X-ray self-emission imaging with spherically bent Bragg crystals on the Z-machine.

An x-ray imaging scheme using spherically bent crystals was implemented on the Z-machine to image x rays emitted by the hot, dense plasma generated by a Magnetized Liner Inertial Fusion (MagLIF) target. This diagnostic relies on a spherically bent crystal to capture x-ray emission over a narrow spectral range (<15 eV), which is established by a limiting aperture placed on the Rowland circle. The spherical crystal optic provides the necessary high-throughput and large field-of-view required to produce a bright image over the entire, one-cm length of the emitting column of a plasma. The average spatial resolution was measured and determined to be 18 µm for the highest resolution configuration. With this resolution, the radial size of the stagnation column can be accurately determined and radial structures, such as bifurcations in the column, are clearly resolved. The success of the spherical-crystal imager has motivated the implementation of a new, two-crystal configuration for identifying sources of spectral line emission using a differential imaging technique.

Demonstration of improved laser preheat with a cryogenically cooled magnetized liner inertial fusion platform.

We report on progress implementing and testing cryogenically cooled platforms for Magnetized Liner Inertial Fusion (MagLIF) experiments. Two cryogenically cooled experimental platforms were developed: an integrated platform fielded on the Z pulsed power generator that combines magnetization, laser preheat, and pulsed-power-driven fuel compression and a laser-only platform in a separate chamber that enables measurements of the laser preheat energy using shadowgraphy measurements. The laser-only experiments suggest that ∼89% ± 10% of the incident energy is coupled to the fuel in cooled targets across the energy range tested, significantly higher than previous warm experiments that achieved at most 67% coupling and in line with simulation predictions. The laser preheat configuration was applied to a cryogenically cooled integrated experiment that used a novel cryostat configuration that cooled the MagLIF liner from both ends. The integrated experiment, z3576, coupled 2.32 ± 0.25 kJ preheat energy to the fuel, the highest to-date, demonstrated excellent temperature control and nominal current delivery, and produced one of the highest pressure stagnations as determined by a Bayesian analysis of the data.

Observation and diagnostic application of Kr K-shell emission in magnetized liner inertial fusion experiments at Z.

In a series of Magnetized Liner Inertial Fusion (MagLIF) experiments performed at the Z pulsed power accelerator of Sandia National Laboratories, beryllium liners filled with deuterium gas pressures in the 4-8 atm range and a tracer amount of krypton were imploded. At the collapse of the cylindrical implosion, temperatures in the 1-3 keV range and atom number densities of ∼1023 cm-3 were expected. The plasma was magnetized with a 10 T axial magnetic field. Krypton was added to the fuel for diagnosing implosion plasma conditions. Krypton K-shell line emission was recorded with the CRITR time-integrated transmission crystal x-ray spectrometer. The observation shows n = 2 to n = 1 line emissions in B-, Be-, Li-, and He-like Kr ions and is characteristic of the highest electron temperatures achieved in the thermonuclear plasma. Detailed modeling of the krypton atomic kinetics and radiation physics permits us to interpret the composite spectral feature, and it demonstrates that the spectrum is temperature sensitive. We discuss temperatures extracted from the krypton data analysis for experiments performed with several filling pressures.

New insights into the effects of ethylene on ABA catabolism, sweetening and dormancy in stored potato tubers.

