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Direct numerical simulations (DNS) are performed in a triply periodic unit cell of a face-centred cubic (FCC) lattice covering the unsteady inertial, to fully turbulent, flow regimes. The DNS data are used to quantify the flow topology, integral scales, turbulent kinetic energy (TKE) transport and anisotropy distribution in the tortuous geometry. Several unique flow features are observed within this low porosity configuration, where the mean flow undergoes strong acceleration and deceleration regions with presence of three-dimensional helical motions, weak wake-like structures behind spheres, stagnation and jet-impingement-like flows together with merging and spreading jets in the main pore space. The jet-impingement and weak wake-like flow structures give rise to regions with negative total TKE production. Unlike flows in complex shaped ducts, the turbulence intensity levels in the cross-stream directions are found to be larger than those in the streamwise direction. Furthermore, due to the compact nature and confined geometry of the FCC packing, the turbulent integral length scales are estimated to be less than 10 % of the bead diameter even for the lowest Reynolds number studied, indicating the absence of macroscale turbulence structures for this configuration. This finding suggests that even for the highly anisotropic flow within the pore, the upscaled flow statistics are captured well by the representative volumes defined by the unit cell.
Childhood adversity is associated with poor mental and physical health outcomes across the life span. Alterations in the hypothalamic–pituitary–adrenal axis are considered a key mechanism underlying these associations, although findings have been mixed. These inconsistencies suggest that other aspects of stress processing may underlie variations in this these associations, and that differences in adversity type, sex, and age may be relevant. The current study investigated the relationship between childhood adversity, stress perception, and morning cortisol, and examined whether differences in adversity type (generalized vs. threat and deprivation), sex, and age had distinct effects on these associations. Salivary cortisol samples, daily hassle stress ratings, and retrospective measures of childhood adversity were collected from a large sample of youth at risk for serious mental illness including psychoses (n = 605, mean age = 19.3). Results indicated that childhood adversity was associated with increased stress perception, which subsequently predicted higher morning cortisol levels; however, these associations were specific to threat exposures in females. These findings highlight the role of stress perception in stress vulnerability following childhood adversity and highlight potential sex differences in the impact of threat exposures.
X-ray excitation causes rare-earth impurities in yttrium oxide and gadolinium oxide to emit intense and highly characteristic optical line fluorescence, which enables their analyses at low concentrations. The limits of detection for praseodymium, ncodymium, samarium, europium, gadolinium, terbium, dysprosium. holmium, erbium, thulium, and ytterbium in these two oxides range from 1 to 100 parts per billion (ppb). In other rare-earth oxides which have been investigated. the fluorescent intensities arc greatly reduced. Successful analyses can be made only by dilution in high-purity Y2O3. This dilution raises the detection limits for rare earths in these other oxides to the part per million range. X-rays from the chromium target of a cual-target X-ray tube are about two times more efficient in exciting rareeaith optical fluorescence than are the tungsten-target X-rays, even though the total energy output of the chromium target is only about one-third that of the tungsten target. With either target material, the rare-earth intensities vary linearly with the X-ray tube current, but a plot of intensity versus the square of the accelerating potential is not linear; it drops off at higher voltages.
In this study, we have examined ceramic matrix composites with silicon carbide fibers in a melt-infiltrated silicon carbide matrix (SiC/SiC). We subjected samples to tensile loads while collecting micro X-ray computed tomography images. The results showed the expected crack slowing mechanisms and lower resistance to crack propagation where the fibers ran parallel and perpendicular to the applied load respectively. Cracking was shown to initiate not only from the surface but also from silicon inclusions. Post heat-treated samples showed longer fiber pull-out than the pristine samples, which was incompatible with previously proposed mechanisms. Evidence for oxidation was identified and new mechanisms based on oxidation or an oxidation assisted boron nitride phase transformation was therefore proposed to explain the long pull-out. The role of oxidation emphasizes the necessity of applying oxidation resistant coatings on SiC/SiC.
To evaluate the impact of changes to urine testing orderables in computerized physician order entry (CPOE) system on urine culturing practices.
Retrospective before-and-after study.
A 1,250-bed academic tertiary-care referral center.
Hospitalized adults who had ≥1 urine culture performed during their stay.
The intervention (implemented in April 2017) consisted of notifications to providers, changes to order sets, and inclusion of the new urine culture reflex tests in commonly used order sets. We compared the urine culture rates before the intervention (January 2015 to April 2016) and after the intervention (May 2016 to August 2017), adjusting for temporal trends.
During the study period, 18,954 inpatients (median age, 62 years; 68.8% white and 52.3% female) had 24,569 urine cultures ordered. Overall, 6,662 urine cultures (27%) were positive. The urine culturing rate decreased significantly in the postintervention period for any specimen type (38.1 per 1,000 patient days preintervention vs 20.9 per 1,000 patient days postintervention; P < .001), clean catch (30.0 vs 18.7; P < .001) and catheterized urine (7.8 vs 1.9; P < .001). Using an interrupted time series model, urine culture rates decreased for all specimen types (P < .05).
