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Realistic characterization of subglacial hydrology necessitates knowledge of the range in form, scale, and spatiotemporal evolution of drainage networks. A relict subglacial meltwater corridor on the deglaciated Antarctic continental shelf encompasses 80 convergent and divergent channels, many of which are hundreds of meters wide and several of which lack a definable headwater source. Without significant surface‐melt contributions to the bed like similarly described landforms in the Northern Hemisphere, channelized drainage capacity varies non‐systematically by three orders of magnitude downstream. This signifies apparent additions and losses of basal water to the bed‐channelized system that relates to bed topography. Larger magnitude grounding‐line retreat events occurred while the channel system was active than once channelized drainage had ceased. Overall, this corridor demonstrates that meltwater drainage styles co‐exist in time and space in response to bed topography, with prolonged impacts on grounding‐line behavior. Plain Language Summary: Water drainage beneath glacial ice can impact flow of the overlying ice, sediment transport underneath the ice toward the glacier's terminus, and the stability of glacial ice as it transitions from resting on the geologic terrain to floating in the ocean. Despite being an important component of glacial systems, the full range of possible modes of water delivery and how these interact and vary across time and space is not well resolved. We describe a relict subglacial meltwater network preserved on the Antarctic seafloor, representing a persistent pathway for water drainage when the East Antarctic Ice Sheet was much larger. The landforms within the drainage network implicate substantial changes in how subglacial water drainage was influenced by the shape of the underlying terrain and demonstrate the prolonged impacts that meltwater corridors have on the retreat of glacial ice. Key Points: Bed topography was the primary control on the morphology and organization of a large paleo‐subglacial meltwater corridor in AntarcticaThe morphology of the corridor supports downstream gains and losses in meltwater supply and/or changes in drainage styleGrounding‐line retreat events were significantly larger when channels were active and smaller when channelized drainage had ceased [ABSTRACT FROM AUTHOR]

Three grazing experiments were carried out in late spring (early lactation), summer (mid-lactation) and autumn (late lactation) to compare the effects of perennial ryegrass cultivar or grass species, sown in binary or multispecies mixtures, on milk yield and nitrogen excretion of dairy cows. Replicated groups of multiparous Holstein Friesian × Jersey cows were offered either a control or high-sugar perennial ryegrass ( Lolium perenne) or tall fescue ( Festuca arundinacea) base grass in a binary mixture with white clover ( Trifolium repens) or in a multispecies mixture with additional legumes, bromegrass ( Bromus willdenowii) and forbs. During each 9-day experiment, botanical composition, milk production and faecal and urine composition were measured. Milk solid ( MS) yield for the control ryegrass, high-sugar ryegrass and tall fescue grass types averaged, respectively, 1.53, 1.64 and 1.70 kg MS cow−1 day−1 for a binary mixture sward, compared with 1.65, 1.54 and 1.53 kg MS cow−1 day−1 for a multispecies sward. Legume content influenced milk production more than the number of species present in a mixture. There was lower urine N concentration from a multispecies sward compared with a binary mixture. Urine N concentration of cows grazing the control ryegrass, high-sugar ryegrass and tall fescue grass types averaged, respectively, 4.6, 5.3 and 6.8 g N L−1 for a binary mixture, compared with 4.1, 3.9 and 3.9 g N L−1 for a multispecies mixture. Feeding dairy cows on multispecies swards containing forbs presents an opportunity to reduce N losses without compromising milk yield. [ABSTRACT FROM AUTHOR]

To determine the zoonotic potential of Cryptosporidium and Giardia in Prince Edward Island (PEI), Canada, 658 human faecal specimens were screened that were submitted to the Queen Elizabeth Hospital diagnostic laboratory. Overall, 143 (22%) samples were Cryptosporidium positive, while three (0.5%) were positive for Giardia. Successful genotyping of 25 Cryptosporidium isolates by sequence analysis of the HSP70 gene revealed that 28 and 72% were C. hominis and C. parvum, respectively. Cryptosporidium isolates from humans and previously genotyped C. parvum from beef cattle were subtyped by sequence analysis of the GP60 gene. Subtyping identified three subtypes belonging to the family IIa. All three subtypes IIaA16G2RI (55%), IIaA16G3RI (22%) and IIaA15G2RI (22%) were found in the animal isolates, while two of the subtypes found in the animals, IIaA16G2RI (80%) and IIaA15G2RI (20%), were also identified in the human isolates. Cryptosporidium infection in humans peaked in April-June. Molecular epidemiological analysis of the human data showed a C. parvum peak in the spring and a relatively smaller peak for C. hominis in July-September. The majority (57%) of human Cryptosporidium isolates were found in children between 5 and 10 years of age. All three Giardia isolates were identified as G. duodenalis assemblage A. The overall Cryptosporidium prevalence in our human samples was high relative to other studies, but because the samples were submitted to a hospital diagnostic laboratory, the results may not be representative of the general population. Further, the presence of the same zoonotic C. parvum subtypes in cattle and human isolates implies that transmission is largely zoonotic and cattle may be a source of sporadic human infections on PEI. The presence of Giardia in people on PEI is rare, and the assemblage A found in humans might originate from humans, livestock or other domestic or wild animals. [ABSTRACT FROM AUTHOR]

