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This work demonstrates the application of a 3D culture system - Cells-in-Gels-in-Paper (CiGiP) - in evaluating the metabolic response of lung cancer cells to ionizing radiation. The 3D tissue-like construct - prepared by stacking multiple sheets of paper containing cell-embedded hydrogels - generates a gradient of oxygen and nutrients that decreases monotonically in the stack. Separating the layers of the stack after exposure enabled analysis of the cellular response to radiation as a function of oxygen and nutrient availability; this availability is dictated by the distance between the cells and the source of oxygenated medium. As the distance between the cells and source of oxygenated media increased, cells show increased levels of hypoxia-inducible factor 1-alpha, decreased proliferation, and reduced sensitivity to ionizing radiation. Each of these cellular responses are characteristic of cancer cells observed in solid tumors. With this setup we were able to differentiate three isogenic variants of A549 cells based on their metabolic radiosensitivity; these three variants have known differences in their metastatic behavior in vivo. This system can, therefore, capture some aspects of radiosensitivity of populations of cancer cells related to mass-transport phenomenon, carry out systematic studies of radiation response in vitro that decouple effects from migration and proliferation of cells, and regulate the exposure of oxygen to subpopulations of cells in a tissue-like construct either before or after irradiation., Chemistry and Chemical Biology

This work describes a 3D, paper-based assay that can isolate subpopulations of cells based on their invasiveness (i.e., distance migrated in a hydrogel) in a gradient of concentration of oxygen (O2). Layers of paper impregnated with a cell-compatible hydrogel are stacked and placed in a plastic holder to form the invasion assay. Stacking the layers of paper assembles them into 3D tissue-like constructs of defined thickness and composition. The plastic holder ensures the layers of paper are in conformal contact; this geometry allows the cells to migrate between adjacent layers through the embedded hydrogel. In most assays, the stack comprises a single layer of paper containing mammalian cells suspended in a hydrogel, sandwiched between multiple layers of paper containing only hydrogel (into which the cells migrate). Cells in the stack consume and produce small molecules; these molecules diffuse throughout the stack to generate gradients both in the stack, and between the stack and the bulk culture medium. Placing the cell-containing layer in different positions of the stack, or modifying the permeability of the holder to oxygen or proteins, alters the profile of the gradients within the stack. Physically separating the layers after culture isolates subpopulations of cells that migrated different distances, and enables their subsequent analysis or culture. Using this system, three independent cell lines derived from A549 cancer cells are shown to produce distinguishable migration behavior in a gradient of oxygen. This result is the first experimental demonstration that oxygen acts as a chemoattractant for cancer cells., Chemistry and Chemical Biology

This paper demonstrates a new soft structure that uses a meso- or macro-scale elastic instability to generate a shape-memory effect similar to that exhibited by a ferroelastic material. It demonstrates the phase transitions, state switching, and shape-memory effects in this system, both in experiment and in simulation. The new class of materials described in the paper is potentially useful, since it comprises what are effectively ‘‘shape-memory alloys’’ of arbitrarily low modulus and arbitrarily large remnant strain. The reproduction of properties of materials usually associated with atomic- or molecular-level changes in structure using meso-scale structural opens the door to development of new, soft materials with new properties and functions., Chemistry and Chemical Biology

Indicator species (IS) are used to monitor environmental changes, assess the efficacy of management, and provide warning signals for impending ecological shifts. Though widely adopted in recent years by ecologists, conservation biologists, and environmental practitioners, the use of IS has been criticized for several reasons, notably the lack of justification behind the choice of any given indicator. In this review, we assess how ecologists have selected, used, and evaluated the performance of the indicator species. We reviewed all articles published in Ecological Indicators (EI) between January 2001 and December 2014, focusing on the number of indicators used (one or more); common taxa employed; terminology, application, and rationale behind selection criteria; and performance assessment methods. Over the last 14 years, 1914 scientific papers were published in EI, describing studies conducted in 53 countries on six continents; of these, 817 (43%) used biological organisms as indicators. Terms used to describe organisms in IS research included “ecological index”, “environmental index”, “indicator species”, “bioindicator”, and “biomonitor,” but these and other terms often were not clearly defined. Twenty percent of IS publications used only a single species as an indicator; the remainder used groups of species as indicators. Nearly 50% of the taxa used as indicators were animals, 70% of which were invertebrates. The most common applications behind the use of IS were to: monitor ecosystem or environmental health and integrity (42%); assess habitat restoration (18%); and assess effects of pollution and contamination (18%). Indicators were chosen most frequently based on previously cited research (40%), local abundance (5%), ecological significance and/or conservation status (13%), or a combination of two or more of these reasons (25%). Surprisingly, 17% of the reviewed papers cited no clear justification for their choice of indicator. The vast majority (99%) of publications used statistical methods to assess the performance of the selected indicators. This review not only improves our understanding of the current uses and applications of IS, but will also inform practitioners about how to better select and evaluate ecological indicators when conducting future IS research., Organismic and Evolutionary Biology

