To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Compound heterozygotes occur when different variants at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of variants at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 Genomes Project participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or infantile spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 Genomes Project data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 Genomes Project participants using minor allele frequency (MAF) cutoffs of 0.5 and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous variants in six genes, including three involved in neuronal growth and development – PRTG (p = 0.00086, 1% MAF, combined ancestries), TNC (p = 0.022, 1% MAF, combined ancestries) and MACF1 (p = 0.0245, 0.5% MAF, EU ancestry). Due to the total number of transcripts considered in these analyses, the enrichment detected was not significant after correction for multiple testing and higher powered or prospective studies are necessary to validate the candidacy of these genes. However, PRTG, TNC and MACF1 are potential novel recessive epilepsy genes and our results highlight that compound heterozygous variants should be considered in sporadic epilepsy.
In experimental and clinical studies, green or black tea consumption has been shown to reduce oxidative stress. However, these studies involved high levels of tea consumption and may not reflect patterns in the general population. Here, we examined the association between black or green tea consumption and oxidative stress in a cross-sectional study of 889 premenopausal US women aged 35–54 years. Tea consumption was measured using the Block-98 FFQ. Urinary 8-iso-PGF2α (F2-IsoP) and 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (15-F2t-IsoP-M) were used as biomarkers of oxidative stress. These compounds were measured by MS and normalised to creatinine. Linear regression was used to calculate the geometric mean differences (GMD) and 95% CI for log-transformed urinary F2-IsoP or 15-F2t-IsoP-M in relation to black or green tea consumption. We further examined whether adjusting for caffeine impacted associations between tea and oxidative stress. Geometric means of urinary F2-IsoP and 15-F2t-IsoP-M were 1·44 (95% CI 1·39, 1·49) and 0·71 (95% CI 0·69, 0·73) ng/mg creatinine, respectively. Overall, green tea consumption was not associated with urinary F2-IsoP or 15-F2t-IsoP-M. High-level black tea consumption (≥5 cups/week compared with 0) was associated with higher 15-F2t-IsoP-M concentrations (adjusted GMD=0·10, 95 % CI 0·02–0.19) but not F2-IsoP. Adjusting for caffeine nullified the association between black tea and 15-F2t-IsoP-M. Our findings do not support the hypothesis that dietary tea consumption is inversely associated with oxidative stress.
The two verse fragments edited in 1936 under the title Mum and the Sothsegger have already proved useful to the historian of ideas and institutions. In 1939, Helen M. Cam made very good use of them to illustrate the relation of English members of parliament to their constituencies. More recently, Ruth Mohl, who followed the editors in considering them parts of a single poem, placed them in relation to the more formal aspects of medieval political thought. The usefulness of Mum and the Sothsegger has not, however, been exhausted. Indeed it remains, as both Miss Cam and Miss Mohl found it, a curiously neglected text. And one reason is that it has not been studied for what the author undoubtedly intended it to be, namely a substantial (if not closely knit) and only partially satirical commentary on the problem of counsel.
Irony plagued the career of Reginald Pecock and has pursued his memory. One of the most vigorous and original minds of his generation, he squandered his vast energies in the cause of a decadent orthodoxy which thanked him by bringing him to trial for heresy. And he resorted with the utmost confidence to the traditional weaponry of the medieval schools which, however, he used at times in ways as disconcerting to his scholastic contemporaries as they have proved tantalizing to historians. Small wonder that he remains an isolated figure, his place in history equivocal. If, in addition, it now turns out that his writings can be made to shed as much light on the origins of the English Renaissance as they ever did on the culture of medieval Christendom in which he gloried, it would be but one more thread in this skein of ironies.
At one point in the development of this paper I contemplated calling it ‘Sir John Fortescue in another context'. I abandoned the title as too cryptic; but my intention remains the same, namely, to place Fortescue's thought in a less familiar but, I hope, a none the less revealing context. For the benefit of those who may well feel that the dominium politicum et regale in any other context would smell no fresher, let me hasten to add that I am not here primarily concerned with that famous formula, nor for that matter with Fortescue considered primarily as a political or legal theorist.
There are few prevalence studies of suicide attempts and non-suicidal self-harm (NSSH).
We aimed to estimate the prevalence of thoughts of NSSH, suicidal thoughts, NSSH and suicide attempts among 18- to 34-year-olds in Scotland.
We interviewed a representative sample of young adults from across Scotland.
We interviewed 3508 young people; 11.3 and 16.2% reported a lifetime history of suicide attempts and NSSH, respectively. The first episode of NSSH tended to precede the first suicide attempt by about 2 years. Age at onset of NSSH and suicide attempt was younger in females. Earlier age at onset was associated with more frequent NSSH/suicide attempts. Women are significantly more likely to report NSSH and suicide attempts compared with men.
One in nine young people has attempted suicide and one in six has engaged in NSSH. Clinicians should be vigilant, as suicide attempts and NSSH are relatively common.
