Neighbourhood socio-economic position, late presentation and outcomes in people living with HIV in Switzerland.

OBJECTIVES: Inequalities and inequities in health are an important public health concern. In Switzerland, mortality in the general population varies according to the socio-economic position (SEP) of neighbourhoods. We examined the influence of neighbourhood SEP on presentation and outcomes in HIV-positive individuals in the era of combination antiretroviral therapy (cART). METHODS: The neighbourhood SEP of patients followed in the Swiss HIV Cohort Study (SHCS) 2000-2013 was obtained on the basis of 2000 census data on the 50 nearest households (education and occupation of household head, rent, mean number of persons per room). We used Cox and logistic regression models to examine the probability of late presentation, virologic response to cART, loss to follow-up and death across quintiles of neighbourhood SEP. RESULTS: A total of 4489 SHCS participants were included. Presentation with advanced disease [CD4 cell count <200 cells/μl or AIDS] and with AIDS was less common in neighbourhoods of higher SEP: the age and sex-adjusted odds ratio (OR) comparing the highest with the lowest quintile of SEP was 0.71 [95% confidence interval (95% CI) 0.58-0.87] and 0.59 (95% CI 0.45-0.77), respectively. An undetectable viral load at 6 months of cART was more common in the highest than in the lowest quintile (OR 1.52; 95% CI 1.14-2.04). Loss to follow-up, mortality and causes of death were not associated with neighbourhood SEP. CONCLUSION: Late presentation was more common and virologic response to cART less common in HIV-positive individuals living in neighbourhoods of lower SEP, but in contrast to the general population, there was no clear trend for mortality.

Pain, frailty and comorbidity on older men: the CHAMP study.

Intrusive pain is likely to have a serious impact on older people with limited ability to respond to additional stressors. Frailty is conceptualised as a functional and biological pattern of decline accumulating across multiple physiological systems, resulting in a decreased capacity to respond to additional stressors. We explored the relationship between intrusive pain, frailty and comorbid burden in 1705 community-dwelling men aged 70 or more who participated in the baseline phase of the CHAMP study, a large epidemiological study of healthy ageing based in Sydney, Australia. 9.4% of men in the study were frail (according to the commonly-used Cardiovascular Health Study frailty criteria).Using a combination of self-report and clinical measures, we found an association between frailty and intrusive pain that remained after accounting for demographic characteristics, number of comorbidities, self-reported depressed mood and arthritis (adjusted odds ratio 1.7 (95% confidence interval (CI) 1.1-2.7), p=0.0149). The finding that adjusting for depressed mood, but not a history of arthritis, attenuated the relationship between frailty and intrusive pain points to a key role for central mechanisms. Additionally, men with the highest overall health burden (frail plus high comorbid burden) were most likely to report intrusive pain (adjusted odds ratio 3.0 (95% CI 1.6-5.5), p=0.0004). These findings provide support for the concept that intrusive pain is an important challenge for older men with limited capacity to respond to additional physical stressors. To our knowledge, this is the first study to explore specifically the relationship between pain and frailty.

Gambling against neglect: unconscious spatial biases induced by reward reinforcement in healthy people and brain-damaged patients.

Orienting attention in space recruits fronto-parietal networks whose damage results in unilateral spatial neglect. However, attention orienting may also be governed by emotional and motivational factors; but it remains unknown whether these factors act through a modulation of the fronto-parietal attentional systems or distinct neural pathways. Here we asked whether attentional orienting is affected by learning about the reward value of targets in a visual search task, in a spatially specific manner, and whether these effects are preserved in right-brain damaged patients with left spatial neglect. We found that associating rewards with left-sided (but not right-sided) targets during search led to progressive exploration biases towards left space, in both healthy people and neglect patients. Such spatially specific biases occurred even without any conscious awareness of the asymmetric reward contingencies. These results show that reward-induced modulations of space representation are preserved despite a dysfunction of fronto-parietal networks associated with neglect, and therefore suggest that they may arise through spared subcortical networks directly acting on sensory processing and/or oculomotor circuits. These effects could be usefully exploited for potentiating rehabilitation strategies in neglect patients.

