Showing papers by "University of Newcastle published in 2010"

A review of biochar and its use and function in soil

Abstract: Agricultural activities and soils release greenhouse gases, and additional emissions occur in the conversion of land from other uses. Unlike natural lands, active management offers the possibility to increase terrestrial stores of carbon in various forms in soil. The potential to sequester carbon as thermally stabilized (charred) biomass using existing organic resource is estimated to be at least 1 Gt yr − 1 and “biochar,” defined by its useful application to soil, is expected to provide a benefit from enduring physical and chemical properties. Studies of charcoal tend to suggest stability in the order of 1000 years in the natural environment, and various analytical techniques inform quantification and an understanding of turnover processes. Other types of biochar, such as those produced under zero-oxygen conditions have been studied less, but costs associated with logistics and opportunity costs from diversion from energy or an active form in soil demand certainty and predictability of the agronomic return, especially until eligibility for carbon credits has been established. The mechanisms of biochar function in soil, which appear to be sensitive to the conditions prevailing during its formation or manufacture, are also affected by the material from which it is produced. Proposed mechanisms and some experimental evidence point to added environmental function in the mitigation of diffuse pollution and emissions of trace gases from soil; precluding the possibility of contaminants accumulating in soil from the incorporation of biochar is important to ensure safety and regulatory compliance.

Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial.

Abstract: Summary Background The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial was designed to compare the efficacy and safety of anastrozole (1 mg) with tamoxifen (20 mg), both given orally every day for 5 years, as adjuvant treatment for postmenopausal women with early-stage breast cancer. In this analysis, we assess the long-term outcomes after a median follow-up of 120 months. Methods We used a proportional hazards model to assess the primary endpoint of disease-free survival, and the secondary endpoints of time to recurrence, time to distant recurrence, incidence of new contralateral breast cancer, overall survival, and death with or without recurrence in all randomised patients (anastrozole n=3125, tamoxifen n=3116) and hormone-receptor-positive patients (anastrozole n=2618, tamoxifen n=2598). After treatment completion, we continued to collect data on fractures and serious adverse events in a masked fashion (safety population: anastrozole n=3092, tamoxifen n=3094). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230. Findings Patients were followed up for a median of 120 months (range 0–145); there were 24 522 woman-years of follow-up in the anastrozole group and 23 950 woman-years in the tamoxifen group. In the full study population, there were significant improvements in the anastrozole group compared with the tamoxifen group for disease-free survival (hazard ratio [HR] 0·91, 95% CI 0·83–0·99; p=0·04), time to recurrence (0·84, 0·75–0·93; p=0·001), and time to distant recurrence (0·87, 0·77–0·99; p=0·03). For hormone-receptor-positive patients, the results were also significantly in favour of the anastrozole group for disease-free survival (HR 0·86, 95% CI 0·78–0·95; p=0·003), time to recurrence (0·79, 0·70–0·89; p=0·0002), and time to distant recurrence (0·85, 0·73–0·98; p=0·02). In hormone-receptor-positive patients, absolute differences in time to recurrence between anastrozole and tamoxifen increased over time (2·7% at 5 years and 4·3% at 10 years) and recurrence rates remained significantly lower on anastrozole than tamoxifen after treatment completion (HR 0·81, 95% CI 0·67–0·98; p=0·03), although the carryover benefit was smaller after 8 years. There was weak evidence of fewer deaths after recurrence with anastrozole compared with tamoxifen treatment in the hormone-receptor-positive subgroup (HR 0·87, 95% CI 0·74–1·02; p=0·09), but there was little difference in overall mortality (0·95, 95% CI 0·84–1·06; p=0·4). Fractures were more frequent during active treatment in patients receiving anastrozole than those receiving tamoxifen (451 vs 351; OR 1·33, 95% CI 1·15–1·55; p vs 112; OR 0·98, 95% CI 0·74–1·30; p=0·9). Treatment-related serious adverse events were less common in the anastrozole group than the tamoxifen group (223 anastrozole vs 369 tamoxifen; OR 0·57, 95% CI 0·48–0·69; p vs 78; OR 0·84, 95% CI 0·60–1·19; p=0·3). No differences in non-breast cancer causes of death were apparent and the incidence of other cancers was similar between groups (425 vs 431) and continue to be higher with anastrozole for colorectal (66 vs 44) and lung cancer (51 vs 34), and lower for endometrial cancer (six vs 24), melanoma (eight vs 19), and ovarian cancer (17 vs 28). No new safety concerns were reported. Interpretation These data confirm the long-term superior efficacy and safety of anastrozole over tamoxifen as initial adjuvant therapy for postmenopausal women with hormone-sensitive early breast cancer. Funding AstraZeneca.

