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Forty years ago, Knut Fladmark (1979) argued that the Pacific Coast offered a viable alternative to the ice-free corridor model for the initial peopling of the Americas—one of the first to support a “coastal migration theory” that remained marginal for decades. Today, the pre-Clovis occupation at the Monte Verde site is widely accepted, several other pre-Clovis sites are well documented, investigations of terminal Pleistocene subaerial and submerged Pacific Coast landscapes have increased, and multiple lines of evidence are helping decode the nature of early human dispersals into the Americas. Misconceptions remain, however, about the state of knowledge, productivity, and deglaciation chronology of Pleistocene coastlines and possible technological connections around the Pacific Rim. We review current evidence for several significant clusters of early Pacific Coast archaeological sites in North and South America that include sites as old or older than Clovis. We argue that stemmed points, foliate points, and crescents (lunates) found around the Pacific Rim may corroborate genomic studies that support an early Pacific Coast dispersal route into the Americas. Still, much remains to be learned about the Pleistocene colonization of the Americas, and multiple working hypotheses are warranted.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
Ten compounds are found in the Ba0-Y203-CuOx system. High temperature (≈950-1000°C) phases identified as Ba4Y2O7 , Ba2Y2O5 , Ba3Y4O9 , BaY2O4 , Y2Cu2O5 , BaCuO2+x, Ba3YCu2OZ BaY2Cu05 and BazYCu306+x are formed in this temperature range. In addition, a new compound with composition of 2BaO:CuO, which possibly has a melting point below 950°C, was prepared at 850°C. A summary o£ the crystallographic data of these 10 phases is given. In particular, results of x-ray studies pertaining to four compounds, BazYCu306+x, which is currently the most promising high To' superconductor material, Ba2Cu03 , BaY2Cu05 , and Ba3YCu20Z are reviewed.
The second year of life is a period of nutritional vulnerability. We aimed to investigate the dietary patterns and nutrient intakes from 1 to 2 years of age during the 12-month follow-up period of the Growing Up Milk – Lite (GUMLi) trial. The GUMLi trial was a multi-centre, double-blinded, randomised controlled trial of 160 healthy 1-year-old children in Auckland, New Zealand and Brisbane, Australia. Dietary intakes were collected at baseline, 3, 6, 9 and 12 months post-randomisation, using a validated FFQ. Dietary patterns were identified using principal component analysis of the frequency of food item consumption per d. The effect of the intervention on dietary patterns and intake of eleven nutrients over the duration of the trial were investigated using random effects mixed models. A total of three dietary patterns were identified at baseline: ‘junk/snack foods’, ‘healthy/guideline foods’ and ‘breast milk/formula’. A significant group difference was observed in ‘breast milk/formula’ dietary pattern z scores at 12 months post-randomisation, where those in the GUMLi group loaded more positively on this pattern, suggesting more frequent consumption of breast milk. No difference was seen in the other two dietary patterns. Significant intervention effects were seen on nutrient intake between the GUMLi (intervention) and cows’ milk (control) groups, with lower protein and vitamin B12, and higher Fe, vitamin D, vitamin C and Zn intake in the GUMLi (intervention) group. The consumption of GUMLi did not affect dietary patterns, however, GUMLi participants had lower protein intake and higher Fe, vitamins D and C and Zn intake at 2 years of age.
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.
The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
Red Supergiant Stars (RSGs) are important probes of stellar and chemical evolution in star-forming environments. They represent the brightest near-IR stellar components of external galaxies and probe the most recent stellar population to provide robust, independent abundance estimates. The Local Group dwarf irregular galaxy, NGC6822, is a reasonably isolated galaxy with an interesting structure and turbulent history. Using RSGs as chemical abundance probes, we estimate metallicities in the central region of NGC6822, finding a suggestion of a metallicity gradient (in broad agreement with nebular tracers), however, this requires further study for confirmation. With intermediate resolution Multi-object spectroscopy (from e.g. KMOS, EMIR, MOSFIRE) combined with state-of-the-art stellar model atmospheres, we demonstrate how RSGs can be used to estimate stellar abundances in external galaxies. In this context, we compare stellar and nebular abundance tracers in NGC 6822 and by combining stellar and nebular tracers we estimate an abundance gradient of −0.18 ± 0.05 dex/kpc.
Although childhood adversity is a potent determinant of psychopathology, relatively little is known about how the characteristics of adversity exposure, including its developmental timing or duration, influence subsequent mental health outcomes. This study compared three models from life course theory (recency, accumulation, sensitive period) to determine which one(s) best explained this relationship.
Prospective data came from the Avon Longitudinal Study of Parents and Children (n = 7476). Four adversities commonly linked to psychopathology (caregiver physical/emotional abuse; sexual/physical abuse; financial stress; parent legal problems) were measured repeatedly from birth to age 8. Using a statistical modeling approach grounded in least angle regression, we determined the theoretical model(s) explaining the most variability (r2) in psychopathology symptoms measured at age 8 using the Strengths and Difficulties Questionnaire and evaluated the magnitude of each association.
Recency was the best fitting theoretical model for the effect of physical/sexual abuse (girls r2 = 2.35%; boys r2 = 1.68%). Both recency (girls r2 = 1.55%) and accumulation (boys r2 = 1.71%) were the best fitting models for caregiver physical/emotional abuse. Sensitive period models were chosen alone (parent legal problems in boys r2 = 0.29%) and with accumulation (financial stress in girls r2 = 3.08%) more rarely. Substantial effect sizes were observed (standardized mean differences = 0.22–1.18).
Child psychopathology symptoms are primarily explained by recency and accumulation models. Evidence for sensitive periods did not emerge strongly in these data. These findings underscore the need to measure the characteristics of adversity, which can aid in understanding disease mechanisms and determining how best to reduce the consequences of exposure to adversity.
