The ongoing need for rates: can physiology and omics come together to co-design the measurements needed to understand complex ocean biogeochemistry?

The necessity to understand the influence of global ocean change on biota has exposed wide-ranging gaps in our knowledge of the fundamental principles that underpin marine life. Concurrently, physiological research has stagnated, in part driven by the advent and rapid evolution of molecular biological techniques, such that they now influence all lines of enquiry in biological oceanography. This dominance has led to an implicit assumption that physiology is outmoded, and advocacy that ecological and biogeochemical models can be directly informed by omics. However, the main modeling currencies are biological rates and biogeochemical fluxes. Here, we ask: how do we translate the wealth of information on physiological potential from omics-based studies to quantifiable physiological rates and, ultimately, to biogeochemical fluxes? Based on the trajectory of the state-of-the-art in biomedical sciences, along with case-studies from ocean sciences, we conclude that it is unlikely that omics can provide such rates in the coming decade. Thus, while physiological rates will continue to be central to providing projections of global change biology, we must revisit the metrics we rely upon. We advocate for the co-design of a new generation of rate measurements that better link the benefits of omics and physiology

The conceptualisation and measurement of DSM-5 Internet Gaming Disorder: the development of the IGD-20 Test

Background: Over the last decade, there has been growing concern about ‘gaming addiction’ and its widely documented detrimental impacts on a minority of individuals that play excessively. The latest (fifth) edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included nine criteria for the potential diagnosis of Internet Gaming Disorder (IGD) and noted that it was a condition that warranted further empirical study. Aim: The main aim of this study was to develop a valid and reliable standardised psychometrically robust tool in addition to providing empirically supported cut-off points. Methods: A sample of 1003 gamers (85.2% males; mean age 26 years) from 57 different countries were recruited via online gaming forums. Validity was assessed by confirmatory factor analysis (CFA), criterion-related validity, and concurrent validity. Latent profile analysis was also carried to distinguish disordered gamers from non-disordered gamers. Sensitivity and specificity analyses were performed to determine an empirical cut-off for the test. Results: The CFA confirmed the viability of IGD-20 Test with a six-factor structure (salience, mood modification, tolerance, withdrawal, conflict and relapse) for the assessment of IGD according to the nine criteria from DSM-5. The IGD-20 Test proved to be valid and reliable. According to the latent profile analysis, 5.3% of the total participants were classed as disordered gamers. Additionally, an optimal empirical cut-off of 71 points (out of 100) seemed to be adequate according to the sensitivity and specificity analyses carried

Risk measures for direct real estate investments with non-normal or unknown return distributions

The volatility of returns is probably the most widely used risk measure for real estate. This is rather surprising since a number of studies have cast doubts on the view that volatility can capture the manifold risks attached to properties and corresponds to the risk attitude of investors. A central issue in this discussion is the statistical properties of real estate returns—in contrast to neoclassical capital market theory they are mostly non-normal and often unknown, which render many statistical measures useless. Based on a literature review and an analysis of data from Germany we provide evidence that volatility alone is inappropriate for measuring the risk of direct real estate. We use a unique data sample by IPD, which includes the total returns of 939 properties across different usage types (56% office, 20% retail, 8% others and 16% residential properties) from 1996 to 2009, the German IPD Index, and the German Property Index. The analysis of the distributional characteristics shows that German real estate returns in this period were not normally distributed and that a logistic distribution would have been a better fit. This is in line with most of the current literature on this subject and leads to the question which indicators are more appropriate to measure real estate risks. We suggest that a combination of quantitative and qualitative risk measures more adequately captures real estate risks and conforms better with investor attitudes to risk. Furthermore, we present criteria for the purpose of risk classification

Intelligence within BAOR and NATO's Northern Army Group

During the Cold War the UK's principal military role was its commitment to the North Atlantic Treaty Organisation (NATO) through the British Army of the Rhine (BAOR), together with wartime command of NATO's Northern Army Group. The possibility of a surprise attack by the numerically superior Warsaw Pact forces ensured that great importance was attached to intelligence, warning and rapid mobilisation. As yet we know very little about the intelligence dimension of BAOR and its interface with NATO allies. This article attempts to address these neglected issues, ending with the impact of the 1973 Yom Kippur War upon NATO thinking about warning and surprise in the mid-1970s. It concludes that the arrangements made by Whitehall for support to BAOR from national assets during crisis or transition to war were - at best - improbable. Accordingly, over the years, BAOR developed its own unique assets in the realm of both intelligence collection and special operations in order to prepare for the possible outbreak of conflict

