Showing papers by "University of Melbourne published in 2006"

Novel methods improve prediction of species' distributions from occurrence data

Abstract: Prediction of species' distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approaches for modelling distributions. To meet this need, we compared 16 modelling methods over 226 species from 6 regions of the world, creating the most comprehensive set of model comparisons to date. We used presence-only data to fit models, and independent presence-absence data to evaluate the predictions. Along with well-established modelling methods such as generalised additive models and GARP and BIOCLIM, we explored methods that either have been developed recently or have rarely been applied to modelling species' distributions. These include machine-learning methods and community models, both of which have features that may make them particularly well suited to noisy or sparse information, as is typical of species' occurrence data. Presence-only data were effective for modelling species' distributions for many species and regions. The novel methods consistently outperformed more established methods. The results of our analysis are promising for the use of data from museums and herbaria, especially as methods suited to the noise inherent in such data improve.

Anticancer activities of histone deacetylase inhibitors.

Abstract: Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. In addition, the activity of non-histone proteins can be regulated through HDAC-mediated hypo-acetylation. In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. However, such studies have also indicated that the effects of HDAC inhibitors could be considerably broader and more complicated than originally understood. Here we summarize recent advances in the understanding of the molecular events that underlie the anticancer effects of HDAC inhibitors, and discuss how such information could be used in optimizing the development and application of these agents in the clinic, either as monotherapies or in combination with other anticancer drugs.

Generation of a functional mammary gland from a single stem cell

Abstract: The existence of mammary stem cells (MaSCs) has been postulated from evidence that the mammary gland can be regenerated by transplantation of epithelial fragments in mice. Interest in MaSCs has been further stimulated by their potential role in breast tumorigenesis. However, the identity and purification of MaSCs has proved elusive owing to the lack of defined markers. We isolated discrete populations of mouse mammary cells on the basis of cell-surface markers and identified a subpopulation (Lin-CD29hiCD24+) that is highly enriched for MaSCs by transplantation. Here we show that a single cell, marked with a LacZ transgene, can reconstitute a complete mammary gland in vivo. The transplanted cell contributed to both the luminal and myoepithelial lineages and generated functional lobuloalveolar units during pregnancy. The self-renewing capacity of these cells was demonstrated by serial transplantation of clonal outgrowths. In support of a potential role for MaSCs in breast cancer, the stem-cell-enriched subpopulation was expanded in premalignant mammary tissue from MMTV-wnt-1 mice and contained a higher number of MaSCs. Our data establish that single cells within the Lin-CD29hiCD24+ population are multipotent and self-renewing, properties that define them as MaSCs.

Dehumanization: An Integrative Review

Abstract: The concept of dehumanization lacks a systematic theoretical basis, and research that addresses it has yet to be integrated. Manifestations and theories of dehumanization are reviewed, and a new model is developed. Two forms of dehumanization are proposed, involving the denial to others of 2 distinct senses of humanness: characteristics that are uniquely human and those that constitute human nature. Denying uniquely human attributes to others represents them as animal-like, and denying human nature to others represents them as objects or automata. Cognitive underpinnings of the "animalistic" and "mechanistic" forms of dehumanization are proposed. An expanded sense of dehumanization emerges, in which the phenomenon is not unitary, is not restricted to the intergroup context, and does not occur only under conditions of conflict or extreme negative evaluation. Instead, dehumanization becomes an everyday social phenomenon, rooted in ordinary social-cognitive processes.

Bone Quality — The Material and Structural Basis of Bone Strength and Fragility

Abstract: This review discusses advances in knowledge regarding the composition and structure of bone, the modeling and remodeling of bone, the formation of bone during growth and its reconstruction in adults, and how age-related abnormalities in these processes compromise the composition and structure of bone.

