bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring immune selection
Authors: CONWAY D. J. , POLLEY S. D.
Published: August 2008

Immune responses that kill pathogens or reduce their reproductive rate are generally important in protecting hosts from infection and disease. Pathogens that escape the full impact of such responses will survive, and any heritable genetic basis of this evasion will be selected. Due to the memory component of vertebrate immune responses, pathogens with rare alleles of a target antigen can have an advantage over those with common alleles, leading to the maintenance of a polymorphism. At the genetic level, there ought to be detectable signatures of balancing selection in the genes encoding these antigens. Here, methods for identifying these selective signatures are reviewed. Their practical utility for identifying which antigens are targets of protective immune responses is discussed.
A perspective on clonal phenotypic (antigenic) variation in protozoan parasites
Authors: TURNER C. M. R.
Published: August 2008

Intra-clonal phenotypic (antigenic) variation is used by many pathogens to evade the consequences of immune-mediated killing by mammalian hosts. In this substantially theoretical article, I emphasise that antigenic variation (sensu stricto) involves no change in genotype; its importance as a mechanism for promoting pathogen transmission and its polyphyletic origin. From a functional perspective, antigenic variation is constrained by the requirement to meet five conditions. These are: capability to express several antigens against which functional immunity predominates; capability to interact with the environment; mutually exclusive expression of variable antigens in each cell within an infection; mutually exclusive expression in the within-host pathogen population and the capability for population growth within a host. Meeting these conditions leads to chronicity of infection and high rates of hierarchical and reversible switching of expression between variable antigens. The organisation of hierarchical expression is discussed in some detail.
Egg-laying patterns and in vivo egg production in the monogenean parasites Heteraxine heterocerca and Benedenia seriolae from Japanese yellowtail Seriola quinqueradiata
Authors: MOONEY A. J. , ERNST I. , WHITTINGTON I. D.
Published: August 2008

Egg-laying patterns and egg production in Heteraxine heterocerca from the gills and Benedenia seriolae from the skin of Japanese yellowtail Seriola quinqueradiata in Japan were investigated in vivo. Eggs were collected every 3 h from sexually mature H. heterocerca and B. seriolae infecting 3 S. quinqueradiata kept individually over 3 consecutive days and exposed to alternating periods of illumination and darkness (LD 12:12; light on 06.00, light off 18.00) and maintained at 23·8±0·1°C and 35 ppt salinity. A well-defined egg-laying rhythm was demonstrated for H. heterocerca while B. seriolae was shown to release eggs continuously. A total of 114 000 H. heterocerca eggs was collected and of these, 45·4 (42·5–49·9)% were collected during the first 3 h period following dark at 18.00 h. A total of 662 857 B. seriolae eggs was collected and these were distributed over each 3 h period ranging from 11·1 to 14·1% of the daily egg output. All eggs extracted from the uterus of each H. heterocerca were joined together forming an ‘egg-string’. The contrasting egg-laying patterns of H. heterocerca and B. seriolae suggest that each species makes use of a different infection strategy to infect the same host species, S. quinqueradiata.
Effects of laboratory culture on compatibility between snails and schistosomes
Authors: THERON A. , COUSTAU C. , ROGNON A. , GOURBIÈRE S. , BLOUIN M. S.
Published: August 2008

The genetic control of compatibility between laboratory strains of schistosomes and their snail hosts has been studied intensively since the 1970s. These studies show (1) a bewildering array of genotype-by-genotype interactions – compatibility between one pair of strains rarely predicts compatibility with other strains, and (2) evidence for a variety of (sometimes conflicting) genetic mechanisms. Why do we observe such variable and conflicting results? One possibility is that it is partly an artifact of the use of laboratory strains that have been in culture for many years and are often inbred. Here we show that results of compatibility trials between snails and schistosomes – all derived from the same natural population – depend very much on whether one uses laboratory-cultured or field-collected individuals. Explanations include environmental effects of the lab on either host or parasite, and genetic changes in either host or parasite during laboratory culture. One intriguing possibility is that genetic bottlenecks during laboratory culture cause the random fixation of alleles at highly polymorphic loci that control the matched/mismatched status of hosts and parasites. We show that a simple model of phenotype matching could produce dose response curves that look very similar to empirical observations. Such a model would explain much of the genotype-by-genotype interaction in compatibility observed among strains.
Political Desire and the Idea of Murder in Machiavelli's The Prince
Authors: Tarlton Charles D.
Published: August 2008

Machiavelli's much advertised science of politics turns out, in the long run, to falter. Machiavelli's various stratagems for controlling political outcomes are workable a small percentage of the time at best. Unpredictability works continually against the theory of practical action. A large part of Machiavelli's adaptation to this deficiency is to turn at many crucial moments, to the unambiguous and startling clarity of murder as a political instrument. It is this central position of murder that helps to account for worrying guiltiness that sticks to The Prince despite many years of efforts to soften the book's message. In the final analysis, one might even suggest that a kind of erotic fascination lurks within the book's texture of murder.
Fame as the Forgotten Philosopher: Meditations on the Headstone of Adam Ferguson
Authors: Sorensen Roy
Published: August 2008