Continuous ethylene supplementation suppresses postharvest sprouting, but it can increase reducing sugars, limiting its use as an alternative to chlorpropham for processing potatoes. To elucidate the mechanisms involved, tubers were treated after curing with or without the ethylene binding inhibitor 1-methylcyclopropene (1-MCP at 1 µL L-1 for 24 h), and then stored in air or air supplemented with continuous ethylene (10 µL L-1). Across three consecutive seasons, changes in tuber physiology were assessed alongside transcriptomic and metabolomic analysis. Exogenous ethylene alone consistently induced a respiratory rise and the accumulation of undesirable reducing sugars. The transient respiratory peak was preceded by the strong upregulation of two genes encoding 1-aminocyclopropane-1-carboxylate oxidase (ACO), typical of wound and stress induced ethylene production. Profiles of parenchymatic tissue highlighted that ethylene triggered abscisic acid (ABA) catabolism, evidenced by a steep fall in ABA levels and a transient rise in the catabolite phaseic acid, accompanied by upregulation of transcripts encoding an ABA 8'-hydroxylase. Moreover, analysis of non-structural carbohydrate-related genes revealed that ethylene strongly downregulated the expression of the Kunitz-type invertase inhibitor, already known to be involved in cold-induced sweetening. All these ethylene-induced effects were negated by 1-MCP with one notable exception: 1-MCP enhanced the sprout suppressing effect of ethylene whilst preventing ethylene-induced sweetening. This study supports the conclusions that: i) tubers adapt to ethylene by regulating conserved pathways (e.g. ABA catabolism); ii) ethylene-induced sweetening acts independently from sprout suppression, and is similar to cold-induced sugar accumulation.

Performance Scaling in Magnetized Liner Inertial Fusion Experiments.

We present experimental results from the first systematic study of performance scaling with drive parameters for a magnetoinertial fusion concept. In magnetized liner inertial fusion experiments, the burn-averaged ion temperature doubles to 3.1 keV and the primary deuterium-deuterium neutron yield increases by more than an order of magnitude to 1.1×10^{13} (2 kJ deuterium-tritium equivalent) through a simultaneous increase in the applied magnetic field (from 10.4 to 15.9 T), laser preheat energy (from 0.46 to 1.2 kJ), and current coupling (from 16 to 20 MA). Individual parametric scans of the initial magnetic field and laser preheat energy show the expected trends, demonstrating the importance of magnetic insulation and the impact of the Nernst effect for this concept. A drive-current scan shows that present experiments operate close to the point where implosion stability is a limiting factor in performance, demonstrating the need to raise fuel pressure as drive current is increased. Simulations that capture these experimental trends indicate that another order of magnitude increase in yield on the Z facility is possible with additional increases of input parameters.

Temperature distributions and gradients in laser-heated plasmas relevant to magnetized liner inertial fusion.

We present two-dimensional temperature measurements of magnetized and unmagnetized plasma experiments performed at Z relevant to the preheat stage in magnetized liner inertial fusion. The deuterium gas fill was doped with a trace amount of argon for spectroscopy purposes, and time-integrated spatially resolved spectra and narrow-band images were collected in both experiments. The spectrum and image data were included in two separate multiobjective analysis methods to extract the electron temperature spatial distribution T_{e}(r,z). The results indicate that the magnetic field increases T_{e}, the axial extent of the laser heating, and the magnitude of the radial temperature gradients. Comparisons with simulations reveal that the simulations overpredict the extent of the laser heating and underpredict the temperature. Temperature gradient scale lengths extracted from the measurements also permit an assessment of the importance of nonlocal heat transport.

Direct Measurement of Single-Molecule Ligand-Receptor Interactions.

Measuring the kinetics that govern ligand-receptor interactions is fundamental to our understanding of pharmacology. For ligand-gated ion channels, binding of an agonist triggers allosteric motions that open an integral ion-permeable pore. By mathematically modeling stochastic electrophysiological responses with high temporal resolution (ms), previous single channel studies have been able to infer the rate constants of ligands binding to these receptors. However, there are no reports of the direct measurement of the single-molecule binding events that are vital to how agonists exert their functional effects. For the first time, we report these direct measurements, the rate constants, and corresponding free energy changes, which describe the transitions between the different binding states. To achieve this, we use the super resolution technique: points accumulation for imaging in nanoscale topography (PAINT) to observe binding of ATP to orthosteric binding sites on the P2X1 receptor. Furthermore, an analysis of time-resolved single-molecule interactions is used to measure elementary rate constants and thermodynamic forces that drive the allosteric motions. These single-molecule measurements unequivocally establish the location of each binding states of the P2X1 receptor and the stochastic nature of the interaction with its native ligand. The analysis leads to the measurement of the forward and reverse rates from a weak ligand-binding state to a strong ligand binding state that is linked to allosteric motion and ion pore formation. These rates (kα = 1.41 sec-1 and kß = 0.32 sec-1) were then used to determine the free energy associated with this critical mechanistic step (3.7 kJ/mol). Importantly, the described methods can be readily applied to all ligand-gated ion channels, and more broadly to the molecular interactions of other classes of membrane proteins.