In this paper we propose a constitutive model to analyze in-plane extension of goat fascia lata. We first perform a histological analysis of the fascia that shows a well-organized bi-layered arrangement of undulated collagen fascicles oriented along two well defined directions. To develop a model consistent with the tissue structure we identify the absolute and relative thickness of each layer and the orientation of the preferred directions. New data are presented showing the mechanical response in uniaxial and planar biaxial extension. The paper proposes a constitutive relation to describe the mechanical response. We provide a summary of the main ingredients of the nonlinear theory of elasticity and introduce a suitable strain-energy function to describe the anisotropic response of the fascia. We validate the model by showing good fit of the numerical results and the experimental data. Comments are included about differences and analogies between goat fascia lata and the human iliotibial band., Organismic and Evolutionary Biology

How does insurgency spread? Existing research on the diffusion of violence at the local level of civil war tends to under-specify the theoretical mechanisms by which conflict can be expanded, relocated or sustained, and overlooks the real-world logistical constraints that combatants face on a daily basis. This paper attempts to address both problems by taking a closer look at the role of road networks in the diffusion of insurgent activity. By explicating the logic of diffusion in a simple epidemic model and exploiting new disaggregated data on violence and road networks in the North Caucasus, this analysis challenges the conventional view that insurgent logistics are either self-sufficient or highly flexible. Roads shape the costs of sustaining and expanding operations, which facilitates the transmission of violence to new locations, but can also intensify competition for limited military resources between nearby battlefronts. At the local level, this dynamic makes the relocation of insurgent activity more likely than its expansion. Methodologically, this paper demonstrates that a failure to account for logistical constraints in the empirical study of civil war can underestimate costs of diffusion and overpredict the transmissibility of violence between neighboring locations. The use of road network distances can yield more conservative inferences and more accurate predictions of how violence spreads., Government

Voxel-Based Morphometry (VBM) is a hypothesis-free, whole-brain, voxel-by-voxel analytic method that attempts to compare imaging data between populations. Schizophrenia studies have utilized this method to localize differences in Diffusion Tensor Imaging (DTI) derived Fractional Anisotropy (FA), a measure of white matter integrity, between patients and healthy controls. The number of publications has grown, although it is unclear how reliable and reproducible this method is, given the subtle white matter abnormalities expected in schizophrenia. Here we analyze and combine results from 23 studies published to date that use VBM to study schizophrenia in order to evaluate the reproducibility of this method in DTI analysis. Coordinates of each region reported in DTI VBM studies published thus far in schizophrenia were plotted onto a Montreal Neurological Institute atlas, and their anatomical locations were recorded. Results indicated that the reductions of FA in patients with schizophrenia were scattered across the brain. Moreover, even the most consistently reported regions were reported independently in less than 35% of the papers studied. Other instances of reduced FA were replicated at an even lower rate. Our findings demonstrate striking inconsistency, with none of the regions reported in much more than a third of the published papers. Poor replication rate suggests that the application of VBM to DTI data may not be the optimal way for studying the subtle microstructural abnormalities that are being hypothesized in schizophrenia.