Assessing Internet addiction using the parsimonious Internet addiction components model - a preliminary study [forthcoming]

Internet usage has grown exponentially over the last decade. Research indicates that excessive Internet use can lead to symptoms associated with addiction. To date, assessment of potential Internet addiction has varied regarding populations studied and instruments used, making reliable prevalence estimations difficult. To overcome the present problems a preliminary study was conducted testing a parsimonious Internet addiction components model based on Griffiths’ addiction components (2005), including salience, mood modification, tolerance, withdrawal, conflict, and relapse. Two validated measures of Internet addiction were used (Compulsive Internet Use Scale [CIUS], Meerkerk et al., 2009, and Assessment for Internet and Computer Game Addiction Scale [AICA-S], Beutel et al., 2010) in two independent samples (ns = 3,105 and 2,257). The fit of the model was analysed using Confirmatory Factor Analysis. Results indicate that the Internet addiction components model fits the data in both samples well. The two sample/two instrument approach provides converging evidence concerning the degree to which the components model can organize the self-reported behavioural components of Internet addiction. Recommendations for future research include a more detailed assessment of tolerance as addiction component

Internet addiction, fatigue, and sleep problems among adolescent students: a large-scale study

Aim: The aim of the present study was to examine the association between Internet Addiction (IA), fatigue, and sleep problems among university students. Methods: A total of 3,000 Turkish students aged 18 to 25 years were approached and 2,350 students (78.3%) participated in this cross-sectional study from April 2017 to September 2017 in public and private universities in Istanbul. Data were collected via a structured questionnaire including socio-demographic details, lifestyle and dietary habits, Internet Addiction Test (IAT), Fatigue Scale, and Epworth Sleepiness Scale [ESS]. Descriptive statistics, multivariate and factorial analyses were performed. Results: The overall prevalence of IA among the studied population was 17.7%. There were significant differences between gender, family income, father’s occupation, school performance, frequency and duration of watching television, physical activity, internet use duration, and sleep duration (all p<0.001). Significant differences were also found between participants with IA and those without IA in having headaches, blurred vision, double vision, hurting eyes, hearing problems, and eating fast food frequently (all p<0.001). Using multivariate regression analysis, the duration of internet use, physical and mental symptoms, headache, hurting eyes, tired eyes, hearing problems and ESS scores were significantly associated with (and primary predictors of) IA. Conclusion: The present study demonstrated that IA was associated with poor dietary habits, sleep problems, and fatigue symptoms

Repeated Assessment of Exploration and Novelty Seeking in the Human Behavioral Pattern Monitor in Bipolar Disorder Patients and Healthy Individuals

Exploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD) and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM), a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD.Twelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability) patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions.Manic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design to characterize exploration and novelty seeking and, in parallel with animal studies, can contribute to developing treatments that target neuropsychiatric disease

Numerical Modeling of Fluid Flow in Solid Tumors

A mathematical model of interstitial fluid flow is developed, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for a predefined tumor geometry. The interstitial fluid pressure and velocity are calculated using a numerical method, element based finite volume. Simulations of interstitial fluid transport in a homogeneous solid tumor demonstrate that, in a uniformly perfused tumor, i.e., one with no necrotic region, because of the interstitial pressure distribution, the distribution of drug particles is non-uniform. Pressure distribution for different values of necrotic radii is examined and two new parameters, the critical tumor radius and critical necrotic radius, are defined. Simulation results show that: 1) tumor radii have a critical size. Below this size, the maximum interstitial fluid pressure is less than what is generally considered to be effective pressure (a parameter determined by vascular pressure, plasma osmotic pressure, and interstitial osmotic pressure). Above this size, the maximum interstitial fluid pressure is equal to effective pressure. As a consequence, drugs transport to the center of smaller tumors is much easier than transport to the center of a tumor whose radius is greater than the critical tumor radius; 2) there is a critical necrotic radius, below which the interstitial fluid pressure at the tumor center is at its maximum value. If the tumor radius is greater than the critical tumor radius, this maximum pressure is equal to effective pressure. Above this critical necrotic radius, the interstitial fluid pressure at the tumor center is below effective pressure. In specific ranges of these critical sizes, drug amount and therefore therapeutic effects are higher because the opposing force, interstitial fluid pressure, is low in these ranges

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

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans