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In proliferating cells and tissues a number of checkpoints (G1/S and G2/M) preceding cell division (M-phase) require the signal provided by growth factors present in serum. IGFs (I and II) have been demonstrated to constitute key intrinsic components of the peptidic active fraction of mammalian serum. In vivo genetic ablation studies have shown that the cellular signal triggered by the IGFs through their cellular receptors represents a non-replaceable requirement for cell growth and cell cycle progression. Retroactive and current evaluation of published literature sheds light on the intracellular circuitry activated by these factors providing us with a better picture of the pleiotropic mechanistic actions by which IGFs regulate both cell size and mitogenesis under developmental growth as well as in malignant proliferation. The present work aims to summarize the cumulative knowledge learned from the IGF ligands/receptors and their intracellular signaling transducers towards control of cell size and cell-cycle with particular focus to their actionable circuits in human cancer. Furthermore, we bring novel perspectives on key functional discriminants of the IGF growth-mitogenic pathway allowing re-evaluation on some of its signal components based upon established evidences.

Primary care healthcare organizations are complex and multidimensional, and there has been much discussion about the potential dangers of focusing on outcomes as quality indicators in isolation without understanding the processes and system characteristics that drive them. Organizational health, as a concept, shifts the focus of measurement upstream and considers the elements needed for sustainable long-term success. This study has both designed and tested the first survey seeking to measure organizational health specifically within the context of primary care. A stepwise approach was taken to ensure that the validity and reliability of the survey was examined at multiple stages.Supplemental data for this article is available online at https://doi.org/10.1080/00185868.2021.1947164.

With an increasing proportion of UK healthcare delivered by independent sector providers (ISPs) it is important that performance data is reviewed with a similar rigour as within the public sector. However, there is a relative paucity of work considering quotients of performance in the independent healthcare sector. This study sets out to measure organizational health within ISPs in the UK and juxtapose this with contemporaneous data taken from public sector NHS organizations. Survey data was tested for construct validity with fit of the existing factor structure of the Healthcare-OH survey examined using confirmatory factor analysis (CFA). Multiple-group CFA was used to establish measurement invariance to permit comparison of latent sum scores between ISP and NHS organizations. Measurement invariance analysis evaluated the fit of sequential invariance models, proceeding iteratively to establish partial metric and scalar invariance. Latent sum scores comparisons demonstrated ISPs outperformed NHS trusts across all elements of organizational health. This is the first time organizational health has been measured in ISPs explicitly for comparison with results in the public sector. Comparative measurement and analysis in this way is novel and has the potential of fostering a two-way learning process for the ultimate benefit of both NHS and ISP organizations.

Healthcare-OH is the only healthcare-specific measure of organizational health currently in use and for this concept to be truly applied in a healthcare context then reliable and valid measurement ...

This study aimed to qualitatively develop a conceptual framework for organizational health, within the setting of GP practices in the UK, through a qualitative interview study utilizing aspects from grounded theory. Data saturation was reached after 33 interviews revealing six themes: Strategy, Resources, Leadership, Staff Wellbeing, Capacity for change and Ways of working. The structure of each theme is discussed in detail. By unpicking the elements of organizational health in GP practices in this way, we hope to shift focus from considering down-stream clinical outcomes in isolation to practices taking a more long-term view centered around fostering ongoing high performance.

Previous work at Monash University has shown that students recognise that inquiry-, problem-, context- and industry- based experiments were better contextualised, more open to decision maki...

Healthy organisations have a strong provision of the vital elements required for long-term sustainable success and proponents of organisational health concern themselves with the recognition and me...

Professor Martha Christensen, an international leader in fungal systematics and ecology, died on 19 March 2017. Martha was a professor of mycology in the Department of Botany at the Univers...

Variation in marks awarded, alongside quality of feedback, is an issue whenever large-scale assessment is undertaken. In particular, variation between sessional teaching staff has been studied for decades resulting in many recorded efforts to overcome this issue. Attempts to curtail variation range from moderation meetings, extended training programmes, electronic tools, automated feedback or even audio/video feedback. Decreased marking variation was observed whenever automated marking was used, potentially due to less academic judgment being used by the markers. This article will focus on a case study of three interventions undertaken at Monash University that were designed to address concerns around the variability of marking and the feedback between sessional teaching staff employed in the chemistry teaching laboratories. The interventions included the use of detailed marking criteria, Excel marking spreadsheets and automated marked Moodle reports. Results indicated that more detailed marking c...