An ill-informed reading of Adam Ferguson's epitaph has given me an idea for securing posthumous recognition. Consider philosophers in the year 2201 who read my epitaph: ‘Here lies Roy Sorensen who will be long remembered for his paradoxes’. If these future scholars remember me, then well and good. If they do not remember me, my epitaph will appear to be rendered false by their failure to recall me. Suppose the poignancy of this self-defeat leads my epitaph to be widely repeated. I thereby acquire ignominy as the forgotten philosopher. But wait! Eventually someone will notice that no one can remember that Roy Sorensen is forgotten. For if someone did remember that Roy Sorensen is forgotten, then he would be forgotten—not remembered. After all, memory implies truth. Thus the self-defeating aspect of my epitaph is itself self-defeating! The happy ending is that my epitaph becomes a self-fulfilling prophesy by a curious kind of double-negation.
A pilot study of cognitive therapy in bipolar disorders
Authors: SCOTT J. , GARLAND A. , MOORHEAD S.
Published: August 2008

Background. The efficacy and effectiveness of cognitive therapy (CT) is well established for unipolar disorders, but little is known about its utility in bipolar disorders. This study aimed to explore the feasibility and efficacy of using CT as an adjunct to usual psychiatric treatment in this patient population.

Method. Subjects referred by general adult psychiatrists were assessed by and independent rater and then randomly allocated to immediate CT (N=21) or 6-month waiting-list control, which was then followed by CT (N=21). Observer and self-ratings of symptoms and functioning were undertaken immediately prior to CT, after a 6-month course of CT and a further 6-months later. Data on relapse and hospitalization rates in the 18 months before and after commencing CT were also collected.

Results. At 6-month follow-up, subjects allocated to CT showed statistically significantly greater improvements in symptoms and functioning as measured on the Beck Depression Inventory, the Internal State Scale, and the Global Assessment of Functioning than those in the waiting-list control group. In the 29 patients who eventually received CT, relapse rates in the 18 months after commencing CT showed a 60% reduction in comparison with the 18 months prior to commencing CT. Seventy per cent of subjects who commenced therapy viewed CT as highly acceptable.

Conclusion. Although the results of this study are encouraging, the use of CT in subjects with bipolar disorders is more complex than in unipolar disorders and requires a high level of therapist expertise. The therapy may prove to be particularly useful in the treatment of bipolar depression.
The relationship between obsessive–compulsive disorder and anxiety and affective disorders: results from the Johns Hopkins OCD Family Study
Authors: NESTADT G. , SAMUELS J. , RIDDLE M. A. , LIANG K.-Y. , BIENVENU O. J. , HOEHN-SARIC R. , GRADOS M. , CULLEN B.
Published: August 2008

Objective. This study investigates the relationship of specific anxiety and affective disorders to obsessive–compulsive disorder (OCD) in a blind, controlled family study.

Method. Eighty case and 73 control probands, as well as 343 case and 300 control first-degree relatives of these probands, participated in the study. Subjects were examined by psychologists or psychiatrists using the Schedule for Affective Disorder and Schizophrenia-Lifetime Anxiety version (SADS-LA). Two experienced psychiatrists independently reviewed all clinical materials, and final diagnoses were made according to DSM-IV criteria, by consensus procedure.

Results. Except for bipolar disorder, all anxiety and affective disorders investigated were more frequent in case than control probands. Substance dependence disorders were not more frequent. Generalized anxiety disorder (GAD), panic disorder, agoraphobia, separation anxiety disorder (SAD) and recurrent major depression were more common in case than control relatives. These disorders occurred more frequently if the relative was diagnosed with OCD. Only GAD and agoraphobia were more frequent in case relatives independent of OCD.

Conclusion. GAD and agoraphobia share a common familial aetiology with OCD. The other anxiety and affective disorders, when comorbid with OCD, may emerge as a consequence of the OCD or as a more complex syndrome.
Discriminating between chronic fatigue syndrome and depression: a cognitive analysis
Authors: MOSS-MORRIS RONA , PETRIE KEITH J.
Published: August 2008

Background. Chronic fatigue syndrome (CFS) and depression share a number of common symptoms and the majority of CFS patients meet lifetime criteria for depression. While cognitive factors seem key to the maintenance of CFS and depression, little is known about how the cognitive characteristics differ in the two conditions.

Methods. Fifty-three CFS patients were compared with 20 depressed patients and 38 healthy controls on perceptions of their health, illness attributions, self-esteem, cognitive distortions of general and somatic events, symptoms of distress and coping. A 6 month follow-up was also conducted to determine the stability of these factors and to investigate whether CFS-related cognitions predict ongoing disability and fatigue in this disorder.

