The pisistratid tyranny at Athens

This thesis is a history of the Pisistratid Tyranny at Athens, with particular concentration on the years 546 to 510, which is often viewed as merely an interim stage between the reforms of Solon and the more important legislation of Cleisthenes leading (with later help from Ephialtes) to democracy. However, the tyranny - which is the first in the history of Athens - marks a much more important stage in Athenian development, as is evident from the source material in existence. The first chapter serves as an Introduction and deals with the rise of Pisistratus to unchallengable power in 546 after the Battle of Pallene, and following two previous attempts to seize power. An examination will also be made of the problem of chronology and the principal source material available for this period. The following chapters are then divided into the constitutional, economic, foreign, religious and cultural aspects of the tyranny, all of which received attention and state guidance. In many areas, for example drama and trade exports, great credit has to be attached to the policies of the tyrants. The final chapter (VII), which is divided into two parts, traces the over throw of the tyrannic rule in 510 owing to Spartan intervention, and also acts as a Conclusion on the tyranny as a whole and its place in the development of Athens. The post-Aristotelian sense of the word tyranny cannot be applied to the reign of the Pisistratids (at least not until 514 following the murder of Hipparchus), which was one of general enlightenment. Although the tyrants' position in the state was unconstitutional, resting on force as opposed to legality, political advancement was not halted, and the loyalty of the people to the city was won not by coercion but by policies designed for the general well-being and the provision of a period of peace from civil disorder

An assessment of the mantle and slab components in the magmas of an oceanic arc volcano: Raoul Volcano, Kermadec arc

Raoul Volcano occupies a simple oceanic subduction setting in the northern part of the Kermadec arc on the Pacific–Australian convergent plate boundary. The primary inputs to the magmatic system that feeds the volcano are a subduction component derived from the subducting old Pacific oceanic lithosphere and its veneer of pelagic sediment, and the overlying peridotitic mantle wedge. Conservative trace elements that are very incompatible during mantle melting are relatively depleted in Raoul lavas indicating a source that has been depleted during an earlier melting event. Major element co-variations indicate magma genesis by 25% near fractional melting of a mantle source that is weakly depleted (2% melt extraction) relative to a fertile MORB source. An important influence on the composition of the mantle component is progressive melt extraction coupled with minimal advection of fresh material into the sub-arc zone followed by melt extraction from a melting column beneath the spreading centre of an adjacent back arc basin. High field strength element and rare earth element systematics indicate involvement of a subduction-related component of constant composition. Two fluid components can be distinguished, one enriched in large ion lithophile elements inferred to be an aqueous fluid that is continuously added to the ascending melt column and the other a less mobile fluid that transfers Th. A homogeneous subduction-related component of constant composition and magnitude arises if the slab-derived flux migrates from the slab–mantle interface to the sub-arc melting column by repeated episodes of amphibole formation and decomposition its composition is then governed by the distribution coefficients of pyroxene and its magnitude by the degree of amphibole saturation of mantle peridotite. The results from Raoul Volcano are comparable to those from other oceanic subduction-related arcs such as South Sandwich and Marianas suggesting that this is a general model for oceanic arcs

Why Did the Successors meet at Triparadeisus?

This note puts forward an alternative suggestion for why the Successors met at Triparadeisus in 320 that calls into doubt the prevailing opinion that they were constantly at loggerheads with each other.Esta nota presenta una sugerencia alternativa de por qué los Diádocos se reunieron en Triparadeiso en 320 que pone en duda la opinión predominante de que estaban constantemente en desacuerdo entre ellos

Calcium calmodulin dependent protein kinase II in the development of atherosclerosis