The Gram-positive bacterium Aerococcus viridans var. homari is a well-documented causative agent of the lethal systemic disease gaffkemia in both the American lobster, Homarus americanus, and the European lobster, Homarus gammarus. Previous phenotypic characterization has been unsuccessful at differentiating avirulent from virulent strains without performing lethal animal infection trials. Recent genetic characterization of A. viridans strains through 16S rRNA sequencing and random amplification of polymorphic DNA fingerprinting has revealed the presence of two subtypes. However, subtype 1 contains both virulent and avirulent strains which are genetically identical. The purpose of this study was to determine the proteomic mediators of virulence in A. viridans. Quantitative proteomic mapping of these two strains has revealed 29 differentially expressed protein spots, seven of which are only expressed in the virulent strain and could act as virulence factors. One protein, chaperonin 60 (Cpn60), is uniquely expressed in the virulent strain and has been shown to act as a virulence factor in many other bacteria. The proteomic mapping strategy employed in this study is the first to show phenotypic differences between virulent and avirulent strains. Cpn60 expression represents a potentially useful tool for identifying the virulent strains of A. viridans in epidemiological studies. [ABSTRACT FROM AUTHOR]

Background and Purpose: Proteinase-activated receptor-2 (PAR2) is widely expressed in the CNS under normal physiological conditions. However, its potential role in modulating neuronal excitability and synaptic transmission remains to be determined. Here, we have investigated whether PAR2 activation modulates synaptic activity in the hippocampus.Experimental Approach: PAR2 activation and its effect on the hippocampus were examined in rat primary cultures and acute slices using whole cell patch clamp and standard extracellular recordings, respectively.Key Results: PAR2 activation leads to a depolarization of hippocampal neurones and a paradoxical reduction in the occurrence of synaptically driven spontaneous action potentials (APs). PAR2-induced neuronal depolarization was abolished following either the inhibition of astrocytic function or antagonism of ionotropic glutamate receptors whilst the PAR2-induced decrease in AP frequency was also reduced when astrocytic function was inhibited. Furthermore, when examined in acute hippocampal slices, PAR2 activation induced a profound long-term depression of synaptic transmission that was dependent on NMDA receptor activation and was sensitive to disruption of astrocytic function.Conclusions and Implications: These novel findings show that PAR2 activation indirectly inhibits hippocampal synaptic activity and indicate that these receptors may play an active role in modulating normal physiological CNS function, in addition to their role in pathophysiological disorders. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute slices.Experimental Approach: The effect of CBD on synaptic transmission was examined in rat hippocampal cultures and acute slices using whole cell patch clamp and standard extracellular recordings respectively.Key Results: Cannabidiol decreased synaptic activity in hippocampal cultures in a concentration-dependent and Pertussis toxin-sensitive manner. The effects of CBD in culture were significantly reduced in the presence of the cannabinoid receptor (CB(1) ) inverse agonist, LY320135 but were unaffected by the 5-HT(1A) receptor antagonist, WAY100135. In hippocampal slices, CBD inhibited basal synaptic transmission, an effect that was abolished by the proposed CB(1) receptor antagonist, AM251, in addition to LY320135 and WAY100135.Conclusions and Implications: Cannabidiol reduces synaptic transmission in hippocampal in vitro preparations and we propose a role for both 5-HT(1A) and CB(1) receptors in these CBD-mediated effects. These data offer some mechanistic insights into the effects of CBD and emphasize that further investigations into the actions of CBD in the CNS are required in order to elucidate the full therapeutic potential of CBD. [ABSTRACT FROM AUTHOR]

Placental system A activity is important for the supply of neutral amino acids needed for fetal growth. There are three system A isoforms: SNAT1, SNAT2 and SNAT4, but the contribution of each to system A-mediated transport is unknown. Here, we have used immunohistochemistry to demonstrate that all three isoforms are present in the syncytiotrophoblast suggesting each plays a role in amino acid transport across the placenta. We next tested the hypothesis that the SNAT4 isoform is functional in microvillous plasma membrane vesicles (MVM) from normal human placenta using a method which exploits the unique property of SNAT4 to transport both cationic amino acids as well as the system A-specific substrate MeAIB. The data show that SNAT4 contribution to system A-specific amino acid transport across MVM is higher in first trimester placenta compared to term (approx. 70% and 33%, respectively, P < 0.01). Further experiments performed under more physiological conditions using intact placental villous fragments suggest a contribution of SNAT4 to system A activity in first trimester placenta but minimal contribution at term. In agreement, Western blotting revealed that SNAT4 protein expression is higher in first trimester MVM compared to term ( P < 0.05). This study provides the first evidence of SNAT4 activity in human placenta and demonstrates the contribution of SNAT4 to system A-mediated transport decreases between first trimester and term: our data lead us to speculate that at later stages of gestation SNAT1 and/or SNAT2 are more important for the supply of amino acids required for normal fetal growth. [ABSTRACT FROM AUTHOR]