In ewe lambs, acceleration of growth and accumulation of both muscle and fat leads to earlier sexual maturity and better reproductive performance. The next stage in the development of this theme is to test whether these aspects of growth in young ewes affect milk production in their first lactation and the growth of their first progeny. We studied 75 young Merino ewes that had known phenotypic values for depth of eye muscle (EMD) and fat (FAT), and known Australian Sheep Breeding Values for post-weaning weight (PWT) and depths of eye muscle (PEMD) and fat (PFAT). They lambed for the first time at 1 year of age. Their lambs were weighed weekly from birth to weaning at 10 weeks to determine live weight gain and weaning weight. Progeny birth weight was positively associated with live weight gain and weaning weight (P<0.001). The PWT of the mothers was positively associated with birth weight (P<0.01), live weight gain and weaning weight of the progeny (P<0.05); however, these progeny traits were not influenced by EMD, FAT, PEMD, PFAT of the mothers (P>0.05). The PWT of the sire was positively associated with live weight gain (P<0.05) and weaning weight of the progeny (P<0.01). At around day 20 postpartum, we measured milk production and milk composition (fat, protein, lactose, total solids). Milk production was influenced positively by birth type (single or twin; P<0.05) and negatively by birth weight (P<0.05), but not by mother phenotype or genotype, sire genotype of the mother or the sex of the progeny (P>0.05). The concentrations of fat, protein, lactose and total solids in the milk were not affected by the phenotype or genotype of the mothers or of the sires of the mothers, or by the sex of the progeny (P>0.05). We conclude that selection of young Merino ewes for better growth, and more rapid accumulation of muscle and fat, will lead to progeny that are heavier at birth, grow faster and are heavier at weaning. Moreover, milk production and composition do not seem to be affected by the genetic merit of the mother for post-weaning live weight or PEMD or PFAT. Therefore, Merino ewes can lamb at 1 year of age without affecting the production objectives of the Merino sheep industry.
Time series of Earth observation (EO) data (Landsat Thematic Mapper (TM), U.S. National Oceanic and Atmospheric Administration Advanced Very High Resolution Radiometer (NOAA AVHRR) and European Remote-sensing Satellite synthetic-aperture radar (ERS SAR)) were obtained for a 2250 km2 mountainous basin in northern Sweden to validate snow-cover area (SCA) estimates produced by a conceptual model (HBV) during three melt seasons. SCA depletion curves derived for each image type, arid coincident images, reveal that the SCA estimate varies with the sensor. Discrepancies betweenTM and AVHRR appear to be an effect of spatial resolution. However, differences betweenTM and SAR are not simply related. Since more AVHRR thanTM data were available, a TM-equivalent SCA was derived from AVHRR by relating TM SCA to AVHRR channel 1 reflectance. The TM-equivalent SCA was used to test SCA simulated by HBV for the 1992 melt season. Although the modelled and TM-equivalent SCA were in reasonable agreement, the modelled SCA declined faster than the TM-equivalent SCA. Partial recalibration of model parameters controlling snowpack accumulation improved the match between the modelled and EO-derived SCA decline. The recalibrated parameters were verified using SCA maps generated for the 1996 and 1998 melt seasons. The adjusted parameter sets had little effect on the Nash-Sutcliffe R2 runoff fit but improved the volume fit in all three years.
Plasmodium knowlesi is increasingly recognized as a major cause of malaria in Southeast Asia. Anopheles leucosphyrous group mosquitoes transmit the parasite and natural hosts include long-tailed and pig-tailed macaques. Despite early laboratory experiments demonstrating successful passage of infection between humans, the true role that humans play in P. knowlesi epidemiology remains unclear. The threat posed by its introduction into immunologically naïve populations is unknown despite being a public health priority for this region. A two-host species mathematical model was constructed to analyse this threat. Global sensitivity analysis using Monte Carlo methods highlighted the biological processes of greatest influence to transmission. These included parameters known to be influential in classic mosquito-borne disease models (e.g. vector longevity); however, interesting ecological components that are specific to this system were also highlighted: while local vectors likely have intrinsic preferences for certain host species, how plastic these preferences are, and how this is shaped by local conditions, are key determinants of parasite transmission potential. Invasion analysis demonstrates that this behavioural plasticity can qualitatively impact the probability of an epidemic sparked by imported infection. Identifying key vector sub/species and studying their biting behaviours constitute important next steps before models can better assist in strategizing disease control.
For two decades, the Hopi Cultural Preservation Office has worked with archaeologists to co-create knowledge about the past and document contemporary values associated with heritage sites. Much of this work has been accomplished within the framework of research mandated by the National Historic Preservation Act and National Environmental Policy Act. Here we describe a case study that illustrates the processes of this community-based participatory research, including research design, implementation of fieldwork, peer review of research findings, and reporting. The case study is a project conducted in 2014 by the Hopi Tribe in partnership with Anthropological Research, LLC, to investigate traditional cultural properties associated with an Arizona Public Service Company transmission line. The Hopi Tribe’s collaborative research with archaeologists provides intellectual benefits for the management of archaeological resources and the humanistic and scientific understanding of the past.