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MODERN-DAY Cumbria is not only one of the largest counties in England, but also the most geographically hostile. The Cumbrian mountains contain the highest peaks in England, many of which are in excess of 600 m (2000 ft) in altitude. In the present day, in a temperate climate such as Britain’s, the climatic conditions above 600 m are sub-Arctic and the vegetation at this level can be considered to be tundra. The decline in temperature with altitude creates conditions which can allow snow to remain on the upper slopes of some peaks for almost one-third of the year, making conditions dangerous for human survival. The mountains are also characterised by heavy rainfall – approximately four times as much as in lower lying areas of Cumbria. Restricted sunlight hampers viable arable agriculture. It must also be remembered, however, that climate can – and does – change, and the conditions just noted are relevant to the modern-day Cumbrian mountains. The climate was at times somewhat milder in the past – old arable fields can be identified on certain slopes, while the course of the Roman road ‘High Street’ reached in places an altitude of over 760 m (2,500 ft). Further afield, arable agriculture was possible on the higher slopes of Lammermuir in Scotland in the middle ages, while short-lived farmsteads were established as high as 385 m (just over 1,250 ft) on the Rossendale moors in southern Lancashire during the nineteenth century. But although climate may change for better or worse, certain other environmental factors will not. Temperature is always lower at higher altitudes and wind speeds are far higher on the upper slopes of peaks than they are lower down in valleys. The ascent gradient of upland areas does not change either and most ascents in the Cumbrian mountains can be quite debilitating. It is thus by no means surprising that there are but a handful of routes through the Cumbrian mountains and Shap Fells, none of which are straightforward and all of which are prone to the vagaries of poor weather conditions. Even today in contemporary Britain, Cumbria's administrative geography is influenced by the mountains, which serve as a centrifugal force in the far north-west of England. It is a land where – to use Braudel's phrase – ‘mountains come first’.
Research has shown that 20–30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders.
To estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD.
We conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16–25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression.
In the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI −2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm.
ADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.
This chapter explores the influence of British Romanticism – its emphasis on the splendors of nature, the wonder of the sublime, the rehabilitation of outcasts, and, above all, the lure of revolutionary change – on Carl Sandburg’s 1916 collection, Chicago Poems. The chapter concludes that Chicago Poems, a book many associate with the advent of modernism, looks instead like the vestiges of Romanticism.
The objective of this study was to evaluate the effect of feeding Bacillus altitudinis spores to sows and/or offspring on growth and health indicators. On day (D) 100 of gestation, twenty-four sows were selected and grouped as: control (CON), fed with a standard diet; and probiotic (PRO), fed the standard diet supplemented with B. altitudinis WIT588 spores from D100 of gestation until weaning. Offspring (n 144) from each of the two sow treatments were assigned to either a CON (no probiotic) or PRO (B. altitudinis-supplemented) treatment for 28 d post-weaning (pw), resulting in four treatment groups: (1) CON/CON, non-probiotic-supplemented sow/non-probiotic-supplemented piglet; (2) CON/PRO, non-probiotic-supplemented sow/probiotic-supplemented piglet; (3) PRO/CON, probiotic-supplemented sow/non-probiotic-supplemented piglet and (4) PRO/PRO, probiotic-supplemented sow/probiotic-supplemented piglet. B. altitudinis WIT588 was detected in the faeces of probiotic-supplemented sows and their piglets, and in the faeces and intestine of probiotic-supplemented piglets. Colostrum from PRO sows had higher total solids (P = 0·02), protein (P = 0·04) and true protein (P = 0·05), and lower lactose (P < 0·01) than colostrum from CON sows. Maternal treatment improved offspring feed conversion ratio at D0–14 pw (P < 0·001) and increased offspring body weight at D105 and D127 pw (P = 0·01), carcass weight (P = 0·05) and kill-out percentage (P < 0·01). It also increased small intestinal absorptive capacity and impacted the haematological profile of sows and progeny. There was little impact of pw treatment on any of the parameters measured. Overall, the lifetime growth benefits in the offspring of B. altitudinis-supplemented sows offer considerable economic advantages for pig producers in search of alternatives to in-feed antibiotics/zinc oxide.