Fundamental movement skills in children and adolescents: review of associated health benefits

Abstract: The mastery of fundamental movement skills (FMS) has been purported as contributing to children's physical, cognitive and social development and is thought to provide the foundation for an active lifestyle. Commonly developed in childhood and subsequently refined into context- and sport-specific skills, they include locomotor (e.g. running and hopping), manipulative or object control (e.g. catching and throwing) and stability (e.g. balancing and twisting) skills. The rationale for promoting the development of FMS in childhood relies on the existence of evidence on the current or future benefits associated with the acquisition of FMS proficiency. The objective of this systematic review was to examine the relationship between FMS competency and potential health benefits in children and adolescents. Benefits were defined in terms of psychological, physiological and behavioural outcomes that can impact public health. A systematic search of six electronic databases (EMBASE, OVID MEDLINE, PsycINFO, PubMed, Scopus and SportDiscus®) was conducted on 22 June 2009. Included studies were cross-sectional, longitudinal or experimental studies involving healthy children or adolescents (aged 3-18 years) that quantitatively analysed the relationship between FMS competency and potential benefits. The search identified 21 articles examining the relationship between FMS competency and eight potential benefits (i.e. global self-concept, perceived physical competence, cardio-respiratory fitness [CRF], muscular fitness, weight status, flexibility, physical activity and reduced sedentary behaviour). We found strong evidence for a positive association between FMS competency and physical activity in children and adolescents. There was also a positive relationship between FMS competency and CRF and an inverse association between FMS competency and weight status. Due to an inadequate number of studies, the relationship between FMS competency and the remaining benefits was classified as uncertain. More longitudinal and intervention research examining the relationship between FMS competency and potential psychological, physiological and behavioural outcomes in children and adolescents is recommended.

International Geomagnetic Reference Field: the eleventh generation

Abstract: The eleventh generation of the International Geomagnetic Reference Field (IGRF) was adopted in December 2009 by the International Association of Geomagnetism and Aeronomy Working Group V-MOD. It updates the previous IGRF generation with a definitive main field model for epoch 2005.0, a main field model for epoch 2010.0, and a linear predictive secular variation model for 2010.0–2015.0. In this note the equations defining the IGRF model are provided along with the spherical harmonic coefficients for the eleventh generation. Maps of the magnetic declination, inclination and total intensity for epoch 2010.0 and their predicted rates of change for 2010.0–2015.0 are presented. The recent evolution of the South Atlantic Anomaly and magnetic pole positions are also examined.

Fat tissue, aging, and cellular senescence

Abstract: Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age-related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mutations affecting fat increase life span. Fat cells turn over throughout the life span. Fat cell progenitors, preadipocytes, are abundant, closely related to macrophages, and dysdifferentiate in old age, switching into a pro-inflammatory, tissue-remodeling, senescent-like state. Other mesenchymal progenitors also can acquire a pro-inflammatory, adipocyte-like phenotype with aging. We propose a hypothetical model in which cellular stress and preadipocyte overutilization with aging induce cellular senescence, leading to impaired adipogenesis, failure to sequester lipotoxic fatty acids, inflammatory cytokine and chemokine generation, and innate and adaptive immune response activation. These pro-inflammatory processes may amplify each other and have systemic consequences. This model is consistent with recent concepts about cellular senescence as a stress-responsive, adaptive phenotype that develops through multiple stages, including major metabolic and secretory readjustments, which can spread from cell to cell and can occur at any point during life. Senescence could be an alternative cell fate that develops in response to injury or metabolic dysfunction and might occur in nondividing as well as dividing cells. Consistent with this, a senescent-like state can develop in preadipocytes and fat cells from young obese individuals. Senescent, pro-inflammatory cells in fat could have profound clinical consequences because of the large size of the fat organ and its central metabolic role.

