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Archaeological research has documented the migration of Neolithic farmers onto the Tibetan Plateau by 4000 BC. How these incoming groups interacted, if at all, with local indigenous foragers, however, remains unclear. New archaeobotanical and zooarchaeological data from the Zongri site in the north-eastern Tibetan Plateau suggest that local foragers continued to hunt but supplemented their diet with agricultural products in the form of millet. The authors propose that, rather than being grown locally, this millet was acquired via exchange with farmers. This article highlights how indigenous foragers engaged in complex patterns of material and cultural exchange through encounters with newly arrived farmers.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
Nutritional therapy is a cornerstone of burns management. The optimal macronutrient intake for wound healing after burn injury has not been identified, although high-energy, high-protein diets are favoured. The present study aimed to identify the optimal macronutrient intake for burn wound healing. The geometric framework (GF) was used to analyse wound healing after a 10 % total body surface area contact burn in mice ad libitum fed one of the eleven high-energy diets, varying in macronutrient composition with protein (P5−60 %), carbohydrate (C20−75 %) and fat (F20−75 %). In the GF study, the optimal ratio for wound healing was identified as a moderate-protein, high-carbohydrate diet with a protein:carbohydrate:fat (P:C:F) ratio of 1:4:2. High carbohydrate intake was associated with lower mortality, improved body weight and a beneficial pattern of body fat reserves. Protein intake was essential to prevent weight loss and mortality, but a protein intake target of about 7 kJ/d (about 15 % of energy intake) was identified, above which no further benefit was gained. High protein intake was associated with delayed wound healing and increased liver and spleen weight. As the GF study demonstrated that an initial very high protein intake prevented mortality, a very high-protein, moderate-carbohydrate diet (P40:C42:F18) was specifically designed. The dynamic diet study was also designed to combine and validate the benefits of an initial very high protein intake for mortality, and subsequent moderate protein, high carbohydrate intake for optimal wound healing. The dynamic feeding experiment showed switching from an initial very high-protein diet to the optimal moderate-protein, high-carbohydrate diet accelerated wound healing whilst preventing mortality and liver enlargement.
Patients with severe mental disorders in low-resource settings have limited access to services, resulting in overwhelming caregiving burden for families. In extreme cases, this has led to the long-term restraining of patients in their homes. China underwent a nationwide initiative to unlock patients and provide continued treatment. This study aims to quantify household economic burden in families after unlocking and treatment, and to identify factors associated with increased burden due to schizophrenia.
A total of 264 subjects were enrolled from three geographically diverse provinces in 2012. Subjects were patients with schizophrenia who were previously put under restraints and had participated in the ‘unlocking and treatment’ intervention. The primary outcome was the current household economic burden, obtained from past year financial information collected through on-site interview. Patient disease characteristics, treatment, outcomes and family caregiving burden were collected as well. Univariate and multivariate linear regression were used to construct risk factor models for indirect economic burden.
After participating in the intervention, 85% of patients continued to receive mental health services, 70% used medication as prescribed and 80% were never relocked. Family members reported significantly decreased caregiving burden after receiving the intervention. Mean direct and indirect household economic burdens were CNY963 (US$31.7) and CNY11 724 (US$1670) per year, respectively, while family total income was on average CNY12 108 (US$1913) per year. Greater disease severity and poorer patient psychosocial function at time of study were found to be independent factors related to increased indirect burden.