Iron-rich meteorites are significantly underrepresented in collection statistics from Antarctica. This has led to a hypothesis that there is a sparse layer of iron-rich meteorites hidden below the surface of the ice, thereby explaining the apparent shortfall. As standard Antarctic meteorite collecting techniques rely upon a visual surface search approach, the need has thus arisen to develop a system that can detect iron objects under a few tens of centimetres of ice, where the expected number density is of the order one per square kilometre. To help answer this hypothesis, a large-scale pulse induction metal detector array has been constructed for deployment in Antarctica. The metal detector array is 6 m wide, able to travel at 15 km h-1 and can scan 1 km2 in ~11 hours. This paper details the construction of the metal detector system with respect to design criteria, notably the ruggedization of the system for Antarctic deployment. Some preliminary results from UK and Antarctic testing are presented. We show that the system performs as specified and should reach the pre-agreed target of the detection of a 100 g iron meteorite at 300 mm when deployed in Antarctica.
Callous-unemotional (CU) traits are early-emerging personality features characterized by deficits in empathy, concern for others, and remorse following social transgressions. One of the interpersonal deficits most consistently associated with CU traits is impaired behavioral and neurophysiological responsiveness to fearful facial expressions. However, the facial expression paradigms traditionally employed in neuroimaging are often ambiguous with respect to the nature of threat (i.e., is the perceiver the threat, or is something else in the environment?). In the present study, 30 adolescents with varying CU traits viewed fearful facial expressions cued to three different contexts (“afraid for you,” “afraid of you,” “afraid for self”) while undergoing functional magnetic resonance imaging (fMRI). Univariate analyses found that mean right amygdala activity during the “afraid for self” context was negatively associated with CU traits. With the goal of disentangling idiosyncratic stimulus-driven neural responses, we employed intersubject representational similarity analysis to link intersubject similarities in multivoxel neural response patterns to contextualized fearful expressions with differential intersubject models of CU traits. Among low-CU adolescents, neural response patterns while viewing fearful faces were most consistently similar early in the visual processing stream and among regions implicated in affective responding, but were more idiosyncratic as emotional face information moved up the cortical processing hierarchy. By contrast, high-CU adolescents’ neural response patterns consistently aligned along the entire cortical hierarchy (but diverged among low-CU youths). Observed patterns varied across contexts, suggesting that interpretations of fearful expressions depend to an extent on neural response patterns and are further shaped by levels of CU traits.
The Late Formative period immediately precedes the emergence of Tiwanaku, one of the earliest South American states, yet it is one of the most poorly understood periods in the southern Lake Titicaca Basin (Bolivia). In this article, we refine the ceramic chronology of this period with large sets of dates from eight sites, focusing on temporal inflection points in decorated ceramic styles. These points, estimated here by Bayesian models, index specific moments of change: (1) cal AD 120 (60–170, 95% probability): the first deposition of Kalasasaya red-rimmed and zonally incised styles; (2) cal AD 240 (190–340, 95% probability): a tentative estimate of the final deposition of Kalasasaya zonally incised vessels; (3) cal AD 420 (380–470, 95% probability): the final deposition of Kalasasaya red-rimmed vessels; and (4) cal AD 590 (500–660, 95% probability): the first deposition of Tiwanaku Redwares. These four modeled boundaries anchor an updated Late Formative chronology, which includes the Initial Late Formative phase, a newly identified decorative hiatus between the Middle and Late Formative periods. The models place Qeya and transitional vessels between inflection points 3 and 4 based on regionally consistent stratigraphic sequences. This more precise chronology will enable researchers to explore the trajectories of other contemporary shifts during this crucial period in Lake Titicaca Basin's prehistory.
The emergence of callous unemotional (CU) traits, and associated externalizing behaviors, is believed to reflect underlying dysfunction in the amygdala. Studies of adults with CU traits or psychopathy have linked characteristic patterns of amygdala dysfunction to reduced amygdala volume, but studies in youths have not thus far found evidence of similar amygdala volume reductions. The current study examined the association between CU traits and amygdala volume by modeling CU traits and externalizing behavior as independent continuous variables, and explored the relative contributions of callous, uncaring, and unemotional traits.
CU traits and externalizing behavior problems were assessed in 148 youths using the Inventory of Callous Unemotional Traits (ICU) and the Child Behavior Checklist (CBCL). For a subset of participants (n = 93), high-resolution T1-weighted images were collected and volume estimates for the amygdala were extracted.
Analyses revealed that CU traits were associated with increased externalizing behaviors and decreased bilateral amygdala volume. These results were driven by the callous and uncaring sub-factors of CU traits, with unemotional traits unrelated to either externalizing behaviors or amygdala volume. Results persisted after accounting for covariation between CU traits and externalizing behaviors. Bootstrap mediation analyses indicated that CU traits mediated the relationship between reduced amygdala volume and externalizing severity.
