Novel high-resolution characterization of ancient DNA reveals C > U-type base modification events as the sole cause of post mortem miscoding lesions

Ancient DNA (aDNA) research has long depended on the power of PCR to amplify trace amounts of surviving genetic material from preserved specimens. While PCR permits specific loci to be targeted and amplified, in many ways it can be intrinsically unsuited to damaged and degraded aDNA templates. PCR amplification of aDNA can produce highly-skewed distributions with significant contributions from miscoding lesion damage and non-authentic sequence artefacts. As traditional PCR-based approaches have been unable to fully resolve the molecular nature of aDNA damage over many years, we have developed a novel single primer extension (SPEX)-based approach to generate more accurate sequence information. SPEX targets selected template strands at defined loci and can generate a quantifiable redundancy of coverage; providing new insights into the molecular nature of aDNA damage and fragmentation. SPEX sequence data reveals inherent limitations in both traditional and metagenomic PCR-based approaches to aDNA, which can make current damage analyses and correct genotyping of ancient specimens problematic. In contrast to previous aDNA studies, SPEX provides strong quantitative evidence that C U-type base modifications are the sole cause of authentic endogenous damage-derived miscoding lesions. This new approach could allow ancient specimens to be genotyped with unprecedented accuracy.

Acute stroke predisposes to oral gram-negative bacilli - a cause of aspiration pneumonia?

Objectives: To assess any change in the oral flora in the mouths of stroke patients during the acute and rehabilitation phases and to determine whether this is related to episodes of aspiration pneumonia and clinical outcome. Materials and Methods: This observational study was carried out in hospital wards in a University teaching hospital. The subjects were patients immediately post-stroke and during the rehabilitation period, acute admissions and a group of healthy volunteers. An assessment of dentition and swallow in the presence or absence of oral aerobic gram-negative bacilli (AGNB) was correlated. Results: Of the acute stroke patients 52% had an unsafe swallow. AGNB carriage was documented in 34% of the acute stroke group. Of the 11 patients who died 55% had AGNB, 73% had an unsafe swallow and 36% had a combination of both. Conclusion: AGNB is a common finding in acute stroke patients. It is not a consequence of age or acute hospitalisation and is associated with an unsafe swallow and a higher mortality. Copyright (C) 2003 S. Karger AG, Basel.

Heat-inactivated peroxidases and the role of calcium abstraction as a cause of their enhanced lipid oxidation activity: potential effects on the flavour quality of heat-processed vegetables

Cationic swede and anionic turnip peroxidases were partially purified by ion-exchange and gel-filtration chromatography, respectively. Heat treatment of these enzymes and of a commercial high purity horseradish peroxidase (HRP) caused a loss of enzyme activity and a corresponding increase in linoleic acid hydroperoxide formation activity. The hydroperoxide levels in model systems increased only in the early stages of the oxidation reaction and then declined as degradation became more significant. The presence of a dialysed blend of cooked swede markedly lowered the hydroperoxide level formed. Analysis of volatile compounds formed showed that hexanal predominated in a buffer system and in a blend of cooked turnip. In dialysed blends of cooked swede, hexanol was the primary volatile compound generated. After inactivation under mild conditions in the presence of EDTA, the peroxidases showed hydroperoxide formation activity and patterns of volatile compounds from linoleic acid that were similar to those found on heat-inactivation. This suggested that calcium abstraction from the peroxidases was critical for the enhancement of lipid oxidation activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

Which drugs cause preventable admissions to hospital? A systematic review

Aim: Previous systematic reviews have found that drug-related morbidity accounts for 4.3% of preventable hospital admissions. None, however, has identified the drugs most commonly responsible for preventable hospital admissions. The aims of this study were to estimate the percentage of preventable drug-related hospital admissions, the most common drug causes of preventable hospital admissions and the most common underlying causes of preventable drug-related admissions. Methods: Bibliographic databases and reference lists from eligible articles and study authors were the sources for data. Seventeen prospective observational studies reporting the proportion of preventable drug-related hospital admissions, causative drugs and/or the underlying causes of hospital admissions were selected. Included studies used multiple reviewers and/or explicit criteria to assess causality and preventability of hospital admissions. Two investigators abstracted data from all included studies using a purpose-made data extraction form. Results: From 13 papers the median percentage of preventable drug-related admissions to hospital was 3.7% (range 1.4-15.4). From nine papers the majority (51%) of preventable drug-related admissions involved either antiplatelets (16%), diuretics (16%), nonsteroidal anti-inflammatory drugs (11%) or anticoagulants (8%). From five studies the median proportion of preventable drug-related admissions associated with prescribing problems was 30.6% (range 11.1-41.8), with adherence problems 33.3% (range 20.9-41.7) and with monitoring problems 22.2% (range 0-31.3). Conclusions: Four groups of drugs account for more than 50% of the drug groups associated with preventable drug-related hospital admissions. Concentrating interventions on these drug groups could reduce appreciably the number of preventable drug-related admissions to hospital from primary care.

fMRI delineation of working memory for emotional prosody in the brain: commonalities with the lexico-semantic emotion network