Results. Between-group analyses confirmed that the depressed group was distinguished by low self-esteem, the propensity to make cognitive distortions across all situations, and to attribute their illness to psychological factors. In contrast, the CFS patients were characterized by low ratings of their current health status, a strong illness identity, external attributions for their illness, and distortions in thinking that were specific to somatic experiences. They were also more likely than depressed patients to cope with their illness by limiting stress and activity levels. These CFS-related cognitions and behaviours were associated with disability and fatigue 6 months later.

Conclusions. CFS and depression can be distinguished by unique cognitive styles characteristic of each condition. The documented cognitive profile of the CFS patients provides support for the current cognitive behavioural models of the illness.
Monozygotic twins discordant for major depression: a preliminary exploration of the role of environmental experiences in the aetiology and course of illness
Authors: KENDLER KENNETH S. , GARDNER CHARLES O.
Published: August 2008

Background. Genetic effects upon behaviour are pervasive. To what extent are the many correlates of major depression (MD) due to individual-specific environmental experiences versus genetic factors correlated with risk for MD?

Methods. From a population-based twin registry, we identified 72 female monozygotic pairs discordant for a lifetime history of MD and compared the affected and unaffected members on a wide range of putative correlates of MD.

Results. The affected twin differed from her unaffected co-twin on many variables, eight of which were maximally discriminating: (i) maternal protectiveness; (ii) conflictual parent–child relationship; (iii) low optimism; (iv) current stressful life events; (v) financial difficulties and a history of (vi) phobia, (vii) nicotine dependence; and (viii) divorce. A cluster analysis suggested three ‘environmental pathways' to MD characterized by: (i) childhood vulnerability and anxiety; (ii) acting-out and demoralization; and (iii) interpersonal difficulties.

Conclusion. Important precursors and sequelae of MD originate in environmental experiences unique to the individual and are not mediated through genetic factors or family-of-origin effects. Such environmental factors cause pervasive differences in monozygotic twins discordant for MD, especially in the areas of interpersonal difficulties, psychopathology, social problems and self-concept. These findings should be interpreted in the context of possible retrospective recall bias and the difficulty of distinguishing risk factors from sequelae in co-twin–control studies.
The NART as an index of prior intellectual functioning: a retrospective validity study covering a 66-year interval
Authors: CRAWFORD J. R. , DEARY I. J. , STARR J. , WHALLEY L. J.
Published: August 2008

Background. The National Adult Reading Test (NART) is widely used in research and clinical practice as an estimate of pre-morbid or prior ability. However, most of the evidence on the NART's validity as a measure of prior intellectual ability is based on concurrent administration of the NART and an IQ measure.

Method. We followed up 179 individuals who had taken an IQ test (the Moray House Test) at age 11 and administered the NART and the Mini-Mental State Examination (MMSE) at age 77. A subset (N=97) were also re-administered the original IQ test.

Results. The correlation between NART performance at age 77 and IQ age 11 was high and statistically significant (r=0·73; P<0·001). This correlation was comparable to the correlation between NART and current IQ, and childhood IQ and current IQ, despite the shared influences on the latter variable pairings. The NART had a significant correlation with the MMSE but this correlation fell to near zero (r=0·02) after partialling out the influence of childhood IQ.

Discussion. The pattern of results provides strong support for the claim that the NART primarily indexes prior (rather than current) intellectual ability.
Post-traumatic stress disorder in primary-care settings: prevalence and physicians' detection
Authors: TAUBMAN-BEN-ARI O. , RABINOWITZ J. , FELDMAN D. , VATURI R.
Published: August 2008

Background. Little is known about the prevalence of PTSD in primary-care settings and regarding the ability of primary-care physicians to detect PTSD. The current study examines prevalence of PTSD in a national sample of primary-care attenders and primary-care physicians' detection of PTSD and general psychological distress in PTSD patients.

Methods. Data are from a national study of 2975 primary-care attenders in Israel. Demographic data, responses to the GHQ-28, PTSD Inventory and physicians' diagnoses were examined.

Results. Twenty-three per cent of all patients who attended clinics (N=684) reported traumatic events, 39% of whom (males 37%, females 40%) met criteria for PTSD on the PTSD Inventory. Eighty per cent of the males and 92% of the females with PTSD were distressed according to the GHQ. According to physicians, 37% of persons who reported trauma (40% of the women, 32% of the men) suffered from psychological distress. Only 2% of patients meeting PTSD criteria on the self-report measure were given a diagnoses of PTSD by physicians.

Conclusions. Many primary-care patients suffer from PTSD, which is usually accompanied by major psychological distress. Attention by primary-care physicians to a history of trauma could improve physicians' detection of this disabling disorder.
Patients' and relatives' assessment of clozapine treatment
Authors: ANGERMEYER M. C. , LÖFFLER W. , MÜLLER P. , SCHULZE B. , PRIEBE S.
Published: August 2008

Background. Subjective evaluations by schizophrenic patients and their relatives of clozapine treatment were assessed as part of an exploratory study.

Methods. A problem-centred interview was carried out with 80 patients at discharge from in-patient or day-hospital treatment. Views of 46 relatives on the treatment were also assessed.