This paper examines how uncertainty and credit constraints affect the cyclical composition of investment and thereby volatility and growth. We develop a model where firms engage in two types of investment: a short-term one; and a long-term one, which contributes more to productivity growth. Because it takes longer to complete, long-term investment has a relatively less cyclical return; but it also has a higher liquidity risk. The first effect ensures that the share of long-term investment to total investment is countercyclical when financial markets are perfect; the second implies that this share may turn procyclical when firms face tight credit constraints. The contribution of the paper is thus to identify a novel propagation mechanism: through its effect on the cyclical composition of investment, tighter credit can lead to both higher volatility and lower mean growth. Evidence from a panel of countries provides support for the model’s key predictions., Economics

The question of why some people do things that are intentionally harmful to themselves continues to puzzle scientists, clinicians, and the public. Prior studies have demonstrated that one fairly extreme, direct form of self-harm, non-suicidal self-injury (NSSI), is maintained by both automatic (i.e., intrapersonal) as well as social (i.e., interpersonal) reinforcement. However, the majority of theoretical and empirical papers on this topic focus almost exclusively on the automatic functions. The purpose of this paper is to provide a more comprehensive analysis of the social functions of NSSI. Evidence is presented supporting the notion that NSSI is maintained by social reinforcement in at least a substantial minority of instances. Moreover, an elaborated theoretical model of the social functions of NSSI is outlined that proposes that this behavior represents a high intensity social signal used when less intense communication strategies fail (e.g., speaking, yelling, crying). The model further proposes that NSSI can serve not only as a signal of distress that is reinforced primarily by the caregiving behavior it elicits from others, but that it also can serve as a signal of strength and fitness that is reinforced by warding off potential threats (e.g., peer victimization), and in some cases can strengthen affiliation with others. Support for this theoretical model is drawn from diverse literatures including psychology, evolutionary biology, and cultural anthropology. The paper concludes with specific recommendations for empirical tests of the proposed model of the social functions of NSSI, as well as other harmful behaviors such as alcohol and drug use., Psychology

The paper considers opportunities to reduce emissions of CO2 through increases in commitments to wind in a representative US power market. A model is applied to simulate market operations for different wind levels focusing on implications of the reduction in clearing prices arising due to increasing inputs of zero marginal cost power from wind, a dilemma referred to as the missing money problem. The resulting decrease in income poses problems for existing thermal and nuclear generating systems, at the same time making investments in wind uneconomic in the absence offsetting policy interventions. Two options are considered to subsidize cost: an investment credit (IC) or a subsidy on production (PC). The dilemma could be addressed also with a carbon tax targeted to increase income. It is assumed that the cost associated with the IC and PC options should be borne by the consumer, offsetting benefits from lower wholesale prices. It is assumed further that income from the carbon tax should be rebated to the consumer offsetting related increases in clearing prices. IC and PC options offer opportunities to reduce emissions at low or even negative net costs to the consumer. Higher costs are associated with the option of a carbon tax., Other Research Unit

This paper studies a model of intermediated exchange with liquidity-constrained traders. Intermediaries are embedded in a trading network and their financial capacities are private information. We characterize our model’s monotone, pure-strategy equilibrium. Agents earn positive intermediation rents in equilibrium. An experimental investigation supports the model’s baseline predictions concerning agents’ strategies, price dynamics, and the division of surplus. While private financial constraints inject uncertainty into the trading environment, our experiment suggests they are also a behavioral speed-bump, preventing traders from experiencing excessive losses due to overbidding.

In connection with an earlier paper on the exchange of live donor kidneys (Roth, Sönmez, and ‹Ünver 2004) the authors entered into discussions with New England transplant surgeons and their colleagues in the transplant community, aimed at implementing a Kidney Exchange program. In the course of those discussions it became clear that a likely first step will be to implement pairwise exchanges, between just two patient-donor pairs, as these are logistically simpler than exchanges involving more than two pairs. Furthermore, the experience of these surgeons suggests to them that patient and surgeon preferences over kidneys should be 0-1, i.e. that patients and surgeons should be indifferent among kidneys from healthy donors whose kidneys are compatible with the patient. This is because, in the United States, transplants of compatible live kidneys have about equal graft survival probabilities, regardless of the closeness of tissue types between patient and donor (unless there is a rare perfect match). In the present paper we show that, although the pairwise constraint eliminates some potential exchanges, there is a wide class of constrained-efficient mechanisms that are strategy-proof when patientdonor pairs and surgeons have 0-1 preferences. This class of mechanisms includes deterministic mechanisms that would accomodate the kinds of priority setting that organ banks currently use for the allocation of cadaver organs, as well as stochastic mechanisms that allow considerations of distributive justice to be addressed., Economics

