The nature and origin of Seyfert warm absorbers

We collate the results of recent high resolution X-ray spectroscopic observations of 23 AGN, and use the resulting information to try to provide answers to some of the main open questions about warm absorbers: where do they originate, what effect do they have on their host galaxies, and what is their importance within the energetics and dynamics of the AGN system as a whole? We find that the warm absorbers of nearby Seyferts and certain QSOs are most likely to originate in outflows from the dusty torus, and that the kinetic luminosity of these outflows accounts for well under 1% of the bolometric luminosities of the AGN. Our analysis supports, however, the view that the relativistic outflows recently observed in two PG quasars have their origin in accretion disc winds, although the energetic importance of these outflows is similar to that of the Seyfert warm absorbers. We find that the observed soft X-ray absorbing ionisation phases fill less than 10% of the available volume. Finally, we show that the amount of matter processed through an AGN outflow system, over the lifetime of the AGN, is probably large enough to have a significant influence on the evolution of the host galaxy and of the AGN itself

Versatile regularisation toolkit for iterative image reconstruction with proximal splitting algorithms

Ill-posed image recovery requires regularisation to ensure stability. The presented open-source regularisation toolkit consists of state-of-the-art variational algorithms which can be embedded in a plug-and-play fashion into the general framework of proximal splitting methods. The packaged regularisers aim to satisfy various prior expectations of the investigated objects, e.g., their structural characteristics, smooth or non-smooth surface morphology. The flexibility of the toolkit helps with the design of more advanced model-based iterative reconstruction methods for different imaging modalities while operating with simpler building blocks. The toolkit is written for CPU and GPU architectures and wrapped for Python/MATLAB. We demonstrate the functionality of the toolkit in application to Positron Emission Tomography (PET) and X-ray synchrotron computed tomography (CT)

Associations of Fully Automated CSF and Novel Plasma Biomarkers With Alzheimer Disease Neuropathology at Autopsy

OBJECTIVE: To study cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) analyzed by fully automated Elecsys immunoassays in comparison to neuropathologic gold standards, and compare their accuracy to plasma phosphorylated tau (p-tau181) measured using a novel Simoa method. METHODS: We studied ante-mortem Elecsys-derived CSF biomarkers in 45 individuals who underwent standardized post-mortem assessments of AD and non-AD neuropathologic changes at autopsy. In a subset of 26 participants, we also analysed ante-mortem levels of plasma p-tau181 and neurofilament light (NfL). Reference biomarker values were obtained from 146 amyloid-PET-negative healthy controls (HC). RESULTS: All CSF biomarkers clearly distinguished pathology-confirmed AD dementia (N=27) from HC (AUCs=0.86-1.00). CSF total-tau (t-tau), p-tau181, and their ratios with Aβ1-42, also accurately distinguished pathology-confirmed AD from non-AD dementia (N=8; AUCs=0.94-0.97). In pathology-specific analyses, intermediate-to-high Thal amyloid phases were best detected by CSF Aβ1-42 (AUC[95% CI]=0.91[0.81-1]), while intermediate-to-high CERAD neuritic plaques and Braak tau stages were best detected by CSF p-tau181 (AUC=0.89[0.79-0.99] and 0.88[0.77-0.99], respectively). Optimal Elecsys biomarker cut-offs were derived at 1097/229/19 pg/ml for Aβ1-42, t-tau, and p-tau181. In the plasma subsample, both plasma p-tau181 (AUC=0.91[0.86-0.96]) and NfL (AUC=0.93[0.87-0.99]) accurately distinguished pathology-confirmed AD (N=14) from HC. However, only p-tau181 distinguished AD from non-AD dementia cases (N=4; AUC=0.96[0.88-1.00]), and showed a similar, though weaker, pathologic specificity for neuritic plaques (AUC=0.75[0.52-0.98]) and Braak stage (AUC=0.71[0.44-0.98]) as CSF p-tau181. CONCLUSIONS: Elecsys-derived CSF biomarkers detect AD neuropathologic changes with very high discriminative accuracy in-vivo. Preliminary findings support the use of plasma p-tau181 as an easily accessible and scalable biomarker of AD pathology. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that fully-automated CSF t-tau and p-tau181measurements discriminate between autopsy-confirmed Alzheimer's disease and other dementias

Prostate Cancer and Race

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72215/1/j.1525-1497.2003.30801.x.pd

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

Peer reviewedPublisher PD

Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49). Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens

Spontaneous vortices in the formation of Bose-Einstein condensates

Phase transitions are ubiquitous in nature, ranging from protein folding and denaturisation, to the superconductor-insulator quantum phase transition, to the decoupling of forces in the early universe. Remarkably, phase transitions can be arranged into universality classes, where systems having unrelated microscopic physics exhibit identical scaling behaviour near the critical point. Here we present an experimental and theoretical study of the Bose-Einstein condensation phase transition of an atomic gas, focusing on one prominent universal element of phase transition dynamics: the spontaneous formation of topological defects during a quench through the transition. While the microscopic dynamics of defect formation in phase transitions are generally difficult to investigate, particularly for superfluid phase transitions, Bose-Einstein condensates (BECs) offer unique experimental and theoretical opportunities for probing such details. Although spontaneously formed vortices in the condensation transition have been previously predicted to occur, our results encompass the first experimental observations and statistical characterisation of spontaneous vortex formation in the condensation transition. Using microscopic theories that incorporate atomic interactions and quantum and thermal fluctuations of a finite-temperature Bose gas, we simulate condensation and observe vortex formation in close quantitative agreement with our experimental results. Our studies provide further understanding of the development of coherence in superfluids, and may allow for direct investigation of universal phase-transition dynamics.Comment: 14 pages, 6 figures. Accepted for publication in Nature. Supplementary movie files are available at http://www.physics.uq.edu.au/people/mdavis/spontaneous_vortice

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment

Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings

Relevance of biomarkers across different neurodegenerative

Background: The panel of fluid- and imaging-based biomarkers available for neurodegenerative disease research is growing and has the potential to close important gaps in research and the clinic. With this growth and increasing use, appropriate implementation and interpretation are paramount. Various biomarkers feature nuanced differences in strengths, limitations, and biases that must be considered when investigating disease etiology and clinical utility. For example, neuropathological investigations of Alzheimer’s disease pathogenesis can fall in disagreement with conclusions reached by biomarker-based investigations. Considering the varied strengths, limitations, and biases of different research methodologies and approaches may help harmonize disciplines within the neurodegenerative disease field. Purpose of review: Along with separate review articles covering fluid and imaging biomarkers in this issue of Alzheimer’s Research and Therapy, we present the result of a discussion from the 2019 Biomarkers in Neurodegenerative Diseases course at the University College London. Here, we discuss themes of biomarker use in neurodegenerative disease research, commenting on appropriate use, interpretation, and considerations for implementation across different neurodegenerative diseases. We also draw attention to areas where biomarker use can be combined with other disciplines to understand issues of pathophysiology and etiology underlying dementia. Lastly, we highlight novel modalities that have been proposed in the landscape of neurodegenerative disease research and care