Results. In addition to expected effects (improvement of or stabilisation of one's state of mental health, antipsychotic effects), patients surprisingly often highlighted the calming and relaxing effect of clozapine as well as improved sleep as particularly positive. While more than half of the respondents expected a worsening of their condition if they stopped taking medication, only every fifth patient feared a relapse. Among the negative effects, fatigue and sedation were cited by far the most often. The absence of extrapyramidal side effects was clearly noted as an advantage of clozapine. Only 10 % of those questioned were aware of the risks for the haemotopoetic system associated with the drug. Differences were found between patients' and relatives' assessments particularly with regard to the negative effects.

Conclusions. Patients and relatives frequently hold specific and distinct views on clozapine treatment. These views should be considered when patients and relatives are informed and when compliance is addressed.
Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis
Authors: RIDLER K. , BULLMORE E. T. , DE VRIES P. J. , SUCKLING J. , BARKER G. J. , MEARA S. J. P. , WILLIAMS S. C. R. , BOLTON P. F.
Published: August 2008

Background. Neuroimaging studies of tuberous sclerosis complex (TSC) have previously focused mainly on tubers or subependymal nodules. Subtle pathological changes in the structure of the brain have not been studied in detail. Computationally intensive techniques for reliable morphometry of brain structure are useful in disorders like TSC, where there is little prior data to guide selection of regions of interest.

Methods. Dual-echo, fast spin-echo MRI data were acquired from 10 TSC patients of normal intelligence and eight age-matched controls. Between-group differences in grey matter, white matter and cerebrospinal fluid were estimated at each intracerebral voxel after registration of these images in standard space; a permutation test based on spatial statistics was used for inference. CSF-attenuated FLAIR images were acquired for neuroradiological rating of tuber number.

Results. Significant deficits were found in patients, relative to comparison subjects, of grey matter volume bilaterally in the medial temporal lobes, posterior cingulate gyrus, thalamus and basal ganglia, and unilaterally in right fronto-parietal cortex (patients −20%). We also found significant and approximately symmetrical deficits of central white matter involving the longitudinal fasciculi and other major intrahemispheric tracts (patients −21%); and a bilateral cerebellar region of relative white matter excess (patients +28%). Within the patient group, grey matter volume in limbic and subcortical regions of deficit was negatively correlated with tuber count.

Conclusions. Neuropathological changes associated with TSC may be more extensive than hitherto suspected, involving radiologically normal parenchymal structures as well as tubers, although these two aspects of the disorder may be correlated.
Fatigue, depression and chronic hepatitis C infection
Authors: WESSELY SIMON , PARIANTE CARMINE
Published: August 2008

Background. We aimed to determine if an association exists between uncomplicated hepatitis C virus (HCV) infection and depression or fatigue.

Method. A review of the literature was undertaken.

Results. There is an association between HCV infection and either depression or fatigue in certain
circumstances – those who are aware they are HCV positive, those with advanced liver disease and
those seen in specialist referral centres. All these studies are subject to important biases. There are
only a few studies in which knowledge of HCV status and assessment of fatigue or depression is
independent. These studies do not suggest an association. There is no association between
conventional markers of liver disease and depression or fatigue.

Conclusions. Despite anecdotal evidence to the contrary, at the moment there is no evidence that
HCV infection per se is associated with fatigue or depression, and there is a suggestion that it is not.
The same risk factors that exist for fatigue in other physical illnesses, such as metabolic disorder,
mood disorder, demographics and lack of exercise, certainly exist for HCV. Although there are
elegant theoretical mechanisms, there is no compelling epidemiological evidence for an additional
HCV specific fatigue or depression factor.
Beliefs, sense of control and treatment outcome in post-traumatic stress disorder
Authors: LIVANOU M. , BAOŞĞLU M. , MARKS I. M. , DE SILVA P. , NOSHIRVANI H. , LOVELL K. , THRASHER S.
Published: August 2008

Background. Few studies have shown that maladaptive beliefs relate to treatment outcome.

Method. In a randomized controlled study, 87 patients with post-traumatic stress disorder (PTSD) had exposure therapy alone or cognitive restructuring alone, or both combined, or relaxation. Independent blind assessors assessed patients at pre-, mid- and post-treatment and at follow-up; at those times patients rated cognitive, behavioural and emotional aspects of their disorder.

Results. Baseline beliefs about mistrust, helplessness, meaninglessness and unjustness of the world related to baseline PTSD symptoms but did not predict treatment outcome, though improvement in certain beliefs correlated with more symptom improvement. Several ‘key’ beliefs changed after, and none before, symptoms improved. At post-treatment, sense of control and attribution of gains to personal efforts predicted maintenance of gains at follow-up.