Understanding predictive uncertainty in hydrologic modeling: The challenge of identifying input and structural errors

Abstract: [1] Meaningful quantification of data and structural uncertainties in conceptual rainfall-runoff modeling is a major scientific and engineering challenge. This paper focuses on the total predictive uncertainty and its decomposition into input and structural components under different inference scenarios. Several Bayesian inference schemes are investigated, differing in the treatment of rainfall and structural uncertainties, and in the precision of the priors describing rainfall uncertainty. Compared with traditional lumped additive error approaches, the quantification of the total predictive uncertainty in the runoff is improved when rainfall and/or structural errors are characterized explicitly. However, the decomposition of the total uncertainty into individual sources is more challenging. In particular, poor identifiability may arise when the inference scheme represents rainfall and structural errors using separate probabilistic models. The inference becomes ill-posed unless sufficiently precise prior knowledge of data uncertainty is supplied; this ill-posedness can often be detected from the behavior of the Monte Carlo sampling algorithm. Moreover, the priors on the data quality must also be sufficiently accurate if the inference is to be reliable and support meaningful uncertainty decomposition. Our findings highlight the inherent limitations of inferring inaccurate hydrologic models using rainfall-runoff data with large unknown errors. Bayesian total error analysis can overcome these problems using independent prior information. The need for deriving independent descriptions of the uncertainties in the input and output data is clearly demonstrated.

On the possible origins of DNA damage in human spermatozoa

Abstract: DNA damage in the male germ line has been linked with a variety of adverse clinical outcomes including impaired fertility, an increased incidence of miscarriage and an enhanced risk of disease in the offspring. The origins of this DNA damage could, in principle, involve: (i) abortive apoptosis initiated post meiotically when the ability to drive this process to completion is in decline (ii) unresolved strand breaks created during spermiogenesis to relieve the torsional stresses associated with chromatin remodelling and (iii) oxidative stress. In this article, we present a two-step hypothesis for the origins of DNA damage in human spermatozoa that highlights the significance of oxidative stress acting on vulnerable, poorly protaminated cells generated as a result of defective spermiogenesis. We further propose that these defective cells are characterized by several hallmarks of 'dysmaturity' including the retention of excess residual cytoplasm, persistent nuclear histones, poor zona binding and disrupted chaperone content. The oxidative stress experienced by these cells may originate from infiltrating leukocytes or, possibly, the entry of spermatozoa into an apoptosis-like cascade characterized by the mitochondrial generation of reactive oxygen species. This oxidative stress may be exacerbated by a decline in local antioxidant protection, particularly during epididymal maturation. Finally, if oxidative stress is a major cause of sperm DNA damage then antioxidants should have an important therapeutic role to play in the clinical management of male infertility. Carefully controlled studies are now needed to critically examine this possibility.

Modelling landscape evolution

Abstract: Geomorphology is currently in a period of resurgence as we seek to explain the diversity, origins and dynamics of terrain on the Earth and other planets in an era of increased environmental awareness. Yet there is a great deal we still do not know about the physics and chemistry of the processes that weaken rock and transport mass across a planet's surface. Discovering and refining the relevant geomorphic transport functions requires a combination of careful field measurements, lab experiments, and use of longer-term natural experiments to test current theory and develop new understandings. Landscape evolution models have an important role to play in sharpening our thinking, guiding us toward the right observables, and mapping out the logical consequences of transport laws, both alone and in combination with other salient processes. Improved quantitative characterization of terrain and process, and an ever-improving theory that describes the continual modification of topography by the many and varied processes that shape it, together with improved observation and qualitative and quantitative modelling of geology, vegetation and erosion processes, will provide insights into the mechanisms that control catchment form and function. This paper reviews landscape theory – in the form of numerical models of drainage basin evolution and the current knowledge gaps and future computing challenges that exist. Copyright © 2010 John Wiley & Sons, Ltd.

