Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

Background: The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy.\ud Design/Methods: We will conduct a non-inferiority andomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm,participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely.This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation.\ud Outcomes/Follow-up: The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal\ud symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day

Breast cancer histological classification: agreement between the Office for National Statistics and the National Health Service Breast Screening Programme

INTRODUCTION: Epidemiological studies rely on data supplied by central cancer registration sources to be timely, accurate and complete. Validation studies of such data at a national level are limited. Data collected for the Million Women Study was used to compare the level of agreement between the Office for National Statistics (ONS) and the National Health Service Breast Screening Programme (NHSBSP) in the recording of incident screen-detected breast cancer histology between 1996 and 2001. METHODS: 1.3 million women aged 50 to 64 years were recruited into the Million Women Study cohort via the NHSBSP. Incident screen-detected breast cancer histologies were notified separately by the ONS and NHSBSP. ICD-10 and ICD-02 ONS codes and NHSBSP histology data were similarly coded to allow for comparison in terms of cancer invasiveness and morphology. The statistical outcome measures are percentage agreement and the kappa statistic. RESULTS: A total of 5,886 incident screen-detected breast cancers were available for analysis. Of the 5,886 screen-detected cancers reported by the ONS and NHSBSP, 5,684 (96.6%, κ = 0.9) agreed in terms of the degree of invasiveness. Of the 5,458 cancers that had been assigned a specific morphology code, there was exact agreement between the ONS and the NHSBSP in 4,922 cases (90.2%, κ = 0.8). CONCLUSION: There is an excellent level of agreement between the ONS and NHSBSP in the recording of the histology of screen-detected breast cancer. From these results it is not possible to comment on which source of data is the more or less accurate, although the differences are very small

An endoscopic modification of the simultaneous ‘above and below’ approach to large pituitary adenomas

Surgical resections of large-to-giant pituitary adenomas (PA) are technically challenging procedures. Tumors with a fibrous consistency or ‘hour-glass’ configurations are particularly difficult to remove completely and safely through the transsphenoidal route alone. Although the transcranial approach can facilitate the removal of a large suprasellar mass, it may be associated with significant bleeding within the intradural space. A simultaneous microscopic transcranial and transsphenoidal approach has been described as an alternative surgical strategy. We have further modified this ‘above and below’ approach by adopting endoscopic techniques for the transsphenoidal part of the procedure. This modified approach has the advantages of requiring only one operating microscope, and permitting freer maneuvers and easier orientation for both surgical teams. We present two patients successfully treated with this approach. Complete tumor removal was achieved and both patients achieved satisfactory functional recovery

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Evolutionary Breakpoints in the Gibbon Suggest Association between Cytosine Methylation and Karyotype Evolution

Gibbon species have accumulated an unusually high number of chromosomal changes since diverging from the common hominoid ancestor 15–18 million years ago. The cause of this increased rate of chromosomal rearrangements is not known, nor is it known if genome architecture has a role. To address this question, we analyzed sequences spanning 57 breaks of synteny between northern white-cheeked gibbons (Nomascus l. leucogenys) and humans. We find that the breakpoint regions are enriched in segmental duplications and repeats, with Alu elements being the most abundant. Alus located near the gibbon breakpoints (<150 bp) have a higher CpG content than other Alus. Bisulphite allelic sequencing reveals that these gibbon Alus have a lower average density of methylated cytosine that their human orthologues. The finding of higher CpG content and lower average CpG methylation suggests that the gibbon Alu elements are epigenetically distinct from their human orthologues. The association between undermethylation and chromosomal rearrangement in gibbons suggests a correlation between epigenetic state and structural genome variation in evolution

Symmetric Sensorimotor Somatotopy

BACKGROUND: Functional imaging has recently been used to investigate detailed somatosensory organization in human cortex. Such studies frequently assume that human cortical areas are only identifiable insofar as they resemble those measured invasively in monkeys. This is true despite the electrophysiological basis of the latter recordings, which are typically extracellular recordings of action potentials from a restricted sample of cells. METHODOLOGY/PRINCIPAL FINDINGS: Using high-resolution functional magnetic resonance imaging in human subjects, we found a widely distributed cortical response in both primary somatosensory and motor cortex upon pneumatic stimulation of the hairless surface of the thumb, index and ring fingers. Though not organized in a discrete somatotopic fashion, the population activity in response to thumb and index finger stimulation indicated a disproportionate response to fingertip stimulation, and one that was modulated by stimulation direction. Furthermore, the activation was structured with a line of symmetry through the central sulcus reflecting inputs both to primary somatosensory cortex and, precentrally, to primary motor cortex. CONCLUSIONS/SIGNIFICANCE: In considering functional activation that is not somatotopically or anatomically restricted as in monkey electrophysiology studies, our methodology reveals finger-related activation that is not organized in a simple somatotopic manner but is nevertheless as structured as it is widespread. Our findings suggest a striking functional mirroring in cortical areas conventionally ascribed either an input or an output somatotopic function

