Identifying state and transition models in the mitchell grasslands

The Mitchell grasslands are the most extensive and productive native pastures of semi -arid western Queensland. The grasslands are dominated by the long -lived perennial Astrebla spp. (Mitchell grasses). Rainfall is highly variable, leading to fluctuations in both pasture yield and composition, particularly of annual and ephemeral species growing between these perennial tussocks (Orr and Holmes 1984). These fluctuations create problems when attempting to assess rangeland condition and trend which is often based upon single, or short term, data. Furthermore, Everist and Webb (1975) concluded "the extrapolation from observations made at any one time can be misleading and inaccurate". This paper summarises an approach by which State and Transition theory (Westoby et al. 1989) and the Degradation Gradient Method (Bosch and Kellner 1991) were used to develop models of vegetation change which were able to account for this inherent variability

Impact of sepsis on risk of postoperative arterial and venous thromboses: large prospective cohort study

Objectives: To evaluate the impact of preoperative sepsis on risk of postoperative arterial and venous thromboses. Design: Prospective cohort study using the National Surgical Quality Improvement Program database of the American College of Surgeons (ACS-NSQIP). Setting: Inpatient and outpatient procedures in 374 hospitals of all types across the United States, 2005-12. Participants: 2 305 380 adults who underwent surgical procedures. Main outcome measures Arterial thrombosis (myocardial infarction or stroke) and venous thrombosis (deep venous thrombosis or pulmonary embolism) in the 30 days after surgery. Results: Among all surgical procedures, patients with preoperative systemic inflammatory response syndrome or any sepsis had three times the odds of having an arterial or venous postoperative thrombosis (odds ratio 3.1, 95% confidence interval 3.0 to 3.1). The adjusted odds ratios were 2.7 (2.5 to 2.8) for arterial thrombosis and 3.3 (3.2 to 3.4) for venous thrombosis. The adjusted odds ratios for thrombosis were 2.5 (2.4 to 2.6) in patients with systemic inflammatory response syndrome, 3.3 (3.1 to 3.4) in patients with sepsis, and 5.7 (5.4 to 6.1) in patients with severe sepsis, compared with patients without any systemic inflammation. In patients with preoperative sepsis, both emergency and elective surgical procedures had a twofold increased odds of thrombosis. Conclusions: Preoperative sepsis represents an important independent risk factor for both arterial and venous thromboses. The risk of thrombosis increases with the severity of the inflammatory response and is higher in both emergent and elective surgical procedures. Suspicion of thrombosis should be higher in patients with sepsis who undergo surgery

Rare Decay Modes of Quarter BPS Dyons

The degeneracy of quarter BPS dyons in N=4 supersymmetric string theories is known to jump across walls of marginal stability on which a quarter BPS dyon can decay into a pair of half BPS dyons. We show that as long as the electric and magnetic charges of the original dyon are primitive elements of the charge lattice, the subspaces of the moduli space on which a quarter BPS dyon becomes marginally unstable against decay into a pair of quarter BPS dyons or a half BPS dyon and a quarter BPS dyon are of codimension two or more. As a result any pair of generic points in the moduli space can be connected by a path avoiding these subspaces and there is no jump in the spectrum associated with these subspaces.Comment: LaTeX file, 9 pages; v2: a minor logical error corrected with no change in the result

Dying Dyons Don't Count

The dyonic 1/4-BPS states in 4D string theory with N=4 spacetime supersymmetry are counted by a Siegel modular form. The pole structure of the modular form leads to a contour dependence in the counting formula obscuring its duality invariance. We exhibit the relation between this ambiguity and the (dis-)appearance of bound states of 1/2-BPS configurations. Using this insight we propose a precise moduli-dependent contour prescription for the counting formula. We then show that the degeneracies are duality-invariant and are correctly adjusted at the walls of marginal stability to account for the (dis-)appearance of the two-centered bound states. Especially, for large black holes none of these bound states exists at the attractor point and none of these ambiguous poles contributes to the counting formula. Using this fact we also propose a second, moduli-independent contour which counts the "immortal dyons" that are stable everywhere.Comment: 27 pages, 2 figures; one minus sign correcte

Two Centered Black Holes and N=4 Dyon Spectrum

The exact spectrum of dyons in a class of N=4 supersymmetric string theories is known to change discontinuously across walls of marginal stability. We show that the change in the degeneracy across the walls of marginal stability can be accounted for precisely by the entropy of two centered small black holes which disappear as we cross the walls of marginal stability.Comment: LaTeX file, 12 pages; v3: added footnote 2 regarding overall sign of the index, expanded footnote 3, added reference

Latrepirdine: Molecular mechanisms underlying potential therapeutic roles in Alzheimer’s and other neurodegenerative diseases

