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This study examines how formal education in biological and behavioral sciences may impact punishment intuitions (views on criminal sentencing, free will, responsibility, and dangerousness) in cases involving neurobiological evidence. In a survey experiment, we compared intuitions between biobehavioral science and non-science university graduates by presenting them with a baseline case without a neurobiological explanation for offending followed by one of two cases with a neurobiological explanation (described as either innate or acquired biological influences to offending). An ordinal logistic regression indicated that both science and non-science graduates selected significantly more severe punishments for the baseline case as compared to when an innate neurobiological explanation for offending was provided. However, across all cases, science graduates selected significantly less severe sentences than non-science graduates, and only science graduates' decisions were mediated by free will and responsibility attributions. Findings are discussed in relation to scientific understandings of behavior, the impact of science education on attitudes towards punishment, and potential criminal-legal implications.

In the eighteenth century, Daniel Bernoulli, Adam Smith and Jeremy Bentham proposed that economic choices rely on the computation and comparison of subjective values

Bisdemethoxycurcumin (BDMC) has biological activities, including anticancer effects in vitro; however, its anticancer effects in human glioblastoma (GBM) cells have not been examined yet. This study aimed to evaluate the tumor inhibitory effect and molecular mechanism of BDMC on human GBM 8401/luc2 cells in vitro and in vivo. In vitro studies have shown that BDMC significantly reduced cell viability and induced cell apoptosis in GBM 8401/luc2 cells. Furthermore, BDMC induced apoptosis via inhibited Bcl-2 (anti-apoptotic protein) and increased Bax (pro-apoptotic proteins) and cytochrome c release in GBM 8401/luc2 cells in vitro. Then, twelve BALB/c-nude mice were xenografted with human glioblastoma GBM 8401/luc2 cancer cells subcutaneously, and the xenograft nude mice were treated without and with BDMC (30 and 60 mg/kg of BDMC treatment) every 3 days. GBM 8401/luc2 cell xenografts experiment showed that the growth of the tumors was significantly suppressed by BDMC administration at both doses based on the reduction of tumor size and weights. BDMC did not change the body weight and the H&E histopathology analysis of liver samples, indicating that BDMC did not induce systemic toxicity. Meanwhile, treatment with BDMC up-regulated the expressions of BAX and cleaved caspase-3, while it down-regulated the protein expressions of Bcl-2 and XIAP in the tumor tissues compared with the control group. This study has demonstrated that BDMC presents potent anticancer activity on the human glioblastoma GBM 8401/luc2 cell xenograft model by inducing apoptosis and inhibiting tumor cell proliferation and shows the potential for further development to the anti-GBM cancer drug.

Objective To advance public health support for the U.S. Department of Housing and Urban Development’s smoke-free rule, the Centers for Disease Control and Prevention collaborated with the Georgia Institute of Technology to develop a geospatial mapping tool. The objective was to create a tool state and local public health agencies could use to tailor smoke-free educational materials and cessation interventions for specific public housing development resident populations. Results The resulting “Extinguish Tool” includes an interactive map of U.S. public housing developments (PHDs) and healthcare facilities that provides detailed information on individual PHDs, their proximity to existing healthcare facilities, and the demographic characteristics of residents. The tool also estimates the number of PHD residents who smoke cigarettes and calculates crude estimates of the potential economic benefits of providing cessation interventions to these residents. The geospatial mapping tool project serves as an example of a collaborative and innovative public health approach to protecting the health and well-being of the nation’s two million public housing residents, including 760,000 children, from the harms of tobacco smoking and secondhand smoke exposure in the places where they live, play, and gather.

The senescence-accelerated mouse (SAM) strain has been established as an inbred strain with an accelerated aging phenotype. SAM prone-8 (SAMP8), one of the SAM strain, exhibits learning disability, immune deficiency, and circadian rhythm loss at a relatively young age. However, it has not been clarified whether aging affects the autonomic nervous activity in SAMP8. The aim of this study was to clarify the utility of SAMP8 in age-related studies of autonomic nervous function. Electrocardiogram (ECG), body temperature, and locomotor activity were recorded to evaluate bio-behavioral activities. Autonomic nervous activity was evaluated via power spectral analysis of heart rate variability from ECG recordings. SAMP8 significantly decreased both biological and autonomic nervous functions, and the animals exhibited circadian rhythm loss of locomotive activity at as early as 40 weeks of age compared with a control strain at the same age. We concluded that the SAMP8 strain can be used as an animal model for age-related studies of autonomic nervous function.

Reproduction is a defining process of biological systems. Every generation, across all species, breeding females repopulate ecosystems with offspring. r/K selection was the first theory to classify animal species by linking the rates with which breeding females repopulated ecosystems, to the stability of ecosystems. Here, I introduce a species classification scheme that extends the reach of r-K selection and CSR selection by linking breeder investments in offspring quantity, quality, and diversity to specific natural selection pressures. The species classification scheme is predicated on the assumption that high rates of predation favor breeders that invest more in offspring quantity than quality; and that spatiotemporal scarcity favors breeders that investment more in offspring quality than quantity. I present equations that convert the species classification scheme into a maternal risk-management model. Thereafter, using the equations, I classify eighty-seven animal species into the model’s natural selection categories. Species of reptiles, fish, and marine invertebrates clustered in the predation selection category. Species of birds and mammals clustered in the scarcity selection category. Several species of apex predators clustered in the weak selection category. Several species of social insects and social mammals clustered in the convergent selection category. In summary, by acknowledging breeding females as the individuals upon which natural selection acts to repopulate ecosystems with offspring, the proposed maternal risk-management model offers a testable, theoretical framework for the field of ecology.

During the past forty years, statistical modelling and simulation have come to frame perceptions of epidemic disease and to determine public health interventions that might limit or suppress the transmission of the causative agent. The influence of such formulaic disease modelling has pervaded public health policy and practice during the Covid-19 pandemic. The critical vocabulary of epidemiology, and now popular debate, thus includes R0, the basic reproduction number of the virus, ‘flattening the curve’, and epidemic ‘waves’. How did this happen? What are the consequences of framing and foreseeing the pandemic in these modes? Focusing on historical and contemporary disease responses, primarily in Britain, I explore the emergence of statistical modelling as a ‘crisis technology’, a reductive mechanism for making rapid decisions or judgments under uncertain biological constraint. I consider how Covid-19 might be configured or assembled otherwise, constituted as a more heterogeneous object of knowledge, a different and more encompassing moment of truth – not simply as a measured telos directing us to a new normal. Drawing on earlier critical engagements with the AIDS pandemic, inquiries into how to have ‘theory’ and ‘promiscuity’ in a crisis, I seek to open up a space for greater ecological, sociological, and cultural complexity in the biopolitics of modelling, thereby attempting to validate a role for critique in the Covid-19 crisis.

