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Conservation of animal genetic resources requires regular monitoring and interventions to maintain population size and manage genetic variability. This study uses genealogical information to evaluate the impact of conservation measures in Europe, using (i) data from the Domestic Animal Diversity Information System (DAD-IS) and (ii) a posteriori assessment of the impact of various conservation measures on the genetic variability of 17 at-risk breeds with a wide range of interventions. Analysis of data from DAD-IS showed that 68% of national breed populations reported to receive financial support showed increasing demographic trends, v. 51% for those that did not. The majority of the 17 at-risk breeds have increased their numbers of registered animals over the last 20 years, but the changes in genetic variability per breed have not always matched the trend in population size. These differences in trends observed in the different metrics might be explained by the tensions between interventions to maintain genetic variability, and development initiatives which lead to intensification of selection.
The objective of this study was to evaluate the relationship between muscle mitochondrial function and residual feed intake (RFI) in growing beef cattle. A 56-day feeding trial was conducted with 81 Angus × Hereford steers (initial BW = 378 ± 43 kg) from the University of California Sierra Foothills Research Station (Browns Valley, CA, USA). All steers were individually fed the same finishing ration (metabolizable energy = 3.28 Mcal/kg DM). Average daily gain (ADG), DM intake (DMI) and RFI were 1.82 ± 0.27, 8.89 ± 1.06 and 0.00 ± 0.55 kg/day, respectively. After the feeding trial, the steers were categorized into high, medium and low RFI groups. Low RFI steers consumed 13.6% less DM (P < 0.05) and had a 14.1% higher G : F ratio (P < 0.05) than the high RFI group. No differences between RFI groups were found in age, ADG or BW (P > 0.10). The most extreme individuals from the low and high RFI groups were selected to assess mitochondrial function (n = 5 low RFI and n = 6 high RFI). Mitochondrial respiration was measured using an oxygraph (Hansatech Instruments Ltd., Norfolk, UK). State 3 and State 4 respiration rates were similar between both groups (P > 0.10). Respiratory control ratios (RCRs, i.e., State 3 : State 4 oxygen uptakes) declined with animal age and were greater in low RFI steers (4.90) as compared to high RFI steers (4.26) when adjusted for age by analysis of covariance (P = 0.003). Mitochondrial complex II activity levels per gram of muscle were 42% greater in low RFI steers than in high RFI steers (P = 0.004). These data suggest that skeletal muscle mitochondria have greater reserve respiratory capacity and show greater coupling between respiration and phosphorylation in low RFI than in high RFI steers.
This paper addresses a methodology to parametrically size thermal control subsystems for high-speed transportation systems during the conceptual design phase. This methodology should be sufficiently general to be exploited for the derivation of Estimation Relationships (ERs) for geometrically sizing characteristics as well as mass, volume and power budgets both for active (turbopumps, turbines and compressors) and passive components (heat exchangers, tanks and pipes). Following this approach, ad-hoc semi-empirical models relating the geometrical sizing, mass, volume and power features of each component to the operating conditions have been derived. As a specific case, a semi-empirical parametric model for turbopumps sizing is derived. In addition, the Thermal and Energy Management Subsystem (TEMS) for the LAPCAT MR2 vehicle is used as an example of a highly integrated multifunctional subsystem. The TEMS is based on the exploitation of liquid hydrogen boil-off in the cryogenic tanks generated by the heat load penetrating the aeroshell throughout the point-to-point hypersonic mission. Eventually, specific comments about the results will be provided together with suggestions for future improvements.
Vaccination coverage (VC) against pertussis can increase when management practices and policies at primary care centres (PCCs) are reinforced. From 2011 to 2015, we performed a case–control study to evaluate VC among pertussis patients treated at PCCs in Barcelona, Spain. We recorded pertussis in patients from 8- to 16-year-olds at 52 PCCs. Pertussis cases had laboratory diagnostic and controls were healthy outpatients visiting the same facility for reasons other than cough. DTaP/dTap VC was recorded as either proper vaccination status (five doses recorded) or improper vaccination status (<5 doses recorded). We used a logistic regression model to estimate OR and 95% CI. We included 229 cases and 576 controls. VC was higher in cases (mean 5.01, s.e.: 0.57) than in controls (4.89, s.e.: 0.73). Around 69% of the cases had received DTaP primary immunisation after 2–5 years and 31.4% of cases had the dTap booster immunisation after 7–10 years. The 87% of children 5–9 years were properly vaccinated. We found no protection from becoming ill among properly vaccinated children (OR 1.87; 95% CI 1.22–2.85). The highest VC was observed in patients with confirmed pertussis, which was likely due to a more exhaustive follow-up of the VC in these patients. Being properly vaccinated against pertussis will probably not increase VC.
There is a long history of exploitation of the South American river turtle Podocnemis expansa. Conservation efforts for this species started in the 1960s but best practices were not established, and population trends and the number of nesting females protected remained unknown. In 2014 we formed a working group to discuss conservation strategies and to compile population data across the species’ range. We analysed the spatial pattern of its abundance in relation to human and natural factors using multiple regression analyses. We found that > 85 conservation programmes are protecting 147,000 nesting females, primarily in Brazil. The top six sites harbour > 100,000 females and should be prioritized for conservation action. Abundance declines with latitude and we found no evidence of human pressure on current turtle abundance patterns. It is presently not possible to estimate the global population trend because the species is not monitored continuously across the Amazon basin. The number of females is increasing at some localities and decreasing at others. However, the current size of the protected population is well below the historical population size estimated from past levels of human consumption, which demonstrates the need for concerted global conservation action. The data and management recommendations compiled here provide the basis for a regional monitoring programme among South American countries.