Atherosclerosis is the leading cause of death in the developed world. The accumulation of low-density lipoprotein cholesterol (LDL-C) in the arterial wall leads to the formation of foam cell lesions. The growth of lesions is influenced by a number of genetic and lifestyle factors. Over-time, lesions encroach the vessel lumen, impeding blood flow and increasing risk of cardiovascular events including myocardial infarction and stroke. Statins have been effective at reducing risk for cardiovascular events, however, even when target LDL-C levels are met there remains a significant residual risk. Clearly, a detailed investigation into the mechanism of foam cell lesion growth is required to explore new drug targets to ease the burden on the health care system. Calcium/calmodulin-dependent protein kinase II (CaMKII) is a nodal signalling protein in endothelial cell (EC) and vascular smooth muscle cell (VSMC) physiology. In vascular disease, CaMKII has been shown to promote endothelial dysfunction and vascular smooth muscle cell proliferation. Both of these pathologies are involved in the early stages of atherosclerosis so it is intriguing to speculate that CaMKII also contributes to atherosclerosis. We have previously shown systemic inhibition of CaMKII in an atherosclerotic model (ApoE-/- mice) reduces foam cell lesion development. However, there are multiple isoforms of CaMKII and associated splice variants. These sub-types are differentially expressed in the tissues of the body and have shown contrasting roles. A global inhibition of CaMKII is not a feasible target due to the important physiological functions of these multiple isoforms. Therefore, it is crucial we identify the isoform(s) contributing to foam cell lesion growth so a more specific therapeutic target can be explored. Firstly, the predominant isoforms of CaMKII were identified in the major cell types of the vasculature. The aortic tree was dissected from ApoE-/- mice at 13- (early atherosclerosis) and 20-weeks (mid-atherosclerosis). In addition, human umbilical vein endothelial cells (HUVECs), human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs) were cultured. PCR and Western blotting was run for CaMKII delta and gamma isoforms. Results showed CaMKII delta as the predominant isoform in human and mouse vascular cells. In addition, at the mRNA level, delta splice variants 2, 3 and 6 were detected. CaMKII delta expression was high at 13-weeks in the ApoE-/- mouse and levels persisted at 20-weeks, suggesting the delta isoform is the most likely isoform contributing to atherosclerosis. To investigate if CaMKII signalling contributed to foam cell lesion development, we next employed a genetic approach. ApoE-/-‑mice were crossed with CaMKIIdelta-/- to generate a novel ApoE-/-CaMKIIdelta-/- (dKO) mouse model. At 20-weeks there was extensive atherosclerosis in the aortic sinus of female, but not male groups. Histological analysis showed there was a strikingly significant reduction in foam cell lesion content in female ApoE-/-CaMKIIdelta-/-, compared to ApoE-/-CaMKIIdelta+/+ litter mate controls. This indicates the CaMKII isoform is a critical player in the early development of atherosclerosis. To further test the mechanistic role of CaMKII delta in foam cell lesion development, an opposite strategy was performed whereby an AAV-mediated overexpression approach was utilised. ApoE-/-CaMKIIdelta-/- mice were put on a high-fat diet at 12-weeks to accelerate atherogenesis. At 16-weeks of age, the left carotid arteries of ApoE-/-CaMKII-/- mice were ligated to increase shear stress and further promote foam cell lesion growth in a localised area. AAV-particles harbouring the CaMKIIdelta2 or control (scrambled) gene sequence were then introduced to the ligated left carotid artery. Ligation of the carotid artery led to a range of variation in foam cell lesion progression. Histological analysis of the carotid artery revealed the foam cell lesion area and stenosis from CaMKIIdelta2-mCherry mice showed a trend towards an increase, despite low n numbers due to adverse complications in 20% of the ligated mice. In summary, a number of genetic and molecular biological techniques have been used to provide evidence to show CaMKII contributes to the early stages of atherosclerosis. Importantly, there is still work that needs to be done to further validate this mechanism and the potential contribution of other delta variants and/or other isoforms. This novel study has provided foundation evidence of CaMKII as a specific target for treatment. The results provide impetus to continue the investigation of CaMKII that ultimately, could lead to a pharmacological intervention to treat the early progression of atherosclerosis

Testing the ecosystem service cascade framework for Atlantic salmon

Aligning nature protection with human well-being for the UN Sustainable Development Goals implies that conservation monitoring should indicate the sustainability of ecosystem services (ES). Here we test the value of the ES cascade framework using national, multi-decadal data for an iconic freshwater fish, the Atlantic salmon Salmo salar. For the first time, we assemble all long-term monitoring data for England and Wales along the ES cascade for this species from resource to benefit: juvenile density to measure the biological resource, returning adult numbers to measure potential ES use, and rod catches and angling effort as measures of actual ES use. We aimed to understand how the ES cascade framework reconciled conservation with ES sustainability targets. Only some linkages along the ES cascade could be evidenced: in catchments where juveniles declined, rod catches also generally decreased, but angling effort declined everywhere irrespective of the biological resource trends. We suggest that i) programmes focused on juvenile monitoring provide an early-warning system for ES provision as well as nature conservation, ii) the ES cascade framework can reconcile nature conservation and ES sustainability if monitoring efforts link biological resources fully to the ES, and ES monitoring explicitly relates biological resources to human use

