AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Being old in our society : health, functional status, and effects of research

This thesis concerns health and functional status in old age, as well as older adults' attitudes towards research participation. Five studies were performed using data from the Kungsholmen Project, a population-based study on ageing and dementia ongoing in Stockholm since 1987. Occurrence of dementia. Both prevalence and incidence of dementia were investigated. In the 75-79 age group the incidence rates for dementia were 19.6 for women and 12.4 for men per 1,000 person-years, whereas the corresponding figures were 86.7 and 15.0 among 90+ year old subjects. A prevalence study with an enlarged sample of nonagenarians showed that the probability of having dementia after the age of 75 increased by 10% each year and 90% every 5 years. AD contributed to 76. 5% and VaD to 17.9% of the prevalent cases. Health and functional status. Higher morbidity prevalence in women than in men was detected only after the age of 85. 90+ year old women compared to men had an OR=2.2 (95% CI 1.1-4-3) for disability after adjustment for age, education, and number of diseases. Functionally independent men in the youngest age group had a higher risk of death than women (OR=0.4; 95% CI 0.3-0.7), whereas no gender difference was found among disabled subjects. Incidence of long term disability in women was higher than in men only in the 90+ years old subjects, although the difference was not statistically significant after adjustment. Effects of research. In a postal questionnaire, 79% of the subjects reported advantages in research participation. Older elderly with impaired cognitive functioning and lower education showed the least positive attitude. The first contact and the cognitive testing were judged as the most stressful situations. Community-based longitudinal surveys also appear to have a social function, thus stressing ethical issues regarding the termination of contact when studies are completed. Conclusions. The dementia incidence increases with age, even in the most advanced ages. This increase is especially evident among women, leading to an increased risk of dementia in the male gender. A large proportion of nonagenarians were functionally independent (73%) despite their advanced age, and 19% had no diseases at all. The gender distribution of morbidity, mortality and disability was modified by age. 90+ year old women were more disabled than men, partially due to the excess of dementia and other chronic diseases. We hypothesise that more women may be at higher risk of developing severe disability than men in the advanced ages due to a longer survival of women with slight disability in earlier ages. Finally, this thesis provides empirical data concerning the impact of longitudinal research on participants that may help researchers in lowering the refusal rate in epidemiological studies, and might assist ethics committees in making their judgements

Higher education as a platform for capacity building to address violence against women and promote gender equality: the Swedish example

Abstract Violence against women is an acknowledged public and global health problem which has adverse consequences for women’s health. Education, especially higher education, has long been identified as an important arena for addressing the problem and promoting gender equality. Two measures recently put in place in the Swedish higher education have brought the role of the sector into focus. The first is the inclusion of gender equality as a measurable outcome in quality assurance in higher education. The second measure is the amendment of the Swedish Higher Education Ordinance to include mandatory knowledge of VAW in the degree programme of seven selected relevant professional groups. The potentials of both measures to positively contribute to the gender equality discourse, as well as improving capacity building for the public health workforce who encounter VAW, are discussed

Incidence of ADL Disability in Older Persons, Physical Activities as a Protective Factor and the Need for Informal and Formal Care--Results from the SNAC-N Project.

The aim of the study was to examine 1) the incidence of disability in Activities of Daily Living (ADL), in persons 78 years and older 2) explore whether being physical active earlier is a significant predictor of being disability free at follow-up and 3) describe the amount of informal and formal care in relation to ADL-disability.Data were used from a longitudinal community-based study in Nordanstig (SNAC-N), a part of the Swedish National Study on Aging and Care (SNAC). To study objectives 1) and 2) all ADL-independent participants at baseline (N = 307) were included; for objective 3) all participants 78 years and older were included (N = 316). Data were collected at baseline and at 3- and 6-year follow-ups. ADL-disability was defined as a need for assistance in one or more activities. Informal and formal care were measured using the Resource utilization in Dementia (RUD)-instrument.The incidence rates for men were similar in the age groups 78-81 and 84 years and older, 42.3 vs. 42.5/1000 person-years. For women the incidence rate for ADL-disability increased significantly from the age group 78-81 to the age group 84 years and older, 20.8 vs.118.3/1000 person-years. In the age group 78-81 years, being physically active earlier (aOR 6.2) and during the past 12 month (aOR 2.9) were both significant preventive factors for ADL-disability. Both informal and formal care increased with ADL-disability and the amount of informal care was greater than formal care. The incidence rate for ADL-disability increases with age for women and being physically active is a protective factor for ADL-disability.The incidence rate for ADL-disability increases with age for women, and being physical active is a protective factor for ADL-disability

Unlicensed personnel administering medications to older persons living at home : a challenge for social and care services

BACKGROUND: Administration of medication to care recipients is delegated to home-care assistants working in the municipal social care, alongside responsibility for providing personal assistance for older people. Home-care assistants have practical administration skills, but lack formal medical knowledge. AIM: The aim of this study was to explore how home-care assistants perceive administration of medication to older people living at home, as delegated to them in the context of social care. METHODS: Four focus groups consisting of 19 home-care assistants were conducted. Data were analysed using qualitative content analysis. RESULTS: According to home-care assistants, health and social care depends on delegation arrangements to function effectively, but in the first place it relieves a burden for district nurses. Even when the delegation had expired, administration of medication continued, placing the statutes of regulation in a subordinate position. There was low awareness among home-care assistants about the content of the statutes of delegation. Accepting delegation to administer medications has become an implicit prerequisite for social care work in the municipality. CONCLUSIONS: Accepting the delegation to administer medication was inevitable and routine. In practice, the regulating statute is made subordinate and consequently patient safety can be threatened. The organisation of health and social care relies on the delegation arrangement to meet the needs of a growing number of older home-care recipients. IMPLICATIONS FOR PRACTICE: This is a crucial task which management within both the healthcare professions and municipal social care needs to address, to bridge the gap between statutes and practice, to create arenas for mutual collaboration in the care recipients' best interest and to ensure patient safety