Reported frequency of physical activity in a large epidemiological study: relationship to specific activities and repeatability over time

<p>Abstract</p> <p>Background</p> <p>How overall physical activity relates to specific activities and how reported activity changes over time may influence interpretation of observed associations between physical activity and health. We examine the relationships between various physical activities self-reported at different times in a large cohort study of middle-aged UK women.</p> <p>Methods</p> <p>At recruitment, Million Women Study participants completed a baseline questionnaire including questions on frequency of strenuous and of any physical activity. About 3 years later 589,896 women also completed a follow-up questionnaire reporting the hours they spent on a range of specific activities. Time spent on each activity was used to estimate the associated excess metabolic equivalent hours (MET-hours) and this value was compared across categories of physical activity reported at recruitment. Additionally, 18,655 women completed the baseline questionnaire twice, at intervals of up to 4 years; repeatability over time was assessed using the weighted kappa coefficient (κ_weighted) and absolute percentage agreement.</p> <p>Results</p> <p>The average number of hours per week women reported doing specific activities was 14.0 for housework, 4.5 for walking, 3.0 for gardening, 0.2 for cycling, and 1.4 for all strenuous activity. Time spent and the estimated excess MET-hours associated with each activity increased with increasing frequency of any or strenuous physical activity reported at baseline (tests for trend, P < 0.003), although the associations for housework were by far the weakest (Spearman correlations, 0.01 and -0.03 respectively for housework, and 0.11-0.37 for all other activities). Repeatability of responses to physical activity questions on the baseline questionnaire declined significantly over time. For strenuous activity, absolute agreement was 64% (κ_weighted= 0.71) for questionnaires administered less than 6 months apart, and 52% (κ_weighted= 0.51) for questionnaires more than 2 years apart. Corresponding values for any physical activity were 57% (κ_weighted= 0.67) and 47% (κ_weighted= 0.58).</p> <p>Conclusions</p> <p>In this cohort, responses to simple questions on the frequency of any physical activity and of strenuous activity asked at baseline were associated with hours spent on specific activities and the associated estimated excess MET-hours expended, reported 3 years later. The weakest associations were with housework. Agreement for identical questions asked on two occasions about the frequency of physical activity decreased over time.</p

Estimated pre-morbid IQ effects on cognitive and functional outcomes in Alzheimer disease: a longitudinal study in a treated cohort

Abstract Background Cognitive reserve is thought to influence the degree of neuropathology needed for diagnosis of Alzheimer disease (AD). Cognitive reserve can be operationally defined as the hypothesized capacity of the mature adult brain to sustain the effects of disease or injury without manifesting clinical symptoms of AD, but sufficient to cause clinical dementia in an individual possessing less cognitive reserve. Its effect on the subsequent course of AD is less clear. Pre-morbid IQ is a useful measure of cognitive reserve. Methods We studied 659 consecutive patients with AD at a tertiary referral memory clinic. Patients were assessed on six cognitive tests at baseline. Activities of Daily Living (ADL) were measured on the Instrumental Activities of Daily Living (IADL) scale and Physical Self-Maintenance Scale (PSMS). The National Adult Reading Test (NART) was used to estimate pre-morbid IQ. Patients were followed up after starting a cholinesterase inhibitor over 78 weeks. Mixed general linear models estimated the effects of NART on cognition and ADL. Results Three hundred and fifty-five patients had NART scored with a mean estimated pre-morbid IQ of 104.7 (standard deviation 18.5). NART increased overall cognitive ability by 2.7% for every 10 IQ points (p Conclusion Our data support the hypothesis that cognitive reserve continues to have a limited influence on cognition after AD has been diagnosed and thus, indirectly, has an impact on ADL.</p