Ischemia reperfusion injury (IRI) is a critical problem in liver transplantation that can lead to life-threatening complications and substantially limit the utilization of livers for transplantation. However, because there are no early diagnostics available, fulminant injury may only become evident post-transplant. Mitochondria play a central role in IRI and are an ideal diagnostic target. During ischemia, changes in the mitochondrial redox state form the first link in the chain of events that lead to IRI. In this study we used resonance Raman spectroscopy to provide a rapid, non-invasive, and label-free diagnostic for quantification of the hepatic mitochondrial redox status. We show this diagnostic can be used to significantly distinguish transplantable versus non-transplantable ischemically injured rat livers during oxygenated machine perfusion and demonstrate spatial differences in the response of mitochondrial redox to ischemia reperfusion. This novel diagnostic may be used in the future to predict the viability of human livers for transplantation and as a tool to better understand the mechanisms of hepatic IRI.

Online shopping behavior has the characteristics of rich granularity dimension and data sparsity and presents a challenging task in e-commerce. Previous studies on user behavior prediction did not seriously discuss feature selection and ensemble design, which are important to improving the performance of machine learning algorithms. In this paper, we proposed an SE-stacking model based on information fusion and ensemble learning for user purchase behavior prediction. After successfully using the ensemble feature selection method to screen purchase-related factors, we used the stacking algorithm for user purchase behavior prediction. In our efforts to avoid the deviation of the prediction results, we optimized the model by selecting ten different types of models as base learners and modifying the relevant parameters specifically for them. Experiments conducted on a publicly available dataset show that the SE-stacking model can achieve a 98.40% F1 score, approximately 0.09% higher than the optimal base models. The SE-stacking model not only has a good application in the prediction of user purchase behavior but also has practical value when combined with the actual e-commerce scene. At the same time, this model has important significance in academic research and the development of this field.

The secretin receptor (SCTR), a prototypical class B G protein-coupled receptor (GPCR), exerts its effects mainly by activating Gαs proteins upon binding of its endogenous peptide ligand secretin. SCTRs can be found in a variety of tissues and organs across species, including the pancreas, stomach, liver, heart, lung, colon, kidney, and brain. Beyond that, modulation of SCTR-mediated signaling has therapeutic potential for the treatment of multiple diseases, such as heart failure, obesity, and diabetes. However, no ligands other than secretin and its peptide analogs have been described to regulate SCTRs, probably due to inherent challenges in family B GPCR drug discovery. Here we report creation of a testing funnel that allowed targeted detection of SCTR small-molecule activators. Pursuing the strategy to identify positive allosteric modulators (PAMs), we established a unique primary screening assay employing a mixture of three orthosteric stimulators that was compared in a screening campaign testing 12,000 small-molecule compounds. Beyond that, we developed a comprehensive set of secondary assays, such as a radiolabel-free target engagement assay and a NanoBiT (NanoLuc Binary Technology)-based approach to detect β-arrestin-2 recruitment, all feasible in a high-throughput environment as well as capable of profiling ligands and hits regarding their effect on binding and receptor function. This combination of methods enabled the discovery of five promising scaffolds, four of which have been validated and further characterized with respect to their allosteric activities. We propose that our results may serve as starting points for developing the first in vivo active small molecules targeting SCTRs.

Glioblastoma (GBM) continues to be the most aggressive cancer of the brain. The dismal prognosis is largely attributed to the microenvironment surrounding tumor cells. Astrocytes, the main component of the GBM microenvironment, play several fundamental physiological roles in the central nervous system. During the development of GBM, tumor-associated astrocytes (TAAs) directly contact GBM cells, which activate astrocytes to form reactive astrocytes, facilitating tumor progression, proliferation and migration through multiple well-understood signaling pathways. Notably, TAAs also influence GBM cell behaviors via suppressing immune responses and enhancing the chemoradiotherapy resistance of tumor cells. These new activities are closely linked with the treatment and prognosis of GBM. In this review, we discuss recent advances regarding new functions of reactive astrocytes, including TAA-cancer cell interactions, mechanisms involved in immunosuppressive regulation, and chemoradiotherapy resistance. It is expected that these updated experimental or clinical studies of TAAs may provide a promising approach for GBM treatment in the near future.

Identifying driving styles using classification models with in-vehicle data can provide automated feedback to drivers on their driving behavior, particularly if they are driving safely. Although several classification models have been developed for this purpose, there is no consensus on which classifier performs better at identifying driving styles. Therefore, more research is needed to evaluate classification models by comparing performance metrics. In this paper, a data-driven machine-learning methodology for classifying driving styles is introduced. This methodology is grounded in well-established machine-learning (ML) methods and literature related to driving-styles research. The methodology is illustrated through a study involving data collected from 50 drivers from two different cities in a naturalistic setting. Five features were extracted from the raw data. Fifteen experts were involved in the data labeling to derive the ground truth of the dataset. The dataset fed five different models (Support Vector Machines (SVM), Artificial Neural Networks (ANN), fuzzy logic, k-Nearest Neighbor (kNN), and Random Forests (RF)). These models were evaluated in terms of a set of performance metrics and statistical tests. The experimental results from performance metrics showed that SVM outperformed the other four models, achieving an average accuracy of 0.96, F1-Score of 0.9595, Area Under the Curve (AUC) of 0.9730, and Kappa of 0.9375. In addition, Wilcoxon tests indicated that ANN predicts differently to the other four models. These promising results demonstrate that the proposed methodology may support researchers in making informed decisions about which ML model performs better for driving-styles classification.

Astronauts on interplanetary missions - such as to Mars - will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56Fe and 28Si. Earth-based preclinical studies show space radiation decreases rodent performance in low- and some high-level cognitive tasks. Given astronaut use of touchscreen platforms during training and space flight and given the ability of rodent touchscreen tasks to assess functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, here we exposed 6-month-old C57BL/6J male mice to whole-body space radiation and subsequently assessed them on a touchscreen battery. Relative to Sham treatment, 56Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly, 56Fe irradiation improved performance on a dentate gyrus-reliant pattern separation task; irradiated mice learned faster and were more accurate than controls. Improved pattern separation performance did not appear to be touchscreen-, radiation particle-, or neurogenesis-dependent, as 56Fe and 28Si irradiation led to faster context discrimination in a non-touchscreen task and 56Fe decreased new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition.