Prevalence of baseline HCV NS5A resistance associated substitutions in genotype 1a, 1b and 3 infection in Australia.

BACKGROUND: Direct-acting antivirals (DAA) have revolutionised hepatitis C virus (HCV) treatment, and most regimens include an NS5A inhibitor. Certain amino-acid substitutions confer resistance to NS5A inhibitors, termed resistance-associated substitutions (RAS). If present at baseline, they can reduce virological response rates. Population-based sequencing (PBS) is generally used for baseline sequencing, however next generation sequencing (NGS) reduces the threshold for detection of sequences encoding RAS from 20% to 5%. We determined the prevalence of NS5A RAS at baseline amongst Australian chronically infected with genotype (GT)1a, GT1b and GT3 HCV, using both PBS and NGS. METHODS: Samples from DAA-naïve individuals were received at the Victorian Infectious Disease Reference Laboratory between June 2016 and December 2018. All samples were analysed for NS5A RAS using PBS. A subset of GT1 HCV samples were processed using NGS technology (Vela Diagnostics, Singapore) to determine the improvement in sensitivity. RESULTS: In total, 672 samples were analysed using PBS. The baseline prevalence of NS5A RAS was 7.6% for GT1a (n = 25/329), 15.7% for GT1b (n = 8/51) and 15.1% for GT3 (n = 44/292). NGS only marginally increased sensitivity for NS5A RAS at baseline in GT1a (16% vs 17%) and GT1b (29% vs 36%). CONCLUSION: The prevalence of NS5A RAS in GT1a HCV in Australia was low compared with international data, and was similar to other reported international prevalence for GT1b and GT3 infection. NGS at baseline only marginally increased sensitivity for the detection of NS5A RAS in patients with GT1 HCV and cannot be recommended for routine use at baseline in clinical practice.

Automatic detection of feeding- and drinking-related agonistic behavior and dominance in dairy cows.

Accurate assessments of social behavior and dominance relationships in cattle can be time consuming. We investigated whether replacements at the feed bunk and water trough-one type of agonistic interaction-can be used to automatically assess dominance relationships. Our study set out to (1) validate a replacement detection algorithm using combined data from electronic feed and water bins, and (2) investigate the applicability of this algorithm to identify individual dominance scores and group-level social hierarchy in freestall-housed dairy cows. We used 4 groups of lactating cows kept in different group sizes (11 to 20 cows) located at 2 research facilities. In both facilities, feed and water were provided via automated feeding systems. A trained observer recorded all agonistic interactions in the pen over multiple days using video. Data from the electronic feed and water bins for the same days were analyzed using an algorithm to detect replacements (i.e., visits where a receiver cow was competitively replaced by an actor cow). Most agonistic interactions at the feed bunk were replacements. These replacements were associated with a brief interval between the time the receiver cow left the bin and the actor cow took her place; the optimal threshold to detect these replacements varied from 22 to 27 s between groups, independent of stocking density. The recall and precision of an algorithm based upon this threshold was high (on average >0.8), comparable to that of trained human observers. We improved data preparation by controlling for detection errors and included filtering to reduce false positives. This resulted in a >20% decrease in false positives and an increase in precision of 0.043. The dominance hierarchy based upon algorithm-detected replacements was similar to that based upon total agonistic interactions observed in the pen; the Spearman rank correlation coefficient between these hierarchies varied among the groups from 0.81 to 0.96. We conclude that data from electronic feed and water bins can accurately estimate agonistic behavior and dominance relationships among dairy cows.