Conclusions. Baseline beliefs and improvement in beliefs did not predict outcome. Post-treatment sense of control/internal attribution predicted maintenance of gains at follow-up. How much sense of control is produced by or causes improvement deserves testing.
Genetic effects on the variation and covariation of attention deficit-hyperactivity disorder (ADHD) and oppositional-defiant disorder/conduct disorder (ODD/CD) symptomatologies across informant and occasion of measurement
Authors: NADDER T. S. , RUTTER M. , SILBERG J. L. , MAES H. H. , EAVES L. J.
Published: August 2008

Background. Previous studies have shown that the presence of conduct disorder may contribute to the persistence of attention deficit-hyperactivity disorder (ADHD) symptomatology into adolescence; however, the aetiological relationship between the two phenotypes remains undetermined. Furthermore, studies utilizing multiple informants have indicated that teacher ratings of these phenotypes are more valid than maternal reports.

Methods. The genetic structure underlying the persistence of ADHD and oppositional-defiant disorder/conduct disorder (ODD/CD) symptomatologies as rated by mothers and teachers at two occasions of measurement was investigated on a sample of 494 male and 603 female same sex adolescent twin pairs participating in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD).

Results. Using structural modelling techniques, one common genetic factor was shown to govern the covariation between the phenotypes across informants and occasion of measurement with additional genetic factors specific to ODD/CD symptomatology and persistence of symptomatology at reassessment. Genetic structures underlying the phenotypes were, to some extent, informant dependent.

Conclusions. The findings indicate that it is unlikely that the co-morbidity between ADHD and ODD/CD is due to environmental influences that are independent of ADHD. Rather it is likely to be due to a shared genetic liability either operating directly, or indirectly through gene–environment correlations or interactions. The covariation between phenotypes across informants and time is governed by a common set of genes, but it seems that ODD/CD is also influenced by additional genetic factors. Developmentally, different forms of genetic liability control ADHD in males and inattention in females.
Parental alcohol use disorders and alcohol use and disorders in offspring: a community study
Authors: LIEB R. , MERIKANGAS K. R. , HÖFLER M. , PFISTER H. , ISENSEE B. , WITTCHEN H.-U.
Published: August 2008

Background. We examined the association between parental alcohol use disorders and patterns of alcohol consumption and DSM-IV alcohol use disorders in their offspring in a community-based sample of young adults.

Methods. Data are based on baseline and 4-year follow-up data of 2427 respondents aged 14–24 at baseline. Alcohol use and disorders in respondents were assessed using the Munich-Composite-International-Diagnostic-Interview with DSM-IV algorithms. Diagnostic information about parents was collected by family history information from the respondents, and by direct interview with one parent (cohort aged 14 to 17 years only).

Results. Although the association between maternal and paternal alcohol use disorders and non-problematical drinking in offspring was minimal, there was a strong effect for the transition to hazardous use and for alcohol abuse and dependence; the effect of parental concordance for transition into hazardous use was particularly striking. Maternal history was associated with a higher probability of progression from occasional to regular use, whereas paternal history was associated with progression from regular to hazardous use. Parental alcoholism increased the risk for first onset of hazardous use and alcohol dependence between the ages of 14–17, and for an earlier onset of the alcohol outcomes in offspring. The impact of parental alcohol use disorders was comparable for male and female offspring.

Conclusions. Parental alcoholism predicts escalation of alcohol use, development of alcohol use disorders and onset of alcohol outcomes in offspring.
Evidence of an early information processing speed deficit in unipolar major depression
Authors: TSOURTOS G. , THOMPSON J. C. , STOUGH C.
Published: August 2008

Background. Slowing of the speed of information processing has been reported in geriatric depression, but it is not clear if the impairment is present in younger patients, if motor retardation is responsible, or if antidepressant medications play a role.

Method. Twenty unmedicated unipolar depressed inpatients were compared with 19 medicated depressed in-patients and 20 age-, sex- and verbal IQ-matched controls on inspection time (IT), a measure of speed of information processing that does not require a speeded motor response. We also examined the relationship between IT and current mood and length of depressive illness.

Results. Unmedicated depressed patients showed slowing of information processing speed when compared to both medicated depressed patients and controls. The latter two groups were not significantly different from each other. Slowing of IT was not associated with current mood, but was negatively correlated with length of illness since first episode. No differences in IT were found between patients receiving medication with anticholinergic effects and patients receiving medication with no anticholinergic effects.

Conclusions. The findings indicate that unipolar depression is associated with a slowing of speed of information processing in younger patients who have not received antidepressant medication. This does not appear to be a result of motor slowing.
Personality and the perception of health in the general population
Authors: GOODWIN RENEE , ENGSTROM GUNNAR
Published: August 2008

Background. Several population-based studies have shown that self-perceived health is a powerful predictor of health outcomes. The extent to which self-perceived health is associated with personality characteristics is, however, largely unknown. We aimed to study the relationship between self-perceived health and personality among adults in the community.

Method. Data were drawn from the Midlife Development in the United States Survey, a representative sample of adults age 25–74. MANOVA was used to determine the relationship between self-perception of health and personality using the five-factor model.