Evidence that opioids may have toll-like receptor 4 and MD-2 effects

Abstract: Opioid-induced proinflammatory glial activation modulates wide-ranging aspects of opioid pharmacology including: opposition of acute and chronic opioid analgesia, opioid analgesic tolerance, opioid-induced hyperalgesia, development of opioid dependence, opioid reward, and opioid respiratory depression. However, the mechanism(s) contributing to opioid-induced proinflammatory actions remains unresolved. The potential involvement of toll-like receptor 4 (TLR4) was examined using in vitro, in vivo, and in silico techniques. Morphine non-stereoselectively induced TLR4 signaling in vitro, blocked by a classical TLR4 antagonist and non-stereoselectively by naloxone. Pharmacological blockade of TLR4 signaling in vivo potentiated acute intrathecal morphine analgesia, attenuated development of analgesic tolerance, hyperalgesia, and opioid withdrawal behaviors. TLR4 opposition to opioid actions was supported by morphine treatment of TLR4 knockout mice, which revealed a significant threefold leftward shift in the analgesia dose response function, versus wildtype mice. A range of structurally diverse clinically-employed opioid analgesics was found to be capable of activating TLR4 signaling in vitro. Selectivity in the response was identified since morphine-3-glucuronide, a morphine metabolite with no opioid receptor activity, displayed significant TLR4 activity, whilst the opioid receptor active metabolite, morphine-6-glucuronide, was devoid of such properties. In silico docking simulations revealed ligands bound preferentially to the LPS binding pocket of MD-2 rather than TLR4. An in silico to in vitro prediction model was built and tested with substantial accuracy. These data provide evidence that select opioids may non-stereoselectively influence TLR4 signaling and have behavioral consequences resulting, in part, via TLR4 signaling.

Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions

Abstract: The current study, in parallel experiments, evaluated the impact of chronic psychological stress on physiological and behavioural measures, and on the activation status of microglia in 15 stress-responsive brain regions. Rats were subjected, for 14 days, to two 30 min sessions of restraint per day, applied at random times each day. In one experiment the effects of stress on sucrose preference, weight gain, core body temperature, and struggling behaviour during restraint, were determined. In the second experiment we used immunohistochemistry to investigate stress-induced changes in ionized calcium-binding adaptor molecule-1 (Iba1), a marker constitutively expressed by microglia, and major histocompatibility complex-II (MHC-II), a marker often expressed on activated microglia, in a total of 15 stress-responsive nuclei. We also investigated cellular proliferation in these regions using Ki67 immunolabelling, to check for the possibility of microglial proliferation. Collectively, the results we obtained showed that chronic stress induced a significant increase in anhedonia, a decrease in weight gain across the entire observation period, a significant elevation in core body temperature during restraint, and a progressive decrease in struggling behaviour within and over sessions. With regard to microglial activation, chronic stress induced a significant increase in the density of Iba1 immunolabelling (nine of 15 regions) and the number of Iba1-positive cells (eight of 15 regions). Within the regions that exhibited an increased number of Iba1-positive cells after chronic stress, we found no evidence of a between group difference in the number of MHC-II or Ki67 positive cells. In summary, these results clearly demonstrate that chronic stress selectively increases the number of microglia in certain stress-sensitive brain regions, and also causes a marked transition of microglia from a ramified-resting state to a non-resting state. These findings are consistent with the view that microglial activation could play an important role in controlling and/or adapting to stress.