Urothelial carcinoma of the bladder (UCB) is a common cancer worldwide with over 430,000 new cases in 2012 and 165,000 deaths and is currently the most expensive cancer per capita to treat in the U...

Transition state theory provides a well established means to compute the rate at which rare events occur; however, this is strictly an equilibrium approach. Here we consider a nonequilibrium proble...

We consider two different methods of calculating the relevant average for the non-equilibrium partition identity (NPI), i.e. , which result in two different values. At best only one of these will a...

When systems are far from equilibrium, the temperature, the entropy and the thermodynamic entropy production are not defined and the Gibbs entropy does not provide useful information about the phys...

V.A. Maklakov, a prominent criminal defence lawyer of turn‐of‐the‐century Russia, was a member of the Constitutional Democratic Party (Kadets) and sat on its central committee from its founding in 1905 until well after the party’s cause was lost in 1917. He also headed its ‘school’ for orators who presented the party’s case in the Duma elections. Despite this close involvement with the party, he had reservations about its commitment to immediate majoritarian democracy and its reluctance to break with the Left. In his voluminous writings in emigration, which are analysed in this article, Maklakov makes a powerful case that the party would have enjoyed a better chance of achieving its goals if it had seized the rule‐of‐law values inherent in the old regime’s concessions as a foundation for building a constitutional monarchy. He also argued that Kadet conduct in the February Revolution manifested an insensitivity to rule‐of‐law values that was comparable to its conduct in 1905–07. His focus on the players’ a...

Subspecies amphochlora of the Lewin’s Honeyeater (Meliphaga lewinii) is confined to a small isolated population in the McIlwraith Range, Cape York Peninsula, north-eastern Australia. The population is poorly known but is thought to be restricted to elevations above 500 m. We aimed to establish reliable estimates of population size and geographical range to enable a better evaluation of the conservation status of the subspecies. We also sought to quantify elevational patterns of density within the range and test the hypothesis that climate is the dominant factor governing range limits. We estimate the area of occupancy to be 183 km2, pending the investigation of three small fragments of predicted suitable habitat in mountain ranges to the north of the McIlwraith Range. Our count data indicate that the population probably consists of fewer than 5000 individuals (best estimate = 4666 individuals, 95% confidence intervals (CI) = 2868–7591). Highest densities were observed in a geographically limited subset of the range above 650 m. Independent validation of our species-climate distribution model suggests that the restricted spatial distribution of the subspecies is attributable to climate associations and implies that warm temperatures in particular act to restrict the lower elevational limit of the subspecies. We discuss the implications of these findings for the future survival of M. l. amphochlora in the context of contemporary climate warming.

The nonequilibrium free energy theorems show how distributions of work along nonequilibrium paths are related to free energy differences between the equilibrium states at the end points of these paths. In this paper we develop a natural way of barostatting a system and give the first deterministic derivation of the Crooks and Jarzynski relations for these isothermal isobaric systems. We illustrate these relations by applying them to molecular dynamics simulations of a model polymer undergoing stretching., 9 pages, 2 figures

Industrialisation facilitates social and economic change and its role in modifying population patterns via the process of urbanisation is well documented. The socially selective nature of population redistribution is widely recognised, but in multi-ethnic states this redistribution of population is also culturally selective and has important ramifications for ethnic relations. This paper suggests that the theory of Internal Colonialism remains a useful theoretical framework for explaining the changes seen in Soviet Estonia. Specifically, it examines the influence of industrialisation on patterns of immigration into Estonia, and their consequent impact on Estonia's ethnic geography. We conclude that industrialisation is an important factor influencing patterns of population movement and distribution and that internal colonialism provides a valuable framework for the analysis of societal change in Soviet Estonia, and in other socialist contexts.

The effectiveness of health promotion educational programs in enhancing the elderly's health status and health behaviors is dependent upon their willingness to participate in such programs. The identification of factors that predict their participation is therefore essential. Of equal importance is determining which components of health promotion programs result in enhanced health status through modified health behaviors in order to design future programs for maximum effectiveness. The research reported here focuses on the use and effect of health promotion educational workshops designed to enhance both the physical and psychological well being of a Medicare Health Maintenance Organization population. Sixty-seven percent of eligible participants attended five or more health promotion workshops, while 14 percent failed to attend one workshop. A multivariate regression analysis revealed increasing age and smoking behavior as significant predictors of absenteeism in this group. Limited behavioral ch...