The ‘unlocking and treatment’ intervention has improved the lives of patients and families. Indirect burden due to disease is still a major economic issue that needs to be addressed, potentially through improving treatment and patient functioning. Our findings contribute to the unravelling and eventual elimination of chronic restraining of mentally ill patients in low-resource settings.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1.Explore the current molecular landscape of pediatric high grade gliomas
2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3.Discuss the current status of NTRK inhibitor clinical trials
Rubber seed oil (RO) that is rich in polyunsaturated fatty acids (FA) can improve milk production and milk FA profiles of dairy cows; however, the responses of digestion and ruminal fermentation to RO supplementation in vivo are still unknown. This experiment was conducted to investigate the effect of RO and flaxseed oil (FO) supplementation on nutrients digestibility, rumen fermentation parameters and rumen FA profile of dairy cows. Forty-eight mid-lactation Holstein dairy cows were randomly assigned to one of four treatments for 8 weeks, including basal diet (CON) or the basal dietary supplemented with 4% RO, 4% FO or 2% RO plus 2% FO on a DM basis. Compared with CON, dietary oil supplementation improved the total tract apparent digestibility of DM, neutral detergent fibre and ether extracts ( P < 0.05). Oil treatment groups had no effects on ruminal digesta pH value, ammonia N and microbial crude protein ( P > 0.05), whereas oil groups significantly changed the volatile fatty acid (VFA) profile by increasing the proportion of propionate whilst decreasing total VFA concentration, the proportion of acetate and the ratio of acetate to propionate ( P < 0.05). However, there were no differences in VFA proportions between the three oil groups (P > 0.05). In addition, dietary oil supplementation increased the total unsaturated FA proportion in the rumen by enhancing the proportion of trans-11 C18:1 vaccenic acid (VA), cis-9, trans-11 conjugated linoleic acid (CLA) and α-linolenic acid (ALA) ( P < 0.05). These results indicate that dietary supplementation with RO and FO could improve nutrients digestibility, ruminal fermentation and ruminal FA profile by enhancing the VA, cis-9, trans-11 CLA and ALA composition of lactating dairy cows. These findings provide a theoretical basis for the application of RO in livestock production.
Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron (SMN1) gene. In the phase 1 trial (NCT02122952), SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of 15 symptomatic SMA1 patients (3 at a lower dose [cohort 1] and 12 at the proposed therapeutic dose [cohort 2]). This report describes long-term follow-up study design and data from the phase 1 study. Methods: Patients in the phase 1 study could rollover into a long-term follow-up study (NCT03421977). The primary objective is to collect long-term safety data (serious adverse events, hospitalizations, and adverse events of special interest). Annual follow-up will occur for 15 years. Additionally, patient record transfers from local clinician(s) will be requested. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include physical examination to assess developmental milestones. Results: As of September 27, 2018, the oldest patients are 59.2 (cohort 1) and 52.1 (cohort 2) months old and free of permanent ventilation. Preliminary data, including survival and developmental milestones, will be presented. Conclusions: Patients treated with a one-time dose of AVXS-101 continue to gain strength, develop, and achieve new milestones, demonstrating a long-term, durable response.
Antioxidants have been always used to improve post-slaughter meat quality in broilers subjected to stress. Forsythia suspensa extract (FSE), a traditional Chinese herbal medicine, is generally regarded as a natural source of antioxidants. Therefore, the objective of this study was to test the hypothesis that FSE could protect post-slaughter breast muscles against oxidative injury induced by dexamethasone (DEX) mimicking chronic physiological stress in poultry production. Average daily gain and feed efficiency of poultry were suppressed by DEX and improved by FSE (P < 0.05). Dexamethasone caused the decrease in the redness value and the increase in the lightness and yellowness values and drip loss of the breast muscles (P < 0.05), and FSE had the converse effects (P < 0.05). Dietary FSE supplementation decreased monounsaturated fatty acid (FA) and increased polyunsaturated FA in breast muscles of broilers (P < 0.05). In addition, FSE decreased malondialdehyde and carbonyl content in the breast muscles of DEX-treated broilers (P < 0.05). The inhibition of 1,1-diphenyl-2-picryl-hydrazyl in the breast muscles was decreased by DEX and increased by FSE (P < 0.05). Total-antioxidant capacity and glutathione peroxidase activity in the breast muscles were decreased in birds subjected to DEX and increased in birds supplemented with FSE (P < 0.05). Totally, DEX suppressed growth performance and induced breast muscle oxidative injury in broilers, and FSE supplementation improved antioxidant capacity to attenuate these adverse effects. Therefore, FSE could be a potential natural antioxidant to alleviate oxidative injury of the breast muscles in broilers and to improve the meat quality for human consumption.