Results. Personality factors were significantly associated with perception of poor health. Among those without self-reported medical problems (N = 834), openness to experience, extraversion and conscientiousness were associated with perception of good health, while neuroticism was associated with the perception of poor health. In subjects with self-reported medical problems (N = 2772), high scores on agreeableness, openness to experience, extraversion and conscientiousness, and low neuroticism scores were associated with perception of good health. These associations remained significant after adjustments for age, gender, race, marital status and education.

Conclusions. Self-perceived health is strongly associated with personality characteristics, both in subjects with and without self-reported medical problems. It is suggested that personality characteristics could contribute to the previously reported associations between self-perceived health and health outcomes.
Mortality in psychiatric patients 5 to 21 years after hospital admission in Italy
Authors: POLITI P. , PICCINELLI M. , KLERSY C. , MADINI S. , SEGAGNI LUSIGNANI G. , FRATTI C. , BARALE F.
Published: August 2008

Background. Mental disorders have an increased mortality risk. However, most data have been provided by few countries, some mental disorders have received little attention, long-term studies of large samples are scarce, and insufficient control for confounding variables has lead to artefactual inconsistencies across studies. The aims of this study were: to quantify the mortality risk in psychiatric patients 5 to 21 years after hospital admission and to investigate temporal trends in mortality risk and predictive factors associated with mortality.

Method. All patients admitted to an in-patient psychiatric unit in Italy between 1978 and 1994 were included and vital status and death causes were determined up to 21 years after admission. The observed number of deaths in the sample was compared with the expected number of deaths in the general population. Cox proportional hazard models were fitted to identify predictors of mortality.

Results. Mortality from natural and unnatural causes was higher than expected across all mental disorders. Standardized mortality risk was higher in males (SMR = 4·55; 95% CI 4·17–4·97) than in females (SMR = 3·43; 95% CI 3·07–3·83). Individuals aged less than 40 years were at higher risk in both sexes. The first several years following admission were characterized by a faster decline in survival. Several demographic and clinical factors were predictors of mortality.

Conclusions. Mortality is high in individuals with mental disorders. Prevention of unnatural death causes is an important goal though insufficient to abate excess mortality, since natural death causes account for it to a larger extent.
Psychiatric, demographic and personality characteristics of elderly sex offenders
Authors: FAZEL S. , HOPE T. , O’DONNELL I. , JACOBY R.
Published: August 2008

Background. Psychiatric disorders are purported to play a role in the aetiology of violent crime, but evidence for their role in sexual offending is less clear. The authors investigated the prevalence of psychiatric morbidity and personality disorders in elderly incarcerated sex offenders compared with elderly non-sex offenders.

Method. One hundred and one sex offenders and 102 non-sex offenders aged over 59 years were interviewed using standardized semi-structured interviews for psychiatric illness (the Geriatric Mental State) and the personality disorder (Structured Clinical Interview for DSM-IV personality disorders). Data on demographic, offence and victim characteristics were collected.

Results. Six per cent of the elderly sex offenders had a psychotic illness, 7% a DSM-IV major depressive episode and 33% a personality disorder; and 1% had dementia. These prevalence figures were not different from the elderly non-sex offenders interviewed in this study. Differences emerged at the level of personality traits with sex offenders having more schizoid, obsessive–compulsive, and avoidant traits, and fewer antisocial traits compared with non-sex offenders.

Conclusions. Elderly sex offenders and non-sex-offenders have similar prevalence rates of mental illness. However, elderly sex offenders have increased schizoid, obsessive–compulsive, and avoidant personality traits, supporting the view that sex offending in the elderly is associated more with personality factors than mental illness or organic brain disease.
Categoric overgeneral autobiographical memory in adolescents with major depressive disorder
Authors: PARK R. J. , GOODYER I. M. , TEASDALE J. D.
Published: August 2008

Background. Categoric, overgeneral autobiographical memory is more common in depressed adults than controls and predicts persistence of depression. This cross-sectional study investigated whether, compared with non-depressed psychiatric cases and community controls, first episode major depressive disorder (MDD) in adolescents is associated with categoric overgeneral memory retrieval.

Methods. Ninety-six clinically referred adolescents (aged 12–17 years) with MDD, 26 non-depressed psychiatric cases and a sample of 33 community controls were recruited. All subjects were assessed using the Kiddie-Schedule for Schizophrenia and Affective Disorders, and completed Williams' cued Autobiographical Memory Test and the Mood and Feelings Questionnaire. Hamilton Depression Rating Scales were completed with MDD subjects, as an index of depression severity.

Results. Adolescents with current first episode MDD retrieved more categoric overgeneral memories than controls, but not than non-depressed psychiatric cases. Adolescents in full remission from a recent episode of MDD retrieved more categoric memories to positive cues than controls. Categoric memory in MDD was related to observer-rated and self-reported severity, but not to the pattern of co-morbid diagnoses. There were negative correlations between IQ and categoric memories in both clinical cases and controls. A positive correlation between categoric memory to negative cues and self-reported depressive symptoms was found in clinical cases (but not controls).