Exploring the use of mobile communications in a sample of older people: Preliminary results of a case study in Los Angeles

This paper introduces a qualitative case study on mobile communication among the older population (60+ years old) conducted in Great Los Angeles (CA, USA) in autumn 2011. Methodology, fieldwork and preliminary results are discussed.Before, country-level data is presented to better understand the specific characteristics of the studied individuals. The section focus is on demographics and on acceptance and use of information and communication technologies (ICT).Preliminary results show that within the sample under study (20 individuals) there is a high number of mobile phone users (15) while among non-mobile users (5), three of them decide to stop using this technology. A majority of mobile phone adopters describe a very limited use of the device for everyday life communications. Finally,while Internet is really popular within the sample (14 users), just 3 individuals go online through their mobile telephone.

Evolution of Gait Performance and Fear of Falling after a 10-Week Program of Exercise Training in Community Dwelling Older People

A pilot study was conducted to determine the effect of a 10-week, low intensity, exercise training program on fear of falling and gait in fifty (mean age 78.1 years, 79% women) community-dwelling volunteers. Fear of falling (measured by falls self-efficacy) and gait performance were assessed at baseline and one week after program completion. At follow-up, participants modestly improved their falls self-efficacy and gait speed. To investigate whether this effect differed according to participants' fear of falling, secondary analyses stratified by subject's baseline falls efficacy were performed. Subjects with lower than average falls efficacy improved significantly their falls efficacy and gait performance, while no significant change occurred in the others. Small but significant improvements occurred after this pilot training program, particularly in subjects with low baseline falls efficacy. These results suggest that measures of falls efficacy might be useful for better targeting individuals most likely to benefit from similar training programs.

Prevalence and predictors of suicide attempt in an incidence cohort of 661 young people with first-episode psychosis

OBJECTIVES: Studies investigating suicidal behaviour in psychosis rarely focus on incidence cohorts of first-episode patients. This is important, because patients who refuse study participation have higher rates of comorbid substance use disorders and longer duration of untreated psychosis as well as worse course illness, variables potentially linked to higher prevalence of suicidal behaviour. The aims of the present study were therefore to examine the prevalence and predictors of suicide and suicide attempt before and during the first 18-24 months of treatment. METHOD: A retrospective file audit of 661 patients was carried out. RESULTS: Six patients (0.9%) died by suicide, 93 (14.3%) attempted suicide prior to entry, and 57 (8.7%) did so during treatment. Predictors of suicide attempt were: previous attempt (odds ratio (OR)=45.54, 95% confidence interval (CI)=9.46-219.15), sexual abuse (OR=8.46, 95%CI=1.88-38.03), comorbid polysubstance (OR=13.63, 95%CI=2.58-71.99), greater insight (OR=0.17, 95%CI=0.06-0.49), lower baseline Global Assessment of Functioning Scale and Scale of Occupational and Functional Assessment score (OR=0.96, 95%CI=0.62-0.91; OR=0.98, 95%CI=0.95-0.99), and longer time in treatment (OR=1.05, 95%CI=1.03-1.08). CONCLUSIONS: The prevalence of suicidal behaviour was high, indicating that suicidal behaviour in incidence populations is higher than in non-epidemiological cohorts of first-episode patients. The rate of repetition of suicide attempt among the sample, however, was lower than expected, suggesting that specialist services can play a role in reducing suicide risk.