The properties of the acoustic modes are sensitive to magnetic activity. The unprecedented long-term Kepler photometry, thus, allows stellar magnetic cycles to be studied through asteroseismology. We search for signatures of magnetic cycles in the seismic data of Kepler solar-type stars. We find evidence for periodic variations in the acoustic properties of about half of the 87 analysed stars. In these proceedings, we highlight the results obtained for two such stars, namely KIC 8006161 and KIC 5184732.
Perennial ryegrass varieties bred to express high water-soluble carbohydrate (WSC) concentrations have been shown to improve liveweight gain in pre-weaned lambs of grazing ewes (Lee et al., 2001) compared to conventional ryegrass. Studies have shown that the largest differential in WSC between ryegrass varieties bred for high WSC concentrations and control ryegrasses occurs 5-6 weeks after the plant is allowed to re-grow following cutting or grazing (Miller et al., 2001). Therefore, the benefits, in terms of lamb performance, of using these grasses with high WSC concentrations may be best achieved when they are rotationally rather than continuously grazed. The aim of this experiment was to compare lambs rotationally or continuously grazing either a ryegrass variety bred for high WSC concentrations or a control ryegrass.
The majority of market lamb produced in UK results from crossing terminal sire rams with crossbred ewes. The selection of terminal sire breeds over the past 15 years for improved carcass composition has shown positive benefits on carcass quality of their crossbred progeny (Simm et al. 2001). However, faster rates of genetic improvement would be achieved if information from these terminal sire crossbred lambs could be used in the genetic evaluation of terminal sire breeds. Incorporating crossbred information into purebred selection programmes has been modelled and the results show that it is an effective way of improving carcass quality (Jones et al. 1999). However, this is currently compromised by limitations on how individual carcass data can be collected for incorporation into breeding programmes. An innovative technology based on Video Image Analysis (VIA) of lamb carcasses is being evaluated for introduction into UK lamb abattoirs. VIA systems can provide an objective, automatic, consistent and accurate way of measuring carcass composition. However, little is known of genetic parameters for VIA measurements of lamb carcasses. Therefore the aim of the present research project was to estimate the genetic parameters of VIA carcass measurements in crossbred lamb population.
Nutritional manipulation during the dry period can alter subsequent animal responses to feeding in terms of milk yield and composition. Previous research has shown interesting differences in milk production and composition due to energy or protein supply in the dry period (Moorby et al., 1996). The objective of this experiment was to test the interaction between energy and protein supplies during the dry period on subsequent milk production and composition. Effects on live weight gains and condition scores are reported in a separate summary (Jaurena et al., 2001).
Previous results have shown that during late gestation even under conditions of live weight (LW) gain, maternal body protein can be in negative balance due to the highly demanding gravid uterus and udder. It has also been claimed that current feeding standards underpredict dry cow nitrogen (N) requirement. Considering that it is not possible to measure maternal body N status independently of the requirements of the conceptus and the udder, estimation of conceptus and udder N requirements by mathematical models can help to predict maternal N requirement. The aim of this study was to assess cow N requirement during late gestation by predicting maternal N balance through a mathematical model. Previous results related with this study were presented in Jaurena et al, (2001).
The high intake characteristics of red clover silage has been recognised for many years (e.g. Thomas et al., 1985). Our previous study (Dewhurst et al., 2000) demonstrated the considerable intake and milk production potential of clover silages made using a new approach based on preparation of big-bales from wilted material with the use of biological inoculant additives. The objective of this study was to verify the positive results obtained with red and white clover silages using material taken from a further series of cuts taken in a subsequent year and to evaluate the legume silages with low levels of concentrate feeding.
Energy and protein supply during the dry period can affect subsequent milk production and composition (Moorby et al., 1996). Grass silage is a common ingredient of dry cow diets, but although it is usually adequate in crude protein concentration (CP), a high proportion is frequently in non-protein forms. Red clover silage has shown interesting characteristics that would increase true protein supply to ruminants (Broderick et al., 2000), which could avoid the use of more expensive concentrate supplements. The objective of this experiment was to compare red clover and ryegrass silage when fed as the sole source of forage to dry cows with a diet comprising ryegrass silage and a protein supplement.
Our earlier studies with dry cows have highlighted a number of factors that affect performance in the subsequent lactation, including forage intake in the peri-parturient period, body condition at calving and supply of Metabolisable Protein (MP) (Moorby et al., 1996; Dewhurst et al., 2000). There is now increased interest in making more use of grazed grass, as a cheap feed, particularly through extending grazing into the late-autumn and winter. Dry cows are suited to extended grazing because they do not need to be brought in for milking each day. The high voluntary intakes of grass may be beneficial for dry cows, though the low MP supply from autumn-grass might be a disadvantage. This experiment evaluated the effects of extended grazing, compared with housing and silage-feeding of dry cows.
With increasing emphasis in the meat sector on better and more consistent quality, carcass leanness and conformation is now an important issue for sheep breeders. In 1999, only 47% of all carcasses in the UK met the target specifications for weight, fat and conformation (MLC, 2000), highlighting the potential for improvement. In the current stratified crossbreeding system, crossbred wether lambs are a by-product of the production of dam line ewes for the lowland sector. If their carcass quality is sufficient, they can give a valuable boost to the economics of the breeding programme. Genetic improvement of carcass quality in crossing sire breeds would benefit the crossbred wethers, as well as filter through to the terminal sire cross lambs produced by the crossbred ewes. This work aims to assess the influence of selection index and live conformation score of crossing sires (in this case Bluefaced Leicesters) on growth and carcass quality traits of their crossbred progeny, as a first step towards designing a genetic improvement programme for crossing sire sheep.