCR targeting the small-subunit ribosomal DNA was performed on all of the samples. When PCR was used as a reference standard, the CELISA PATH kit showed 28% sensitivity and 100% specificity. The TechLab ELISA (enzyme-linked immunosorbent assay) kit did not prove to be useful in detecting E. histolytica, as it failed to identify any of the E. histolytica samples which were positive by PCR. With the TechLab kit, cross-reactivity was observed for three specimens, one of which was positive for both E. dispar and E. moshkovskii while the other two samples contained E. moshkovskii. Quantitative assessment of the PCR and ELISA results obtained showed that the ELISA kits were 1,000 to 10,000 times less sensitive, and our results show that the CELISA PATH kit and the TechLab ELISA are not useful for the detection of E. histolytica in stool samples from patients in geographical regions where this parasite is not endemic.

Phosphorylation sites on calcium channel alpha1 and beta subunits regulate ERK-dependent modulation of neuronal N-type calcium channels.

Voltage-dependent calcium channels (VDCCs) in sensory neurones are tonically up-regulated via Ras/extracellular signal regulated kinase (ERK) signalling. The presence of putative ERK consensus sites within the intracellular loop linking domains I and II of neuronal N-type (Ca(v)2.2) calcium channels and all four neuronal calcium channel beta subunits (Ca(v)beta), suggests that Ca(v)2.2 and/or Ca(v)betas may be ERK-phosphorylated. Here we report that GST-Ca(v)2.2 I-II loop, and to a lesser extent Ca(v)beta1b-His(6), are substrates for ERK1/2 phosphorylation. Serine to alanine mutation of Ser-409 and/or Ser-447 on GST-Ca(v)2.2 I-II loop significantly reduced phosphorylation. Loss of Ser-447 reduced phosphorylation to a greater extent than mutation of Ser-409. Patch-clamp recordings from wild-type Ca(v)2.2,beta1b,alpha2delta1 versus mutant Ca(v)2.2(S447A) or Ca(v)2.2(S409A) channels revealed that mutation of either site significantly reduced current inhibition by UO126, a MEK (ERK kinase)-specific inhibitor that down-regulates ERK activity. However, no additive effect was observed by mutating both residues together, suggesting some functional redundancy between these sites. Mutation of both Ser-161 and Ser-348 on Ca(v)beta1b did not significantly reduce phosphorylation but did reduce UO126-induced current inhibition. Crucially, co-expression of Ca(v)2.2(S447A) with Ca(v)beta1b(S161,348A) had an additive effect, abolishing the action of UO126 on channel current, an effect not seen when Ca(v)beta1b(S161,348A) was co-expressed with Ca(v)2.2(S409A). Thus, Ser-447 on Ca(v)2.2 and Ser-161 and Ser-348 of Ca(v)beta1b appear to be both necessary and sufficient for ERK-dependent modulation of these channels. Together, our data strongly suggest that modulation of neuronal N-type VDCCs by ERK involves phosphorylation of Ca(v)2.2alpha1 and to a lesser extent possibly also Ca(v)beta subunits.

Second intermediate host land snails and definitive host animals of Brachylaima cribbi in southern Australia.

This study of infection of southern Australian land snails with Brachylaima cribbi metacercariae has shown that all commonly encountered native and introduced snails are susceptible second intermediate hosts. The range of infected snails is extensive with metacercariae-infected snails being present in all districts across southern Australia. C. virgata has the highest average natural metacercarial infection intensity of 6.1 metacercariae per infected snail. The susceptibility of birds, mammals and reptiles to B. cribbi infection was studied in South Australia by capturing, dissecting and examining the intestinal tract contents of animals which commonly eat land snails as a food source. Indigenous Australian little ravens (Corvus mellori), which are a common scavenger bird, and two other passeriform birds, the black bird (Turdus merula) and the starling (Sturnus vulgaris), which are both introduced European birds, were found to have the highest infection rates of all animals examined. Other birds found infected with B. cribbi were an emu (Dromaius novaehollandiae), chickens (Gallus gallus) and a pigeon (Columba livia). Natural infections were also detected in field mice (Mus domesticus) and shingleback lizards (Tiliqua rugosa) although the intensity of infection was lower than that observed in birds. Susceptibility studies of laboratory mice, rats and ducks showed that mice developed patent infections which persisted for several weeks, rats developed a short-lived infection of three weeks' duration and ducks did not support infection. This study has shown for the first time that a brachylaimid can infect a wide host range of birds, mammals and reptiles in nature.

Field prevalence and laboratory susceptibility of southern Australian land snails to Brachylaima cribbi sporocyst infection.

