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 email@example.com
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.
Neuropsychopharmacologic effects of long-term opioid therapy (LTOT) in the context of chronic pain may result in subjective anhedonia coupled with decreased attention to natural rewards. Yet, there are no known efficacious treatments for anhedonia and reward deficits associated with chronic opioid use. Mindfulness-Oriented Recovery Enhancement (MORE), a novel behavioral intervention combining training in mindfulness with savoring of natural rewards, may hold promise for treating anhedonia in LTOT.
Veterans receiving LTOT (N = 63) for chronic pain were randomized to 8 weeks of MORE or a supportive group (SG) psychotherapy control. Before and after the 8-week treatment groups, we assessed the effects of MORE on the late positive potential (LPP) of the electroencephalogram and skin conductance level (SCL) during viewing and up-regulating responses (i.e. savoring) to natural reward cues. We then examined whether these neurophysiological effects were associated with reductions in subjective anhedonia by 4-month follow-up.
Patients treated with MORE demonstrated significantly increased LPP and SCL to natural reward cues and greater decreases in subjective anhedonia relative to those in the SG. The effect of MORE on reducing anhedonia was statistically mediated by increases in LPP response during savoring.
MORE enhances motivated attention to natural reward cues among chronic pain patients on LTOT, as evidenced by increased electrocortical and sympathetic nervous system responses. Given neurophysiological evidence of clinical target engagement, MORE may be an efficacious treatment for anhedonia among chronic opioid users, people with chronic pain, and those at risk for opioid use disorder.
The elm zigzag sawfly, Aproceros leucopoda Takeuchi (Hymenoptera: Argidae), was reported for the first time in North America during the summer of 2020. Characteristic zigzag defoliation was reported in the province of Québec, Canada, on the community science website, iNaturalist. Field trips conducted to the site resulted in the collection of live specimens (a few larvae and a cocoon from which an adult emerged) and onsite observation of diagnostic defoliation and empty cocoons, confirming the presence of this exotic species in Canada. Subsequent inspection of elm trees by naturalists and scientists in the south of the province led to the conclusion that the species is more widely distributed than first expected and that the invasion is not localised to a small area. Preliminary genetic data pointed to a possible European origin of the Canadian population, but conclusive assignment to source will require examination of more specimens and the collection of reference sequences from different European and Asian populations. This is a good example of the importance of community science in the detection of new invasive species.
Antibiotics are widely used in neonatal intensive care units (NICUs). We conducted a cross-sectional analysis of antibiotic use across US NICUs to evaluate overall, broad-spectrum, and combination antibiotic use. Patterns of antibiotic use varied by medical versus surgical service line, hospital, and geographic location.
Many studies of wildlife poaching acknowledge the challenges of detecting poaching activities, but few address the issue. Data on poaching may be an inaccurate reflection of the true spatial distribution of events because of low detection rates. The deployment of conservation and law enforcement resources based on biased data could be ineffective or lead to unintended outcomes. Here, we present a rigorous method for estimating the probabilities of detecting poaching and for evaluating different patrol strategies. We illustrate the method with a case study in which imitation snares were set in a private nature reserve in South Africa. By using an experimental design with a known spatial distribution of imitation snares, we estimated the detection probability of the current patrol strategy used in the reserve and compared it to three alternative patrol strategies: spatially focused patrols, patrols with independent observers, and systematic search patterns. Although detection probabilities were generally low, the highest proportion of imitation snares was detected with systematic search strategies. Our study provides baseline data on the probability of detecting snares used for poaching, and presents a method that can be modified for use in other regions and for other types of wildlife poaching.
The Benedictine priory of St Martin at Dover was a convenient resting place for those just arrived in England. On 6 March 1263 the priory's chronicler noted the arrival from France of three young men of the highest pedigree: John, Earl Warenne, Henry of Almain, son of Richard of Cornwall, and Henry de Montfort. This trio of young nobles heralded the return, seven weeks later, of Simon de Montfort, earl of Leicester, which, in turn, precipitated a protracted but violent descent into civil war the following year. What is really surprising about this incident, however, is not that Earl Warenne and Henry of Almain ended up fighting against Henry de Montfort and his father in the civil war of 1264-5 but that they were ever minded to go against the king in the first place. The political grouping which Warenne and Henry of Almain headed, that of the former friends of the king's son, Lord Edward, has long been recognised by historians as one of the powerful factions in English politics during the period of Reform and Rebellion, and their role in precipitating Montfort's return has been likewise acknowledged. Their immediate motive for doing so was the political isolation imposed on them in 1261 by the queen and the Savoyard faction at court which she led, a culmination of a tug of war over the affections of Lord Edward which had been waged since the mid 1250s. This grouping of young English lords around Edward has, in turn, been linked to the factional struggles at Henry III's court between the Savoyard relatives of his queen and his own Lusignan halfbrothers from Poitou.
What will be argued in this article is that for Warenne, the wealthiest and most prominent member of this faction, his antagonism towards the Savoyards stretched back much further, to the early 1240s, and that it was caused by the manner of Henry III's settlement of the Savoyards in England. The crisis which overwhelmed Henry's kingship in 1263 had thus been brewing for over twenty years and was the direct result of his own policies. Linked to this, the article will suggest that Henry's very introduction of the Savoyards to England was profoundly damaging to his kingship in both foreign and domestic policy and was symptomatic of the broader failure of his rule.