Improved early detection of ovarian cancer using longitudinal multimarker models

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Background: Ovarian cancer has a poor survival rate due to late diagnosis and improved methods are needed for its early detection. Our primary objective was to identify and incorporate additional biomarkers into longitudinal models to improve on the performance of CA125 as a first-line screening test for ovarian cancer. Methods: This case–control study nested within UKCTOCS used 490 serial serum samples from 49 women later diagnosed with ovarian cancer and 31 control women who were cancer-free. Proteomics-based biomarker discovery was carried out using pooled samples and selected candidates, including those from the literature, assayed in all serial samples. Multimarker longitudinal models were derived and tested against CA125 for early detection of ovarian cancer. Results: The best performing models, incorporating CA125, HE4, CHI3L1, PEBP4 and/or AGR2, provided 85.7% sensitivity at 95.4% specificity up to 1 year before diagnosis, significantly improving on CA125 alone. For Type II cases (mostly high-grade serous), models achieved 95.5% sensitivity at 95.4% specificity. Predictive values were elevated earlier than CA125, showing the potential of models to improve lead time. Conclusions: We have identified candidate biomarkers and tested longitudinal multimarker models that significantly improve on CA125 for early detection of ovarian cancer. These models now warrant independent validation.Peer reviewe

Chronic Trichuris muris infection in C57BL/6 mice causes significant changes in most microbiota and metabolome:effects reversed by pathogen clearance

Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation

Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia

Background: Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in persons who have received mechanical ventilation for at least 48 hours. VAP is a potentially serious complication in these patients who are already critically ill. Oral hygiene care (OHC), using either a mouthrinse, gel, toothbrush, or combination, together with aspiration of secretions may reduce the risk of VAP in these patients. Objectives: To assess the effects of OHC on the incidence of VAP in critically ill patients receiving mechanical ventilation in intensive care units (ICUs) in hospitals. Search methods: We searched the Cochrane Oral Health Group's Trials Register (to 14 January 2013), CENTRAL (The Cochrane Library 2012, Issue 12), MEDLINE (OVID) (1946 to 14 January 2013), EMBASE (OVID) (1980 to 14 January 2013), LILACS (BIREME) (1982 to 14 January 2013), CINAHL (EBSCO) (1980 to 14 January 2013), Chinese Biomedical Literature Database (1978 to 14 January 2013), China National Knowledge Infrastructure (1994 to 14 January 2013), Wan Fang Database (January 1984 to 14 January 2013), OpenGrey and ClinicalTrials.gov (to 14 January 2013). There were no restrictions regarding language or date of publication. Selection criteria: We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, swab, toothbrush or combination) in critically ill patients receiving mechanical ventilation. Data collection and analysis: Two review authors independently assessed all search results, extracted data and undertook risk of bias. We contacted study authors for additional information. Trials with similar interventions and outcomes were pooled reporting odds ratios (OR) for dichotomous outcomes and mean differences (MD) for continuous outcomes using random-effects models unless there were fewer than four studies. Main results: Thirty-five RCTs (5374 participants) were included. Five trials (14%) were assessed at low risk of bias, 17 studies (49%) were at high risk of bias, and 13 studies (37%) were assessed at unclear risk of bias in at least one domain. There were four main comparisons: chlorhexidine (CHX mouthrinse or gel) versus placebo/usual care, toothbrushing versus no toothbrushing, powered versus manual toothbrushing and comparisons of oral care solutions. There is moderate quality evidence from 17 RCTs (2402 participants, two at high, 11 at unclear and four at low risk of bias) that CHX mouthrinse or gel, as part of OHC, compared to placebo or usual care is associated with a reduction in VAP (OR 0.60, 95% confidence intervals (CI) 0.47 to 0.77, P < 0.001, I2 = 21%). This is equivalent to a number needed to treat (NNT) of 15 (95% CI 10 to 34) indicating that for every 15 ventilated patients in intensive care receiving OHC including chlorhexidine, one outcome of VAP will be prevented. There is no evidence of a difference between CHX and placebo/usual care in the outcomes of mortality (OR 1.10, 95% CI 0.87 to 1.38, P = 0.44, I2 = 2%, 15 RCTs, moderate quality evidence), duration of mechanical ventilation (MD 0.09, 95% CI -0.84 to 1.01 days, P = 0.85, I2 = 24%, six RCTs, moderate quality evidence), or duration of ICU stay (MD 0.21, 95% CI -1.48 to 1.89 days, P = 0.81, I2 = 9%, six RCTs, moderate quality evidence). There was insufficient evidence to determine whether there is a difference between CHX and placebo/usual care in the outcomes of duration of use of systemic antibiotics, oral health indices, microbiological cultures, caregivers preferences or cost. Only three studies reported any adverse effects, and these were mild with similar frequency in CHX and control groups. From three trials of children aged from 0 to 15 years (342 participants, moderate quality evidence) there is no evidence of a difference between OHC with CHX and placebo for the outcomes of VAP (OR 1.07, 95% CI 0.65 to 1.77, P = 0.79, I2 = 0%), or mortality (OR 0.73, 95% CI 0.41 to 1.30, P = 0.28, I2 = 0%), and insufficient evidence to determine the effect on the outcomes of duration of ventilation, duration of ICU stay, use of systemic antibiotics, plaque index, microbiological cultures or adverse effects, in children. Based on four RCTs (828 participants, low quality evidence) there is no evidence of a difference between OHC including toothbrushing (- CHX) compared to OHC without toothbrushing (- CHX) for the outcome of VAP (OR 0.69, 95% CI 0.36 to 1.29, P = 0.24, I2 = 64%) and no evidence of a difference for mortality (OR 0.85, 95% CI 0.62 to 1.16, P = 0.31, I2 = 0%, four RCTs, moderate quality evidence). There is insufficient evidence to determine whether there is a difference due to toothbrushing for the outcomes of duration of mechanical ventilation, duration of ICU stay, use of systemic antibiotics, oral health indices, microbiological cultures, adverse effects, caregivers preferences or cost. Only one trial compared use of a powered toothbrush with a manual toothbrush providing insufficient evidence to determine the effect on any of the outcomes of this review. A range of other oral care solutions were compared. There is some weak evidence that povidone iodine mouthrinse is more effective than saline in reducing VAP (OR 0.35, 95% CI 0.19 to 0.65, P = 0.0009, I2 = 53%) (two studies, 206 participants, high risk of bias). Due to the variation in comparisons and outcomes among the trials in this group there is insufficient evidence concerning the effects of other oral care solutions on the outcomes of this review. Authors' conclusions: Effective OHC is important for ventilated patients in intensive care. OHC that includes either chlorhexidine mouthwash or gel is associated with a 40% reduction in the odds of developing ventilator-associated pneumonia in critically ill adults. However, there is no evidence of a difference in the outcomes of mortality, duration of mechanical ventilation or duration of ICU stay. There is no evidence that OHC including both CHX and toothbrushing is different from OHC with CHX alone, and some weak evidence to suggest that povidone iodine mouthrinse is more effective than saline in reducing VAP. There is insufficient evidence to determine whether powered toothbrushing or other oral care solutions are effective in reducing VAP