Cell salvage for minimising perioperative allogeneic blood transfusion

Abstract: Background Concerns regarding the safety of transfused blood have prompted reconsideration of the use of allogeneic (from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques to minimise transfusion requirements. Objectives To examine the evidence for the efficacy of cell salvage in reducing allogeneic blood transfusion and the evidence for any effect on clinical outcomes. Search methods We identified studies by searching CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (1950 to June 2009), EMBASE (1980 to June 2009), the internet (to August 2009) and bibliographies of published articles. Selection criteria Randomised controlled trials with a concurrent control group in which adult patients, scheduled for non-urgent surgery, were randomised to cell salvage (autotransfusion) or to a control group who did not receive the intervention. Data collection and analysis Data were independently extracted and the risk of bias assessed. Relative risks (RR) and weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Data were pooled using a random-effects model. The primary outcomes were the number of patients exposed to allogeneic red cell transfusion and the amount of blood transfused. Other clinical outcomes are detailed in the review. Main results A total of 75 trials were included. Overall, the use of cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 38% (RR 0.62; 95% CI 0.55 to 0.70). The absolute reduction in risk (ARR) of receiving an allogeneic RBC transfusion was 21% (95% CI 15% to 26%). In orthopaedic procedures the RR of exposure to RBC transfusion was 0.46 (95% CI 0.37 to 0.57) compared to 0.77 (95% CI 0.69 to 0.86) for cardiac procedures. The use of cell salvage resulted in an average saving of 0.68 units of allogeneic RBC per patient (WMD -0.68; 95% CI -0.88 to -0.49). Cell salvage did not appear to impact adversely on clinical outcomes. Authors' conclusions The results suggest cell salvage is efficacious in reducing the need for allogeneic red cell transfusion in adult elective cardiac and orthopaedic surgery. The use of cell salvage did not appear to impact adversely on clinical outcomes. However, the methodological quality of trials was poor. As the trials were unblinded and lacked adequate concealment of treatment allocation, transfusion practices may have been influenced by knowledge of the patients' treatment status potentially biasing the results in favour of cell salvage.

Effectiveness of web-based interventions in achieving weight loss and weight loss maintenance in overweight and obese adults: a systematic review with meta-analysis.

Abstract: The objectives of this systematic review are to evaluate the effectiveness of web-based interventions on weight loss and maintenance and identify which components of web-based interventions are associated with greater weight change and low attrition rates. A literature search from 1995 to April 2008 was conducted. Studies were eligible for inclusion if: participants were aged >or=18 years with a body mass index >or=25, at least one study arm involved a web-based intervention with the primary aim of weight loss or maintenance, and reported weight-related outcomes. Eighteen studies met the inclusion criteria. Thirteen studies aimed to achieve weight loss, and five focused on weight maintenance. Heterogeneity was evident among the studies with seven research questions examined across interventions of varying intensity. Seven studies were assessed for effectiveness based on percentage weight change, with four studies deemed effective. Although the four meta-analyses suggest meaningful weight change, it is not possible to determine the effectiveness of web-based interventions in achieving weight loss or maintenance due to heterogeneity of designs and thus the small number of comparable studies. Higher usage of website features may be associated with positive weight change, but we do not know what features improve this effect or reduce attrition.

β-Carotene Is an Important Vitamin A Source for Humans

Abstract: Experts in the field of carotenoids met at the Hohenheim consensus conference in July 2009 to elucidate the current status of β-carotene research and to summarize the current knowledge with respect to the chemical properties, physiological function, and intake of β-carotene. The experts discussed 17 questions and reached an agreement formulated in a consensus answer in each case. These consensus answers are based on published valid data, which were carefully reviewed by the individual experts and are justified here by background statements. Ascertaining the impact of β-carotene on the total dietary intake of vitamin A is complicated, because the efficiency of conversion of β-carotene to retinol is not a single ratio and different conversion factors have been used in various surveys and following governmental recommendations within different countries. However, a role of β-carotene in fulfilling the recommended intake for vitamin A is apparent from a variety of studies. Thus, besides elucidating the various functions, distribution, and uptake of β-carotene, the consensus conference placed special emphasis on the provitamin A function of β-carotene and the role of β-carotene in the realization of the required/recommended total vitamin A intake in both developed and developing countries. There was consensus that β-carotene is a safe source of vitamin A and that the provitamin A function of β-carotene contributes to vitamin A intake.

Schizophrenia is associated with an increase in cortical microRNA biogenesis.