Studying the molecular causes of ageing in ants

RÉSUMÉ DE THÈSE Au cours de ma thèse, je me suis intéressée aux causes physiologiques du vieillissement en utilisant les fourmis comme modèle. Les trois castes de fourmis - les mâles, les ouvrières et les reines - présentent des longévités très différentes, tout en étant génétiquement identiques. Ceci implique que les différences de longévité sont dues à des variations entre castes dans le pattern d'expression de gènes. Mon travail chez la fourmi a consisté d'une part à mettre en place les outils pour identifier de tels gènes à grande échelle, de l'autre à étudier le rôle de gènes et de mécanismes qui affectent la longévité chez d'autres espèces. Pour identifier de nouveaux gènes potentiellement impliqués dans le vieillissement, nous avons développé des puces à ADN. Cette technique permet la comparaison du niveau d'expression de milliers de gènes entre deux échantillons. L'application de cette méthode aux reines et ouvrières adultes nous a jusqu'à présent permis d'identifier neuf gènes surexprimés chez les reines. Trois d'entre eux sont potentiellement impliqués dans le maintien et la réparation du soma, deux processus qui sont supposés avoir un impact crucial sur la longévité. Parmi les mécanismes impliqués dans le vieillissement chez d'autres espèces, nous nous sommes principalement intéressés aux télomères, qui sont les extrémités des chromosomes. Chez les vertébrés, les télomères se raccourcissent à chaque division cellulaire, entre autres parce que l'ADN polymérase ne peut répliquer cette partie des chromosomes en entier. Or des télomères courts entravent la prolifération des cellules et peuvent même induire l'apoptose, ce qui pourrait se répercuter sur la capacité des organismes à régénérer des tissus. J'ai pu montrer que chez les fourmis mâles (la caste qui vit le moins longtemps) les télomères se raccourcissent beaucoup plus vite que chez les reines et les ouvrières. L'explication la plus plausible pour cette différence est que les mâles, étant adapté à une vie très éphémère, n'investissent qu'un minimum d'énergie dans la machinerie de maintenance qui assure le bon fonctionnement des cellules. Ces résultats sont intéressants car ils permettent pour la première fois de faire le lien entre les théories évolutives du vieillissement et la biologie des télomères. THESIS ABSTRACT During my thesis I used ants as a model to study the proximate (i.e., molecular) causes of ageing and lifespan determination. Ant queens, workers and males differ tremendously in lifespan, although all three castes are genetically identical. Importantly, this implies that genes and molecular pathways responsible for modulating lifespan are regulated in a caste-specific manner. To find new genes potentially involved in ageing, we first constructed 371-gene-cDNA microarrays for the ant L. niger. This molecular tool can be used to survey the relative gene expression levels of two samples for thousands of genes simultaneously. By applying this method to adult queens and workers we identified nine genes that are overexpressed in queens. Three of them are putatively involved in somatic maintenance and repair, two processes that have been previously suggested as important for ageing and lifespan determination. We expect to identify many more candidate genes in the near future by using the 9000-gene fire ant microarrays we have recently developed. We also investigated whether factors linked to ageing in other organisms could affect lifespan determination in ants. One project was on telomeres, the ends of linear chromosomes. For various reasons telomeres shorten with every cell division. Since short telomeres can lead to cellular defects such as impaired cell division, telomeres have been hypothesized as playing a role in ageing. We tested whether telomere length in ant somatic tissues correlates with caste-specific lifespan in young adults. The short-lived L. niger mates did indeed have significantly shorter telomeres than the longer-lived queens and workers, probably because telomere attrition is faster in males than in queens and workers. Queens did not, however, have longer telomeres than the shorter-lived workers. These findings are consistent with the idea that telomere length may play a role in ageing under some circumstances, but they also clearly demonstrate that other factors must be involved. We argue that sex-specific telomere length patterns in ants ultimately reflect adaptive differences in the level of somatic maintenance between males and females, and thus create a link between telomere biology and the evolutionary theory of ageing.

Reinforcement learning utilizes proxemics: an avatar learns to manipulate the position of people in immersive virtual reality

A reinforcement learning (RL) method was used to train a virtual character to move participants to a specified location. The virtual environment depicted an alleyway displayed through a wide field-of-view head-tracked stereo head-mounted display. Based on proxemics theory, we predicted that when the character approached within a personal or intimate distance to the participants, they would be inclined to move backwards out of the way. We carried out a between-groups experiment with 30 female participants, with 10 assigned arbitrarily to each of the following three groups: In the Intimate condition the character could approach within 0.38m and in the Social condition no nearer than 1.2m. In the Random condition the actions of the virtual character were chosen randomly from among the same set as in the RL method, and the virtual character could approach within 0.38m. The experiment continued in each case until the participant either reached the target or 7 minutes had elapsed. The distributions of the times taken to reach the target showed significant differences between the three groups, with 9 out of 10 in the Intimate condition reaching the target significantly faster than the 6 out of 10 who reached the target in the Social condition. Only 1 out of 10 in the Random condition reached the target. The experiment is an example of applied presence theory: we rely on the many findings that people tend to respond realistically in immersive virtual environments, and use this to get people to achieve a task of which they had been unaware. This method opens up the door for many such applications where the virtual environment adapts to the responses of the human participants with the aim of achieving particular goals.