Latrepirdine (DimebonTM) was originally marketed as a non-selective antihistamine in Russia. It was repurposed as an effective treatment for patients suffering from Alzheimer’s disease (AD) and Huntington’s disease (HD) following preliminary reports showing its neuroprotective functions and ability to enhance cognition in AD and HD models. However, latrepirdine failed to show efficacy in phase III trials in AD and HD patients following encouraging phase II trials. The failure of latrepirdine in the clinical trials has highlighted the importance of understanding the precise mechanism underlying its cognitive benefits in neurodegenerative diseases before clinical evaluation. Latrepirdine has shown to affect a number of cellular functions including multireceptor activity, mitochondrial function, calcium influx and intracellular catabolic pathways; however, it is unclear how these properties contribute to its clinical benefits. Here, we review the studies investigating latrepirdine in cellular and animal models to provide a complete evaluation of its mechanisms of action in the central nervous system. In addition, we review recent studies that demonstrate neuroprotective functions for latrepirdine-related class of molecules including the β-carbolines and aminopropyl carbazoles in AD, Parkinson’s disease and amyotrophic lateral sclerosis models. Assessment of their neuroprotective effects and underlying biological functions presents obvious value for developing structural analogues of latrepirdine for dementia treatment

P2‐304: Application Of Systems Medicine To Alzheimer’S Disease And Dementia Research: A Systematic Review

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152602/1/alzjjalz201405983.pd

Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-β-dependent mechanisms

ACKNOWLEDGMENTS. We thank Phillip B. Murray for help with the shRNA mapping pipeline and Francesc Lopez-Giraldez for help with RNAseq mapping software.Peer reviewedPostprintPostprin

Circulating levels of anti-angiogenic VEGF-A isoform (VEGF-Axxxb) in colorectal cancer patients predicts tumour VEGF-A ratios

Purpose: Bevacizumab as an adjunct to chemotherapy improves survival for some patients with metastatic colorectal cancer. Immunohistochemical staining of samples from the registration ECOG E3200 trial of bevacizumab with FOLFOX demonstrated that only patients with carcinomas expressing low levels of VEGF-A(165)b, an anti-angiogenic splice variant of the Vascular Endothelial Growth Factor family of proteins, benefited from bevacizumab treatment. To identify a more useful biomarker of response we tested the hypothesis that circulating VEGF-A(165)b levels correlate with immunohistochemical staining. Experimental Design: 17 patients with biopsy proven colorectal adenocarcinoma had pre-operative blood samples drawn. They underwent resection and had post-resection blood drawn. The plasma was analysed for levels of VEGF-A(xxx)b using enzyme-linked immunosorbent assay (ELISA) and the tumour blocks stained for VEGF-A(xxx)b and pan-VEGF-A. The normalised ratio of VEGF-A(xxx)b expression to that of panVEGF-A expression scored by IHC was calculated and correlated with plasma VEGF-A(165)b levels. Results: Plasma levels of VEGF-A(xxx)b significantly correlated with the VEGF-A(xxx)b:panVEGF-A ratio (r=0.594, P<0.02) in colorectal cancers. Median plasma VEGF-A(xxx)b levels were 151 pg/ml. The mean (1.5±0.17) and median, IQR (1.8, 1-2) IHC scores of the patients with greater than median plasma VEGF-A(xxx)b were significantly greater than those with less than median plasma VEGF-A(xxx)b levels (mean ± SEM=0.85±10.12, median, IQR=1, 0.54-1). Conclusion: These results suggest that plasma VEGF-A(xxx)b levels could be an effective biomarker of response to Bevacizumab. These results indicate that a prospective trial is warranted to explore the use of plasma VEGF-A(xxx)b levels to stratify patients for colorectal cancer treatment by bevacizumab

Perspective influences eye movements during real-life conversation: Mentalising about self versus others in autism

Socio-communication is profoundly impaired among autistic individuals. Difficulties representing others’ mental states have been linked to modulations of gaze and speech, which have also been shown to be impaired in autism. Despite these observed impairments in ‘real-world’ communicative settings, research has mostly focused on lab-based experiments, where the language is highly structured. In a pre-registered experiment, we recorded eye movements and verbal responses while adults (N=50) engaged in a real-life conversation. Using a novel approach, we also manipulated the perspective that participants adopted by asking them questions that were related to the self, a familiar other, or an unfamiliar other. Results replicated previous work, showing reduced attention to socially-relevant information among autistic participants (i.e. less time looking at the experimenter’s face, and more time looking around the background), compared to typically-developing controls. Importantly, perspective modulated social attention in both groups; talking about an unfamiliar other reduced attention to potentially distracting or resource-demanding social information, and increased looks to non-social background. Social attention did not differ between self and familiar other contexts, reflecting greater shared knowledge for familiar/similar others. Autistic participants spent more time looking at the background when talking about an unfamiliar other vs. themselves. Future research should investigate the developmental trajectory of this effect and the cognitive mechanisms underlying it