Abstract: MicroRNA expression profiling and quantitative reverse transcription-PCR analysis of the superior temporal gyrus and the dorsolateral prefrontal cortex revealed a significant schizophrenia-associated increase in global microRNA expression. This change was associated with an elevation of primary microRNA processing and corresponded with an increase in the microprocessor component DGCR8. The biological implications for this extensive increase in gene silencing are profound, and were exemplified by members of the miR-15 family and other related microRNA, which were significantly upregulated in both brain regions. This functionally convergent influence is overrepresented in pathways involved in synaptic plasticity and includes many genes and pathways associated with schizophrenia, some of which were substantiated in vitro by reporter gene assay. Given the magnitude of microRNA changes and their wide sphere of influence, this phenomenon could represent an important dimension in the pathogenesis of schizophrenia.

At the interface: solvation and designing ionic liquids

Abstract: Ionic liquids' (ILs) remarkable and tunable physicochemical properties mean they have distinct performance advantages over conventional solvents in many settings. However, the use of ILs in surface-dependent processes (e.g. electrodeposition, heterogeneous catalysis, dye solar cells) is hindered by the lack of a systematic understanding of IL interfacial structure. In this Perspective, we highlight recent experiments which show interfacial IL nanostructure is a consequence of both surface-specific and bulk liquid interactions. These results enable us to develop molecular design rules for controlling interfacial IL behavior.

What is a clinical pathway? Development of a definition to inform the debate

Abstract: Background Clinical pathways are tools used to guide evidence-based healthcare that have been implemented internationally since the 1980s. However, there is widespread lack of agreement on the impact of clinical pathways on hospital resources and patient outcomes. This can be partially attributed to the confusion for both researchers and healthcare workers regarding what constitutes a clinical pathway. This paper describes efforts made by a team of Cochrane Review authors to develop criteria to assist in the objective identification of clinical pathway studies from the literature.

Analysis of the relationships between oxidative stress, DNA damage and sperm vitality in a patient population: development of diagnostic criteria

Abstract: BACKGROUND: DNA damage in human spermatozoa is known to be associated with a variety of adverse clinical outcomes affecting both reproductive efficiency and the health and wellbeing of the offspring. However, the origin of this damage, its biochemical nature and strategies for its amelioration, still await resolution. METHODS: Using novel methods to simultaneously assess DNA fragmentation (modified TUNEL assay), DNA-base adduct formation (8-hydroxy-2'-deoxyguanosine [80HdG]) and cell vitality, spermatozoa from a cohort of 50 assisted conception patients were examined and compared with a group of donors. Receiver operating characteristic (ROC) curve analysis was then used to examine the frequency distribution of the data and to determine optimized thresholds for identifying patients exhibiting abnormally high levels of DNA damage. RESULTS: BOHdG formation and DNA fragmentation were highly correlated with each other and frequently associated with cell death. Percoll centrifugation improved sperm quality but, unexpectedly, increased BOHdG formation in live cells, as did sperm fractionation using Puresperm ® gradients. ROC analysis indicated that the frequency distribution of 8OHdG and DNA fragmentation data were significantly different between patients and donors (P < 0.001), permitting the development of thresholds that would allow the accurate diagnosis of DNA damage in the male germ line. CONCLUSION: The aetiology of DNA damage in spermatozoa involves a cascade of changes that progress from the induction of oxidative stress and oxidized DNA base adduct formation to DNA fragmentation and cell death. Preparation of spermatozoa on discontinuous density gradients aggravates the problem by stimulating the formation of 8OHdG in live cells. However, the development of novel methods and optimized thresholds for diagnosing oxidative DNA damage in human spermatozoa should assist in the clinical management of this pathology.

Education, the brain and dementia: neuroprotection or compensation?

