How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases.

Macroscopic quantum effects in living systems have been studied widely in pursuit of fundamental explanations for biological energy transport and sensing. While it is known that type II endonucleases, the largest class of restriction enzymes, induce DNA double-strand breaks by attacking phosphodiester bonds, the mechanism by which simultaneous cutting is coordinated between the catalytic centers remains unclear. We propose a quantum mechanical model for collective electronic behavior in the DNA helix, where dipole-dipole oscillations are quantized through boundary conditions imposed by the enzyme. Zero-point modes of coherent oscillations would provide the energy required for double-strand breakage. Such quanta may be preserved in the presence of thermal noise by the enzyme's displacement of water surrounding the DNA recognition sequence. The enzyme thus serves as a decoherence shield. Palindromic mirror symmetry of the enzyme-DNA complex should conserve parity, because symmetric bond-breaking ceases when the symmetry of the complex is violated or when physiological parameters are perturbed from optima. Persistent correlations in DNA across longer spatial separations-a possible signature of quantum entanglement-may be explained by such a mechanism.

Turning principles into practice in Alzheimer's disease.

The prevalence of dementia is reaching epidemic proportions globally, but there remain a number of issues that prevent people with dementia, their families and caregivers, from taking control of their condition. In 2008, Alzheimer's Disease International (ADI) launched a Global Alzheimer's Disease Charter, which comprises six principles that underscore the urgency for a more ambitious approach to diagnosis, treatment and care. This review highlights some of the most important aspects and challenges of dementia diagnosis and treatment. These issues are reviewed in light of the six principles of the recent ADI Charter: promoting dementia awareness and understanding; respecting human rights; recognizing the key role of families and caregivers; providing access to health and social care; stressing the importance of optimal diagnosis and treatment; and preventing dementia through improvements in public health. The authors continue to hope that, one day, a cure for Alzheimer's disease will be found. Meanwhile, healthcare professionals need to unite in rising to the challenge of managing all cases of dementia, using the tools available to us now to work toward improved patient care.

Alcohol in moderation, premorbid intelligence and cognition in older adults: results from the Psychiatric Morbidity Survey.

AIMS: To test the hypothesis that the association previously reported between moderate alcohol use and better cognition is an artefact of confounding by (a) higher premorbid education and socioeconomic status; (b) a lifestyle of moderation (using smoking as a risk marker); and (c) decreased alcohol consumption in people with physical illnesses. METHOD: Data were analysed from people aged 60-74 years interviewed for the 2000 British National Psychiatric Morbidity Survey, representative of people living in private homes. Alcohol use information was available for 1985 (98.9%) of the eligible participants, of whom 1735 (87.4%) who drank moderately or abstained were included in the analyses. Our main outcome measures were the Alcohol Use Disorders Identification Test (AUDIT), the Telephone Interview for Cognitive Status Screen for Cognitive Impairment and the National Adult Reading Test to measure crystallised (premorbid) intelligence. Our physical health measures were the number of prescribed medications and physical illness reported, and the 12 item Short Form Health Survey's Physical Component Score. RESULTS: The relationship between current cognition and alcohol use was reduced and no longer significant after considering premorbid intelligence or physical health. In our final model, the significant predictors of current cognition among non-problem drinkers were: age (B = -0.13, -0.18 to -0.08; p<0.001) and crystallised intelligence (B = 0.14, 0.12 to 0.17; p<0.001). Smoking was not associated with cognition. CONCLUSIONS: In people who were not problem drinkers, higher alcohol intake was not associated with improved current cognition after controlling for premorbid intelligence and physical health. Our findings suggest that, despite previous suggestions, moderate alcohol consumption does not protect older people from cognitive decline.

60 years of suicide in England and Wales. A cohort study.

In a cohort analysis of suicides recorded in England and Wales from 1921 to 1980, there was no discernible trend across the younger cohorts, but there was a fall in the suicide rates of successive older cohorts over this period. The impact of period events (eg, World War II and the detoxification of domestic gas) is demonstrated in these cohorts. In addition to the period effects, there was evidence of a more prolonged cohort effect on suicide rates of the middle-aged and elderly associated with these events. Little relationship was found between early and later suicide rates within cohorts, casting doubt on the usefulness of predicting the future rates of cohorts from their early behavior.

Validity of the General Health Questionnaire (GHQ) in detecting psychiatric disturbance in amputees with phantom pain.

The 28-item General Health Questionnaire (GHQ) was validated against the PSE-derived Index of Definition in a sample of amputees with long-standing phantom and stump pain attending a Limb Fitting Centre. This form of the GHQ is a sensitive identifier of overt psychiatric disorder in this setting.

Best place of care for older people after acute and during subacute illness: a systematic review.