Conclusions. In adolescents, increased categoric overgeneral memory is associated with, but not specific to first episode MDD. Positive categoric memories are also increased in fully remitted MDD as compared to controls.
The impact of personality disorder in UK primary care: a 1-year follow-up of attenders
Authors: MORAN P. , RENDU A. , JENKINS R. , TYLEE A. , MANN A.
Published: August 2008

Background. The usefulness of the concept of personality disorder has not been properly tested outside psychiatric services. We set out to examine this in primary care, by examining the ability of the diagnosis to predict health status and patterns of service use.

Method. A cohort of consecutive attenders, who had previously been rated for the presence of personality disorder using a standardized assessment, was followed-up at 1 year. The participating general practitioners also rated the personalities of, and their attitudes towards, a proportion of this sample of attenders.

Results. After adjusting for the effects of all covariates, a rating of personality disorder (generated by the standardized assessment) was associated with frequent attendance to general practice and fewer referrals to secondary care. A GP rating of personality disorder was associated with the prescription of psychotropic medication. The level of agreement between a GP rating of personality disorder and the standardized assessment was poor. GPs rated personality disorder more frequently in participants who were perceived to be less compliant, less likeable and more stressful to deal with. Participants with a psychiatric rating of personality disorder did not attract these negative perceptions.

Conclusions. Personality disorder, as rated by a research interview, is a predictor of health service usage. There is a significant disparity between a research rating of personality disorder and the diagnostic ratings made by GPs. The GP ratings of personality disorder were strongly associated with adverse perceptions of the patient's consulting behaviour.
Pathways from science findings to health benefits
Authors: Rutter M. , Plomin R.
Published: August 2008

There have been numerous exhortations for more ‘translational research’. A selective review of historical examples of research leading to health benefits is used to consider the various forms of successful interplay between basic science and clinical applications. This is followed by a consideration of key neuroscience findings that might be relevant for translation, and then by a discussion of the challenges and opportunities in relation to mental disorders. The time-frame for the pathway from science findings to health benefits is usually long, and generally requires an interactive interplay among different scientific strategies. There is a false dichotomy between so-called basic and applied research and translation needs to proceed from the bedside to the laboratory as well as in the opposite direction. There is a key need for bridging research of the hypothesis-testing experimental medicine variety. Health benefits may involve either public health considerations or the treatment of individual patients, or both. There are now some opportunities for direct translational research but there is a much greater need for hypothesis-based bridging studies that occupy a crucial mid-phase in the pathway from science findings to health benefits.
Psychopathy, attention and emotion
Authors: Blair R. J. R. , Mitchell D. G. V.
Published: August 2008

Psychopathy is a developmental disorder marked by emotional hypo-responsiveness and an increased risk for antisocial behavior. Influential attention-based accounts of psychopathy have long been made; however, these accounts have made relatively little reference to general models of attention in healthy individuals. This review has three aims: (1) to summarize current cognitive neuroscience data on differing attentional systems; (2) to examine the functional integrity of these attentional systems in individuals with psychopathy; and (3) to consider the implications of these data for attention and emotion dysfunction accounts of psychopathy.
Role of DNA sequence in nucleosome stability and dynamics
Authors: Widom J.
Published: August 2008

1. Introduction 270

1.1 Overview of nucleosome structure 271

2. Relative equilibrium stability (affinity) of histone–DNA interactions in
nucleosomes 272

2.1 Relative affinity equals relative equilibrium stability 272

2.2 Competition assays for relative free-energy measurements 273

2.3 Technical issues in relative free-energy measurements 275

2.4 Range of affinities 278

3. Relation of nucleosome stability to nucleosome positioning 279

3.1 Translational nucleosome positioning 279

3.2 Rotational positioning 280

3.3 Unfavorable positioning 281

3.4 Experiments 281

4. Physical basis of DNA sequence preferences 282

4.1 Free-energy cost of DNA bending 283

4.2 Molecular mechanics of DNA bending and bendability 284

4.3 Bent and bendable DNA sequences 286

4.4 Parameter sets for prediction of DNA bending and bendability 288

4.5 DNA twisting 290

4.6 Energetics of nucleosomal DNA packaging 291

5. DNA sequence motifs for nucleosome packaging 292

5.1 Natural and designed nucleosomal DNAs 293

5.2 New rules and reagents from physical selection studies 294

5.3 Molecular basis of DNA sequence preferences 299

5.4 Special properties of the TA step 300

5.5 Unfavorable sequences 302

5.6 Natural genomes 303

5.7 Evolutionary approach toward an optimal sequence 305

5.8 Optimization by design 305

6. Dynamic nucleosome instability 308

6.1 Site-exposure equilibria 308

6.2 DNA sequence-dependence to site-exposure equilibria 312

6.3 Nucleosome translocation 315

6.4 Action of processive enzymes 319

7. Conclusions 319

8. Acknowledgements 320

9. References 320

The nucleosome core particle is the fundamental repeating subunit of chromatin. It consists
of two molecules each of the four ‘core histone’ proteins, H2A, H2B, H3 and H4, and a
147 bp stretch of DNA. The lowest level of chromatin organization consists of a repeated
array of nucleosome core particles separated by variable lengths of ‘linker DNA’. In many,
but not all, cases, each core particle plus its linker DNA is associated with one molecule of
a fifth ‘linker’ histone protein, H1. The complex of the core particle plus its linker DNA and
H1 (when present) is called a ‘nucleosome’.
Atonement without satisfaction
Authors: CROSS RICHARD
Published: August 2008