Introduction: Intravenous insertion (IVI) is identified by children as extremely painful and the resultant distress can have lasting negative consequences. There is an urgent need to effectively manage such procedures. Our primary objective was to compare the pain and distress of IVI with the addition of humanoid robot-based distraction to standard care, versus standard care alone. Methods: This two-armed randomized controlled trial (RCT) was conducted from April 2017 to May 2018 at the Stollery Children's Hospital emergency department (ED). Children aged 6 to 11 years who required IVI were included. Exclusion criteria included hearing or visual impairments, neurocognitive delays, sensory impairment to pain, previous enrolment, and discretion of the ED clinical staff. Primary outcomes were measured using the Observational Scale of Behavioural Distress-Revised (OSBD-R) (distress) and the Faces Pain Scale-Revised (FPS-R) (pain). A total of 426 pediatric patients were screened and 340 were excluded. Results: We recruited 86 children, of which 55% (47/86) were male; 9% (7/82) were premature at birth; 82% (67/82) had a previous ED visit; 30% (25/82) required previous hospitalization; 78% (64/82) had previous IV placement and 96% (78/81) received topical anesthesia. The mean total OSBD-R score was 1.49 ± 2.36 (standard care) compared to 0.78 ± 1.32 (robot group) (p = 0.047). The median FPS-R during the IV procedure was 4 (IQR 2,6) in the standard care group alone, compared to 2 (IQR 0,4) with the addition of humanoid robot-based distraction (p = 0.10). Change in parental state anxiety pre-procedure versus post-procedure was not significantly different between groups (p = 0.49). Parental satisfaction with the IV start was 93% (39/42) in the robot arm compared to 74% (29/39) in the standard care arm (p = 0.03). Parents were also more satisfied with management of their child's pain in the robot group (95% very satisfied) compared with standard care (72% very satisfied) (p = 0.002). Conclusion: A statistically significant reduction in distress was observed with the addition of robot-based distraction to standard care. Humanoid robot-based distraction therapy reduces distress and to a lesser extent, pain, in children undergoing IVI in the ED. Further trials are required to confirm utility in other age groups and settings.
Imprinted genes uniquely drive and support fetoplacental growth by controlling the allocation of maternal resources to the fetus and affecting the newborn’s growth. We previously showed that alterations of the placental imprinted gene expression are associated with suboptimal perinatal growth and respond to environmental stimuli including socio-economic determinants. At the same time, maternal psychosocial stress during pregnancy (MPSP) has been shown to affect fetal growth. Here, we set out to test the hypothesis that placental imprinted gene expression mediates the effects of MPSP on fetal growth in a well-characterized birth cohort, the Stress in Pregnancy (SIP) Study. We observed that mothers experiencing high MPSP deliver infants with lower birthweight (P=0.047). Among the 109 imprinted genes tested, we detected panels of placental imprinted gene expression of 23 imprinted genes associated with MPSP and 26 with birthweight. Among these genes, five imprinted genes (CPXM2, glucosidase alpha acid (GAA), GPR1, SH3 and multiple ankyrin repeat domains 2 (SHANK2) and THSD7A) were common to the two panels. In multivariate analyses, controlling for maternal age and education and gestational age at birth and infant gender, two genes, GAA and SHANK2, each showed a 22% mediation of MPSP on fetal growth. These data provide new insights into the role that imprinted genes play in translating the maternal stress message into a fetoplacental growth pattern.
Several grass and broadleaf weed species around the world have evolved multiple-herbicide resistance at alarmingly increasing rates. Research on the biochemical and molecular resistance mechanisms of multiple-resistant weed populations indicate a prevalence of herbicide metabolism catalyzed by enzyme systems such as cytochrome P450 monooxygenases and glutathione S-transferases and, to a lesser extent, by glucosyl transferases. A symposium was conducted to gain an understanding of the current state of research on metabolic resistance mechanisms in weed species that pose major management problems around the world. These topics, as well as future directions of investigations that were identified in the symposium, are summarized herein. In addition, the latest information on selected topics such as the role of safeners in inducing crop tolerance to herbicides, selectivity to clomazone, glyphosate metabolism in crops and weeds, and bioactivation of natural molecules is reviewed.