Brachylaima cribbi is a terrestrial trematode of birds and mammals with helicid and hygromiid land snails reported as first and second intermediate hosts. However, reports describing the first intermediate host range of B. cribbi have been limited to those snail species present in a small number of geographical locations in South Australia. The natural first intermediate host range, distribution and prevalence of B. cribbi in land snails in southern Australia were determined. A total of 6,432 introduced and native land snails were collected from eight geographical districts across 3,000 km of southern Australia and examined microscopically for B. cribbi sporocysts. Four introduced European snails, Theba pisana, Cernuella virgata, Cochlicella acuta and Cochlicella barbara were natural first intermediate hosts. Sporocyst-infected snails were detected in all districts from Victoria to the west coast of South Australia, a distance of over 1,300 km. Natural sporocyst infection was not observed in introduced European snails Microxeromagna armillata and Helix aspersa or in native Australian land snails Succinea australis and Strangesta gawleri. Egg feeding experiments in the laboratory with B. cribbi confirmed the susceptibility of those species of snails found to be natural first intermediate hosts. Of those species not found to be infected in nature, only M. armillata could be infected in the laboratory. Although this study has shown that five different species of European land snails are suitable first intermediate hosts for B. cribbi there are as yet no reports of B. cribbi from these snails in Europe or from other countries where they have been introduced. Further investigations are needed in Europe to clarify the origins of this parasite.

Brachylaima cribbi (Digenea: Brachylaimidae): scanning electron microscopical observations of the life-cycle stages.

Brachylaima cribbi is a recently described species of terrestrial trematode that infects mammals and birds with helicid land snails as its first and second intermediate hosts. The adult worm is 2.5-6.0 mm long by 0.5-0.8 mm wide being a long slender cylindrical worm with oral and ventral suckers in the anterior quarter and genital pore in the posterior quarter. Scanning electron microscopy shows that there is a dense covering of tegumental spines at the anterior end which diminishes towards the posterior extremities of the worm. Development of spines was observed in juvenile and mature adult worms. In young worms 1-3 weeks post infection (wpi) spines appear as buds with a serrated edge each having 1-4 spikes per spine. As the worm ages the spines broaden and by 5 wpi the number of spikes per spine increases to an average of 8.1. The serial development of oral sucker papillae in the cercaria, metacercaria and adult worm was observed with the finding of an elongated papilla with a bifurcated tip on the cercaria becoming a shorter and thicker elongated papilla with a large central stoma on the metacercaria. In the adult worm, this papilla becomes dome-shaped with a small central stoma. For some of these papillae a cilium could be seen extended from the central stoma. Other life-cycle stages illustrated were the hatched egg with an extruded egg membrane minus an operculum and a portion of the branched sporocyst dissected from the digestive gland of the land snail Theba pisana showing a terminal birth pore. Scanning electron microscopy morphological features of the adult worm observed for the first time in a Brachylaima were the unarmed cirrus extended from the genital pore with released sperm present and the Laurer's canal opening visible in tegumental folds on the dorsal surface approximately 300 microm posterior to the genital pore.

Cardiovascular risk assessment in patients with retinal vein occlusion.

AIM: Patients with retinal vein occlusions (RVO) are at increased risk of cardiovascular disease (CVD). The risk of future CVD was determined using the Framingham algorithm and this risk estimate was used to guide decisions about preventative treatment for CVD in RVO patients. METHODS: 107 unselected RVO patients were studied. After excluding 18 patients because of age, missing data, or pre-existing cardiovascular disease, the calculated coronary heart disease risks (cCHDR) and calculated cardiovascular disease risks (cCVDR) were calculated on the 89 remaining and compared with both the standardised risk and the published incidence of CHD in England by t test or chi(2) test. RESULTS: The mean 10 year cCVDR was significantly higher than the Framingham standardised risk for all RVOs (20.6% (1.2%) v 15.7% (1.1%), p = 0.009) and female RVOs (17.8% (1.2%) v 12.7% (1.0%), p = 0.022) in particular. The 10 year cCHDR, compared to the actual incidence of CHD in England between the ages of 30 and 74 years, was > 15% in twice as many males than expected (62% v 28%, p <0.0001). This rose to almost six times when cCHDRs greater than 30% were compared (17% v 3%, p = 0.002). There was a fourfold increase in the proportion of female RVO patients with a cCHDR above 15% (40% v 9%, p <0.0001) and at a cCHDR of 30% and above (10% v 0%, p = 0.004). There were also significant differences in the cCHDR between central and branch RVO (both sexes). The branch form of RVO (BRVO) having higher cCHDRs because of systolic hypertension (164.1 (21.6) mm Hg v 149.5 (23.5) mm Hg, p = 0.003) and age (61.7 (8.3) years v 56.7 (10.6) years, p = 0.017). CONCLUSIONS: RVO is the presenting complaint in a group of patients at increased risk of CVD and is in agreement with the long term follow up data demonstrating an increased mortality from CVD in patients with RVO. The Framingham algorithm can accurately determine the cCHDR (or cCVDR) to assist the clinician in deciding who to treat in accordance with the Joint British Societies' guidelines, with particular regard to hypertension, lipid lowering, and the use of aspirin therapy.