According to Swinburne, one way of dealing with the guilt that attaches
to a morally bad action is satisfaction, consisting of repentance, apology, reparation,
and penance. Thus, Christ's life and death make atonement for human sin by
providing a reparation which human beings would otherwise be unable to pay. I
argue that the nature of God's creative activity entails that human beings can by
themselves make reparation for their sins, merely by apology. So there is no need
for additional reparation, and the satisfaction theory of the atonement is otiose.
Following an insight of Swinburne's, I argue that satisfaction is not sufficient for
forgiveness, since satisfaction does not place the wronged party under any
obligation to forgive the wrongdoer. Christ's death merits the forgiveness of those
sins for which human beings have made satisfaction. It does this in virtue of a
divine promise to reward Christ's meritorious life with the forgiveness of such
human sin.
The ens realissimum and necessary being in The Critique of Pure Reason
Authors: PASTERNACK LAWRENCE
Published: August 2008

Just prior to The Critique of Pure Reason's examination of the various
arguments for God's existence, Kant discusses the conceptual relationship between
the idea of an ens realissimum and that of a necessary being. The purpose of this
paper is to illustrate the extent to which this discussion informs his claim that the
cosmological argument depends upon the ontological argument.
Kierkegaard on truth
Authors: JACOBY MATTHEW GERHARD
Published: August 2008

The following paper focuses upon what is possibly the most controversial passage in Kierkegaard's writings. On the basis of this passage Kierkegaard's notion of truth as ‘subjectivity’ has been interpreted as being ‘non-objective referential’, that is, as having severed itself from ‘eternal truth’ altogether, so that the emphasis in the question of truth is entirely upon the relationship a person has to what he thinks and that the object of the relationship is a matter of indifference. We shall defend here a reading of Kierkegaard in which the subjectivity that Kierkegaard defines as truth is entirely conditioned by its relation to a specific revelation of eternal truth. In line with this we will also interpret the passage at the centre of the controversy as an ‘impossible hypothetical’ used for the sake of making a provocation.
The religious adequacy of free-will theism
Authors: CIOCCHI DAVID M.
Published: August 2008

In this paper I question the claim that the increasingly popular position known as ‘free-will theism’ or ‘the open view of God’ supports a rich religious life. To do this I advance a notion of ‘religious adequacy’, and then argue that free-will theism fails to be religiously adequate with respect to one of the principal practices of the religious life – petitionary prayer. Drawing on current work in libertarian free-will theory, I consider what are likely the only two lines of defence free-will theists might use in response to my argument. I argue that these defences either fail or have features that make them unacceptable to free-will theists. I then suggest that this failure with petitionary prayer is an instance of a larger problem for free-will theism, that the position's distinctive views often differ more dramatically from the common beliefs and practices of most believers than is usually recognized or acknowledged. I conclude that free-will theism can support a rich religious life only for those who make the requisite changes in belief and practice, including changing their expectations about petitionary prayer.
A response to Oppy, and to Davey and Clifton
Authors: GALE RICHARD M. , PRUSS ALEXANDER R.
Published: August 2008

Our paper ‘A new cosmological argument’ gave an argument for the existence of God making use of the weak Principle of Sufficient Reason (W-PSR) which states that for every proposition p, if p is true, then it is possible that there is an explanation for p. Recently, Graham Oppy, as well as Kevin Davey and Rob Clifton, have criticized the argument. We reply to these criticisms. The most interesting kind of criticism in both papers alleges that the W-PSR can be justifiably denied by the atheist, and constitutes no improvement on the strong Principle of Sufficient Reason (S-PSR) which claims that every true proposition in fact has an explanation. The criticism is predicated on the fact that it can be shown that the W-PSR entails the S-PSR. We argue that the W-PSR's plausibility remains despite the criticisms. From this it can be seen to follow that the entailment relation between the W-PSR and the S-PSR gives one reason to believe the S-PSR.
‘Seeing-as' in religion: discovery and community
Authors: KELLENBERGER J.
Published: August 2008

‘Seeing-as’, or aspect seeing, is generally recognized as having significance for religion, especially so since Wittgenstein. Two questions arise regarding religiously seeing the world as God's creation: have the religious seen the world aright, and does the world religiously require a community that uses religious concepts? I argue that a particular strain of religious tradition provides us with a way to understand the issue of discovery, and that a traditional understanding of the power of God requires that a religious seeing of the world as God's creation, or a place of God's presence, can occur without there being a community that uses such religious concepts.