Theoretical investigations on ferroelectric tunnel junctions (FTJs) with asymmetric electrodes and a composite barrier are presented. A large tunneling electroresistance effect exists for the Pt/SrTiO3/BaTiO3/SrRuO3 junction; on the other hand, exchange of the dielectric and ferroelectric layer stacking sequence can seriously degrade the performance. These correlations are rationalized by the proposed concept of an asymmetry factor, defined as the ratio between the average barrier heights of FTJs for two opposite polarization orientations. We show that a large asymmetry factor is beneficial to FTJs. This work may provide a way to enhance the performance of FTJs by structure engineering.
This study investigated Echinococcus genotypes in patients with hydatidosis that reside in Inner Mongolia, Tibet or Qinghai Province by partially sequencing the cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase 1 (nad1) genes. Cyst fluids were collected from 23 patients with hydatidosis and DNA was extracted. Portions of the cox1 and nad1 genes were amplified and subsequently sequenced. Sequencing analysis determined that one of the isolates contained Echinococcus multilocularis, and the other 22 isolates contained E. granulosus sensu lato. The isolates were then further classified based on genotype, and E. granulosus sensu stricto (s.s.) G1 (n = 20), E. granulosus s.s. G3 (n = 1) and E. canadensis G6/7 (n = 1) were identified. Additionally, the sequences were concatenated (pcox1 + pnad1) and 11 haplotypes were identified among the E. granulosus s.s. isolates (G1 and G3), with a shared common haplotype (H1) identified. Overall, these findings provide further understanding of the genetic patterns of Echinococcus in western and northern China.
Inadequate knowledge in maternal nutrition is one of the determinants of low birth weight. However, little evidence is available on whether maternal nutrition counselling alone can influence birth weight among women from low socioeconomic households. This study assessed the effect of prenatal maternal nutritional counselling on birth weight and examined the related risk factors. A cluster randomized controlled trial was conducted to assess the effectiveness of home-based maternal nutritional counselling on nutritional outcomes, morbidity, breastfeeding, and infant feeding practices by the African Population and Health Research Center in two urban informal settlements of Nairobi. The intervention group received monthly antenatal and nutritional counselling from trained community health volunteers; meanwhile, the control group received routine antenatal care. A total of 1001 participants were included for analysis. Logistic regression was applied to determine associations between low birth weight and maternal characteristics. A higher prevalence of low birth weight was observed in the control group (6.7%) than in the intervention group (2.5%; P<0.001). Logistic regression identified significant associations between birth weight and intervention group (adjusted odds ratio (AOR)=0.26; 95% confidence interval (CI), 0.10–0.64); maternal height <154.5 cm (AOR=3.33; 95% CI, 1.01–10.96); last antenatal care visits at 1st or 2nd trimesters (AOR=9.48; 95% CI, 3.72–24.15); pre-term delivery (AOR=3.93; 95% CI, 1.93–7.98); maternal mid-upper arm circumference <23 cm (AOR=2.57; 95% CI, 1.15–5.78); and cesarean delivery (AOR=2.27; 95% CI, 1.04–4.94). Nutrition counselling during pregnancy reduced low birth weight and preterm births, which was determined by women of short stature, early stoppage of antenatal visit, and cesarean delivery.
Coherent cuboidal B2 nanoprecipitation in body-centered cubic (BCC)-based high-entropy alloys (HEAs) is important for the improvement of mechanical strength. The present work primarily investigated the effect of Ti substitution for Al on the cuboidal B2 nanoprecipitates in BCC Al0.7NiCoFeCr2 HEAs. A series of (Al,Ti)0.7NiCoFeCr2 HEAs with different Al/Ti ratios were prepared by suction-cast processing, and their microstructures and mechanical properties were then characterized comprehensively. It was found that the substitution of Ti for Al can change the phase structures of ordered precipitation, from the B2-AlNi to a highly ordered L21-Ni2AlTi phase. Especially, a small amount addition of Ti (≤4.2 at.%, Al/Ti ratio ≥2/1) renders the HEAs with cuboidal L21 nanoparticles coherently precipitated into the BCC matrix, which is attributed to the moderate lattice misfit (ε = 0.5–0.6%) between BCC and L21 phases. HEAs with such coherent microstructures exhibit high compressive yield strength of about 1700–1800 MPa. When the Ti content reaches up to 6.25 at.%, the matrix of the alloy will be turned into the σ phase, rather than BCC, leading to a heavy brittleness.