These findings provide evidence that callous-uncaring traits account for reduced amygdala volume among youths with conduct problems. These findings provide a framework for further investigation of abnormal amygdala development as a key causal pathway for the development of callous-uncaring traits and conduct problems.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Callous–unemotional (CU) traits characterize a subgroup of youths with conduct problems who exhibit low empathy, fearlessness, and elevated externalizing behaviors. The current study examines the role of aberrant amygdala activity and functional connectivity during a socioemotional judgment task in youths with CU traits, and links these deficits to externalizing behaviors. Functional magnetic resonance imaging was used to compare neural responses in 18 healthy youths and 30 youths with conduct problems and varying levels of CU traits as they evaluated the acceptability of causing another person to experience each of several emotions, including fear. Neuroimaging analyses examined blood oxygenation level dependent responses and task-dependent functional connectivity. High-CU youths exhibited left amygdala hypoactivation relative to healthy controls and low-CU youths primarily during evaluations of causing others fear. CU traits moderated the relationship between externalizing behavior and both amygdala activity and patterns of functional connectivity. The present data suggest that CU youths' aberrant amygdala activity and connectivity affect how they make judgments about the acceptability of causing others emotional distress, and that these aberrations represent risk factors for externalizing behaviors like rule breaking and aggression. These findings suggest that reducing externalizing behaviors in high-CU youths may require interventions that influence affective sensitivity.
Symptoms of anxiety relating to Parkinson's disease (PD) occur commonly and include symptomatology associated with motor disability and complications arising from PD medication. However, there have been relatively few attempts to profile such disease-specific anxiety symptoms in PD. Consequently, anxiety in PD is underdiagnosed and undertreated. The present study characterizes PD-related anxiety symptoms to assist with the more accurate assessment and treatment of anxiety in PD.
Ninety non-demented PD patients underwent a semi-structured diagnostic assessment targeting anxiety symptoms using relevant sections of the Mini International Neuropsychiatric Interview (MINI-plus). In addition, they were assessed for the presence of 30 PD-related anxiety symptoms derived from the literature, the clinical experience of an expert panel and the PD Anxiety-Motor Complications Questionnaire (PDAMCQ). The onset of anxiety in relation to the diagnosis of PD was determined.
Frequent (>25%) PD-specific anxiety symptoms included distress, worry, fear, agitation, embarrassment, and social withdrawal due to motor symptoms and PD medication complications, and were experienced more commonly in patients meeting DSM-IV criteria for an anxiety disorder. The onset of common anxiety disorders was observed equally before and after a diagnosis of PD. Patients in a residual group of Anxiety Not Otherwise Specified had an onset of anxiety after a diagnosis of PD.
Careful characterization of PD-specific anxiety symptomatology provides a basis for conceptualizing anxiety and assists with the development of a new PD-specific measure to accurately assess anxiety in PD.
The island of Cyprus was a major producer of copper and stood at the heart of east Mediterranean trade networks during the Late Bronze Age. It may also have been the source of the Red Lustrous Wheelmade Ware that has been found in mortuary contexts in Egypt and the Levant, and in Hittite temple assemblages in Anatolia. Neutron Activation Analysis (NAA) has enabled the source area of this special ceramic to be located in a geologically highly localised and geochemically distinctive area of western Cyprus. This discovery offers a new perspective on the spatial organisation of Cypriot economies in the production and exchange of elite goods around the eastern Mediterranean at this time.
Autism spectrum disorders (ASDs) are characterized by social impairments, including inappropriate responses to affective stimuli and nonverbal cues, which may extend to poor face-emotion recognition. However, the results of empirical studies of face-emotion recognition in individuals with ASD have yielded inconsistent findings that occlude understanding the role of face-emotion recognition deficits in the development of ASD. The goal of this meta-analysis was to address three as-yet unanswered questions. Are ASDs associated with consistent face-emotion recognition deficits? Do deficits generalize across multiple emotional expressions or are they limited to specific emotions? Do age or cognitive intelligence affect the magnitude of identified deficits? The results indicate that ASDs are associated with face-emotion recognition deficits across multiple expressions and that the magnitude of these deficits increases with age and cannot be accounted for by intelligence. These findings suggest that, whereas neurodevelopmental processes and social experience produce improvements in general face-emotion recognition abilities over time during typical development, children with ASD may experience disruptions in these processes, which suggested distributed functional impairment in the neural architecture that subserves face-emotion processing, an effect with downstream developmental consequences.