Spatially extended ecological public goods, such as forests, grasslands, and fish stocks, are at risk of being overexploited by selfish consumers–a phenomenon widely recognized as the ‘tragedy of the commons.’ The interplay of spatial and ecological dimensions introduces new features absent in non-spatial ecological contexts, such as consumer mobility, local information availability, and strategy evolution through social learning in neighborhoods. It is unclear how these features interact to influence the harvesting and dispersal strategies of consumers. To answer these questions, we develop and analyze an individual-based, spatially structured, eco-evolutionary model with explicit resource dynamics. We report the following findings. (1) When harvesting efficiency is low, consumers evolve a sedentary consumption strategy, through which the resource is harvested sustainably, but with harvesting rates far below their maximum sustainable value. (2) As harvesting efficiency increases, consumers adopt a mobile ‘consume-and-disperse’ strategy, which is sustainable, equitable, and gives maximum sustainable yield. (3) A further increase in harvesting efficiency leads to large-scale overexploitation. (4) If costs of dispersal are significant, increased harvesting efficiency also leads to social inequality between frugal sedentary consumers and overexploitative mobile consumers. Whereas overexploitation can occur without social inequality, social inequality always leads to overexploitation. Thus, we identify four conditions that–while being characteristic of technological progress in modern societies–risk social inequality and overexploitation: high harvesting efficiency, moderately low costs of dispersal, high consumer density, and the tendency of consumers to adopt new strategies rapidly. We also show how access to global information–another feature widespread in modern societies–helps mitigate these risks., Author summary Throughout history, humans have shaped ecological landscapes, which in turn have influenced human behavior. This mutual dependence is epitomized when human consumers harvest a spatially extended renewable resource. Simple models predict that, when multiple consumers harvest a shared resource, each is tempted to harvest faster than his/her peers, putting the resource at risk of overexploitation. It is unclear, however, how the interplay among resource productivity, consumer mobility, and social learning in spatial ecological public goods games influences evolved consumer behavior. Here, using an individual-based, spatially structured, eco-evolutionary model of consumers and a resource, we find that increasing resource productivity initially promotes efficient resource use by enabling mobile consumption strategies, but eventually leads to inequality and overexploitation, as overexploitative mobile consumers coexist with frugal sedentary consumers. When consumers are impatient (i.e., eager to imitate successful strategies) or myopic (i.e., unaware of conditions outside of their neighborhoods), inequality and overexploitation tend to aggravate.

Background People with a history of interpersonal trauma, including intimate partner violence, sexual assault, and adverse childhood experiences, are disproportionately affected by the current opioid epidemic. Interpersonal trauma has been shown to increase risk for chronic pain conditions, prescription opioid use, and opioid misuse. Stress, cognition, and affective function have been examined as potential mechanisms that may influence opioid misuse among individuals with a history of interpersonal trauma. However, no studies have examined these factors simultaneously, despite their interrelatedness. Objective The purpose of this study was to 1) examine perceived stress, perceived cognitive function, depressive symptoms, and PTSD symptoms as potential mechanisms of opioid misuse among individuals with a history of interpersonal trauma, 2) examine the types of interpersonal trauma that are associated with opioid misuse, and 3) assess the mediating role of pain and opioid prescription. Methods A cross-sectional, observational study design was conducted. Data were collected through a confidential self-report online survey using validated instruments (n = 230). A series of regression analyses were conducted to identify mechanistic factors and interpersonal trauma types associated with opioid misuse, opioid prescription, and pain intensity. Structural equation modeling was used to examine mediating effects of pain intensity and opioid prescription. Results Opioid prescription, depressive symptoms, and intimate partner violence increased the odds of reporting opioid misuse. Pain intensity and adverse childhood experiences increased the odds of opioid prescription. Higher levels of perceived stress and depressive symptoms were associated with increased pain intensity. Pain intensity emerged as a mediator of the relationship between depressive symptoms and opioid misuse. Conclusions Our work shows that there are likely several pathways through which interpersonal trauma can lead to opioid misuse. Interventions aimed at improving depressive symptoms and coping with traumatizing events should be included as part of comprehensive trauma-informed pain management practices.

Although developmental science has always been evolving, these times of fast-paced and profound social and scientific changes easily lead to disorienting fragmentation rather than coherent scientific advances. What directions should developmental science pursue to meaningfully address real- world problems that impact human development throughout the lifespan? What conceptual or policy shifts are needed to steer the field in these directions? The present manifesto is proposed by a group of scholars from various disciplines and perspectives within developmental science to spark conversations and action plans in response to these questions. After highlighting four critical content domains that merit concentrated and often urgent research efforts, two issues regarding “how” we do developmental science and “what for” are out- lined. This manifesto concludes with five proposals, calling for integrative, inclusive, transdisciplinary, transparent, and actionable developmental science. Specific recommendations, prospects, pitfalls, and challenges to reach this goal are discussed.

Emotional intelligence (EI) is the ability to perceive, use, understand, and regulate emotions. Higher scores on this ability measured through performance tests (but no through self-reports) appears to be related to better performance on “hot” (emotionally laden) cognitive tasks. However, there are relatively few studies concerning how EI may benefit the working memory capacity (WMC). Thus, the objective of this study is to analyse the relationship between EI (as measured through a performance-based ability test, a self-report mixed test, and a self-report ability test) and the WMC during the performance of hot and “cool” (i.e., non-emotionally laden) “2-back” tasks. 203 participants completed three EI tests as well as two 2-back tasks. The results provide evidence for better performance of higher EI participants (specifically in the managing branch) measured through the performance-based ability test, but only on the hot task. For the self-report mixed model, incongruent results were found, and no correlations were obtained using the self-report ability model. The implications of these findings are discussed in terms of the validity of the various EI models.

Progressive pulmonary fibrosis is the most characteristic feature of subacute PQ poisoning. Epithelial-to-mesenchymal transition (EMT) is reported to be involved in the pulmonary fibrosis after PQ exposure. Recent evidence suggested Notch signaling is required for EMT. In this study, we investigated whether Notch1 and TGF-β1/Smad3 signaling was involved in EMT caused by PQ. It is demonstrated that A549 cells underwent EMT after treated with PQ at dose of 300 μmol/L for 6 days, charactered by increasing expression of mesenchymal marker α-SMA and decreasing expression of epithelial marker E-cadherin. We found that there was an apparent increased expression of Notch1 and jagged-1 in PQ induced EMT process. EMT could be enhanced by Jagged-1 ligand of Notch1, and be blocked by DAPT, a γ-secretase inhibitor. Our data also showed that the expression of TGF-β1/Smad3 increased after Notch1 is elevated in EMT caused by PQ. Jagged-1 significantly induced SMA expression, and this induction was completely inhibited by SB431542 in A549 cells. In conclusion, we demonstrated that Notch1 pathway was important in EMT induced by PQ, and TGF-β1/Smad3 signaling partly plays a role as the downstream of Notch1.