How Accurate Are Blood (or Breath) Tests for Identifying Self-Reported Heavy Drinking Among People with Alcohol Dependence?

AIMS: Managing patients with alcohol dependence includes assessment for heavy drinking, typically by asking patients. Some recommend biomarkers to detect heavy drinking but evidence of accuracy is limited. METHODS: Among people with dependence, we assessed the performance of disialo-carbohydrate-deficient transferrin (%dCDT, ≥1.7%), gamma-glutamyltransferase (GGT, ≥66 U/l), either %dCDT or GGT positive, and breath alcohol (> 0) for identifying 3 self-reported heavy drinking levels: any heavy drinking (≥4 drinks/day or >7 drinks/week for women, ≥5 drinks/day or >14 drinks/week for men), recurrent (≥5 drinks/day on ≥5 days) and persistent heavy drinking (≥5 drinks/day on ≥7 consecutive days). Subjects (n = 402) with dependence and current heavy drinking were referred to primary care and assessed 6 months later with biomarkers and validated self-reported calendar method assessment of past 30-day alcohol use. RESULTS: The self-reported prevalence of any, recurrent and persistent heavy drinking was 54, 34 and 17%. Sensitivity of %dCDT for detecting any, recurrent and persistent self-reported heavy drinking was 41, 53 and 66%. Specificity was 96, 90 and 84%, respectively. %dCDT had higher sensitivity than GGT and breath test for each alcohol use level but was not adequately sensitive to detect heavy drinking (missing 34-59% of the cases). Either %dCDT or GGT positive improved sensitivity but not to satisfactory levels, and specificity decreased. Neither a breath test nor GGT was sufficiently sensitive (both tests missed 70-80% of cases). CONCLUSIONS: Although biomarkers may provide some useful information, their sensitivity is low the incremental value over self-report in clinical settings is questionable.

Gait disturbances as specific predictive markers of the first fall onset in elderly people: a two-year prospective observational study

Falls are common in the elderly, and potentially result in injury and disability. Thus, preventing falls as soon as possible in older adults is a public health priority, yet there is no specific marker that is predictive of the first fall onset. We hypothesized that gait features should be the most relevant variables for predicting the first fall. Clinical baseline characteristics (e.g., gender, cognitive function) were assessed in 259 home-dwelling people aged 66 to 75 that had never fallen. Likewise, global kinetic behavior of gait was recorded from 22 variables in 1036 walking tests with an accelerometric gait analysis system. Afterward, monthly telephone monitoring reported the date of the first fall over 24 months. A principal components analysis was used to assess the relationship between gait variables and fall status in four groups: non-fallers, fallers from 0 to 6 months, fallers from 6 to 12 months and fallers from 12 to 24 months. The association of significant principal components (PC) with an increased risk of first fall was then evaluated using the area under the Receiver Operator Characteristic Curve (ROC). No effect of clinical confounding variables was shown as a function of groups. An eigenvalue decomposition of the correlation matrix identified a large statistical PC1 (termed "Global kinetics of gait pattern"), which accounted for 36.7% of total variance. Principal component loadings also revealed a PC2 (12.6% of total variance), related to the "Global gait regularity." Subsequent ANOVAs showed that only PC1 discriminated the fall status during the first 6 months, while PC2 discriminated the first fall onset between 6 and 12 months. After one year, any PC was associated with falls. These results were bolstered by the ROC analyses, showing good predictive models of the first fall during the first six months or from 6 to 12 months. Overall, these findings suggest that the performance of a standardized walking test at least once a year is essential for fall prevention.