Background In fetal growth restriction (FGR) abnormal umbilical artery (UA) Doppler waveform indices suggest increased vascular resistance and impaired placental blood flow. This study aimed to determine whether UA Doppler waveform indices were related to the vasoreactivity of placental chorionic plate small arteries in normal and FGR pregnancies. Materials and methods UA Doppler waveform analysis was performed 24 h before delivery in 23 normal term and 15 FGR pregnancies. Post-delivery responses of chorionic plate arteries to vasoactive agents were examined using the technique of wire myography. Results Altered vascular reactivity to agonists was demonstrated in chorionic plate arteries in FGR pregnancy. Constriction to U46619 (thromboxane mimetic) and relaxation to sodium nitroprusside (nitric oxide donor) were significantly increased in the arteries of FGR pregnancies compared with normal pregnancies. No relationship existed between Doppler indices and chorionic plate responses in normal or FGR pregnancies. Conclusions Fetoplacental vascular reactivity is altered in FGR pregnancy independently of UA Doppler waveform indices. Altered function may be additive to the pathophysiology underlying abnormal Doppler waveforms and could contribute to the inappropriate control of vascular tone in FGR. [ABSTRACT FROM AUTHOR]

Background: It is important to determine relative and absolute reliability values in outcome measures that are used in clinical practice so as to discriminate between true changes following exercise interventions for patients with chronic kidney disease (CKD)., Objective: The study aimed to assess test-retest reliability of the incremental shuttle walk test (ISWT), sit-to-stand transfers in 60 seconds (STS-60), timed up and go (TUAG), Duke's activity status index (DASI) and hospital anxiety and depression scale (HAD) in patients with CKD., Study Design: This study was a pragmatic non-randomised controlled trial., Methods: Forty people attended two study visits within a 16-day window involving the ISWT, STS-60, TUAG, DASI and HAD tests. Relative reliability was assessed using intraclass correlation coefficient (ICC) and absolute reliability using the standard error of measurement (SEM) and minimal detectable change (MDC)., Results: Good test-retest reliability was found for the entire sample size across all outcome measures, with TUAG having the highest (ICC = 0.96) and HAD the lowest (ICC = 0.71). The MDC scores at 90% confidence interval (CI) were: 79.6 m for the ISWT, 2.9 seconds for the TUAG, 7.0 repetitions for the STS-60, 8.4 for the DASI, 3.8 for the anxiety HAD subscale and 4.4 for the depression HAD subscale., Conclusions: This study demonstrated good test-retest reliability for all outcome measures across the CKD trajectory but caution needs to be taken when interpreting the findings for each CKD sub-group separately. The MDC scores at 90% CI can support therapists in determining a true improvement in CKD patients' physical or mental performance., (© 2019 European Dialysis and Transplant Nurses Association/European Renal Care Association.)

The origins of informatics lie in the development of computers and data processing techniques since the 1950s. The subsequent application of these to the practice of healthcare continues to the present day, so that information technology now holds the potential to revolutionise healthcare through more rapid and efficient management of an ever increasing quantity of clinical information. In dentistry, no less than in medicine, electronic systems can make an extremely valuable contribution to clinical practice. For these systems to be clinically useful, however, they need to be properly understood by clinicians. This review paper outlines the scope of clinical informatics and argues that a grounding in clinical informatics is now essential for today's undergraduates to equip them to meet the challenge of practice in the 21st century.

The effects of the 'loop diuretics' bumetanide, furosemide and piretanide on fluid reabsorption from the rat proximal convoluted tubule have been tested to assess whether a Na(+)-Cl- cotransport mechanism can support fluid reabsorption from this nephron segment. Proximal convoluted tubules were perfused in vivo at 25 nl min-1 with chloride Ringer solutions containing [3H]inulin. Fluid reabsorptive rate (Jv) was 2.05 +/- 0.07 nl mm-1 min-1 (n = 115) from control chloride Ringer. Bumetanide at 10(-6) and 10(-5) M reduced Jv by about 40%. Bumetanide at 10(-7) M, furosemide (10(-4) and 10(-5) M) and piretanide (10(-4) and 10(-5) M) had no effect on Jv. At 10(-3) M, furosemide and piretanide reduced Jv by about 45%. The results show that luminal application of loop diuretics lowers fluid reabsorption from the proximal convoluted tubule and the order of potency for inhibiting reabsorption is bumetanide greater than furosemide identical to piretanide. The specificity of the loop diuretics at their effective concentrations needs to be confirmed, however, before attribution of a role for Na(+)-Cl- co-transport in the support of proximal tubule fluid reabsorption.