Systematic, in-depth exploration of news media coverage of aggression and older adults remains sparse, with little attention to how and why particular frames manifest in coverage across differing settings and relationships. Frame analysis was used to analyze 141 English-language Canadian news media articles published between 2008 and 2019. Existing coverage tended towards stigmatizing, fear-inducing, and biomedical framings of aggression, yet also reflected and reinforced ambiguity, most notably around key differences between settings and relations of care. Mainstream news coverage reflects tensions in public understandings of aggression and older adults (e.g., as a medical or criminal issue), reinforced in particular ways because of the nature of news reporting. More nuanced coverage would advance understanding of differences among settings, relationships, and types of actions, and of the need for multifaceted prevention and policy responses based on these differences.
Archaeologists have long subjected Clovis megafauna kill/scavenge sites to the highest level of scrutiny. In 1987, a Columbian mammoth (Mammuthus columbi) was found in spatial association with a small artifact assemblage in Converse County, Wyoming. However, due to the small tool assemblage, limited nature of the excavations, and questions about the security of the association between the artifacts and mammoth remains, the site was never included in summaries of human-killed/scavenged megafauna in North America. Here we present the results of four field seasons of new excavations at the La Prele Mammoth site that confirm the presence of an associated cultural occupation based on geologic context, artifact attributes, spatial distributions, protein residue analysis, and lithic microwear analysis. This new work identified a more extensive cultural occupation including the presence of multiple discrete artifact clusters in close proximity to the mammoth bone bed. This study confirms the presence of a second Clovis mammoth kill/scavenge site in Wyoming and shows the value in revisiting proposed terminal Pleistocene kill/scavenge sites.
WHILE Edward's place among the more successful of England's medieval monarchs has remained secure since the above lines were penned in the aftermath of his death in 1307, his reputation among scholars of medieval England has to some extent waxed and waned. Bishop Stubbs, the leading English medieval historian of the late nineteenth century, had no doubt of Edward's greatness; and for the ‘Whig’ school of history, his reign represented the pinnacle of English constitutional achievement in the Middle Ages (a characterisation accurately skewered by Sellar and Yeatman's chapter on Edward, headed ‘A Strong King’). Edward's work, Stubbs argued:
was crowned with the success that patience, wisdom, and faith amply deserve, and his share in the result is that of the direction of national growth and adaptation of the means and design of government to the consolidation and conscious exercise of national strength. He saw what was best for his age and his people; he led the way and kept the faith.
Edward's reputation remained high in the early twentieth century, though Frederick Tout was less forgiving of the king's autocratic tendencies than was Stubbs.5 His standing reached its zenith, however, under the admiring gaze of Maurice Powicke, who had been taught by Tout in Manchester before working alongside him there in the 1920s, though it was during his time in Oxford that he began to write extensively on the thirteenth century. Both Henry III and the Lord Edward (1947) and The Thirteenth Century (1953) saw Powicke describe Edward in glowing terms:
He lived intensely in conformity with the ideas and tendencies of his time, and found independence in applying them with vigour and precision. He was autocratic not in opposition to them but in full accordance with them … considering how busy he was, how incessant were the calls on his judgement, and how much self-seeking and conflicts of interest lay beneath the discipline of daily routine in every form of the life about him, he was a very great king.
Structural brain abnormalities have been described in autism but studies are often small and contradictory. We aimed to identify which brain regions can reliably be regarded as different in autism compared to healthy controls.
A systematic search was conducted for magnetic resonance imaging studies of regional brain size in autism. Data were extracted and combined using random effects meta-analysis. The modifying effects of age and IQ were investigated using meta-regression.
The total brain, cerebral hemispheres, cerebellum and caudate nucleus were increased in volume, whereas the corpus callosum area was reduced. There was evidence for a modifying effect of age and IQ on the cerebellar vermal lobules VI–VII and for age on the amygdala.
Autism may result from abnormalities in specific brain regions and a global lack of integration due to brain enlargement. Inconsistencies in the literature partly relate to differences in the age and IQ of study populations. Some regions may show abnormal growth trajectories.
White matter development during adolescents is crucial for a mature integration of neural networks in the brain. Autism spectrum condition (ASC), characterized by social and communication difficulties and rigid behaviour may interact with white matter development observed during adolescence. Changes in white matter development may link autistic symptoms to its genetic underpinnings and explain a 10-fold increase in susceptibility to ASC among siblings of individuals with ASC.
We used diffusion tensor imaging to study an association between age and white matter integrity measures, fractional anisotropy (FA) and mean diffusivity (MD), in adolescents with ASC, their siblings and age-matched healthy controls. Diffusion-weighted data were acquired with 64-direction protocol with 3mm slices and TR of 6600ms and tract-based spatial statistics analysis was performed.
The control subjects showed robust signs of increase in white matter integrity correlated with age. In contrast, individuals with ASC showed significantly lower negative correlation between MD and age in a broad area centred in the right superior longitudinal fasciculus (rSLF). When the three eigenvalues constituting a tensor ellipsoid were considered separately, siblings of individuals with ASC showed a diminished negative correlation between the second eigenvalue and age also centred in the rSLF.
Adolescents with ASC and their siblings experience alterations in white matter development in comparison to age-matched healthy controls, which are similar in direction yet different in scale for the two affected groups. The alterations are observed in the area associated with flexibility of behaviour and may explain both symptoms of ASC and increased susceptibility to ASC.
Validation of a biomarker-based medical product development tool or clinical test is an evidentiary process that must be tailored to the proposed use. Appropriate data and analyses are needed to demonstrate that the biomarker meets analytical and clinical performance criteria consistent with favorable benefit: risk balance.
Drug Safety Communications (DSCs) are used by the Food and Drug Administration (FDA) to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone between July 1, 2012 and June 30, 2013. Among the 594 respondents (32.7% response rate), two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited (overall median 2 correct out of 5, with men and those reporting higher educational level scoring higher [2/5 vs. 1/5, p=0.001]). Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep (70%) and seek out more information about the safety of their specific sleeping pill (59-78%). Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications.