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The transgenic Liberty Link® (LL) soybean is tolerant to glufosinate, conferred by the enzyme phosphinothricin acetyltransferase (PAT), which is encoded by the pat gene from Streptomyces viridochromogenes. Because symptoms of injury can be observed in soybean [Glycine max (L.) Merr.] plants in some situations, this study evaluated the effects of rates of glufosinate on agronomic performance; quality of LL soybean seeds; and the ammonia, glufosinate, and N-acetyl-l-glufosinate concentration (NAG) in soybeans with and without the pat gene after application of increasing glufosinate rates. Field and greenhouse experiments were conducted; the first evaluated the selectivity of glufosinate in LL soybeans, and the second evaluated the metabolic changes in soybeans with (LL) and without (RR2) the pat gene, after application of glufosinate. For fieldwork, application of glufosinate at rates up to four times the maximum recommended caused initial injury symptoms (up to 38.5%) in LL soybean plants. However, no negative effect was found on seed quality and agronomic performance of LL plants, including yield. This shows the selectivity of glufosinate promoted by pat gene insertion for application in POST (V4), in LL soybean. For the greenhouse experiment, it was concluded that the LL soybean plants presented high glufosinate metabolism, lower ammonia concentration, and no reduction in dry matter, in comparison with RR2 soybean, after application of high rates of glufosinate.
To explore tolerability, safety and treatment response of flexible doses of paliperidone ER in adult non-acute patients with schizophrenia previously unsuccessfully treated with oral antipsychotics.
International prospective 6-month open-label study. Endpoints were the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity Scale (CGI-S), patient satisfaction, adverse events (AEs), extrapyramidal symptoms (Extrapyramidal Symptom Rating Scale; ESRS) and weight change.
1812 patients were included (59.9% male, mean age 40.1±12.6 years, 75.8% paranoid schizophrenia); most were enrolled because of lack of efficacy (n=1026) or lack of tolerability (n=490) with prior antipsychotic treatment. The median mode dose of paliperidone ER was 6 mg/day. 70.7% of patients completed the 6-month study. Most frequent reasons for early discontinuation were patient choice (8.8%), lack of efficacy or adverse event (5.1% each) independent of the reason for switching. Mean total PANSS decreased significantly from 79.4±20.4 at baseline to 66.1±21.5 at endpoint (mean change -13.3±19.7; 95% confidence interval -14.2;-12.3, p< 0.0001). The percentage of patients rated mildly ill or less in CGI-S increased from 27.0% to 52.2% at endpoint, and the rate of patients with mild functional impairment increased from 15.8% to 34.9%. AEs reported in greater-than-or-equal-to 5% of patients were insomnia (9.2%) and anxiety (7.2%). Extrapyramidal symptoms in ESRS decreased significantly from 3.5±5.8 to 2.1±4.6 (p< 0.0001). Mean weight gain from baseline to endpoint was 0.3±4.8kg.
These data support results from recent randomized controlled studies that paliperidone ER is safe, well tolerated and effective in patients previously unsuccessfully treated with other oral antipsychotics.
The majority of children requiring emergency care are treated in general emergency departments (EDs) with variable levels of pediatric care expertise. The goal of the Translating Emergency Knowledge for Kids (TREKK) initiative is to implement the latest research in pediatric emergency medicine in general EDs to reduce clinical variation.
To determine national pediatric information needs, seeking behaviours, and preferences of health care professionals working in general EDs.
An electronic cross-sectional survey was conducted with health care professionals in 32 Canadian general EDs. Data were collected in the EDs using the iPad and in-person data collectors.
Total of 1,471 surveys were completed (57.1% response rate). Health care professionals sought information on children’s health care by talking to colleagues (n=1,208, 82.1%), visiting specific medical/health websites (n=994, 67.7%), and professional development opportunities (n=941, 64.4%). Preferred child health resources included protocols and accepted treatments for common conditions (n=969, 68%), clinical pathways and practice guidelines (n=951, 66%), and evidence-based information on new diagnoses and treatments (n=866, 61%). Additional pediatric clinical information is needed about multisystem trauma (n=693, 49%), severe head injury (n=615, 43%), and meningitis (n=559, 39%). Health care professionals preferred to receive child health information through professional development opportunities (n=1,131, 80%) and printed summaries (n=885, 63%).
By understanding health care professionals’ information seeking behaviour, information needs, and information preferences, knowledge synthesis and knowledge translation initiatives can be targeted to improve pediatric emergency care. The findings from this study will inform the following two phases of the TREKK initiative to bridge the research-practice gap in Canadian general EDs.
A review is presented of Synchrotron X-ray Topography and KOH etching studies carried out on n type 4H-SiC offcut substrates before and after homo-epitaxial growth to study defect replication and strain relaxation processes and identify the nucleation sources of both interfacial dislocations (IDs) and half-loop arrays (HLAs) which are known to have a deleterious effect on device performance. We show that these types of defects can nucleate during epilayer growth from: (1) short segments of edge oriented basal plane dislocations (BPDs) in the substrate which are drawn by glide into the epilayer; and (2) segments of half loops of BPD that are attached to the substrate surface prior to growth which also glide into the epilayer. It is shown that the initial motion of the short edge oriented BPD segments that are drawn from the substrate into the epilayer is caused by thermal stress resulting from radial temperature gradients experienced by the wafer whilst in the epi-chamber. This same stress also causes the initial glide of the surface half-loop into the epilayer and through the advancing epilayer surface. These mobile BPD segments provide screw oriented segments that pierce the advancing epilayer surface that initially replicate as the crystal grows. Once critical thickness is reached, according to the Mathews-Blakeslee model , these screw segments glide sideways under the action of the mismatch stress leaving IDs and HLAs in their wake. The origin of the mismatch stress is shown to be associated with lattice parameter differences at the growth temperature, arising from the differences in doping concentration between substrate and epilayer.
The present study was conducted to obtain a comprehensive overview of oligosaccharides present in the milk of a variety of important domestic animals including cows, goats, sheep, pigs, horses and dromedary camels. Using an analytical workflow that included ultra-performance liquid chromatography–hydrophilic interaction liquid chromatography with fluorescence detection coupled to quadrupole time-of-flight MS, detailed oligosaccharide libraries were established. The partial or full characterisation of the neutral/fucosylated, phosphorylated and sialylated structures was facilitated by sequencing with linkage- and sugar-specific exoglycosidases. Relative peak quantification of the 2-aminobenzamide-labelled oligosaccharides provided additional information. Milk from domestic animals contained a much larger variety of complex oligosaccharides than was previously assumed, and thirteen of these structures have been identified previously in human milk. The direct comparison of the oligosaccharide mixtures reflects their role in the postnatal maturation of different types of gastrointestinal systems, which, in this way, are prepared for certain post-weaning diets. The potential value of animal milk for the commercial extraction of oligosaccharides to be used in human and animal health is highlighted.
Hospital readmissions are a current target of initiatives to reduce healthcare costs. This study quantified the association between having a clinical culture positive for 1 of 3 prevalent hospital-associated organisms and time to hospital readmission.
Retrospective cohort study.
Patients and Setting.
Adults admitted to an academic, tertiary care referral center from January 1, 2001, through December 31, 2008.
The primary exposure of interest was a clinical culture positive for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), or Clostridium difficile obtained more than 48 hours after hospital admission during the index hospital stay. The primary outcome of interest was time to readmission to the index facility. Multivariable Cox proportional hazards models were used to model the adjusted association between positive clinical culture result and time to readmission and to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).
Among 136,513 index admissions, the prevalence of hospital-associated positive clinical culture result for 1 of the 3 organisms of interest was 3%, and 35% of patients were readmitted to the index facility within 1 year after discharge. Patients with a positive clinical culture obtained more than 48 hours after hospital admission had an increased hazard of readmission (HR, 1.40; 95% CI, 1.33–1.46) after adjusting for age, sex, index admission length of stay, intensive care unit stay, Charlson comorbidity index, and year of hospital admission.
Patients with healthcare-associated infections may be at increased risk of hospital readmission. These findings may be used to impact health outcomes after discharge from the hospital and to encourage better infection prevention efforts.