The Gaussian Mixture Probability Hypothesis Density Filter

Abstract: A new recursive algorithm is proposed for jointly estimating the time-varying number of targets and their states from a sequence of observation sets in the presence of data association uncertainty, detection uncertainty, noise, and false alarms. The approach involves modelling the respective collections of targets and measurements as random finite sets and applying the probability hypothesis density (PHD) recursion to propagate the posterior intensity, which is a first-order statistic of the random finite set of targets, in time. At present, there is no closed-form solution to the PHD recursion. This paper shows that under linear, Gaussian assumptions on the target dynamics and birth process, the posterior intensity at any time step is a Gaussian mixture. More importantly, closed-form recursions for propagating the means, covariances, and weights of the constituent Gaussian components of the posterior intensity are derived. The proposed algorithm combines these recursions with a strategy for managing the number of Gaussian components to increase efficiency. This algorithm is extended to accommodate mildly nonlinear target dynamics using approximation strategies from the extended and unscented Kalman filters

A systematic review of empirical research on self-reported racism and health

Abstract: This paper reviews 138 empirical quantitative population-based studies of self-reported racism and health. These studies show an association between self-reported racism and ill health for oppressed racial groups after adjustment for a range of confounders. The strongest and most consistent findings are for negative mental health outcomes and health-related behaviours, with weaker associations existing for positive mental health outcomes, self-assessed health status, and physical health outcomes. Most studies in this emerging field have been published in the past 5 years and have been limited by a dearth of cohort studies, a lack of psychometrically validated exposure instruments, poor conceptualization and definition of racism, conflation of racism with stress, and debate about the aetiologically relevant period for self-reported racism. Future research should examine the psychometric validity of racism instruments and include these instruments, along with objectively measured health outcomes, in existing large-scale survey vehicles as well as longitudinal studies and studies involving children. There is also a need to gain a better understanding of the perception, attribution, and reporting of racism, to investigate the pathways via which self-reported racism affects health, the interplay between mental and physical health outcomes, and exposure to intra-racial, internalized, and systemic racism. Ensuring the quality of studies in this field will allow future research to reveal the complex role that racism plays as a determinant of population health.

Identifying the Dominant Soil Bacterial Taxa in Libraries of 16S rRNA and 16S rRNA Genes

Abstract: From near to far , from here to there , funny things are everywhere. —Dr. Seuss, One Fish Two Fish Red Fish Blue Fish In 1909, H. Joel Conn ([25][1]) expressed the hope that methods would soon be at hand by which the significance of the different bacteria present in any soil could be

Enriched environments, experience-dependent plasticity and disorders of the nervous system.

Abstract: Behavioural, cellular and molecular studies have revealed significant effects of enriched environments on rodents and other species, and provided new insights into mechanisms of experience-dependent plasticity, including adult neurogenesis and synaptic plasticity The demonstration that the onset and progression of Huntington's disease in transgenic mice is delayed by environmental enrichment has emphasized the importance of understanding both genetic and environmental factors in nervous system disorders, including those with Mendelian inheritance patterns A range of rodent models of other brain disorders, including Alzheimer's disease and Parkinson's disease, fragile X and Down syndrome, as well as various forms of brain injury, have now been compared under enriched and standard housing conditions Here, we review these findings on the environmental modulators of pathogenesis and gene-environment interactions in CNS disorders, and discuss their therapeutic implications

New specifications for exponential random graph models

Abstract: The most promising class of statistical models for expressing structural properties of social networks observed at one moment in time is the class of exponential random graph models (ERGMs), also known as p∗ models. The strong point of these models is that they can represent a variety of structural tendencies, such as transitivity, that define complicated dependence patterns not easily modeled by more basicpr obability models. Recently, Markov chain Monte Carlo (MCMC) algorithms have been developed that produce approximate maximum likelihood estimators. Applying these models in their traditional specification to observed network data often has led to problems, however, which can be traced back to the fact that important parts of the parameter space correspond to nearly degenerate distributions, which may lead to convergence problems of estimation algorithms, and a poor fit to empirical data. This paper proposes new specifications of exponential random graph models. These specifications represent structural properties such as transitivity and heterogeneity of degrees by more complicated graph statistics than the traditional star and triangle counts. Three kinds of statistics are proposed: geometrically weighted degree distributions, alternating k-triangles, and alternating independent two-paths. Examples are presented both of modeling graphs and digraphs, in which the new specifications lead to much better results than the earlier existing specifications of the ERGM. It is concluded that the new specifications increase the range and applicability of the ERGM as a tool for the statistical analysis of social networks.

