Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice

Psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder and autism spectrum disorder are common and result in significant morbidity and mortality. Although currently classified into distinct disorder categories, they show clinical overlap and familial co-aggregation, and share genetic risk factors. Recent advances in psychiatric genomics have provided insight into the potential mechanisms underlying the overlap between these disorders, implicating genes involved in neurodevelopment, synaptic plasticity, learning and memory. Furthermore, evidence from copy number variant, exome sequencing and genome-wide association studies supports a gradient of neurodevelopmental psychopathology indexed by mutational load or mutational severity, and cognitive impairment. These findings have important implications for psychiatric research, highlighting the need for new approaches to stratifying patients for research. They also point the way for work aiming to advance our understanding of the pathways from genotype to clinical phenotype, which will be required in order to inform new classification systems and to develop novel therapeutic strategies

Singlet levels of the NV−^{-} centre in diamond

The characteristic transition of the NV- centre at 637 nm is between ${}^3\mathrm{A}_2$ and ${}^3\mathrm{E}$ triplet states. There are also intermediate ${}^1\mathrm{A}_1$ and ${}^1\mathrm{E}$ singlet states, and the infrared transition at 1042 nm between these singlets is studied here using uniaxial stress. The stress shift and splitting parameters are determined, and the physical interaction giving rise to the parameters is considered within the accepted electronic model of the centre. It is established that this interaction for the infrared transition is due to a modification of electron-electron Coulomb repulsion interaction. This is in contrast to the visible 637 nm transition where shifts and splittings arise from modification to the one-electron Coulomb interaction. It is also established that a dynamic Jahn-Teller interaction is associated with the singlet ${}^1\mathrm{E}$ state, which gives rise to a vibronic level 115 $\mathrm{cm}^{-1}$ above the ${}^1\mathrm{E}$ electronic state. Arguments associated with this level are used to provide experimental confirmation that the ${}^1\mathrm{A}_1$ is the upper singlet level and ${}^1\mathrm{E}$ is the lower singlet level.Comment: 19 pages, 6 figure

Vastus medialis motor unit properties in knee osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Maximal isometric quadriceps strength deficits have been widely reported in studies of knee osteoarthritis (OA), however little is known about the effect of osteoarthritis knee pain on submaximal quadriceps neuromuscular function. The purpose of this study was to measure vastus medialis motor unit (MU) properties in participants with knee OA, during submaximal isometric contractions.</p> <p>Methods</p> <p>Vastus medialis motor unit potential (MUP) parameters were assessed in 8 patients with knee OA and 8 healthy, sex and age-matched controls during submaximal isometric contractions (20% of maximum isometric torque). Unpaired t-tests were used to compare groups for demographic and muscle parameters.</p> <p>Results</p> <p>Maximum knee extension torque was ~22% lower in the OA group, a difference that was not statistically significantly (p = 0.11). During submaximal contractions, size related parameters of the needle MUPs (e.g. negative peak duration and amplitude-to-area ratio) were greater in the OA group (p < 0.05), with a rightward shift in the frequency distribution of surface MUP negative peak amplitude. MUP firing rates were significantly lower in the OA group (p < 0.05).</p> <p>Conclusions</p> <p>Changes in MU recruitment and rate coding strategies in OA may reflect a chronic reinnervation process or a compensatory strategy in the presence of chronic knee pain associated with OA.</p

Using Organizational, Coordination, and Contingency Theories to Examine Project Manager Insights on Agile and Traditional Success Factors for Information Technology Projects

Two dominant research views addressing disappointing success rates for information technology (IT) projects suggest project success may depend on the presence of a large number of critical success factors or advocate for agile project management as an alternative to traditional practice. However, after two decades of research, success rates remain low, and the role of critical success factors or project management approach remains unclear. The purpose of this study was to use views of experienced project managers to explore the contribution of success factors and management approach to project success. Applying organizational, coordination, and contingency theories, the research questions examined IT project manager perceptions about success factors, how those success factors interrelate, and the role of management approach in project success. A Q methodology mixed method design was used to analyze subjective insights of project managers about the important critical success factors for IT projects. Two critical success factors emerged as important: a sustained commitment from upper management to the project and clear, measurable project goals and objectives. Three composite factors also surfaced representing the importance of people-project interactions, user/client involvement, and traditional project management tasks. The analyses found no broad support for agile project management and could not confirm principles of organizational or coordination theories as critical for project success. However, a contingent relationship might exist between some critical success factors and merits further investigation. Helping the project management community understand IT project success factors could improve project execution and reduce failure rates leading to sizeable savings for project clients