The main aim of the present study was to examine the effects of long-term supplementing diets with saturated or unprotected polyunsaturated fatty acids from two different plant oils rich in either n-3 or n-6 fatty acids (FAs) plus docosahexaenoic acid (DHA)-rich algae on mammary gene expression and milk fat composition in lactating dairy cows. Gene expression was determined from mammary tissue and milk epithelial cells. Eighteen primiparous German Holstein dairy cows in mid-lactation were randomly assigned into three dietary treatments that consist of silage-based diets supplemented with rumen-stable fractionated palm fat (SAT; 3.1% of the basal diet dry matter, DM), or a mixture of linseed oil (2.7% of the basal diet DM) plus DHA-rich algae (LINA; 0.4% of the basal diet DM) or a mixture of sunflower oil (2.7% of the basal diet DM) plus DHA-rich algae (SUNA; 0.4% of the basal diet DM), for a period of 10 weeks. At the end of the experimental period, the cows were slaughtered and mammary tissues were collected to study the gene expression of lipogenic enzymes. During the last week, the milk yield and composition were determined, and milk was collected for FA measurements and the isolation of milk purified mammary epithelial cells (MECs). Supplementation with plant oils and DHA-rich algae resulted in milk fat depression (MFD; yield and percentage). The secretion of de novo FAs in the milk was reduced, whereas the secretion of trans-10,cis-12-CLA and DHA were increased. These changes in FA secretions were associated in mammary tissue with a joint down-regulation of mammary lipogenic enzyme gene expression (stearoyl-CoA desaturase, SCD1; FA synthase, FASN) and expression of the regulatory element binding transcription factor (SREBF1), whereas no effect was observed on lipoprotein lipase (LPL) and glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM). A positive relationship between mammary SCD1 and SREBF1 mRNA abundances was observed, suggesting a similar regulation for these genes. Such data on mammary gene expression in lactating cows presenting MFD contribute to strengthen the molecular mechanisms that govern milk fat synthesis in the mammary glands. In purified MEC, the dietary treatments had no effect on gene expressions. Differences between mammary tissue and milk purified MEC gene expression were attributed to the effect of lipid supplements on the number of milk purified MEC and its RNA quality, which are determinant factors for the analysis of gene expression using milk cells.
National and international policies have encouraged the establishment of a representative network of marine protected areas (MPAs) in South Africa, with the aim of protecting marine biodiversity. The extent to which these marine and estuarine protected areas (EPAs) represent marine fish species and communities was assessed by comparing their species compositions with those of exploited areas, as sampled using four fishing techniques. Seven hundred fish species were sampled, representing one-third of South Africa's marine fishes. MPAs in coastal habitats scored c. 40% on the Bray-Curtis measure of similarity for species representativeness, but this score declined markedly for offshore ‘trawlable’ fishing grounds. The combined effects of sampling error, temporal variation and the effects of fishing on relative abundance suggest that 80% similarity would be the maximum achieveable. Forty-nine per cent of all fish species that were recorded were found in the 14 MPAs sampled. Redundancy in the MPA network was low, with fish species most commonly being represented in only one MPA or absent. There was greater redundancy in the 33 EPAs, with 40% of species being found in two or more EPAs, but many of these estuaries were adjacent to each other and embedded in large MPAs. Deep water fish communities (>80 m deep) and communities located on the west and south-east coasts of South Africa were most poorly represented by MPAs. Routine fishery surveys provide a robust and repeatable opportunity to assess species representativeness in MPAs, and the method used could form the basis of an operational definition of ‘representative’. In contrast to an assessment based on presence-absence data, this analysis of quantitative data presents a more pessimistic assessment of protection.
Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ.
Multivariate familial models were run on data from 1265 individuals aged 6–18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice–delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI).
Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41–0.71) and IQ (rF=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80–87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ.
The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.
ATP-binding cassette (ABC) transporters play a pivotal role in human physiology, and mutations in these genes often result in severe hereditary diseases. ABC transporters are expressed in the bovine mammary gland but their physiological role in this organ remains elusive. Based on findings in the context of human disorders we speculated that candidate ABC transporters are implicated in lipid and cholesterol transport in the mammary gland. Therefore we investigated the expression pattern of selected genes that are associated with sterol transport in lactating and nonlactating mammary glands of dairy cows. mRNA levels from mammary gland biopsies taken during lactation and in the first and second week of the dry period were analysed using quantitative PCR. Five ABC transporter genes, namely ABCA1, ABCA7, ABCG1, ABCG2 and ABCG5, their regulating genes LXRα, PPARγ, SREBP1 and the milk proteins lactoferrin and α-lactalbumin were assessed. A significantly enhanced expression in the dry period was observed for ABCA1 while a significant decrease of expression in this period was detected for ABCA7, ABCG2, SREBP1 and α-lactalbumin. ABCG1, ABCG5, LXRα, PPARγ and lactoferrin expression was not altered between lactation and dry period. These results indicate that candidate ABC transporters involved in lipid and cholesterol transport show differential mRNA expression between lactation and the dry period. This may be due to physiological changes in the mammary gland such as immigration of macrophages or the accumulation of fat due to the loss of liquid in the involuting mammary gland. The current mRNA expression analysis of transporters in the mammary gland is the prerequisite for elucidating novel molecular mechanisms underlying cholesterol and lipid transfer into milk.