Decoding emotional prosody is crucial for successful social interactions, and continuous monitoring of emotional intent via prosody requires working memory. It has been proposed by Ross and others that emotional prosody cognitions in the right hemisphere are organized in an analogous fashion to propositional language functions in the left hemisphere. This study aimed to test the applicability of this model in the context of prefrontal cortex working memory functions. BOLD response data were therefore collected during performance of two emotional working memory tasks by participants undergoing fMRI. In the prosody task, participants identified the emotion conveyed in pre-recorded sentences, and working memory load was manipulated in the style of an N-back task. In the matched lexico-semantic task, participants identified the emotion conveyed by sentence content. Block-design neuroimaging data were analyzed parametrically with SPM5. At first, working memory for emotional prosody appeared to be right-lateralized in the PFC, however, further analyses revealed that it shared much bilateral prefrontal functional neuroanatomy with working memory for lexico-semantic emotion. Supplementary separate analyses of males and females suggested that these language functions were less bilateral in females, but their inclusion did not alter the direction of laterality. It is concluded that Ross et al.'s model is not applicable to prefrontal cortex working memory functions, that evidence that working memory cannot be subdivided in prefrontal cortex according to material type is increased, and that incidental working memory demands may explain the frontal lobe involvement in emotional prosody comprehension as revealed by neuroimaging studies. (c) 2007 Elsevier Inc. All rights reserved.

Age-related decline in the ability to decode emotional prosody: primary or secondary phenomenon?

Emotion processing deficits can cause catastrophic damage to a person's ability to interact socially. While it is known that older adults have difficulty identifying facial emotions, it is still not clear whether this difficulty extends to identification of the emotion conveyed by prosody. This study investigated whether the ability of older adults to decode emotional prosody falls below that of young adults after controlling for loss of hearing sensitivity and key features of cognitive ageing. Apart from frontal lobe load, only verbal IQ was associated with the age-related reduction in performance displayed by older participants, but a notable deficit existed after controlling for its effects. It is concluded that older adults may indeed have difficulty deducing the emotion conveyed by prosody, and that while this difficulty can be exaggerated by some aspects of cognitive ageing, it is primary in origin.

Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise

Recent brain imaging studies using functional magnetic resonance imaging (fMRI) have implicated insula and anterior cingulate cortices in the empathic response to another's pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices) during meditation (versus rest). During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ), and right posterior superior temporal sulcus (pSTS) in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in response to emotional stimuli.

The perception of emotion from body movement in point-light displays of interpersonal dialogue

We examined whether it is possible to identify the emotional content of behaviour from point-light displays where pairs of actors are engaged in interpersonal communication. These actors displayed a series of emotions, which included sadness, anger, joy, disgust, fear, and romantic love. In experiment 1, subjects viewed brief clips of these point-light displays presented the right way up and upside down. In experiment 2, the importance of the interaction between the two figures in the recognition of emotion was examined. Subjects were shown upright versions of (i) the original pairs (dyads), (ii) a single actor (monad), and (iii) a dyad comprising a single actor and his/her mirror image (reflected dyad). In each experiment, the subjects rated the emotional content of the displays by moving a slider along a horizontal scale. All of the emotions received a rating for every clip. In experiment 1, when the displays were upright, the correct emotions were identified in each case except disgust; but, when the displays were inverted, performance was significantly diminished for some ernotions. In experiment 2, the recognition of love and joy was impaired by the absence of the acting partner, and the recognition of sadness, joy, and fear was impaired in the non-veridical (mirror image) displays. These findings both support and extend previous research by showing that biological motion is sufficient for the perception of emotion, although inversion affects performance. Moreover, emotion perception from biological motion can be affected by the veridical or non-veridical social context within the displays.

On the nature and cause of Specific Language Impairment: a view from sentence processing and infant research

This paper addresses the nature and cause of Specific Language Impairment (SLI) by reviewing recent research in sentence processing of children with SLI compared to typically developing (TD) children and research in infant speech perception. These studies have revealed that children with SLI are sensitive to syntactic, semantic, and real-world information, but do not show sensitivity to grammatical morphemes with low phonetic saliency, and they show longer reaction times than age-matched controls. TD children from the age of 4 show trace reactivation, but some children with SLI fail to show this effect, which resembles the pattern of adults and TD children with low working memory. Finally, findings from the German Language Development (GLAD) Project have revealed that a group of children at risk for SLI had a history of an auditory delay and impaired processing of prosodic information in the first months of their life, which is not detectable later in life. Although this is a single project that needs to be replicated with a larger group of children, it provides preliminary support for accounts of SLI which make an explicit link between an early deficit in the processing of phonology and later language deficits, and the Computational Complexity Hypothesis that argues that the language deficit in children with SLI lies in difficulties integrating different types of information at the interfaces.

The experience of immediacy: emotion and enlistment in fact-based theatre

This article discusses emotion as a strategy of political agency in post-Thatcherite documentary theatre. The 1990s saw a renaissance in theatre writing based in directness and immediacy but based in two quite different forms of drama, In-Yer-Face theatre and fact-based drama. There are clear distinctions between these forms: the new brutalist writing was aggressively provocative; documentary theatre engaged the audience by revealing an urgent truth. Both claimed a kind of realism that confronted actuality, be that of situation or experience, through forms of theatre that cultivated emotional engagement. In-Yer-Face theatre used emotional shock to penetrate the numb cynicism that its creators perceived. Documentary theatre used observation and the cultivation of sympathy to enlist its audience in a shared understanding of what was hidden, not understood or not noticed. The article analyses the functioning of emotional enlistment to engage the audience politically in two examples of documentary theatre, Black Watch and Guantanamo