Bacillus Calmette–Guerin (BCG) therapy for non-muscle invasive bladder cancer (NMIBC) can significantly reduce the risk of recurrence and progression. However, BCG therapy may fail in up to a half of treated patients and may also cause toxicities. Biomarkers to predict the effectiveness of BCG therapy are desired to pre-select patients for BCG therapy to maximize efficacy while avoid unnecessary toxicity. Twelve cytokines were measured in 100 blood and 112 urine samples using cytokine antibody array and correlated with recurrence-free survival in overall and BCG-treated NMIBC patients. Of the 12 cytokines, interleukin (IL) -2, IL-8, IL-10, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-γ were measurable in more than 30% of peripheral blood leukocyte (PBL) samples. Only IL-8 in PBL was found to be significantly associated with tumor recurrence, especially in those who receiving BCG therapy (hazard ratio [HR] = 4.24; 95% confidence interval [95%CI] = 1.65–10.88; p = 0.003). The median recurrence-free survival time for BCG-treated patients with high baseline IL-8 levels were much shorter than those with low IL-8 levels (7.9 vs. >78.4 mo, p = 0.004). Furthermore, consistent associations between urinary IL-8 levels and tumor recurrence in patients receiving BCG therapy were observed in 58 pre-BCG and 54 long-term post-BCG-treated urine samples (both p ≤ 0.005). High urinary baseline IL-8 level also predicted shorter time to tumor recurrence in NMIBC patients (both p ≤ 0.004). By using antibody array-based technology in two separate cohorts of NMIBC patients, we found that PBL and urinary baseline IL-8 levels were significantly associated with tumor recurrence after BCG therapy.

In museum settings, subjecting objects to temperatures below 0°C has become an acceptable treatment for controlling pests, stabilizing water-saturated materials, and preserving organismal materials. Questions regarding the effect of “freezing” on collagen stability prompted an investigation of the temperatures at which collagen shrinks using microscopic analysis. Results indicate that both desiccation and freezing of mammal skin tissue tend to reduce shrinkage temperature, and that freezing for pest control and stabilization of water-saturated skin material has minimal initial effect on shrinkage temperature. Fresh skin material that is frozen, thawed, and dried showed significantly lower shrinkage temperatures, compared to other groups tested.

A computer program was developed which takes experimental orientation analysis data from the transmission electron microscope and determines the corresponding best fit crystal orientation. This program was used to analyse the relative orientations between pearlitic ferrite and cementite in annealed and as-rolled eutectoid steel in terms of near-coincident site lattice (NCSL) solutions.The NCSL theory predicted not only the “standard” orientation relationships, i.e. Bagaryatskii and 2nd Petch, but also “non-standard” orientation relationships. Certain observed ferrite/cementite relative orientations showed significant deviations from any NCSL. The explanation of these deviations and of the non-observation of certain low-sigma solutions probably requires the consideration of inter-atomic forces, rather than only the near-coincidence of lattice points.

Two studies found that left-handed children had significantly poorer academic records than did right-handed children, though the effect was small. Study 1 provided evidence that, for some academic disciplines, the important difference appeared to be between those children whose family history of handedness was concordant with their own handedness and those children whose family history of handedness was discordant with their own handedness. The inclusion of gender in asymmetry research was bolstered by Study 2. When predicting idiosyncrasies in left-handers' cognitive performance, it should be borne in mind that left-handers form a minority group as well as a neurologically distinct one.

A performance index measures the return experienced by a holder of a specific option position. A parameter index reflects the behavior of variables considered to be important determinants of option values, hence option investment performance. A value index provides a measure of option value over time. Index values will not be economically meaningful, however, unless standardization techniques are used to control for variations in such contract terms as time to expiration and the difference between the stock price and the option striking price. The Complete Options Indexes (COI) comprise value indexes for both calls and puts and a parameter index of implicit volatility. The indexes are based on standardized option series that are closely related to actual contracts trading in the marketplace. Used as inputs to investment decision-making, the COI numbers can provide valuable information. Correlations between historical values of the indexes, the riskless return, dividend yield and stock market return underscore the predominant role of stock volatility in the determination of option value. Correlations between the level of stock prices and the level of index values suggest that high stock prices are associated with high values for option premiums. Increases in stock prices tend to be accompanied by decreases in option premiums and decreases in the assessment of stock volatility.

Extract The purpose of this communication is to describe an apparently little-known granulomatous condition affecting the skin and subcutaneous tissues of domestic cats. The disease was first encountered in 1958 in the course of a sporadic histological sampling of animal tumours submitted through the interest and enterprise of local veterinary surgeons. Since then, a total of nine cases has been collected, all of which were seen in routine veterinary practice in the Auckland urban area.