Background: We recently demonstrated that late functional improvement between 3-12 months post-stroke occurs in about one-fourth of patients with ischaemic stroke. It is unknown whether this improvement is associated with better long-term clinical or health-economic outcomes. Methods: In a prospective, population-based cohort of 1-year ischaemic stroke survivors (Oxford Vascular Study;2002-2014), we determined changes in functional status (modified Rankin Scale[mRS], Rivermead Mobility Index[RMI], Barthel Index[BI]) from 3-12 months post-stroke. We examined the association of late improvement (by ≥1 mRS grades, ≥1 RMI points, and/or ≥2 BI points) with 5-year mortality, institutionalization (Cox regressions), and health/social-care costs (generalized linear models), adjusted for age/sex/3-month disability/stroke subtype. Results: Among 1,288 1-year survivors, 1,135 had 3-month mRS>0, with 319(28.1%) demonstrating late improvement. 1-year survivors with late mRS improvement had lower 5-year mortality (aHR:0.68,95%CI 0.51-0.91,p=0.009), institutionalization (aHR:0.48,0.33-0.72,p<0.001), and costs (margin -$17,369,-25,271 to -9,469,p<0.001). These associations remained on excluding patients with recurrent strokes during follow-up (e.g. 5-year death/institutionalization aHR:0.59,0.44-0.79,p<0.001) and on examining late improvement per RMI and/or BI (e.g. 5-year death/institutionalization aHR:0.67,0.53-0.84,p=0.001). Conclusions: Late functional improvement post-stroke is associated with lower 5-year mortality, institutionalization, and costs. These findings should motivate patients and clinicians to maximize late recovery and encourage payers to consider access to rehabilitative services for at least 1-year post-stroke.
Disease surveillance in wildlife populations presents a logistical challenge, yet is critical in gaining a deeper understanding of the presence and impact of wildlife pathogens. Erinaceus coronavirus (EriCoV), a clade C Betacoronavirus, was first described in Western European hedgehogs (Erinaceus europaeus) in Germany. Here, our objective was to determine whether EriCoV is present, and if it is associated with disease, in Great Britain (GB). An EriCoV-specific BRYT-Green® real-time reverse transcription PCR assay was used to test 351 samples of faeces or distal large intestinal tract contents collected from casualty or dead hedgehogs from a wide area across GB. Viral RNA was detected in 10.8% (38) samples; however, the virus was not detected in any of the 61 samples tested from Scotland. The full genome sequence of the British EriCoV strain was determined using next generation sequencing; it shared 94% identity with a German EriCoV sequence. Multivariate statistical models using hedgehog case history data, faecal specimen descriptions and post-mortem examination findings found no significant associations indicative of disease associated with EriCoV in hedgehogs. These findings indicate that the Western European hedgehog is a reservoir host of EriCoV in the absence of apparent disease.
Neutron powder diffraction techniques have been used to characterize the pseudo-macro (PM) residual stresses in ZrO2(CeO2)/Al2O3 ceramic composites as a function of ZrO2(CeO2) volume fraction and fabrication procedures. The diffraction data were analyzed using the Rietveld structure refinement technique. From the refinement, we found that the CeO2 stabilized tetragonal ZrO2 particles were in tension and the Al2O3 matrix was in compression. Different sintering time had little impact on the PM stresses. On the other hand, the magnitude of the PM stresses in both ZrO2 and Al2O3 decreased linearly with the increase of their volume fractions.
The multiple scattering contributions to the emitted intensity of a thin homogeneous sample under X-Ray excitation are studied with recourse to the Boltzmann transport theory. The corrective terms to the XRF characteristic line due to a second collision of either the photoelectric effect (secondary XRF), or the Compton, or the Rayleigh scattering, are deduced for reflection geometry. Analytical expressions for the intensities are given that allow their computation for variable incidence and take-off beam directions and source wavelength.
The days of Debye-Scherrer film as a recording medium for X-ray powder patterns are all but gone with the development of precise, high sensitivity diffractometer systems. However, film does present some advantages over diffractometry (digital positioning and recording) for certain applications, A scanning densitometer system is described which totally automates the analysis of Debye-Scherrer film. It is much more precise and more capable than the simple line readers available in the past and can reduce the analysis time of complicated patterns from hours to minutes.
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.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
The Coneybury ‘Anomaly’ is an Early Neolithic pit located just south-east of Stonehenge, Wiltshire. Excavations recovered a faunal assemblage unique in its composition, consisting of both wild and domestic species, as well as large quantities of ceramics and stone tools, including a substantial proportion of blades/bladelets. We present a suite of new isotope analyses of the faunal material, together with ancient DNA sex determination, and reconsider the published faunal data to ask: What took place at Coneybury, and who was involved? We argue on the basis of multiple lines of evidence that Coneybury represents the material remains of a gathering organised by a regional community, with participants coming from different areas. One group of attendees provided deer instead of, or in addition to, cattle. We conclude that the most likely scenario is that this group comprised local hunter-gatherers who survived alongside local farmers.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
An experimental Taenia crassiceps mouse model was used to assess the role of Taenia solium metacestode factor (Fac) in human neurocysticercosis. Intraperitoneal infection with T. crassiceps metacestodes or subcutaneous inoculation with a T. crassiceps metacestode factor (Fac) produced significant impairment of performance (learning) in the Barnes maze and induced bilateral hippocampal sclerosis in mice. Several staining techniques revealed important cell dispersion, extensive apoptosis and cell loss in the dentate gyrus, hilus and CA1-CA3 regions of both hippocampi, as well as intense deterioration of the adjacent cortex. An outstanding disruption of its histoarchitecture in the surrounding tissue of all these regions and apoptosis of the endothelial cells were also observed.