Dancing and playing music require people to coordinate actions with auditory rhythms. In laboratory perception-action coordination tasks, people are asked to synchronize taps with a metronome. When synchronizing with a metronome, people tend to anticipate stimulus onsets, tapping slightly before the stimulus. The anticipation tendency increases with longer stimulus periods of up to 3500ms, but is less pronounced in trained individuals like musicians compared to non-musicians. Furthermore, external factors influence the timing of tapping. These factors include the presence of auditory feedback from one’s own taps, the presence of a partner performing coordinated joint tapping, and transmission latencies (TLs) between coordinating partners. Phenomena like the anticipation tendency can be explained by delay-coupled systems, which may be inherent to the sensorimotor system during perception-action coordination. Here we tested whether a dynamical systems model based on this hypothesis reproduces observed patterns of human synchronization. We simulated behavior with a model consisting of an oscillator receiving its own delayed activity as input. Three simulation experiments were conducted using previously-published behavioral data from 1) simple tapping, 2) two-person alternating beat-tapping, and 3) two-person alternating rhythm-clapping in the presence of a range of constant auditory TLs. In Experiment 1, our model replicated the larger anticipation observed for longer stimulus intervals and adjusting the amplitude of the delayed feedback reproduced the difference between musicians and non-musicians. In Experiment 2, by connecting two models we replicated the smaller anticipation observed in human joint tapping with bi-directional auditory feedback compared to joint tapping without feedback. In Experiment 3, we varied TLs between two models alternately receiving signals from one another. Results showed reciprocal lags at points of alternation, consistent with behavioral patterns. Overall, our model explains various anticipatory behaviors, and has potential to inform theories of adaptive human synchronization., Author summary When navigating a busy sidewalk, people coordinate their behavior in an orderly manner. Other activities require people to carefully synchronize periodic actions, as in a group rowing or marching. When individuals tap in synchrony with a metronome, their taps tend to anticipate the metronome. Experiments have revealed that factors like musical expertise, the presence of a synchronizing partner, auditory feedback, and the sound travel time, all systematically affect the tendency to anticipate. While researchers have hypothesized a number of potential mechanisms for such anticipatory behavior, none have successfully accounted for all of the effects. Previous research on coupled physical systems has shown that when one system receives input from a second system, plus its own delayed signal as input, this causes system 1 to anticipate system 2. We hypothesize that the tendency to anticipate is the result of delayed communication between neurons. Our work demonstrates the ability of delay-coupled physical systems to capture human anticipation and the effect of external factors in the anticipation tendency. Our model supports the theory that delayed communication within the nervous system is crucial to understanding anticipatory coordinative behavior.

Background Self-monitoring of behavior (namely, diet and physical activity) and physiology (namely, glucose) has been shown to be effective in type 2 diabetes (T2D) and prediabetes prevention. By combining self-monitoring technologies, the acute physiological consequences of behaviors could be shown, prompting greater consideration to physical activity levels today, which impact the risk of developing diabetes years or decades later. However, until recently, commercially available technologies have not been able to show individuals the health benefits of being physically active. Objective The objective of this study was to examine the usage, feasibility, and acceptability of behavioral and physiological self-monitoring technologies in individuals at risk of developing T2D. Methods A total of 45 adults aged ≥40 years and at moderate to high risk of T2D were recruited to take part in a 3-arm feasibility trial. Each participant was provided with a behavioral (Fitbit Charge 2) and physiological (FreeStyle Libre flash glucose monitor) monitor for 6 weeks, masked according to group allocation. Participants were allocated to glucose feedback (4 weeks) followed by glucose and physical activity (biobehavioral) feedback (2 weeks; group 1), physical activity feedback (4 weeks) followed by biobehavioral feedback (2 weeks; group 2), or biobehavioral feedback (6 weeks; group 3). Participant usage (including time spent on the apps and number of glucose scans) was the primary outcome. Secondary outcomes were the feasibility (including recruitment and number of sensor displacements) and acceptability (including monitor wear time) of the intervention. Semistructured qualitative interviews were conducted at the 6-week follow-up appointment. Results For usage, time spent on the Fitbit and FreeStyle Libre apps declined over the 6 weeks for all groups. Of the FreeStyle Libre sensor scans conducted by participants, 17% (1798/10,582) recorded rising or falling trends in glucose, and 24% (13/45) of participants changed ≥1 of the physical activity goals. For feasibility, 49% (22/45) of participants completed the study using the minimum number of FreeStyle Libre sensors, and a total of 41 sensors were declared faulty or displaced. For acceptability, participants wore the Fitbit for 40.1 (SD 3.2) days, and 20% (9/45) of participants and 53% (24/45) of participants were prompted by email to charge or sync the Fitbit, respectively. Interviews unearthed participant perceptions on the study design by suggesting refinements to the eligibility criteria and highlighting important issues about the usability, wearability, and features of the technologies. Conclusions Individuals at risk of developing T2D engaged with wearable digital health technologies providing behavioral and physiological feedback. Modifications are required to both the study and to commercially available technologies to maximize the chances of sustained usage and behavior change. The study and intervention were feasible to conduct and acceptable to most participants. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN) 17545949; isrctn.com/ISRCTN17545949

INTRODUCTION: Studying the role of the immune system in the interaction between mental and physical health is challenging. To study individuals with an intensive, longitudinal study design that requires repetitive sampling in their daily life, non-invasive sampling techniques are a necessity. Urine can be collected in a non-invasive way, but this may be demanding for participants and little is known about fluctuation of inflammatory markers in urine over time. The aim of this study was to investigate the feasibility of non-invasive sampling, and to explore intra-individual differences in inflammatory markers in urine.MATERIALS & METHODS: Ten healthy individuals collected 24-hour urine for 63 consecutive days. In a pilot analysis, 39 inflammatory markers were examined for detectability in urine, stability over time and under storage conditions, and daily fluctuations. Multiplex analyses were used to quantify levels of eight selected markers: C-reactive protein (CRP), Fractalkine, Interleukin-1 receptor-antagonist (IL-1RA), interferon-α (IFNα), interferon-γ (IFNγ), Interferon gamma-induced protein 10 (IP10), Macrophage inflammatory protein-1β (MIP-1β), and Vascular Endothelial Growth Factor (VEGF). Cross-correlations were calculated between the overnight and 24-hour samples were calculated, to examine whether 24-hour urine could be replaced by the overnight portion for better feasibility. We examined intra- and interindividual differences in the levels of inflammatory markers in urine and the fluctuations thereof.RESULTS: This study showed that levels of selected inflammatory markers can be detected in urine. Cross-correlation analyses showed that correlations between levels of inflammatory markers in the night portion and the 24-hour urine sample varied widely between individuals. In addition, analyses of time series revealed striking inter- and intra-individual variation in levels of inflammatory markers and their fluctuations.CONCLUSION: We show that the assessment of urinary inflammatory markers is feasible in an intensive day-to-day study in healthy individuals. However, 24-hour urine cannot be replaced by an overnight portion to alleviate the protocol burden. Levels of inflammatory markers show substantial variation between and within persons.

