Dynamic Functional Connectivity Analysis Reveals Transient States of Dysconnectivity in Schizophrenia

Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients.However, observed connectivity differences in schizophrenia have been inconsistent between studies,with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on amulti-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using slidingwindows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spendmuch less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical–subcortical antagonism (anticorrelations) and strong positive connectivity between sensory networks are those that showthe group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivitywith sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences

Geology and petrology of part of the Archaean inlier north-east of Yankalilla on the Fleurieu Peninsula

This item is only available electronically.The Archaean inlier to the east of Yankalilla on the Fleurieu Peninsula forms the core of an overturned anticlinal structure whose limbs and hinge line dip and plunge to the south-east. The fold is delineated by the overlying unconformable Proterozoic and Cambrian sediments. There is evidence of a sheared boundary along the north-western edge of the inlier. The schistosity and layering of the basement schists, quartzofeldspathic schists, gneisses and feldspar gneisses parallels the axial plane structure of the anticline. The basement has possibly undergone intense deformation before the deposition of the Adelaidean in the form of tight isoclinal folding. It is intruded by amphibolite dykes and pegmatites. The metamorphic grade has reached at least upper amphibolite facies and has been retrograded to Greenschist facies.Thesis (B.Sc.(Hons)) -- University of Adelaide, School of Physical Sciences, 197

Genetic Correlations between Days to Calving across Joinings and Lactation Status in a Tropically Adapted Composite Beef Herd

Female fertility is essential to any beef breeding program. However, little genetic gain has been made due to long generation intervals and low levels of phenotyping. Days to calving (DC) is a fertility trait that may provide genetic gain and lead to an increased weaning rate. Genetic parameters and correlations were estimated and compared for DC across multiple joinings (first, second and third+) and lactation status (lactating and non-lactating) for a tropical composite cattle population where cattle were first mated as yearlings. The genetic correlation between first joining DC and mature joining DC (third+) was moderate–high (0.55–0.83). DC was uncorrelated between multiparous lactating and non-lactating cows (rG = −0.10). Mature joining DC was more strongly correlated with second joining lactating DC (0.41–0.69) than with second joining non-lactating DC (−0.14 to −0.16). Thus, first joining DC, second joining DC and mature joining DC should be treated as different traits to maximise genetic gain. Further, for multi-parous cows, lactating and non-lactating DC should be treated as different traits. Three traits were developed to report back to the breeding programs to maximise genetic gain: the first joining days to calving, the second joining days to calving lactating and mature days to calving lactating

Regulatory authority and clinical acceptability: Physicians’ responses to regulatory drug safety warnings

Aim Medicines regulators issue post-market safety warnings to advise of newly uncovered risks, but with mixed impacts. We aimed to identify factors influencing the use of regulatory warnings by primary care and specialist physicians in the US and Australia. Methods Semi-structured qualitative interviews with 40 primary care physicians, endocrinologists, and other generalist specialists in Boston USA and Australia. Coding and analysis were carried out inductively and iteratively to identify and examine key factors. Analysis centred around four areas; physicians’ awareness of drug safety information, preferred information sources, opinion-forming, and sharing of information with patients. Results Uncertainty, trust, and clinical authority emerged as factors influencing use of advisories. Although regulators were trusted as authoritative institutions, they appeared to lack clinical authority, and physicians validated regulatory information against other trusted sources including evidence, expert opinion, and experience. Specialists became aware of drug safety issues through specialised literature, using evidence and clinical consensus to form opinions. Primary care physicians, fielding high volumes of information, relied on convenient, accessible information sources including the media and the ‘clinical grapevine’ for awareness, and on clinical colleagues, specialists, and experience for interpretation. Communicating risk to patients was complicated by uncertainty; physicians tailored information to patients’ health literacy and information needs. US physicians were more aware of their national regulator’s post-market safety role than Australian physicians of theirs. Conclusion Drug safety warnings may not be optimally received or used. Regulators should consider strategies that increase trust, clinical relevance, and accessibility, and address physicians’ needs in communicating risk to patients

Comparison of Methods to Select Candidates for High-Density Genotyping; Practical Observations in a Cattle Breeding Program

Imputation can be used to obtain a large number of high-density genotypes at the cost of procuring low-density panels. Accurate imputation requires a well-formed reference population of high-density genotypes to enable statistical inference. Five methods were compared using commercial Wagyu genotype data to identify individuals to produce a “well-formed” reference population. Two methods utilised a relationship matrix (MCG and MCA), two of which utilised a haplotype block library (AHAP2 and IWS), and the last selected high influential sires with greater than 10 progeny (PROG). The efficacy of the methods was assessed based on the total proportion of genetic variance accounted for and the number of haplotypes captured, as well as practical considerations in implementing these methods. Concordance was high between the MCG and MCA and between AHAP2 and IWS but was low between these groupings. PROG-selected animals were most similar to MCA. MCG accounted for the greatest proportion of genetic variance in the population (35%, while the other methods accounted for approximately 30%) and the greatest number of unique haplotypes when a frequency threshold was applied. MCG was also relatively simple to implement, although modifications need to be made to account for DNA availability when running over a whole population. Of the methods compared, MCG is the recommended starting point for an ongoing sequencing project