1,026 Experimental treatments in acute stroke

Abstract: Objective: Preclinical evaluation of neuroprotectants fostered high expectations of clinical efficacy. When not matched, the question arises whether experiments are poor indicators of clinical outcome or whether the best drugs were not taken forward to clinical trial. Therefore, we endeavored to contrast experimental efficacy and scope of testing of drugs used clinically and those tested only experimentally. Methods: We identified neuroprotectants and reports of experimental efficacy via a systematic search. Controlled in vivo and in vitro experiments using functional or histological end points were selected for analysis. Relationships between outcome, drug mechanism, scope of testing, and clinical trial status were assessed statistically. Results: There was no evidence that drugs used clinically (114 drugs) were more effective experimentally than those tested only in animal models (912 drugs), for example, improvement in focal models averaged 31.3 16.7% versus 24.4 32.9%, p > 0.05, respectively. Scope of testing using Stroke Therapy Academic Industry Roundtable (STAIR) criteria was highly variable, and no relationship was found between mechanism and efficacy. Interpretation: The results question whether the most efficacious drugs are being selected for stroke clinical trials. This may partially explain the slow progress in developing treatments. Greater rigor in the conduct, reporting, and analysis of animal data will improve the transition of scientific advances from bench to bedside. Ann Neurol 2006;59:467– 477 A common perception of neuroprotection research is that everything works in animals but nothing works in people. This perception has been reinforced again and again by reports of unsuccessful or mixed outcomes in trials of candidate neuroprotectants in acute stroke patients. If animal experiments are indeed unable to inform clinical decision making, then serious doubts are raised about the utility of animal models of stroke and about the ethics of continuing current animal experimentation practices. 1 In response to this challenge, several excellent reviews and commentaries have tackled the issue of the apparent failure to translate neuroprotection successes from the laboratory to the clinical setting (for examples, see previously published studies 2–7 ). Such com

Inverted files for text search engines

Abstract: The technology underlying text search engines has advanced dramatically in the past decade. The development of a family of new index representations has led to a wide range of innovations in index storage, index construction, and query evaluation. While some of these developments have been consolidated in textbooks, many specific techniques are not widely known or the textbook descriptions are out of date. In this tutorial, we introduce the key techniques in the area, describing both a core implementation and how the core can be enhanced through a range of extensions. We conclude with a comprehensive bibliography of text indexing literature.

Neonatal MRI to Predict Neurodevelopmental Outcomes in Preterm Infants

Abstract: Background Very preterm infants are at high risk for adverse neurodevelopmental outcomes. Magnetic resonance imaging (MRI) has been proposed as a means of predicting neurodevelopmental outcomes in this population. Methods We studied 167 very preterm infants (gestational age at birth, 30 weeks or less) to assess the associations between qualitatively defined white-matter and gray-matter abnormalities on MRI at term equivalent (gestational age of 40 weeks) and the risks of severe cognitive delay, severe psychomotor delay, cerebral palsy, and neurosensory (hearing or visual) impairment at 2 years of age (corrected for prematurity). Results At two years of age, 17 percent of infants had severe cognitive delay, 10 percent had severe psychomotor delay, 10 percent had cerebral palsy, and 11 percent had neurosensory impairment. Moderate-to-severe cerebral white-matter abnormalities present in 21 percent of infants at term equivalent were predictive of the following adverse outcomes at two years of age: cognitive ...

