A novel phenotyping strategy in schizophrenia, targeting different neurocognitive domains, neurobehavioral features, and selected personality traits, has allowed us to identify a homogeneous familial subtype of the disease, characterized by pervasive neurocognitive deficit. Our genome scan data indicate that this subtype, which accounts for up to 50% of our sample, has a distinct genetic basis and explains linkage to chromosome 6p24 reported previously. If representative of other populations, the ratio of schizophrenia subtypes observed in our families could have a profound impact on sample heterogeneity and on the power of genetic studies to detect linkage and association. Our proposed abbreviated battery of tests should facilitate phenotype characterization for future genetic analyses and allow a focus on a crisply defined schizophrenia subtype, thus promoting a more informed search for susceptibility genes.

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research.

Objective: Access to services and workforce shortages are major challenges in rural areas worldwide. In order to improve access to mental health care, it is imperative to understand what services are available, what their capacity is and where existing funds might be spent to increase availability and accessibility. The aim of this study is to investigate mental health service provision in a selection of rural and remote areas across Australia by analysing service availability, placement capacity and diversity. Method: This research studies the health regions of Western New South Wales and Country Western Australia and their nine health areas. Service provision was analysed using the DESDE-LTC system for long-term care service description and classification that allows international comparison. Rates per 100,000 inhabitants were calculated to compare the care availability and placement capacity for children and adolescents, adults and older adults. Results: The lowest diversity was found in northern Western Australia. Overall, Western New South Wales had a higher availability of non-acute outpatient services for adults, but hardly any acute outpatient services. In Country Western Australia, substantially fewer non-acute outpatient services were found, while acute services were much more common. Acute inpatient care services were more common in Western New South Wales, while sub-acute inpatient services and non-acute day care services were only found in Western New South Wales. Conclusion: The number and span of services in the two regions showed discrepancies both within and between regions, raising issues on the equity of access to mental health care in Australia. The standard description of the local pattern of rural mental health care and its comparison across jurisdictions is critical for evidence-informed policy planning and resource allocation.

The metabolic stability of a drug is an important property that should be optimized during drug design and development. Nitrogen incorporation is hypothesized to increase the stability by coordination of nitrogen to the heme iron of cytochrome P450, a binding mode that is referred to as type II binding. However, we noticed that the type II binding compound 1 has less metabolic stability at subsaturating conditions than a closely related type I binding compound 3. Three kinetic models will be presented for type II binder metabolism; 1) Dead-end type II binding, 2) a rapid equilibrium between type I and II binding modes before reduction, and 3) a direct reduction of the type II coordinated heme. Data will be presented on reduction rates of iron, the off rates of substrate (using surface plasmon resonance) and the catalytic rate constants. These data argue against the dead-end, and rapid equilibrium models, leaving the direct reduction kinetic mechanism for metabolism of the type II binding compound 1.