Introduction: Intravenous (IV) cannulation is commonly performed in emergency departments (ED), often causing substantial pain and distress. Distraction has been shown to reduce child-reported pain, but there is currently little published about the effects of using iPad technology as a distraction tool. Our primary objective was to compare the reduction of pain and distress using iPad distraction (games, movies, books of the child’s choice) in addition to standard care, versus standard care alone. Methods: This randomized clinical trial, conducted at the Stollery Childrens Hospital ED, recruited children between ages 6 to 11 years requiring IV cannulation. Study arm assignment was performed using REDCaps randomization feature. Due to the nature of the intervention, blinding was not possible for the children, parents or research and ED staff, but the data analyst was blinded to intervention assignment until completion of analysis. Pain, distress, and parental anxiety were measured using the Faces Pain Scale-Revised, the Observed Scale of Behavioural Distress-Revised, and the State Trait Anxiety Inventory, respectively. The pain scores and observed behavioural distress scores were compared using the Mann-Whitney U test. Other co-variates were analyzed using a linear regression analysis. Results: A total of 85 children were enrolled, with 42 receiving iPad distraction and 43 standard care, of which 40 (95%) and 35 (81%) children received topical anesthesia, respectively (p=0.09). There were 40 girls (47.1%) with a mean age of 8.32 +/− 1.61 years. The pain scores during IV cannulation (p=0.35) and the change in pain score during the procedure compared to baseline (p=0.79) were not significantly different between the groups, nor were the observed distress scores during IV cannulation (p=0.09), or the change in observed distress during the procedure compared to baseline (p=0.44). A regression analysis showed children in both groups had greater total behavioural stress if it was their first ED visit (p=0.01), had prior hospitalization experience (p=0.04) or were admitted to hospital during this visit (p=0.007). A previous ED visit, however, was predictive of a greater increase in parental anxiety from baseline (p=0.02). When parents were asked whether they would use the same methods to manage pain for their child, parents of the iPad group were more likely to say yes than were parents of the standard care group (p=0.03). Conclusion: iPad distraction during IV cannulation in school-aged children was not found to decrease pain or distress more than standard care alone, but parents preferred its use. The effects of iPad distraction may have been over-shadowed by potent topical anesthetic effect. Future directions include exploring iPad distraction for other age groups, and studying novel technology such as virtual reality and interactive humanoid robots.
Social anxiety disorder (SAD) (formerly called social phobia) is among the most common mental health diagnoses among older adults; however, the research on late-life social anxiety is scarce. A limited number of studies have examined the assessment and diagnosis of social anxiety disorder in this population, and there are few social anxiety measures that are validated for use with older adults. One such measure, the Older Adult Social Evaluative Scale (OASES), was designed for use with this population, but until now has lacked validation against a gold-standard diagnostic interview.
Using a sample of 47 community-dwelling older adults (aged 60 years and over) with anxiety, the present study compared OASES performance to that of the Structured Clinical Interview for DSM-5 Disorders (SCID-5), as well as other measures of anxiety and depression.
The OASES demonstrated convergent validity with other measures of anxiety, and demonstrated discriminant validity on other measures (e.g. depression, somatic symptoms). Receiver operating characteristic (ROC) analysis revealed that a cut-point of ≥76 optimized sensitivity and specificity compared to SCID-5 derived diagnoses of social anxiety disorder.
This study is the first study to provide psychometric validation for the OASES and one of the first to administer the SCID-5 to an older adult sample. In addition to establishing a clinically significant cut-off, this study also describes the clinical utility of the OASES, which can be used to identify distressing situations, track anxiety severity, and monitor behavioral avoidance across a variety of social situations.