Electrical resistivity measurements performed under applied hydrostatic pressure and in magnetic fields have been used to probe the hidden order (HO) and superconducting (SC) states of URu2Si2, which have ambient-pressure transition temperatures TO = 17.5 K and Tc = 1.5 K, respectively. TO increases with applied pressure and a distinct kink in its pressure dependence is observed at 15 kbar; this feature is associated with the onset of antiferromagnetism. The pressure dependence of the SC upper critical field has been measured with the external field aligned parallel to both crystalline axes. The SC phase is smoothly suppressed to a critical pressure of about 15 kbar and no qualitative change in the critical field curves is observed. The co-evolution of the HO and SC phases is discussed within the context of a model in which the two phases compete for Fermi surface fraction.
Measurements on URu2-xRexSi2 single crystals indicate that substitution of Re for Ru in URu2Si2 reduces the transition temperature of the hidden order state and quickly destroys superconductivity. At intermediate Re concentrations, weak ferromagnetism emerges and non Fermi liquid (NFL) behavior is observed in the low-temperature specific heat and electrical resistivity. A scaled Arrott analysis of the magnetization indicates the onset of ferromagnetism at x =0.15, where the hidden order disappears, and that the quantum phase transition is associated with novel critical exponents.
High-pressure studies have been performed on heavy rare earth metals Terbium (Tb) to 155 GPa and Holmium (Ho) to 134 GPa in a diamond anvil cell at room temperature. The following crystal structure sequence was observed in both metals hcp ⟶ Sm-type ⟶ dhcp ⟶ distorted fcc (hR-24) ⟶ monoclinic (C2/m) with increasing pressure. The last transformation to a low symmetry monoclinic phase is accompanied by a volume collapse of 5 % for Tb at 51 GPa and a volume collapse of 3 % for Ho at 103 GPa. This volume collapse under high pressure is reminiscent of f-shell delocalization in light rare earth metal Cerium (Ce), Praseodymium (Pr), and heavy actinide metals Americium (Am) and Curium (Cm). The orthorhombic Pnma phase that has been reported in Am and Cm after f-shell delocalization is not observed in heavy rare earth metals under high pressures.
Recently we reported the observation of near-infrared photoluminescence from metal-centered 5f electronic excited states of PuO22+ doped into polycrystalline Cs2U(Pu)O2Cl4. Photoluminescence dynamics following pulsed excitation show complicated decay patterns suggesting that multiple luminescent states are involved. Here we report the results of two recent sets of experiments showing that photoluminescence processes depend significantly on the energy of photoexcitation. In the first case, decay kinetics following excitation at a lower energy are missing an in-growth term that is present when exciting at higher energy. In the second case, we have observed that lower excitation energy produces significantly reduced number of emission transitions than higher excitation energy. Both observations suggest that higher energy excitation populates feeder states that decay to emitting states, causing signal from the latter to have an in-growth followed by a decay characteristic of their intrinsic lifetimes, whereas lower energy excitation leads to more direct population of luminescent states.
The gallium-stabilized Pu-2.0 at. % Ga alloy undergoes a partial or incomplete low-temperature martensitic transformation from the metastable δ phase to the gallium-containing, monoclinic α′ phase near -100 °C. This transformation has been shown to occur isothermally and it displays anomalous double-C kinetics in a time-temperature-transformation (TTT) diagram, where two nose temperatures anchoring an upper- and lower-C describe minima in the time for the initiation of transformation. The underlying mechanisms responsible for the double-C behavior are currently unresolved, although recent experiments suggest that a conditioning treatment—wherein, following an anneal at 375 °C, the sample is held at a sub-anneal temperature for a period of time—significantly influences the upper-C of the TTT diagram. As such, elucidating the effects of the conditioning treatment upon the δ⟶α′ transformation can provide valuable insights into the fundamental mechanisms governing the double-C kinetics of the transition. Following a high-temperature anneal, a differential scanning calorimeter (DSC) was used to establish an optimal conditioning curve that depicts the amount of α′ formed during the transformation as a function of conditioning temperature for a specified time. With the optimal conditioning curve as a baseline, the DSC was used to explore the circumstances under which the effects of the conditioning treatment were destroyed, resulting in little or no transformation.
Under ambient conditions, a Pu-2.0 at.% Ga alloy is retained in the metastable δ phase. Upon cooling to approximately -120 °C, the face-centered-cubic δ phase partially transforms to the metastable monoclinic α′ phase via a martensitic transformation. The kinetics of the δ⟶α′ transformation are reported to have double-C curve kinetics in a time-temperature-transformation (TTT) diagram, but the mechanisms responsible for this unusual behavior are not understood. Our work focuses on determining the underlying cause of the two noses. Optical microscopy has been used to investigate the role of “conditioning”—an isothermal hold at sub-anneal temperatures—on the δ⟶α′ transformation and to illuminate any disparities in transformation products. Conditioning was found to affect substantially the amount of transformation that occurs at particular points corresponding to both the upper- and lower-C of the TTT diagram.