Our intervention of changes to order sets and inclusion of the new urine culture reflex tests resulted in a 45% reduction in the urine cultures ordered. CPOE system format plays a vital role in reducing the burden of unnecessary urine cultures and should be implemented in combination with other efforts.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.
Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.
In NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.
There was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.
A detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.
Adolescence is a critical time point in the lifecourse. LifeLab is an educational intervention engaging adolescents in understanding Developmental Origins of Health and Disease (DOHaD) concepts and the impact of the early life environment on future health, benefitting both their long-term health and that of the next generation. We aimed to assess whether engaging adolescents with DOHaD concepts improves scientific literacy and whether engagement alone improves health behaviours.
Six schools were randomized, three to intervention and three to control. Outcome measures were changed in knowledge, and intended and actual behaviour in relation to diet and lifestyle. A total of 333 students completed baseline and follow-up questionnaires. At 12 months, intervention students showed greater understanding of DOHaD concepts. No sustained changes in behaviours were identified.
Adolescents’ engagement with DOHaD concepts can be improved and maintained over 12 months. Such engagement does not itself translate into behaviour change. The intervention has consequently been revised to include additional components beyond engagement alone.
Mechanical forces during machine milking induce changes in teat condition which can be differentiated into short-term and long-term changes. Machine milking-induced short-term changes in teat condition (STC) are defined as tissue responses to a single milking and have been associated with the risk of new intramammary infection. Albeit, their association with teat characteristics, such as teat-end shape, has not been investigated by rigorous methods. The primary objective was to determine the association of STC, as measured by ultrasonography, with teat-end shape. The second objective was to describe possible differences in the recovery time of teat tissue after machine milking among teats with different teat-end shapes. Holstein cows (n=128) were enrolled in an observational study, housed in free-stall pens with sand bedding and milked three times a day. Ultrasonography of the left front and right hind teat was performed after teat preparation before milking (t−1), immediately after milking (t0) and 1, 3, 5 and 7 h after milking (t1, t3, t5, t7). The teat tissue parameters measured from ultrasound scans were teat canal length, teat-end diameter, teat-end diameter at the midpoint between the distal and proximal end of the teat canal, teat wall thickness, and teat cistern width. Teat-end shape was assessed visually and classified into three categories: pointed, flat and round. Multivariable linear regression analyses showed differences in the relative change of teat tissue parameters (compared with t−1) at t0 among teats with different teat-end shapes, with most parameters showing the largest change for round teats. The premilking values were reached (recovery time) after 7 h in teats with a pointed teat-end shape, whereas recovery time was greater than 7 h in teats with flat and round teat-end shapes. Under the same liner and milking machine conditions, teats with a round teat-end shape had the most severe short-term changes. The results of this observational study indicated that teat-end shape may be one of the factors that contribute to the severity of STC.
Following the B777 accident at Heathrow in 2008, the certification authorities required Boeing, Airbus, and Rolls-Royce to conduct icing analysis and tests of their Rolls-Royce Trent engined aircraft fuel systems. The experience and the test data gained from these activities were distilled and released by Airbus to the EASA ICAR project for research and analysis. This paper provided an overview of the Airbus ice accretion and release tests. Brief narratives on the test rigs, the test procedure and methodology were given and key findings from the ice release investigations were presented. The accreted ice thickness was non-uniform; however, it is found typically c.
thick. Analysis of the accreted ice collected from the rig tests showed the ice was very porous. The porosity is very much dependant on how the water was introduced and mixed in the icing test rigs. The standard Airbus method produced accreted ice of higher porosity compared to that produced by the injection method. The porosity of the accreted ice from Airbus icing investigations was found to be c. 0.90. The relationship of permeability with porosity was inferred from published data and models for freshly fallen snow in the atmosphere. Derived permeability
was then applied in the CFD analysis of pipe flow with a porous wall lining to determine the shear stress on the accreted ice. It showed that 25%, 50% and 75% of the accreted ice has interface shear strength of less than
The use of monthly intranasal mupirocin was associated with a significant reduction in the rate of methicillin-resistant Staphylococcus aureus transmission and Staphylococcus aureus invasive infection in a large neonatal intensive care unit. Resistance to mupirocin emerged over time, but it was rare and was not associated with adverse clinical outcomes.