Improving linkage analysis in outcrossed forest trees - an example from Acacia mangium.

Mapping in forest trees generally relies on outbred pedigrees in which genetic segregation is the result of meiotic recombination from both parents. The currently available mapping packages are not optimal for outcrossed pedigrees as they either cannot order phase-ambiguous data or only use pairwise information when ordering loci within linkage groups. A new package, OUTMAP, has been developed for mapping codominant loci in outcrossed trees. A comparison of maps produced using linkage data from two pedigrees of Acacia mangium Willd demonstrated that the marker orders produced using OUTMAP were consistently of higher likelihood than those produced by JOINMAP. In addition, the maps were produced more efficiently, without the need for recoding data or the detailed investigation of pairwise recombination fractions which was necessary to select the optimal marker order using JOINMAP. Distances between markers often varied from those calculated by JOINMAP, resulting in an increase in the estimated genome length. OUTMAP can be used with all segregation types to determine phase and to calculate the likelihood of alternative marker orders, with a choice of three optimisation methods.

Evidence for two concentration-dependent processes for beta-subunit effects on alpha1B calcium channels.

beta-Subunits of voltage-dependent Ca(2+) channels regulate both their expression and biophysical properties. We have injected a range of concentrations of beta3-cDNA into Xenopus oocytes, with a fixed concentration of alpha1B (Ca(V)2.2) cDNA, and have quantified the corresponding linear increase of beta3 protein. The concentration dependence of a number of beta3-dependent processes has been studied. First, the dependence of the a1B maximum conductance on beta3-protein occurs with a midpoint around the endogenous concentration of beta3 (approximately 17 nM). This may represent the interaction of the beta-subunit, responsible for trafficking, with the I-II linker of the nascent channel. Second, the effect of beta3-subunits on the voltage dependence of steady-state inactivation provides evidence for two channel populations, interpreted as representing alpha1B without or with a beta3-subunit, bound with a lower affinity of 120 nM. Third, the effect of beta3 on the facilitation rate of G-protein-modulated alpha1B currents during a depolarizing prepulse to +100 mV provides evidence for the same two populations, with the rapid facilitation rate being attributed to Gbetagamma dissociation from the beta-subunit-bound alpha1B channels. The data are discussed in terms of two hypotheses, either binding of two beta-subunits to the alpha1B channel or a state-dependent alteration in affinity of the channel for the beta-subunit.

Description of the life-cycle stages of Brachylaima cribbi n. sp. (Digenea: Brachylaimidae) derived from eggs recovered from human faeces in Australia.

The life-cycle of Brachylaima cribbi n. sp. was established in the laboratory. Asymmetrical brachylaimid eggs, measuring 26-32 microm (29.1 microm) long and 16 -17.5 microm (16.6 microm) wide, were recovered from human faeces and fed to the helicid land snail Theba pisana as the first intermediate host. Sporocysts and cercariae were recovered from the T. pisana eight weeks after infection. The cercariae were used to infect the helicid land snails Cernuella virgata and Helix aspersa as second intermediate hosts. Metacercariae were recovered from the kidneys of these snails and used to infect mice. Adults of Brachylaima cribbi n. sp. were recovered from the small intestine of the mice. The differential features of B. cribbi n. sp. are the specificity for helicid snails as first and second intermediate hosts; characteristic ventral sucker and body cercarial chaetotaxy; and a long slender adult worm with equal size suckers in the first quarter of the worm, the ventral sucker occupying 41% of the body width, the uterus extending anterior to the ventral sucker and the vitelline follicles falling short of the posterior margin of the ventral sucker. No other known Brachylaima species exhibits all of these features. B. cribbi n. sp. is the first brachylaimid known to have infected humans and is probably of European origin, as the intermediate host snails were all introduced into Australia from Europe.

Biophysical properties, pharmacology, and modulation of human, neuronal L-type (alpha(1D), Ca(V)1.3) voltage-dependent calcium currents.