The majority of the research studying punishment has focused on an aversive stimulus delivered immediately after an action. However, in real-world decision-making, negative consequences often occur long after a decision has been made. This can engender myopic decisions that fail to appropriately respond to consequences. Whereas discounting of delayed rewards has been well studied in both human and animal models, systematic discounting of delayed consequences remains largely unexplored. To address this gap in the literature, we developed the Delayed Punishment Decision-making Task (DPDT). Rats chose between a small, single pellet reinforcer and a large, three pellet reinforcer accompanied by a mild foot shock. The shock was preceded by a delay, which systematically increased throughout the session (0s, 4s, 8s, 12s, 16s). On average, rats discounted the negative value of delayed punishment, as indicated by increased choice of the large, punished reward as the delay preceding the shock lengthened. Female rats discounted delayed punishment less than males, and this behavior was not influenced by estrous cycling. The addition of a cue light significantly decreased the undervaluation of delayed consequences for both sexes. Finally, there was no correlation between the discounting of delayed punishments and a traditional reward delay discounting task for either sex. These data indicate that the ability of punishment to regulate decision-making is attenuated when punishment occurs later in time. This task provides an avenue for exploration of the neural circuitry underlying the devaluation of delayed punishment and may assist in developing treatments for substance use disorders. Significance Statement Consequences that occur long after a decision are often undervalued, particularly in substance use disorder. However, “delayed punishment discounting” is widely understudied in decision neuroscience. Here, we present a novel delayed punishment decision-making task in rats that reveals robust sex differences, demonstrates the efficacy of punishment predictive cues for reducing punishment discounting, and shows that punishment discounting is independent of reward-discounting. This provides critical information regarding a cognitive process that can contribute to maladaptive decision-making.

BACKGROUND: Tissue engineering represents a promising approach for the production of bone substitutes. The use of perfusion bioreactors for the culture of bone-forming cells on a three-dimensional porous scaffold resolves mass transport limitations and provides mechanical stimuli. Despite the recent and important development of bioreactors for tissue engineering, the underlying mechanisms leading to the production of bone substitutes remain poorly understood. METHODS: In order to study cell proliferation in a perfusion bioreactor, we propose a simplified experimental set-up using an impermeable scaffold model made of 2 mm diameter glass beads on which mechanosensitive cells, NIH-3T3 fibroblasts are cultured for up to 3 weeks under 10 mL/min culture medium flow. A methodology combining histological procedure, image analysis and analytical calculations allows the description and quantification of cell proliferation and tissue production in relation to the mean wall shear stress within the bioreactor. RESULTS: Results show a massive expansion of the cell phase after 3 weeks in bioreactor compared to static control. A scenario of cell proliferation within the three-dimensional bioreactor porosity over the 3 weeks of culture is proposed pointing out the essential role of the contact points between adjacent beads. Calculations indicate that the mean wall shear stress experienced by the cells changes with culture time, from about 50 mPa at the beginning of the experiment to about 100 mPa after 3 weeks. CONCLUSION: We anticipate that our results will help the development and calibration of predictive models, which rely on estimates and morphological description of cell proliferation under shear stress.

Visual selective attention acts as a filter on perceptual information, facilitating learning and inference about important events in an agent’s environment. A role for visual attention in reward-based decisions has previously been demonstrated, but it remains unclear how visual attention is recruited during aversive learning, particularly when learning about multiple stimuli concurrently. This question is of particular importance in psychopathology, where enhanced attention to threat is a putative feature of pathological anxiety. Using an aversive reversal learning task that required subjects to learn, and exploit, predictions about multiple stimuli, we show that the allocation of visual attention is influenced significantly by aversive value but not by uncertainty. Moreover, this relationship is bidirectional in that attention biases value updates for attended stimuli, resulting in heightened value estimates. Our findings have implications for understanding biased attention in psychopathology and support a role for learning in the expression of threat-related attentional biases in anxiety., Author summary To make inferences and learn efficiently in the face of a multiplicity of stimuli we need to allocate attention preferentially to those that are most motivationally relevant. It is unclear how this is achieved in aversive environments. We investigated how value (the likelihood of an unpleasant event) and uncertainty (akin to ignorance about its probability) influence visual attention during aversive learning. Our results show that attention is influenced by value but not by uncertainty. Attention in turn results in heightened value estimates for attended stimuli. The findings have implications for understanding the development of pathological threat-related attentional biases that are a feature of anxiety disorders.