Populations of high-value predators reflect the traits of their prey

The extent to which prey traits combine to influence the abundance of predators is still poorly understood, particularly for mixed predators in sympatry and in aquatic ecosystems. In this study, we characterise prey use and distribution in iconic bird (grey wagtails and Eurasian dippers) and fish species (brown trout and Atlantic salmon) to assess whether prey traits could predict populations of these four riverine predators. Specifically, we hypothesised that: 1) prey key traits would predict predator populations more effectively than 2) diversity of prey traits, 3) the taxonomic abundance or richness of prey (known as traditional or mass‐effect types of biodiversity) or 4) the prevailing environmental conditions. Combined predator population sizes were predicted better by a few key traits – specifically those revealing prey habitat use, size and drifting behaviour – than by prey diversity or prey trait diversity or environmental conditions. Our findings demonstrate that the complex relationships between prey assemblages and multiple predator species can be represented mechanistically when the key prey traits that govern encounter and consumption rates are identified. Given their apparent potential to reveal trophic relationships, and to complement more traditional measures of prey abundance, we advocate further development of trait‐based approaches in predator–prey research

Towards the Development of a Standard for the PS Suspension Logger

The PS logger is a well-established seismic tool for measuring P and S wave velocities in a single borehole, using low frequency indirect excitation originating from a dipole source. Because of its low operating frequency, it is capable of generating seismic waves in slow, unconsolidated materials such as those found in offshore environments where S wave velocity is often used to estimate the small strain stiffness, Gmax (of particular interest to offshore construction). Despite its widespread use, there is no current standard for the use of the PS logger, even though other methods operating on similar principles have well-established reference methodologies and guidelines. As such, PS logger methodology is largely dictated by user manuals written by manufacturers, which likely introduces inconsistencies in operation guidelines, and may impede consistency in data obtained by different users. In this paper, the authors conduct a literature review of existing standards for relevant methods including CPT, SPT, SCPT and downhole and crosshole seismic testing, as well as relevant ground investigation standards, identifying the need for standardisation of the PS logging method. Examination of the current state of standardisation concludes that although existing seismic testing standards could possibly be expanded to include the PS logging method, the differing constraints and operational requirements are such that the development of a specific PS logger testing standard is highly recommended. An initial framework is presented for a PS logger standard, identifying the required components, in terms of borehole requirements, testing procedure, data interpretation and best practice