A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer

Abstract: Purpose: A phase I study was conducted to assess the safety of adoptive immunotherapy using gene-modified autologous T cells for the treatment of metastatic ovarian cancer. Experimental Design: T cells with reactivity against the ovarian cancer–associated antigen α-folate receptor (FR) were generated by genetic modification of autologous T cells with a chimeric gene incorporating an anti-FR single-chain antibody linked to the signaling domain of the Fc receptor γ chain. Patients were assigned to one of two cohorts in the study. Eight patients in cohort 1 received a dose escalation of T cells in combination with high-dose interleukin-2, and six patients in cohort 2 received dual-specific T cells (reactive with both FR and allogeneic cells) followed by immunization with allogeneic peripheral blood mononuclear cells. Results: Five patients in cohort 1 experienced some grade 3 to 4 treatment-related toxicity that was probably due to interleukin-2 administration, which could be managed using standard measures. Patients in cohort 2 experienced relatively mild side effects with grade 1 to 2 symptoms. No reduction in tumor burden was seen in any patient. Tracking 111 In-labeled adoptively transferred T cells in cohort 1 revealed a lack of specific localization of T cells to tumor except in one patient where some signal was detected in a peritoneal deposit. PCR analysis showed that gene-modified T cells were present in the circulation in large numbers for the first 2 days after transfer, but these quickly declined to be barely detectable 1 month later in most patients. An inhibitory factor developed in the serum of three of six patients tested over the period of treatment, which significantly reduced the ability of gene-modified T cells to respond against FR + tumor cells. Conclusions: Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term. Future studies need to employ strategies to extend T cell persistence. This report is the first to document the use of genetically redirected T cells for the treatment of ovarian cancer.

A Review of the Integrate-and-fire Neuron Model: I. Homogeneous Synaptic Input

Abstract: The integrate-and-fire neuron model is one of the most widely used models for analyzing the behavior of neural systems. It describes the membrane potential of a neuron in terms of the synaptic inputs and the injected current that it receives. An action potential (spike) is generated when the membrane potential reaches a threshold, but the actual changes associated with the membrane voltage and conductances driving the action potential do not form part of the model. The synaptic inputs to the neuron are considered to be stochastic and are described as a temporally homogeneous Poisson process. Methods and results for both current synapses and conductance synapses are examined in the diffusion approximation, where the individual contributions to the postsynaptic potential are small. The focus of this review is upon the mathematical techniques that give the time distribution of output spikes, namely stochastic differential equations and the Fokker–Planck equation. The integrate-and-fire neuron model has become established as a canonical model for the description of spiking neurons because it is capable of being analyzed mathematically while at the same time being sufficiently complex to capture many of the essential features of neural processing. A number of variations of the model are discussed, together with the relationship with the Hodgkin–Huxley neuron model and the comparison with electrophysiological data. A brief overview is given of two issues in neural information processing that the integrate-and-fire neuron model has contributed to – the irregular nature of spiking in cortical neurons and neural gain modulation.

MPI-DING reference glasses for in situ microanalysis: New reference values for element concentrations and isotope ratios

Abstract: We present new analytical data of major and trace elements for the geological MPI-DING glasses KL2-G, ML3B-G, StHs6/80-G, GOR128-G, GOR132-G, BM90/21-G, T1-G, and ATHO-G. Different analytical methods were used to obtain a large spectrum of major and trace element data, in particular, EPMA, SIMS, LA-ICPMS, and isotope dilution by TIMS and ICPMS. Altogether, more than 60 qualified geochemical laboratories worldwide contributed to the analyses, allowing us to present new reference and information values and their uncertainties (at 95% confidence level) for up to 74 elements. We complied with the recommendations for the certification of geological reference materials by the International Association of Geoanalysts (IAG). The reference values were derived from the results of 16 independent techniques, including definitive (isotope dilution) and comparative bulk (e.g., INAA, ICPMS, SSMS) and microanalytical (e.g., LA-ICPMS, SIMS, EPMA) methods. Agreement between two or more independent methods and the use of definitive methods provided traceability to the fullest extent possible. We also present new and recently published data for the isotopic compositions of H, B, Li, O, Ca, Sr, Nd, Hf, and Pb. The results were mainly obtained by high-precision bulk techniques, such as TIMS and MC-ICPMS. In addition, LA-ICPMS and SIMS isotope data of B, Li, and Pb are presented.