In bio-behavioural surveys measuring prevalence of infection with human immunodeficiency virus (HIV), respondents should be asked the results of their last HIV test. However, many government authorities, nongovernmental organizations, researchers and other civil society stakeholders have stated that respondents involved in such surveys should not be asked to self-report their HIV status. The reasons offered for not asking respondents to report their status are that responses may be inaccurate and that asking about HIV status may violate the respondents' human rights and exacerbate stigma and discrimination. Nevertheless, we contend that, in the antiretroviral therapy era, asking respondents in bio-behavioural surveys to self-report their HIV status is essential for measuring and improving access to - and coverage of - services for the care, treatment and prevention of HIV infection. It is also important for estimating the true size of the unmet needs in addressing the HIV epidemic and for interpreting the behaviours associated with the acquisition and transmission of HIV infection correctly. The data available indicate that most participants in health-related surveys are willing to respond to a question about HIV status - as one of possibly several sensitive questions about sexual and drug use behaviours. Ultimately, normalizing the self-reporting of HIV status could help the global community move from an era of so-called exceptionalism to one of destigmatization - and so improve the epidemic response worldwide.Dans les enquêtes bio-comportementales évaluant la prévalence de l'infection par le virus de l'immunodéficience humaine (VIH), il conviendrait de demander aux répondants le résultat de leur dernier test de dépistage du VIH. Mais nombre d'autorités gouvernementales, d'organisations non gouvernementales, de chercheurs et d'acteurs de la société civile sont défavorables à ce que l’on demande aux répondants de déclarer leur statut VIH dans ce type d'enquêtes. Parmi les raisons invoquées pour ne pas demander le statut VIH figure le fait que les réponses peuvent être inexactes et qu'une telle demande pourrait transgresser les droits humains des répondants et accentuer les problèmes de stigmatisation et de discrimination. Néanmoins, nous soutenons qu'aujourd'hui, à l'ère de la thérapie antirétrovirale, le fait de demander leur statut VIH aux répondants des enquêtes bio-comportementales est essentiel à des fins d'évaluation des services de soins, traitement et prévention de l'infection à VIH et pour en optimiser l'accès et la couverture. Cela est également fondamental pour évaluer la véritable ampleur des besoins non satisfaits dans la gestion de l'épidémie de VIH et pour correctement interpréter les comportements associés à l'acquisition et à la transmission du VIH. Les données disponibles indiquent que la plupart des participants aux enquêtes liées à la santé acceptent de répondre à une question sur leur statut VIH, parmi d'autres questions sensibles concernant les comportements sexuels et l'usage de drogues. Enfin, une normalisation de l'auto-déclaration du statut VIH pourrait aider la communauté mondiale à dépasser ce que l'on appelle « l'exceptionnalisme » pour ouvrir une ère de déstigmatisation, ce qui permettrait d'améliorer la réponse face à l'épidémie dans le monde entier.Durante la realización de encuestas bioconductuales que miden la prevalencia del contagio del virus de la inmunodeficiencia humana (VIH), los encuestados deberían entregar los resultados de la última prueba de VIH a la que se hayan sometido. No obstante, muchas autoridades gubernamentales, organizaciones no gubernamentales, investigadores y otras partes interesadas de la sociedad civil han declarado que las personas encuestadas implicadas en dichas encuestas no deberían tener que realizar una autodeclaración de su estado con relación al VIH. Las razones expuestas para no pedir a los encuestados que informen de su condición son que las respuestas pueden ser inexactas y que preguntarles por su estado en relación al VIH puede violar sus derechos humanos y exacerbar la estigmatización y la discriminación. Sin embargo, se sostiene que, en la era de terapias antirretrovirales, solicitar a los encuestados en encuestas bioconductuales que declaren su estado en relación al VIH es fundamental para medir y mejorar el acceso a, y la cobertura de, servicios para la atención, el tratamiento y la prevención del contagio del VIH. También es importante para estimar el verdadero alcance de las necesidades insatisfechas a la hora de abordar la epidemia de VIH, así como para interpretar las conductas asociadas a la adquisición y transmisión del virus de forma adecuada. Los datos disponibles indican que la mayor parte de los participantes en encuestas relacionadas con la salud están dispuestos a responder una pregunta sobre su estado en relación al VIH como una de las muchas posibles preguntas delicadas sobre comportamientos sexuales y de consumo de drogas. Por último, normalizar las declaraciones sobre el estado en relación al VIH podría ayudar a la comunidad mundial a pasar de una época caracterizada por el “excepcionalismo” a una caracterizada por la “desestigmatización”, y, de este modo, mejorar la respuesta frente a las epidemias a nivel mundial.يجب أن يُسأل المشاركون في المسوح السلوكية الحيوية التي تقيس معدل انتشار العدوى بفيروس العوز المناعي البشري (HIV) عن نتائج آخر اختبار خضعوا له للكشف عن الإصابة بالفيروس. إلا أن العديد من السلطات الحكومية والمنظمات غير الحكومية والباحثين وغيرهم من الجهات المعنية في المجتمع المدني قد أعلنوا أن المشاركين في مثل هذه المسوح لا يجب أن يُطلب منهم الإفصاح عن وضعية إصابتهم بفيروس العوز المناعي البشري. وتتمثل الأسباب المقدمة لعدم توجيه الطلب إلى المشاركين للإبلاغ عن حالتهم في شبهة عدم دقة الإجابات، كما أن السؤال عن حالة الإصابة بفيروس العوز المناعي البشري قد ينتهك حقوق الإنسان للمشاركين ويثير في نفوسهم الشعور بالحرج الاجتماعي والتمييز. ومع ذلك، فإننا نؤكد على أنه في أوقات العلاج بمضادات الفيروسات، يكون طلب الإبلاغ ذاتيًا عن حالة الإصابة بفيروس العوز المناعي البشري من المشاركين في المسوح السلوكية الحيوية أمرًا ضروريًا لقياس وتحسين سبل الوصول إلى خدمات الرعاية والعلاج والوقاية من عدوى فيروس العوز المناعي البشري، ومدى التغطية التي تقدمها تلك الخدمات. وهذا الأمر مهم أيضًا للوقوف على الحجم الحقيقي لمقدار العجز في تلبية احتياجات التصدي لوباء فيروس العوز المناعي البشري، والوصول إلى تفسير سليم للسلوكيات المرتبطة بانتقال والإصابة بعدوى فيروس العوز المناعي. تشير البيانات المتاحة إلى أن معظم المشاركين في المسوح المتعلقة بالصحة على استعداد للرد عن أي سؤال يتعلق بحالة إصابتهم بفيروس العوز المناعي البشري – باعتباره سؤالاً من بين عدة أسئلة حساسة محتمل طرحها عن السلوكيات الجنسية وتعاطي المخدرات. وأخيرًا، يمكن أن يسهم تطبيع إجراءات الإبلاغ الذاتي عن حالة الإصابة بفيروس العوز المناعي البشري في مساعدة المجتمع العالمي للمضي قدمًا من عصر ما يسمى "الاستثنائية" إلى عصر "التخلص من الحرج الاجتماعي" – وبذلك يتم تحسين سبل التصدي للوباء في جميع أنحاء العالم.在开展测量人体免疫缺损病毒 (HIV) 发病率的生物行为调查中，应该询问受访者上次的 HIV 检测结果。 但是，许多政府主管部门、非政府组织、研究人员以及其他民间社会利益相关者表示不应该要求参与此类调查的受访者自我报告其 HIV 状况。 他们对此给出的解释是受访者给出的回答可能不准确，而且询问受访者的 HIV 状况可能侵犯了他们的人权，并加剧其耻辱感和受歧视感。 然而，我们认为在抗逆转录病毒治疗时期，要求受访者在生物行为调查中自我报告其 HIV 状况对衡量和改进 HIV 感染护理、治疗和预防服务以及此类服务的覆盖面至关重要。 此外，在评估在应对 HIV 流行病方面未满足的真正需求量以及正确解释与 HIV 的感染与传播相关的行为方面，自我报告也非常重要。 现有数据表明，大多数健康相关调查的参与者愿意回答与 HIV 状况相关的问题，该问题为可能与性和吸毒行为相关的若干敏感问题之一。 最后，对 HIV 状况的自我报告的标准化有助于国际社会从所谓的例外主义转向一种反污名化态度，从而改善全球范围内对流行病的应对水平。.В рамках биоповеденческих исследований, нацеленных на определение распространенности заражения вирусом иммунодефицита человека (ВИЧ), респондентов следует опрашивать относительно результатов их последнего тестирования на ВИЧ. Однако многие государственные органы, неправительственные организации, исследователи и прочие заинтересованные члены гражданского общества заявляли, что респондентам, участвующим в таких исследованиях, не следует задавать вопросы относительно собственного ВИЧ-статуса. Доводы против просьб о самостоятельном сообщении респондентами своего статуса сводятся к тому, что ответы могут быть неточными и что вопросы о ВИЧ-статусе могут являться нарушением человеческих прав респондентов и усугубить стигматизацию и дискриминацию. Несмотря на это, авторы данной статьи настаивают, что в эпоху антиретровирусной терапии необходимо просить респондентов, участвующих в биоповеденческих исследованиях, самостоятельно сообщить о своем ВИЧ-статусе. С помощью этих сообщений удастся определить и улучшить доступность служб для предоставления людям, зараженным ВИЧ, соответствующей помощи и лечения, для профилактики этой инфекции, а также охват такими службами. Кроме того, это важно для оценки реального объема неудовлетворенных потребностей в борьбе с эпидемией ВИЧ и для правильной интерпретации поведения, сопряженного с заражением и передачей ВИЧ. Судя по имеющимся данным, большинство участников исследований состояния здоровья готовы ответить на вопрос о ВИЧ-статусе, являющийся одним из нескольких возможных вопросов конфиденциального характера, касающихся сексуального поведения и употребления наркотиков. В конечном счете признание самостоятельных сообщений о ВИЧ-статусе нормальным явлением могло бы содействовать переходу мирового сообщества от эпохи так называемой исключительности к эпохе дестигматизации, а также совершенствованию реагирования на эпидемию во всем мире.