OBJECTIVES: To assess the evaluative research literature on the costs, quality and effectiveness of different locations of care for older patients. METHODS: A systematic review of evaluative research from 1988 using CRD4 guidelines. Twenty-five databases were searched, using processes developed specially for this review. Library OPACS, the Internet and research registers were also searched for relevant material. The final stage of the review was confined to randomised and pseudorandomised trials. Studies were selected for review by pairs of researchers working independently who then met to reach a decision. Analysis was predominantly descriptive; simple pooled odds ratios were used to explore some outcomes. RESULTS: Eighty-four papers from 45 trials were included. Firm conclusions were difficult to draw, except in relation to some outcomes for stroke units, early discharge schemes and geriatric assessment units. Few trials in this area have adequately addressed issues of patients' quality of life and costs to health services, social care providers, patients and their families. CONCLUSIONS: Despite considerable recent development of different forms of care for older patients, evidence about effectiveness and costs is weak. However, evidence is also weak for longer-standing care models. A substantial service evaluation agenda emerges from this review. This study also raises questions about the usefulness of systematic review techniques in the area of service delivery and organisation.

Multiple pain complaints in amputees.

A group of amputees complaining of longstanding phantom pain was compared with another comparable group of non-complainers. It was found that those with phantom pain made significantly more complaints of other painful conditions, both related and unrelated to the amputation; they were also more depressed. It is suggested that this association is due to a lowered pain tolerance in the group with phantom pain complaints, and that depression is one factor contributing to this lowered tolerance.

An evaluation of the multidisciplinary approach to psychiatric diagnosis in elderly people.

OBJECTIVE: To determine the accuracy of psychiatric diagnoses made by two community psychogeriatric teams operating a multidisciplinary assessment procedure. DESIGN: Comparison of team diagnosis with independent formal assessment and consensus diagnosis by research psychiatrists. SETTING: Two community psychogeriatric teams with similar operational policies in an inner London health district. SUBJECTS: 100 people aged 65-90 (70 women) newly referred to the teams. MAIN OUTCOME MEASURES: Concordance between team and research diagnoses. RESULTS: Agreement between team and research diagnoses ranged from 90% to 99% for the specific psychiatric disorders studied. There was no significant difference between medical and non-medical team members in their diagnostic performance compared with the research psychiatrists. Increased diagnostic accuracy by team members was associated with longer experience of team working, regardless of the team members' professional background. CONCLUSIONS: The multidisciplinary approach to the assessment of referrals to these community teams for the elderly is not associated with misdiagnosis of psychiatric disorder.

Attempted suicide and the lunar cycle.

An analysis of 383 cases of attempted suicide presented to the Accident and Emergency Department during 12 complete lunar cycles (one year) gave no support for an association between attempted suicide and the lunar cycle, especially the full moon. No control for weekends or holidays was made.

Study of the use of antidepressants for depression in dementia: the HTA-SADD trial--a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine.

OBJECTIVE: Depression is common in dementia, causing considerable distress and other negative impacts. Treating it is a clinical priority, but the evidence base is sparse and equivocal. This trial aimed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post randomisation compared with placebo. DESIGN: Multicentre, parallel-group, double-blind placebo-controlled randomised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up. SETTING: Nine English old-age psychiatry services. PARTICIPANTS: A pragmatic trial. Eligibility: probable or possible Alzheimer's disease (AD), depression (4+ weeks) and Cornell Scale for Depression in Dementia (CSDD) score of 8+. EXCLUSIONS: clinically too critical (e.g. suicide risk); contraindication to medication; taking antidepressants; in another trial; and having no carer. INTERVENTIONS: (1) Sertraline; (2) mirtazapine; and (3) placebo, all with normal care. Target doses: 150 mg of sertraline or 45 mg of mirtazapine daily. OUTCOME: CSDD score. Randomisation: Allocated 1 : 1 : 1 through Trials Unit, independently of trial team. Stratified block randomisation by centre, with randomly varying block sizes; computer-generated randomisation. Blinding: Double blind: medication and placebo identical for each antidepressant. Referring clinicians, research workers, participants and pharmacies were blind. Statisticians blind until analyses completed. RESULTS: Numbers randomised: 326 participants randomised (111 placebo, 107 sertraline and 108 mirtazapine). OUTCOME: Differences in CSDD at 13 weeks from an adjusted linear-mixed model: mean difference (95% CI) placebo-sertraline 1.17 (-0.23 to 2.78; p = 0.102); placebo-mirtazapine 0.01 (-1.37 to 1.38; p = 0.991); and mirtazapine-sertraline 1.16 (-0.27 to 2.60; p = 0.112). HARMS: Placebo group had fewer adverse reactions (29/111, 26%) than sertraline (46/107, 43%) or mirtazapine (44/108, 41%; p = 0.017); 39-week mortality equal, five deaths in each group. CONCLUSIONS: This is a trial with negative findings but important clinical implications. The data suggest that the antidepressants tested, given with normal care, are not clinically effective (compared with placebo) for clinically significant depression in AD. This implies a need to change current practice of antidepressants being the first-line treatment of depression in AD. From the data generated we formulated the following recommendations for future work. (1) The secondary analyses presented here suggest that there would be value in carrying out a placebo-controlled trial of the clinical effectiveness and cost-effectiveness of mirtazapine in the management of Behavioural and Psychological Symptoms of Dementia. (2) A conclusion from this study is that it remains both ethical and essential for trials of new medication for depression in dementia to have a placebo arm. (3) Further research is required to evaluate the impact that treatments for depression in people with dementia can have on their carers not only in terms of any impacts on their quality of life, but also the time they spend care-giving. (4) There is a need for research into alternative biological and psychological therapies for depression in dementia. These could include evaluations of new classes of antidepressants (such as venlafaxine) or antidementia medication (e.g. cholinesterase inhibitors). (5) Research is needed to investigate the natural history of depression in dementia in the community when patients are not referred to secondary care services. (6) Further work is needed to investigate the cost modelling results in this rich data set, investigating carer burden and possible moderators to the treatment effects. (7) There is scope for reanalysis of the primary outcome in terms of carer and participant CSDD results.