Lameness and lying behavior in grazing dairy cows.

Lameness is a serious welfare issue for dairy cows. To date, the majority of studies have focused on its effect on health and behavior at the herd level. The objectives of this study were to identify (1) between-cow and (2) within-cow changes in lying behavior associated with consistent and changing lameness status in grazing dairy cows. Previous studies of lying behavior in grazing dairy cows have not considered the effect of precipitation, so a third aim was to determine the effect of precipitation on lying behavior. A total of 252 dairy cows from 6 pasture-based farms in southern Brazil were gait scored weekly to assess lameness using a 5-point scale [1-5, numerical rating score (NRS)] for 4 consecutive weeks. Cows were considered to have consistent lameness if they were scored as lame (NRS ≥3) on each of the 4 visits and considered to have a changing lameness status if scored as being nonlame (NRS <3) on at least 1 of the 4 visits. Cows classified as having a changing lameness status were further classified as developed, recovered, or inconsistent. Lying behavior (daily lying time, mean lying bout duration, and daily number of lying bouts) was recorded continuously for 3 wk using leg-mounted accelerometers. Cow-level variables included parity, days in milk, and body condition score. Regional precipitation and temperature were recorded hourly. Because only 1 primiparous cow was identified as lame at each of the 4 visits, the between-cow analysis of lameness was run on multiparous cows only. The overall prevalence of clinical lameness on the first visit was 39%, with development and recovery rates of 16 and 10% over the 4 visits, respectively. The between-cow effect of consistent lameness status on daily lying time and number of lying bouts was dependent on precipitation; consistently lame cows had reduced lying time and lying bouts on days with rain compared with days without rain. There was no within-cow effect of changing lameness status on any of the lying behaviors. Precipitation was associated with decreased daily lying time, increased mean lying bout duration, and decreased daily number of lying bouts. The results of this research provide the first evidence that the effect of consistent lameness status on lying behavior is associated with rainfall in grazing dairy cows. Future work measuring lying behavior of grazing dairy cows should include precipitation as a covariate.

Fructans redistribution prior to sprouting in stored onion bulbs is a potential marker for dormancy break.

Continuous supply of high quality onion bulbs to meet year-round demand is dependent on maintaining dormancy and bulb quality during storage. Sprouting impacts negatively on the storage quality of onion bulbs. Ethylene supplementation has previously been revealed to inhibit sprout growth in stored onion bulbs. Fructans content, especially those at higher degree of polymerisation (DP), are reported to positively correlate with delayed sprouting. However, little is known about the impact of pre-harvest irrigation regimes on fructans accumulation and redistribution in relation to onion bulb dormancy and quality in store. Across two seasons, onion plants of cultivars 'Red Baron' and 'Sherpa' were subjected to full irrigation (FI) (100% replenishment of crop evapotranspiration) or deficit irrigation (DI) (50% of FI treatment) from bulb initiation to harvest. Bulbs were harvested at full maturity and stored at 1 °C for five months. Bulbs were treated with or without 1-MCP (1 µL L-1) for 24 h before storage under continuous ethylene supplementation (10 µL L-1) or air. DI had no effect on dormancy-break, sprout emergence, total fructans content and total sugar content. In contrast, ethylene delayed sprout emergence and suppressed sprout growth; added 1-MCP enhanced this effect. The concentration of DP3-8 fructans were higher in top and bottom sections compared to the baseplate. Before sprout emergence, fructans of DPs 7-8 were no longer present in the top and bottom wedges, while they accumulated in the baseplate; irrespective of pre- or postharvest treatments. This redistribution of fructans within the bulb suggested a transition in dormancy state and could be used as a predictive marker for sprouting in stored onion bulbs.

Humoral and cellular immunity to RSV in infants, children and adults.