Background\ud \ud Understanding the spread of sexually transmitted infections (STIs) in a population is of great importance to the planning and delivery of health services globally. The worldwide rise of HIV since the 1980’s, and the recent increase in common STIs (including HPV and Chlamydia) in many countries, means that there is an urgent need to understand transmission dynamics in order to better predict the spread of such infections in the population. Unlike many other infections which can be captured by assumptions of random mixing, STI transmission is intimately linked to the number and pattern of sexual contacts. In fact, it is the huge variation in the number of new sexual partners that gives rise to the extremes of risk within populations which need to be captured in predictive models of STI transmission. Such models are vital in providing the necessary scientific evidence to determine whether a range of controls (from education to screening to vaccination) are cost-effective.\ud \ud Method and results\ud \ud We use probability sample survey data from Britain’s third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) to determine robust distributions for the rate of new partnerships that involve condomless sex and can therefore facilitate the spread of STIs. Different distributions are defined depending on four individual-level characteristics: age, sex, sexual orientation, and previous sexual experience. As individual behaviour patterns can change (e.g. by remaining in a monogamous relationship for a long period) we allow risk-percentiles to be randomly redrawn, to capture longer term behaviour as measured by Natsal-3. We demonstrate how this model formulation interacts with the transmission of infection by constructing an individual-based SIS-P (Susceptible—Infected—Susceptible—Protected) transmission model for the spread of a generic STI, and observing overall population demographics when varying the transmission probability within a partnership, recovery rate and the level of population protection (e.g. from vaccination where applicable).

Childhood obesity is a major public health challenge. This article describes an overview of the National Institutes of Health (NIH) behavioral and social sciences childhood obesity research efforts. The overview will highlight five areas of childhood obesity research supported by the NIH: (a) basic behavioral and social sciences; (b) early childhood; (c) policies, programs, and environmental strategies; (d) health disparities; and (e) transagency and public-private collaboration. The article also describes potential gaps and opportunities in the areas of childhood obesity and severe obesity, measurement, and sleep.

Understanding how gene alterations induce oncogenesis plays an important role in cancer research and may be instructive for cancer prevention and treatment. We conducted a parameter sensitivity analysis to the mitochondrial apoptosis model. Both a nonlinear bifurcation analysis of the deterministic dynamics and energy barrier analysis of the corresponding stochastic models were performed. We found that the parameter sensitivity ranking according to the change of the bifurcation-point locations in deterministic models and the change of the barrier heights from a living to death state of the cell in stochastic models are highly correlated. For the model we considered, in combination with previous knowledge that the parameters significantly affecting the system's bifurcation point are strongly associated with frequently mutated oncogenic genes, we conclude that the energy barrier height can be used as indicator of oncogenesis as well as bifurcation point. We provide a possible mechanism that may help elucidate the logic of cancer initiation from the view of stochastic dynamics and energy landscape. And we show the equivalence of energy barrier height and bifurcation-point location in determining the parameter sensitivity spectrum for the first time.

Research indicates that stigma serves as a barrier to the recruitment of participants into mental health intervention studies. Some participants, such as those for depression intervention studies that target people with human immunodeficiency virus (HIV), may face multiple sources of stigma. The purpose of this brief report was to describe recruitment strategies used during the initial months of an ongoing preliminary pilot study designed to develop a web-based intervention for young African American and Latino gay and bisexual men living with HIV who reported symptoms of depression. We employed four primary recruitment strategies to identify potential participants in the Los Angeles metropolitan area for the study. These strategies included social media, referrals, direct contact, and recruitment flyers. Preliminary data indicated that recruitment efforts generated 57 responses from potential participants during the first four months of recruitment and study implementation. The monthly response rate from potential participants represented slightly more than 71% of the study’s minimum level targeted for participant enrollment. Findings from this preliminary study are discussed in terms of the role of stigma as a barrier to mental health participant research recruitment. Implications for both depression research and clinical interventions are considered.

Cooperation is ubiquitous in biological and social systems, even though cooperative behavior is often costly and at risk of exploitation by non-cooperators. Several studies have demonstrated that indirect reciprocity, whereby some members of a group observe the behaviors of their peers and use this information to discriminate against previously uncooperative agents in the future, can promote prosocial behavior. Some studies have shown that differential propensities of interacting among and between different types of agents (interaction assortment) can increase the effectiveness of indirect reciprocity. No previous studies have, however, considered differential propensities of observing the behaviors of different types of agents (information assortment). Furthermore, most previous studies have assumed that discriminators possess perfect information about others and incur no costs for gathering and storing this information. Here, we (1) consider both interaction assortment and information assortment, (2) assume discriminators have limited information about others, and (3) introduce a cost for information gathering and storage, in order to understand how the ability of discriminators to stabilize cooperation is affected by these steps toward increased realism. We report the following findings. First, cooperation can persist when agents preferentially interact with agents of other types or when discriminators preferentially observe other discriminators, even when they have limited information. Second, contrary to intuition, increasing the amount of information available to discriminators can exacerbate defection. Third, introducing costs of gathering and storing information makes it more difficult for discriminators to stabilize cooperation. Our study broadens the set of circumstances in which it is known that cooperation can be maintained and is one of only a few studies to date that show how negative interaction assortment can promote cooperation.