Age, sex and suicide rates within birth cohorts in England and Wales.

The relationships between suicide rates at different ages within male and female birth cohorts in England and Wales are examined. There is a sex difference in the pattern of mean correlations of within-cohort rates for various time intervals, with females showing a significant negative correlation between rates separated by 10-15 years. The full correlation matrix of age-specific rates indicates that this negative mean interval correlation is due to negative correlations between rates at age 35-44 years and rates at other ages. This suggests that the acceleration-deceleration model of suicide may be applicable to female rates, with a reduction in suicide associated with pregnancy and motherhood and a rebound increase in rates thereafter.

Nonsuicidal mortality in late-life depression.

While suicide is the most dramatic cause of premature death in depressed older persons, it is a rare event in old age. Most of the excess mortality associated with late-life depression is due to "natural causes," especially cardiovascular illness. In the past much of the premature death related to psychiatric disorders was the result of epidemics in large, overcrowded institutions, and even today institutional factors may account for some excess mortality. A recent prospective study comparing depressed patients with nondepressed controls found that neither the initial level of physical health nor social factors explained the excess mortality, but it suggested that some of the excess is due to physical causes not readily apparent or disabling. The effects of grief, tricyclic antidepressants, chronic dysphoria, smoking and alcohol abuse, and organic brain disease are considered. Evidence suggests a complex interaction between depression and physical illness (particularly cardiovascular disease) that develops throughout life. Pursuant to these findings, some questions for future research are offered.

Phobic disorders in the elderly.

Sixty confirmed cases of phobic disorder identified in an urban elderly community sample were compared with 60 controls matched pairwise for age and sex. Cases reported higher rates of specific and non-specific neurotic symptoms, and all were assigned to a diagnostic CATEGO class, compared with seven of the controls. A past history of chronic psychiatric disorder other than phobia was commoner in the cases. Most cases had more than one fear; agoraphobic main fears were predominantly of late onset and associated with moderate to severe social impairment, whereas specific main fears were associated with early onset and minimal social impairment. The onset of agoraphobic fears in old age was attributed by most cases to an episode of physical illness or other traumatic event. Increased rates of palpitations, dyspnoea, giddiness and tinnitus not attributable to anxiety were identified in the cases. Cases did not differ from the controls in socio-economic status, or in the number or quality of current intimate confiding relationships, but they reported higher rates than controls of parental loss before the age of 18 years. Cases reported higher rates of contact with general practitioners, but only one was in contact with psychiatric services at the time of interview. Cases also reported receiving more help in personal care from family members.

The concept of delirium.

The concept of delirium has a long and confusing history. This article outlines the development of ideas relating to core features of the syndrome: disturbance of consciousness, disturbance of cognition, its course and its external causation. The modern concept of delirium, and the diagnostic criteria found in current classifications are based upon a long tradition of clinical observation in younger patients, and their emphasis on positive symptoms and identifiable external causes may not be applicable to our ageing population.

Residential care for elderly people: the prevalence of cognitive impairment and behavioural problems.

AIMS: to investigate the prevalence of and interrelationship between cognitive impairment and behavioural problems in older people in residential care. SUBJECTS: all those aged 65 years and over resident on one night in any type of residential care within the Leicestershire District Health Authority. METHODS: an assessment form for each resident was completed by care staff. The assessment included demographic information and functioning (both mental and physical) during the previous week. Cognitive impairment was measured by the confusion sub-scale of the Crichton Royal Behavioural Rating Scale. RESULTS: 6079 people were enumerated in 241 establishments, including hospitals, homes and hostels provided by the National Health Service (NHS), local authority social services and private and voluntary agencies. Thirty-eight percent (2219) were moderately or severely cognitively impaired and behavioural problems were present in 11.5%, most being associated with the presence of cognitive impairment. Compared with elderly people in private residential homes, residents in local authority (part III) homes had significantly higher odds of demonstrating offensive behaviour of 1.40 (95% confidence interval 1.11-1.78) after adjustment for age, sex and cognitive impairment. No significant association between number of patients in the home and the proportion exhibiting offensive behaviour was found in any of the non-NHS facilities. CONCLUSIONS: this survey of old people in institutional care found that most of those with behavioural problems were cognitively impaired. This has implications for staff training in the management of behavioural problems in demented people.