Entanglement of indistinguishable particles in condensed matter physics

The concept of entanglement in systems where the particles are indistinguishable has been the subject of much recent interest and controversy. In this paper we study the notion of entanglement of particles introduced by Wiseman and Vaccaro [Phys. Rev. Lett. 91, 097902 (2003)] in several specific physical systems, including some that occur in condensed matter physics. The entanglement of particles is relevant when the identical particles are itinerant and so not distinguished by their position as in spin models. We show that entanglement of particles can behave differently to other approaches that have been used previously, such as entanglement of modes (occupation-number entanglement) and the entanglement in the two-spin reduced density matrix. We argue that the entanglement of particles is what could actually be measured in most experimental scenarios and thus its physical significance is clear. This suggests entanglement of particles may be useful in connecting theoretical and experimental studies of entanglement in condensed matter systems.Comment: 13 pages, 6 figures, comments welcome, published version (minor changes, added references

NASA/DOE/DOD nuclear propulsion technology planning: Summary of FY 1991 interagency panel results

Interagency (NASA/DOE/DOD) technical panels worked in 1991 to evaluate critical nuclear propulsion issues, compare nuclear propulsion concepts for a manned Mars mission on a consistent basis, and to continue planning a technology development project for the Space Exploration Initiative (SEI). Panels were formed to address mission analysis, nuclear facilities, safety policy, nuclear fuels and materials, nuclear electric propulsion technology, and nuclear thermal propulsion technology. A summary of the results and recommendations of the panels is presented

Individualizing therapies with responsive epilepsy neurostimulation — A mirtazapine case study of hippocampal excitability

AbstractObjectivesThis study aimed to investigate mirtazapine-induced changes in responsive neurostimulator (RNS) recordings in a patient with epilepsy.Materials and methodsCortical detection/stimulation counts from an RNS implanted in a patient with bitemporal epilepsy were matched to mirtazapine use to see if that drug altered hippocampal excitability.ResultsMirtazapine decreased hippocampal stability; when mirtazapine was held after a washout period, DSC counts declined, but when it was retrialed, DSC counts increased. Responsive epilepsy neurostimulator system data helped design an optimal and individualized medication regimen for our patient with drug-resistant focal epilepsy.ConclusionsResponsive neurostimulator systems in epilepsy may assess a medication's effect on hippocampal excitability. Mirtazapine worsened hippocampal excitability in a patient with bitemporal epilepsy

A descriptive epidemiological study of mastitis in 12 Irish dairy herds

<p/> <p>Factors relating to the occurrence of mastitis were studied on 12 Irish dairy herds with histories of elevated somatic cell count (SCC) and/or increased incidence of clinical mastitis cases. Milk recording data were analysed, housing conditions and calving areas were examined; dry cow therapy, clinical mastitis records, milking technique and aspects of milking machine function were assessed.</p> <p>Herds with a ratio of less than 110 cubicles per 100 cows were more likely to experience environmental mastitis. Herds with inadequate calving facilities, where cows spent prolonged periods on straw bedding, were likely to acquire environmental mastitis. In the majority of the herds, the selection of dry cow therapy lacked adequate planning. The majority of farmers took no action to reduce pain experienced by cows suffering mastitis. Deficiencies in parlour hygiene were evident in all herds experiencing elevation in SCC.</p

Pregnancy outcomes in women with epilepsy and MTHFR mutations supplemented with methylated folate and methylcobalamin (methylated B12).

Antiseizure medications (ASM) may contribute to adverse fetal outcomes in pregnant women with epilepsy (WWE). Folate processing (Methylenetetrahydrofolate reductase, MTHFR) gene abnormalities are common in women with epilepsy and depression. L-methylfolate supplements may bypass MTHFR deficiencies, yet their use in WWE during gestation or on fetal development is not well studied. We examine pregnancy histories of three WWE who supplemented with either folate or L-methylfolate and methylcobalamin (methylated B12) during pregnancies. Their pregnancy outcomes improved with L-methylfolate and methylcobalamin supplementation. L-methylfolate and methylcobalamin supplementation merits further study in WWE who have MTHFR mutations, fertility, recurrent miscarriage and or depression histories