Limits to the adaptive potential of small populations

Abstract: Small populations are predicted to have reduced capacity to adapt to environmental change for two reasons. First, population genetic models indicate that genetic variation and potential response to selection should be positively correlated with population size. The empirical support for this prediction is mixed: DNA markers usually reveal low heterozygosity in small populations, whereas quantitative traits show reduced heritability only in the smallest and most inbred populations. Quantitative variation can even increase in bottlenecked populations although this effect seems unlikely to increase the adaptive potential of populations. Second, individuals in small populations have lower fitness owing to environmental stress and genetic problems such as inbreeding, which can substantially increase the extinction probability of populations in changing environments. This second reason has not been included in assessments of critical population size assuring evolvability and makes it likely that many sm...

Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions

Abstract: Diagnosis in psychiatry increasingly struggles to fulfil its key purposes, namely, to guide treatment and to predict outcome. The clinical staging model, widely used in clinical medicine yet virtually ignored in psychiatry, is proposed as a more refined form of diagnosis which could restore the utility of diagnosis, promote early intervention and also make more sense of the confusing array of biological research findings in psychiatry by organizing data into a coherent clinicopathological framework. A selective review of key papers in clinical medicine and psychiatry which describe clinical and clinicopathological staging, and a range of related issues. Clinical staging has immediate potential to improve the logic and timing of interventions in psychiatry just as it does in many complex and potentially serious medical disorders. Interventions could be evaluated in terms of their ability to prevent or delay progression from earlier to later stages of disorder, and they could be selected on clear-cut risk/benefit criteria. Biological variables and a range of candidate risk factors could be studied within and across stages, and their role, specificity and centrality in risk, onset and progression of disorder could be greatly clarified. A clinicopathological framework could be progressively constructed. Clinical staging with a restructure across and within diagnostic boundaries with the explicit operationalization of criteria for extent and progression of disorder should be actively explored in psychiatry as a heuristic strategy for the development and evaluation of earlier, safer, and more effective clinical interventions, and for clarifying the biological basis of psychiatric disorders.

Interleukin-6 Increases Insulin-Stimulated Glucose Disposal in Humans and Glucose Uptake and Fatty Acid Oxidation In Vitro via AMP-Activated Protein Kinase

Abstract: Although interleukin-6 (IL-6) has been associated with insulin resistance, little is known regarding the effects of IL-6 on insulin sensitivity in humans in vivo. Here, we show that IL-6 infusion increases glucose disposal without affecting the complete suppression of endogenous glucose production during a hyperinsulinemic-euglycemic clamp in healthy humans. Because skeletal muscle accounts for most of the insulin-stimulated glucose disposal in vivo, we examined the mechanism(s) by which IL-6 may affect muscle metabolism using L6 myotubes. IL-6 treatment increased fatty acid oxidation, basal and insulin-stimulated glucose uptake, and translocation of GLUT4 to the plasma membrane. Furthermore, IL-6 rapidly and markedly increased AMP-activated protein kinase (AMPK). To determine whether the activation of AMPK mediated cellular metabolic events, we conducted experiments using L6 myotubes infected with dominant-negative AMPK alpha-subunit. The effects described above were abrogated in AMPK dominant-negative-infected cells. Our results demonstrate that acute IL-6 treatment enhances insulin-stimulated glucose disposal in humans in vivo, while the effects of IL-6 on glucose and fatty acid metabolism in vitro appear to be mediated by AMPK.

MUSTANG: a multiple structural alignment algorithm.