Voltage-dependent calcium channels (VDCCs) are multimeric complexes composed of a pore-forming alpha(1) subunit together with several accessory subunits, including alpha(2)delta, beta, and, in some cases, gamma subunits. A family of VDCCs known as the L-type channels are formed specifically from alpha(1S) (skeletal muscle), alpha(1C) (in heart and brain), alpha(1D) (mainly in brain, heart, and endocrine tissue), and alpha(1F) (retina). Neuroendocrine L-type currents have a significant role in the control of neurosecretion and can be inhibited by GTP-binding (G-) proteins. However, the subunit composition of the VDCCs underlying these G-protein-regulated neuroendocrine L-type currents is unknown. To investigate the biophysical and pharmacological properties and role of G-protein modulation of alpha(1D) calcium channels, we have examined calcium channel currents formed by the human neuronal L-type alpha(1D) subunit, co-expressed with alpha(2)delta-1 and beta(3a), stably expressed in a human embryonic kidney (HEK) 293 cell line, using whole cell and perforated patch-clamp techniques. The alpha(1D)-expressing cell line exhibited L-type currents with typical characteristics. The currents were high-voltage activated (peak at +20 mV in 20 mM Ba2+) and showed little inactivation in external Ba2+, while displaying rapid inactivation kinetics in external Ca2+. The L-type currents were inhibited by the 1,4 dihydropyridine (DHP) antagonists nifedipine and nicardipine and were enhanced by the DHP agonist BayK S-(-)8644. However, alpha(1D) L-type currents were not modulated by activation of a number of G-protein pathways. Activation of endogenous somatostatin receptor subtype 2 (sst2) by somatostatin-14 or activation of transiently transfected rat D2 dopamine receptors (rD2(long)) by quinpirole had no effect. Direct activation of G-proteins by the nonhydrolyzable GTP analogue, guanosine 5'-0-(3-thiotriphospate) also had no effect on the alpha(1D) currents. In contrast, in the same system, N-type currents, formed from transiently transfected alpha(1B)/alpha(2)delta-1/beta(3), showed strong G-protein-mediated inhibition. Furthermore, the I-II loop from the alpha(1D) clone, expressed as a glutathione-S-transferase (GST) fusion protein, did not bind Gbetagamma, unlike the alpha(1B) I-II loop fusion protein. These data show that the biophysical and pharmacological properties of recombinant human alpha(1D) L-type currents are similar to alpha(1C) currents, and these currents are also resistant to modulation by G(i/o)-linked G-protein-coupled receptors.

Electropalatographic and cephalometric assessment of tongue function in open bite and non-open bite subjects.

Anterior open bite (AOB) and tongue thrust swallowing are frequently associated, but the relationship between the two remains unclear. Electropalatography (EPG), which is used in speech pathology to measure dynamic tongue function for diagnostic, therapeutic, and research purposes, is a suitable technique for the investigation of this relationship. The present clinical study examined the dentofacial pattern and tongue function in AOB and non-open bite children. EPG recordings of speech and swallowing, and lateral head radiographs were obtained from eight 10-year-old boys with tongue thrust swallowing behaviour and AOB, and from eight age-matched non-open bite controls. Analysis of data from the two groups indicated that although differences were small, the open bite children displayed trends for longer face morphology and greater upper incisor proclination, less consistent production of closures during speech, a more posterior pattern of EPG contact, and relatively sparse EPG contact during swallowing. The discovery of differing patterns of contact for the /d[symbol: see text]/ and /t[symbol: see text]/ phonemes indicates that these should be included when speech is used to test for the presence of fronted tongue behaviour.

Performance of the COBAS AMPLICOR HCV MONITOR test, version 2.0, an automated reverse transcription-PCR quantitative system for hepatitis C virus load determination.

A clinical evaluation of an automated quantitative PCR assay, the COBAS AMPLICOR HCV MONITOR test, version 2.0 (v2.0), was carried out to assess the performance of this test in comparison with that of the previous, manual version, the AMPLICOR HCV MONITOR test, and with that of nested PCR. Serial dilutions of serum samples infected with genotype 1b, 2a, or 3, as well as synthetic RNA transcripts and serum samples derived from 87 patients with chronic hepatitis C and infected with genotype 1a, 1b, 2a, 2b, 3a, 3b, 4, or 5, were analyzed to determine the ability of the system to efficiently quantify various hepatitis C virus (HCV) genotypes. These experiments showed that the COBAS AMPLICOR HCV MONITOR test, v2.0, has mean intra-assay, interassay, and interoperator coefficients of variation that range from 22 to 34.5% and a 3-logarithm dynamic range, which spans from 10(3) to 10(6) copies/ml. Compared to the previous, manual version of the test, the COBAS AMPLICOR HCV MONITOR test, v2.0, showed an improved efficacy for all genotypes, especially genotypes 2, 3, and 4, whose estimated concentrations were on average 1 logarithm higher. When used to monitor patients under treatment, however, both versions showed the same patterns of viremia, indicating that the COBAS AMPLICOR HCV MONITOR test, v2.0, and the AMPLICOR HCV MONITOR test were equally effective at detecting relative viremia changes in serial samples. As expected, the automated test was less sensitive than nested PCR; among specimens from a cohort of patients treated with interferon, nested PCR identified three more viremic specimens, which probably contained very low concentrations of HCV RNA.