This study examined state-trait models of diurnal cortisol (morning level and diurnal slope), and whether income, cumulative risk and parenting behaviors predicted variance in trait and state levels of cortisol. The sample of 306 mothers and their preschool children included 29% families at or near poverty, 27% families below the median income, and the remaining families at middle and upper income. Diurnal cortisol, income, cumulative risk, and parenting were measured at 4 time points, once every 9 months, starting when children were 36-40 months. State-trait models fit the data, suggesting significant state but not trait variance in cortisol. Low income and cumulative risk were related to trait levels of diurnal cortisol with little evidence of time-varying or state effects. Stable levels of parenting predicted trait levels of diurnal cortisol and time-varying levels of parenting predicted time-varying state levels of diurnal cortisol. Findings highlight the allostatic process of adaptation to risk as well as time-specific reactivity to variability in experience.

Background Despite global gains, women in hard-to-reach areas are at a relatively higher risk of death and disability related to childbirth. Traditional methods of measuring satisfaction may mask negative experiences (such as disrespect and abuse) that can drive down demand for institutional care. Better measurement of women’s perceptions of care quality, especially among marginalized populations with historically low utilization of institutional care, are needed to inform how to improve services and foster greater utilization of (potentially life-saving) clinical care. Methods A population-based household survey was conducted in 15 purposively selected villages in the rural Western Highlands of Guatemala among women who gave birth to a child within the last 5 years. Demographic and health information including experiences and perceptions of maternity care were collected. Two sets of nested multivariate logistic regression models were estimated to identify factors associated with future intention to give birth in a health facility, separately among women who gave birth to their last child at home and women who gave birth to their last child in a facility. The independent variables of interest were access to care, perceived need for maternity care, and two measures of perceived quality: satisfaction with last birth and disrespect and abuse (perceived or experienced). Thematic analysis was performed on open-ended responses. Results Perceived need for facility-based childbirth services and satisfaction with last childbirth experience, either at home or in a facility, emerged as the key factors influencing intention to give birth in a health institution in the future. Among the facility birth group, reporting disrespect and abuse is a deterrent to seeking facility-based care in the future. However, select perceptions of disrespect and abuse did not have an association with future intention (among the home birth group). Conclusions Women’s perceptions of care quality influence care-seeking. Women who feel they were mistreated in health facilities are more likely to avoid or delay seeking care in the future. Health systems need to reinforce trust and positive perceptions of respectful care. Developing better measures of women’s perceptions of maternity care experiences among indigenous populations in Guatemala can inform improvements in care provision.

Animal behaviour is increasingly seen as an important component in maintaining functional connectivity between patches in fragmented landscapes. However, models that explicitly incorporate behavioural trade-offs are rarely applied to landscape planning problems like connectivity. The aim of this study was to explore how state-dependent behaviour influenced functional connectivity between patches from a theoretical perspective. We investigated how inter-patch distances influenced functional connectivity using a dynamic state variable model framework. The decision making process of an individual ruminant facing fitness trade-offs in staying in its patch of origin or moving to another patch at various distances were explicitly modelled. We incorporated energetic costs and predation costs of feeding, ruminating, and resting while in the patch and for transit between patches based on inter-patch distance. Functional connectivity was maintained with isolated patches when they offered high intake and the inactivity of rumination associated with rapid gut fill resulted in reduced predation risk. Nevertheless, individuals in high energetic state often would forgo moving to another patch, whereas individuals in poor energetic states were forced to accept the cost of movement to best meet their requirements in the distant patch. The inclusion of state-dependent behavioural models provides important insights into functional connectivity in fragmented landscapes and helps integrate animal behaviour into landscape planning. We discuss the consequences of our findings for landscape planning to show how the approach provides a heuristic tool to assess alternative scenarios for restoring landscape functional connectivity.

The Triple Code Model (TCM) of numerical cognition argues for the existence of three representational codes for number: Arabic digits, verbal number words, and analog nonsymbolic magnitude representations, each subserved by functionally dissociated neural substrates. Despite the popularity of the TCM, no study to date has explored all three numerical codes within one fMRI paradigm. We administered three tasks, associated with each of the aforementioned numerical codes, in order to explore the neural correlates of numerosity processing in a sample of adults (N=46). Independent task-control contrast analyses revealed task-dependent activity in partial support of the model, but also highlight the inherent complexity of a distributed and overlapping fronto-parietal network involved in all numerical codes. The results indicate that the TCM correctly predicts the existence of some functionally dissociated neural substrates, but requires an update that accounts for interactions with attentional processes. Parametric contrasts corresponding to differences in task difficulty revealed specific neural correlates of the distance effect, where closely spaced numbers become more difficult to discriminate than numbers spaced further apart. A conjunction analysis illustrated overlapping neural correlates across all tasks, in line with recent proposals for a fronto-parietal network of number processing. We additionally provide tentative results suggesting the involvement of format-independent numerosity-sensitive retinotopic maps in the early visual stream, extending previous findings of nonsymbolic stimulus selectivity. We discuss the functional roles of the components associated with the model, as well as the purported fronto-parietal network, and offer arguments in favor of revising the TCM. Funding Agencies|Linkoping University [LiU-2009-01356]; Marianne and Marcus Wallenberg Foundation [2014-0173]

BACKGROUND: The International Classification of Functioning, Disability and Health is a classification of human functioning and disability and is based on a biopsychosocial model of health. As such, International Classification of Functioning, Disability and Health seems suitable as a basis for constructing models defining the clinical P&O process. The aim was to use International Classification of Functioning, Disability and Health to facilitate development of such a model. Proposed model: A model, the Prosthetic and Orthotic Process (POP) model, is proposed. The Prosthetic and Orthotic Process model is based on the concepts of the International Classification of Functioning, Disability and Health and comprises four steps in a cycle: (1) Assessment, including the medical history and physical examination of the patient. (2) Goals, specified on four levels including those related to participation, activity, body functions and structures and technical requirements of the device. (3) Intervention, in which the appropriate course of action is determined based on the specified goal and evidence-based practice. (4) Evaluation of outcomes, where the outcomes are assessed and compared to the corresponding goals. After the evaluation of goal fulfilment, the first cycle in the process is complete, and a broad evaluation is now made including overriding questions about the patient's satisfaction with the outcomes and the process. This evaluation will determine if the process should be ended or if another cycle in the process should be initiated. CONCLUSION: The Prosthetic and Orthotic Process model can provide a common understanding of the P&O process. Concepts of International Classification of Functioning, Disability and Health have been incorporated into the model to facilitate communication with other rehabilitation professionals and encourage a holistic and patient-centred approach in clinical practice. Clinical relevance The Prosthetic and Orthotic Process model can support the implementation of International Classification of Functioning, Disability and Health in P&O practice, thereby providing a common understanding of the P&O process and a common language to facilitate communication with other rehabilitation professionals.