BACKGROUND: Respiratory syncytial virus (RSV) causes respiratory disease throughout life. Here we report differences in naturally acquired immunity with age and presumed exposure. METHODS: A longitudinal, non-interventional, observational study was performed in healthy adults (20 paediatric healthcare workers and 10 non-healthcare workers), children (10 aged 3-6 years) and infants (5 aged 2-4 months and 20 aged 6-12 months). Blood samples were analysed for RSV-neutralising antibody titre, F/Ga/Gb-specific antibody titres, F-specific IgG/IgA memory B-cell frequencies and T-cell production of IFNγ, IL-4, IL-13 and IL-17. RESULTS: Serum G-specific antibody titres were significantly lower in infants and children than adults. However, serum titres of F-specific and RSV-neutralising antibody and IFNγ-producing T-cell frequencies were low or absent in the infants, but comparable between children and adults. Interestingly, F-specific memory IgA B-cells could not be detected in paediatric samples and in samples from non-healthcare workers, but recordable IgA memory B-cells were found in 9/18 paediatric healthcare workers and 2/8 non-healthcare workers at the end of the RSV season. These responses waned 4-6 months later. By contrast, F-specific IgG memory B-cells were detectable in samples from all adults without significant variation across time points. T-cells producing IL-4, IL-13 and IL-17 responses were not detectable in peripheral blood from a subset of volunteers. CONCLUSIONS: Repeated RSV exposure in early life generates immune responses that are inversely related to frequency of severe disease. Induction of F-specific antibody and cellular immune responses through infant vaccination might help to accelerate the development of protective immune responses at an early age. Clinicaltrials.gov reference NCT01563692 and NCT01640652.

Structural cortical network reorganization associated with early conversion to multiple sclerosis.

Brain structural covariance networks (SCNs) based on pairwise statistical associations of cortical thickness data across brain areas reflect underlying physical and functional connections between them. SCNs capture the complexity of human brain cortex structure and are disrupted in neurodegenerative conditions. However, the longitudinal assessment of SCN dynamics has not yet been explored, despite its potential to unveil mechanisms underlying neurodegeneration. Here, we evaluated the changes of SCNs over 12 months in patients with a first inflammatory-demyelinating attack of the Central Nervous System and assessed their clinical relevance by comparing SCN dynamics of patients with and without conversion to multiple sclerosis (MS) over one year. All subjects underwent clinical and brain MRI assessments over one year. Brain cortical thicknesses for each subject and time point were used to obtain group-level between-area correlation matrices from which nodal connectivity metrics were obtained. Robust bootstrap-based statistical approaches (allowing sampling with replacement) assessed the significance of longitudinal changes. Patients who converted to MS exhibited significantly greater network connectivity at baseline than non-converters (p = 0.02) and a subsequent connectivity loss over time (p = 0.001-0.02), not observed in non-converters' network. These findings suggest SCN analysis is sensitive to brain tissue changes in early MS, reflecting clinically relevant aspects of the condition. However, this is preliminary work, indicated by the low sample sizes, and its results and conclusions should be treated with caution and confirmed with larger cohorts.

Community-based provision of direct-acting antiviral therapy for hepatitis C: study protocol and challenges of a randomized controlled trial.

BACKGROUND: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to treatment. Direct-acting antiviral (DAA) treatment can be provided in primary healthcare services (PHCS), improving accessibility, and, potentially, retention in care. Here, we describe our protocol for assessing the effectiveness of providing DAAs in PHCS, and the impact on the HCV care cascade. In addition, we reflect on the challenges of conducting a model of care study during a period of unprecedented change in HCV care and treatment. METHODS: Consenting patients with HCV infection attending 13 PHCS in Australia or New Zealand are randomized to receive DAA treatment at the local tertiary institution (standard care arm), or their PHCS (intervention arm). The primary endpoint is the proportion commenced on DAAs and cured. Treatment providers at the PHCS include: hepatology nurses, primary care practitioners, or, in two sites, a specialist physician. All PHCS offer opioid substitution therapy. DISCUSSION: The Prime Study is the first real-world, randomized, model of care study exploring the impact of community provision of DAA therapy on HCV-treatment uptake and cure. Although the study has faced challenges unique to this period of time characterized by changing treatment and service delivery, the data gained will be of critical importance in shaping health service policy that enables the elimination of HCV. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT02555475 . Registered on 15 September 2015.

ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process. METHODS: This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories - very high, high, low and very low - according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique. RESULTS: A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 20 recommendations were agreed by the guideline working group members after three rounds of consensus.

Sofosbuvir and velpatasvir with or without voxilaprevir in direct-acting antiviral-naïve chronic hepatitis C: patient-reported outcomes from POLARIS 2 and 3.

BACKGROUND: Chronic hepatitis C infection leads to impairment of patient-reported outcomes (PROs). Treatment with direct-acting antiviral regimens results in short- and long-term improvement of these outcomes. AIM: To assess PROs in patients treated with a newly developed direct-acting antiviral, a fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) with/without voxilaprevir (VOX). METHODS: The PRO data were collected from participants of POLARIS-2 and POLARIS-3 clinical trials (DAA-naïve, all HCV genotypes). Participants self-administered SF-36v2, FACIT-F, CLDQ-HCV and WPAI:SHP instruments at baseline, during treatment, and in follow-up. RESULTS: Of 1160 patients, 611 received SOF/VEL/VOX and 549 received SOF/VEL (52.8 ± 11.0 years, 55.9% male, 75.4% treatment-naïve, 33.9% cirrhotic). The sustained viral response at 12 weeks (SVR12) rates were 95%-98%. During treatment, improvements in most PRO scores were significant (all but one P < .01) and ranged from, on average, +2.3 to +15.0 points (on a 0-100 scale) by the end of treatment. These improvements were similar between SOF/VEL/VOX and SOF/VEL arms (all P > .05). After treatment discontinuation, patients treated with both regimens achieved significant and clinically meaningful PRO gains (+2.7 to +16.7 by post-treatment week 12, +3.9 to +20.1 by post-treatment week 24; all but one P < .001). Multivariate analysis showed that depression, anxiety and cirrhosis were the most consistent independent predictors of PRO impairment while no association of PROs with the treatment regimen choice was found (all P > .05). CONCLUSIONS: The pan-genotypic regimens with SOF/VEL with or without VOX not only have excellent efficacy and safety, but also significantly positively impact patients' experience both during treatment and after achieving sustained virologic response in DAA-naïve patients with HCV.

Sofosbuvir and daclatasvir therapy in patients with hepatitis C-related advanced decompensated liver disease (MELD ≥ 15).

BACKGROUND: Antiviral therapy for hepatitis C has the potential to improve liver function in patients with decompensated cirrhosis. AIMS: To examine the virological response and effect of viral clearance in patients with decompensated hepatitis C cirrhosis all with MELD scores ≥15 following sofosbuvir/daclatasvir ± ribavirin. METHODS: We prospectively collected data on patients who commenced sofosbuvir/daclatasvir for 24-weeks under the Australian patient supply program (TOSCAR) and analysed outcomes including sustained viral response at 12 weeks (SVR12), death and transplant. RESULTS: 108 patients (M/F, 79/29; median age 56years; Child-Pugh 10; MELD 16; genotype 1/3, 55/47) received sofosbuvir/daclatasvir and two also received ribavirin. On intention-to-treat, the SVR12 rate was 70% (76/108). Seventy-eight patients completed 24-weeks therapy. SVR12 was achieved in 56 of these patients on per-protocol-analysis (76%). SVR12 was 80% in genotype 1 compared to 69% in genotype 3. Thirty patients failed to complete therapy. In patients achieving SVR12, median MELD and Child-Pugh fell from 16(IQR15-17) to 14(12-17) and 10(9-11) to 8(7-9), respectively (P<.001). In those who died, MELD increased from 16 to 23 at death (P=.036). Patients who required transplantation had a significantly higher baseline MELD (20) compared to those patients completing treatment (16) (P=.0010). The odds ratio for transplant in patients with baseline MELD ≥20 was 13.8(95%CI 2.78-69.04). CONCLUSIONS: SVR12 rates with sofosbuvir/daclatasvir in advanced liver disease are lower than in compensated disease. Although treatment improves MELD and Child-Pugh in most patients, a significant proportion will die or require transplantation. In those with MELD ≥20, it may be better to delay treatment until post-transplant.

Pain intensity and pain self-management strategies following discharge after surgery: An Australian prospective observational study.

WHAT IS KNOWN AND OBJECTIVE: Up to 80% of patients experience acute pain following surgery. This study aimed to improve the current understanding about the strategies individuals use to self-manage pain following discharge after surgery, stratified by pain intensity. METHODS: A prospective observational study conducted at the Royal Hobart Hospital, Australia, between November 2014 and March 2015. Eligible participants were 18 years or older and had undergone surgery requiring an incision. Patients who had undergone surgery related to cancer, childbirth or multitrauma or those with dementia were excluded. Participants were identified through hospital records and mailed a survey within 1 week of discharge. This survey asked about post-discharge pain, management strategies utilized and advice on self-management of pain provided during their inpatient stay. RESULTS: Five hundred surveys were mailed, with 169 (33.8%) being returned. The median age of the respondents was 57 years (range: 18-92 years); 53% were female. The majority (89.3%) of participants recalled receiving information about pain self-management. Analgesic use was reported by 95.4% of participants in the week following discharge. Moderate-severe pain was reported by 80 participants (47.3%); 63.7% and 11.3% of patients reported underuse and overuse of analgesics compared to what was recommended, respectively. WHAT IS NEW AND CONCLUSION: A high proportion of patients underused analgesics despite experiencing moderate-severe pain. Although the vast majority of participants reported receiving advice regarding pain self-management, this did not appear to translate into optimal pain management after discharge. Different approaches to the provision of advice appear to be required.

A small-scale, rolled-membrane microfluidic artificial lung designed towards future large area manufacturing.

Artificial lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic artificial lungs (µAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the µl/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic artificial lung in which the structure is assembled via a continuous "rolling" and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10 µm tall artificial capillaries, and a 66 µm thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1-1.25 ml/min) for two different sweep gases (pure O2, atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO2 removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic artificial lungs. Although designed for microfluidic artificial lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS.

Technical note: Mining data from on-farm electronic equipment to identify the time dairy cows spend away from the pen.

The electronic equipment used on farms can be creatively co-opted to collect data for which it was not originally designed. In the current study, we describe 2 novel algorithms that harvest data from electronic feeding equipment and data loggers used to record standing and lying behavior, to estimate the time that dairy cows spend away from their pen to be milked. Our 2 objectives were to (1) measure the ability of the first algorithm to estimate the time cows spend away from the pen as a group and (2) determine the capability of a second algorithm to estimate the time it takes for individual cows to return to their pen after being milked. To achieve these objectives, we conducted 2 separate experiments: first, to estimate group time away, the feeding behavior of 1 pen of 20 Holstein cows was monitored electronically for 1 mo; second, to measure individual latency to return to the pen, feeding and lying behavior of 12 healthy Holstein cows was monitored electronically from parturition to 21 d in milk. For both experiments, we monitored the time each individual cow exited the pen before each milking and when she returned to the pen after milking using video recordings. Estimates generated by our algorithms were then compared with the times captured from the video recordings. Our first algorithm provided reliable pen-based estimates for the minimum time cows spent away from the pen to be milked in the morning [coefficient of determination (R2) = 0.92] and afternoon (R2 = 0.96). The second algorithm was able to estimate of the time it took for individual cows to return to the pen after being milked in the morning (R2 = 0.98), but less so in the afternoon (R2 = 0.67). This study illustrates how data from electronic systems used to assess feeding and lying behavior can be mined to estimate novel measures. New work is now required to improve the estimates of our algorithm for individuals, for example by adding data from other electronic monitoring systems on the farm.