Abstract: Multiple structural alignment is a fundamental problem in structural genomics. In this article, we define a reliable and robust algorithm, MUSTANG (MUltiple STructural AligNment AlGorithm), for the alignment of multiple protein structures. Given a set of protein structures, the program constructs a multiple alignment using the spatial information of the C(alpha) atoms in the set. Broadly based on the progressive pairwise heuristic, this algorithm gains accuracy through novel and effective refinement phases. MUSTANG reports the multiple sequence alignment and the corresponding superposition of structures. Alignments generated by MUSTANG are compared with several handcurated alignments in the literature as well as with the benchmark alignments of 1033 alignment families from the HOMSTRAD database. The performance of MUSTANG was compared with DALI at a pairwise level, and with other multiple structural alignment tools such as POSA, CE-MC, MALECON, and MultiProt. MUSTANG performs comparably to popular pairwise and multiple structural alignment tools for closely related proteins, and performs more reliably than other multiple structural alignment methods on hard data sets containing distantly related proteins or proteins that show conformational changes.

Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes

Abstract: Immediate precursors of the many subtypes of dendritic cells (DCs) remain obscure. Here we purified a splenic precursor population that produced all splenic CD8+ and CD8− conventional DCs (cDCs) but not plasmacytoid DCs or other lineages. This 'pre-cDC' population included cells 'precommitted' to form either CD8+ or CD8− cDCs. The pre-cDCs, which comprised 0.05% of splenocytes, expressed a CD11cintCD45RAloCD43intSIRP-αintCD4−CD8− major histocompatibility complex class II–negative surface phenotype. The pre-cDCs were not monocytes. Monocytes generated few cDCs in steady-state recipient mice. However, when transferred into mice with an inflammatory milieu dependent on granulocyte-macrophage colony-stimulating factor, monocytes produced a distinct type of splenic DC. Thus, the inflammatory status of the host influences the developmental origin and type of DC present in lymphoid tissues.

Quantum phase transitions of light

Abstract: The ability to conduct experiments at length scales and temperatures at which interesting and potentially useful quantum-mechanical phenomena emerge in condensed-matter or atomic systems is now commonplace. In optics, though, the weakness with which photons interact with each other makes exploring such behaviour more difficult. Here we describe an optical system that exhibits strongly correlated dynamics on a mesoscopic scale. By adding photons to a two-dimensional array of coupled optical cavities each containing a single two-level atom in the photon-blockade regime, we form dressed states, or polaritons, that are both long-lived and strongly interacting. Our results predict that at zero temperature the system will undergo a characteristic Mott insulator (excitations localized on each site) to superfluid (excitations delocalized across the lattice) quantum phase transition. Moreover, the ability to couple light to and from individual cavities of this system could be useful in the realization of tuneable quantum simulators and other quantum-mechanical devices.

Coherent optical orthogonal frequency division multiplexing

Abstract: Coherent optical orthogonal frequency division multiplexing is proposed to combat dispersion in optical media. It is shown that optical-signal-to-noise ratio penalty at 10 Gbit/s is maintained below 2 dB for 3000 km transmission of standard-singlemode fibre without dispersion compensation.

Response styles in cross-national survey research: A 26-country study

Abstract: Studies of attitudes across countries generally rely on a comparison of aggregated mean scores to Likert-scale questions. This presupposes that when people complete a questionnaire, their answers are based on the substantive meaning of the items to which they respond. However, people's responses are also influenced by their response style. Hence, the studies we conduct might simply reflect differences in the way people respond to surveys, rather than picking up real differences in management phenomena across countries. Our 26-country study shows that there are major differences in response styles between countries that both confirm and extend earlier research. Country-level characteristics such as power distance, collectivism, uncertainty avoidance and extraversion all significantly influence response styles such as acquiescence and extreme response styles. Further, English-language questionnaires are shown to elicit a higher level of middle responses, while questionnaires in a respondent's native languag...