Nitrogen-deficient fibrous crop residues are widely used as basal diets in less developed countries, particularly in dry seasons when alternative foods are often in short supply. One approach to improving animal performance on crop residue based diets is to include a supplement of improved quality food to provide fermentable protein and energy. There are no established in vitro methods for investigating interactions between foods but the in vitro gas production method shows promise in this regard (Prasad et al., 1994). This paper describes the interactions observed in vitro; an accompanying paper (Murray et al., 1998) describes in vivo responses to supplementation and relationships between in vitro and in vivo data.
Achieving adequate fertility is essential in any dairy unit, but is compromised by genetic selection for increased yield. Selection has altered the somatotrophic axis and resulted in cows which mobilise more body tissue for milk production in early lactation, thus prolonging both the depth and duration of the post partum negative energy balance. Poor energy status is reflected in altered metabolic parameters including raised urea and decreased insulin-like growth factor-I (IGF-I) and insulin concentrations, which adversely affect ovarian cyclicity and early embryo survival. Attempts to optimise the diet in terms of energy and protein content have generally been aimed at increasing milk production further rather than improving fertility. Advances in biosensor technology now provide us with the opportunity to monitor production, fertility and health parameters of each cow. Integration of this information should improve the timing for inseminations and could assist in selecting diets more suited to the needs of the individual cow. Genetic selection may in future be used to produce cows optimised for a particular type of management system. In both cases we need a greater understanding of the rules governing nutrient partitioning at different stages of the cows' life cycle to ensure that diets selected are cost effective and achieve an appropriate balance in promoting production, reproduction and health.
The pre-requisites for nutritional management of dairy cows are information about how much feed is being consumed as well as the nutrients that are being derived from that feed. Studies of feed intake and nutrient supply have been limited by difficult experimental techniques, particularly with grazing animals. The models derived from much earlier work are of only general applicability and there is a need for more site-specific information in order to benefit further from conceptual advances.
We have adopted a different approach to studying herbage intake and nutrient supply, using less-invasive approaches as well as techniques that monitor more accessible aspects of these processes, such as jaw movements. These techniques have a major advantage, in addition to their value as research tools, because they could translate directly into commercial applications in on-farm monitoring. The use of diagnostics and behavioural recording is well explored in relation to health monitoring; here we argue for its potential to advance the application of knowledge about grazing and nutrition. We will illustrate this approach using our experiences in measuring grazing behaviour, using IGER behaviour recorders and assessing rumen function, using a series of non-invasive techniques.
The IGER grazing behaviour recorder allows us to record jaw movements and hence grazing and ruminating time and bite dynamics. It also allows the recording of steps and is now being developed to incorporate non-invasive rumen state sensors. It has made a major contribution to our understanding of the foraging strategies of grazing animals and their effect on herbage intake. This technology has the potential to be developed for on-farm monitoring of foraging behaviour providing valuable inputs to the prediction of herbage intake, in decision support systems for grazing.
The introduction of concept of protein degradation and microbial synthesis in the rumen are significant advances in protein rationing schemes. However, real progress has been limited because the lack of consistent experimental results means that models have little relevance to specific farm situations. We foresee considerable opportunities to monitor products of rumen degradation and synthesis that appear in milk (e.g. odd-chain fatty acids) or breath (e.g. sulphides).
Taken together these technologies open the possibilities of an entirely new approach to nutritional management of dairy cows, with site-specific recommendations based on information gathered using new sensors that are incorporated into computerised feeding equipment and milking parlours.
Livestock systems are comprised of sets of complex interconnected processes each with their own outputs eg growth, yield, animal health, welfare and environmental emissions. Livestock management decisions are currently based almost entirely on the judgement and experience of the stockman who has to estimate or guess the likely effects of any control action.
An integrated management system for a livestock production enterprise would be one which controlled all relevant processes. For example if the purpose of the system was to regulate nutritional input in order to control animal growth and pollutant emissions, the controller would calculate input values which would enable growth and emissions criteria to be satisfied simultaneously.
The essential components of an integrated management system are sensors and models. Developments in sensor technology will make available increasing amounts of information relevant to monitoring animals and their environment. Model-based control systems are particularly appropriate for accommodating the variability of most livestock production processes. Models exist for most of the economically important and scientifically interesting processes in livestock production. However the requirements of a process model that is to be incorporated into a controller are different from those of a model which is aimed at demonstrating understanding of the process. Areas where process models are lacking include those involving interactions between production and environmental factors.
This review considers the likely impact of changing consumer requirements, political pressure, economics and technological advances on the dairy production industry of the future. The vision is one of diverse strategies of production, the majority of milk being produced from cows managed technologically with much greater regard for welfare, with a number of ‘romantic’ strategies such as organic, extensive or dual-purpose production supplying niche markets. The important novel feature of the technological strategy will be an escape from the intensive twelve-month lactation cycle to extended lactations of, say, eighteen months, since this will reduce the number of times the cow is exposed to metabolic and other stresses associated with parturition, peak lactation and rebreeding.