Abstract: The potential protective role of education for dementia is an area of major interest. Almost all older people have some pathology in their brain at death but have not necessarily died with dementia. We have explored these two observations in large population-based cohort studies (Epidemiological Clinicopathological Studies in Europe; EClipSE) in an investigation of the relationships of brain pathology at death, clinical dementia and time in education, testing the hypothesis that greater exposure to education reduces the risk of dementia. EClipSE has harmonized longitudinal clinical data and neuropathology from three longstanding population-based studies that included post-mortem brain donation. These three studies started between 1985 and 1991. Number of years of education during earlier life was recorded at baseline. Incident dementia was detected through follow-up interviews, complemented by retrospective informant interviews, death certificate data and linked health/social records (dependent on study) after death. Dementia-related neuropathologies were assessed in each study in a comparable manner based on the Consortium to Establish a Registry for Alzheimer's Disease protocol. Eight hundred and seventy-two brain donors were included, of whom 56% were demented at death. Longer years in education were associated with decreased dementia risk and greater brain weight but had no relationship to neurodegenerative or vascular pathologies. The associations between neuropathological variables and clinical dementia differed according to the 'dose' of education such that more education reduced dementia risk largely independently of severity of pathology. More education did not protect individuals from developing neurodegenerative and vascular neuropathology by the time they died but it did appear to mitigate the impact of pathology on the clinical expression of dementia before death. The findings suggest that an understanding of the mechanisms leading to functional protection in the presence of pathology may be of considerable value to society.

Cortico-striatal connections predict control over speed and accuracy in perceptual decision making

Abstract: When people make decisions they often face opposing demands for response speed and response accuracy, a process likely mediated by response thresholds. According to the striatal hypothesis, people decrease response thresholds by increasing activation from cortex to striatum, releasing the brain from inhibition. According to the STN hypothesis, people decrease response thresholds by decreasing activation from cortex to subthalamic nucleus (STN); a decrease in STN activity is likewise thought to release the brain from inhibition and result in responses that are fast but error-prone. To test these hypotheses—both of which may be true—we conducted two experiments on perceptual decision making in which we used cues to vary the demands for speed vs. accuracy. In both experiments, behavioral data and mathematical model analyses confirmed that instruction from the cue selectively affected the setting of response thresholds. In the first experiment we used ultra-high-resolution 7T structural MRI to locate the STN precisely. We then used 3T structural MRI and probabilistic tractography to quantify the connectivity between the relevant brain areas. The results showed that participants who flexibly change response thresholds (as quantified by the mathematical model) have strong structural connections between presupplementary motor area and striatum. This result was confirmed in an independent second experiment. In general, these findings show that individual differences in elementary cognitive tasks are partly driven by structural differences in brain connectivity. Specifically, these findings support a cortico-striatal control account of how the brain implements adaptive switches between cautious and risky behavior.

Negative Intergroup Contact Makes Group Memberships Salient: Explaining Why Intergroup Conflict Endures

Abstract: Drawing from the intergroup contact model and self-categorization theory, the authors advanced the novel hypothesis of a valence-salience effect, whereby negative contact causes higher category salience than positive contact. As predicted, in a laboratory experiment of interethnic contact, White Australians (N = 49) made more frequent and earlier reference to ethnicity when describing their ethnic contact partner if she had displayed negative (vs. positive, neutral) nonverbal behavior. In a two-wave experimental study of retrieved intergenerational contact, American young adults (N = 240) reported age to be more salient during negative (vs. positive) contact and negative contact predicted increased episodic and chronic category salience over time. Some evidence for the reverse salience-valence effect was also found. Because category salience facilitates contact generalization, these results suggest that intergroup contact is potentially biased toward worsening intergroup relations; further implications for theory and policy making are discussed.

Convex Functions: Constructions, Characterizations and Counterexamples

Abstract: Like differentiability, convexity is a natural and powerful property of functions that plays a significant role in many areas of mathematics, both pure and applied. It ties together notions from topology, algebra, geometry and analysis, and is an important tool in optimization, mathematical programming and game theory. This book, which is the product of a collaboration of over 15 years, is unique in that it focuses on convex functions themselves, rather than on convex analysis. The authors explore the various classes and their characteristics and applications, treating convex functions in both Euclidean and Banach spaces. The book can either be read sequentially for a graduate course, or dipped into by researchers and practitioners. Each chapter contains a variety of specific examples, and over 600 exercises are included, ranging in difficulty from early graduate to research level.