Supply chain management: a structured literature review and implications for future research

Abstract: Purpose – The field of supply chain management (SCM) has historically been informed by knowledge from narrow functional areas. While some effort towards producing a broader organizational perspective has been made, nonetheless, SCM continues to be largely eclectic with little consensus on its conceptualization and research methodological bases. This paper seeks to clarify aspects of this emerging perspective.Design/methodology/approach – A total of 100 randomly selected refereed journal articles were systematically analyzed.Findings – A number of key findings emerged: the field is a relatively “new” one; several disciplines claim ownership of the field; consensus is lacking on the definition of the term; contextual focus is mostly on the manufacturing industry; predominantly “process” conceptual framing prevails; research methods employed are mostly analytical conceptual, empirical surveys or case studies; the positivist research paradigmatic stance is prevalent; and theories related to transaction cost e...

Room-temperature coherent coupling of single spins in diamond

Abstract: Coherent coupling between single quantum objects is at the very heart of modern quantum physics. When the coupling is strong enough to prevail over decoherence, it can be used to engineer quantum entangled states. Entangled states have attracted widespread attention because of applications to quantum computing and long-distance quantum communication. For such applications, solid-state hosts are preferred for scalability reasons, and spins are the preferred quantum system in solids because they offer long coherence times. Here we show that a single pair of strongly coupled spins in diamond, associated with a nitrogen-vacancy defect and a nitrogen atom, respectively, can be optically initialized and read out at room temperature. To effect this strong coupling, close proximity of the two spins is required, but large distances from other spins are needed to avoid deleterious decoherence. These requirements were reconciled by implanting molecular nitrogen into high-purity diamond.

Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals.

Abstract: Context Magnetic resonance imaging studies have identified hippocampal volume reductions in schizophrenia and amygdala volume enlargements in bipolar disorder, suggesting different medial temporal lobe abnormalities in these conditions. These studies have been limited by small samples and the absence of patients early in the course of illness. Objective To investigate hippocampal and amygdala volumes in a large sample of patients with chronic schizophrenia, patients with first-episode psychosis, and patients at ultra-high risk for psychosis compared with control subjects. Design Cross-sectional comparison between patient groups and controls. Setting Individuals with chronic schizophrenia were recruited from a mental health rehabilitation service, and individuals with first-episode psychosis and ultra-high risk were recruited from the ORYGEN Youth Health Service. Control subjects were recruited from the community. Participants The study population of 473 individuals included 89 with chronic schizophrenia, 162 with first-episode psychosis, 135 at ultra-high risk for psychosis (of whom 39 subsequently developed a psychotic illness), and 87 controls. Main Outcome Measures Hippocampal, amygdala, whole-brain, and intracranial volumes were estimated on high-resolution magnetic resonance images and compared across groups, including first-episode subgroups. We used 1- and 2-way analysis of variance designs to compare hippocampal and amygdala volumes across groups, correcting for intracranial volume and covarying for age and sex. We investigated the effects of medication and illness duration on structural volumes. Results Patients with chronic schizophrenia displayed bilateral hippocampal volume reduction. Patients with first-episode schizophrenia but not schizophreniform psychosis displayed left hippocampal volume reduction. The remaining first-episode subgroups had normal hippocampal volumes compared with controls. Amygdala volume enlargement was identified only in first-episode patients with nonschizophrenic psychoses. Patients at ultra-high risk for psychosis had normal baseline hippocampal and amygdala volumes whether or not they subsequently developed a psychotic illness. Structural volumes did not differ between patients taking atypical vs typical antipsychotic medications, and they remained unchanged when patients treated with lithium were excluded from the analysis. Conclusions Medial temporal structural changes are not seen until after the onset of a psychotic illness, and the pattern of structural change differs according to the type of psychosis. These findings have important implications for future neurobiological studies of psychotic disorders and emphasize the importance of longitudinal studies examining patients before and after the onset of a psychotic illness.