The development of reproducible folding in the gyrencephalic cerebral cortex is a topic of great interest to neuroscientists. In a recent paper in Cell, del Toro et al. (2017) show that changing the adhesive properties of neurons in the normally lissencephalic mouse cortex leads to the formation of stereotyped folding., Stem Cell and Regenerative Biology

Elastomeric seals are essential to two great technological advances in oilfields: horizontal drilling and hydraulic fracturing. This paper describes a method to study elastomeric seals by using the pressure-extrusion curve (i.e., the relation between the drop of pressure across a seal and the volume of extrusion of the elastomer). Emphasis is placed on a common mode of failure found in oilfields: leak caused by a crack across the length of a long seal. We obtain an analytical solution of large elastic deformation, which is analogous to the Poiseuille flow of viscous liquids. We further obtain analytical expressions for the energy release rate of a crack and the critical pressure for the onset of its propagation. The theory predicts the pressure-extrusion curve using material parameters (elastic modulus, sliding stress, and fracture energy) and geometric parameters (thickness, length, and precompression). We fabricate seals of various parameters in transparent chambers on a desktop, and watch the seals extrude, slide, rupture and leak. The experimentally measured pressure-extrusion curves agree with theoretical predictions remarkably well., Engineering and Applied Sciences, Physics, Other Research Unit

The molecular linkage between neocortical projection neuron subtype and area development, which enables the establishment of functional areas by projection neuron populations appropriate for specific sensory and motor functions, is poorly understood. Here, we report that Ctip1 controls precision of neocortical development by regulating subtype identity in deep-layer projection neurons. Ctip1 is expressed by postmitotic callosal and corticothalamic projection neurons, but is excluded over embryonic development from corticospinal motor neurons, which instead express its close relative, Ctip2. Loss of Ctip1 function results in a striking bias in favor of subcerebral projection neuron development in sensory cortex at the expense of corticothalamic and deep-layer callosal development, while misexpression of Ctip1 in vivo represses subcerebral gene expression and projections. As we report in a paired paper, Ctip1 also controls acquisition of sensory area identity. Therefore, Ctip1 couples subtype and area specification, enabling specific functional areas to organize precise ratios of appropriate output projections., Stem Cell and Regenerative Biology

This paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual elements. The most important design details of individual components are described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI longterm performance, are also discussed., Physics

Development of shale gas resources is expected to play an important role in China's projected transition to a low-carbon energy future. The question arises whether the availability of water could limit this development. The paper considers a range of scenarios to define the demand for water needed to accommodate China's projected shale gas production through 2020. Based on data from the gas field at Fuling, the first large-scale shale gas field in China, it is concluded that the water intensity for shale gas development in China (water demand per unit lateral length) is likely to exceed that in the US by about 50%. Fuling field would require a total of 39.9–132.9 Mm3 of water to achieve full development of its shale gas, with well spacing assumed to vary between 300 and 1000 m. To achieve the 2020 production goal set by Sinopec, the key Chinese developer, water consumption is projected to peak at 7.22 Mm3 in 2018. Maximum water consumption would account for 1% and 3%, respectively, of the available water resource and annual water use in the Fuling district. To achieve China's nationwide shale gas production goal set for 2020, water consumption is projected to peak at 15.03 Mm3 in 2019 in a high-use scenario. It is concluded that supplies of water are adequate to meet demand in Fuling and most projected shale plays in China, with the exception of localized regions in the Tarim and Jungger Basins., Engineering and Applied Sciences

Urban intensity, in this paper, is measured by four related concepts: compactness, diversity, density, and connectivity. Together they lead to a single idea when considering spatial distributions potentially in a virtuous manner with regard to resource consumption, economic opportunity, social integration and environmental performance. The methodologies applied here included Moran's I, Shannon's index entropy, and accessibility isotimelines, which were then applied to real case scenarios in 20 towns in Zhejiang Province, selected based on their economic performances, population sizes, and geographical locations. Further inspection discovered that density, an outcome of urban form, is highly correlated to compactness, leading to its elimination. The results showed that among the varying spatial arrangements of urban activities, building footprints and infrastructural elements characterized by monocentric centers of use inscribed with well-defined and relatively uniform grids of streets and related networks, alongside of relatively integrated zones of use, seemed to perform best with regard to urban intensity. At the other end of the morphological spectrum, towns with sharp separations of uses and zones of development, often resulting in overall bifurcation of a town's spatial layout, performed less well. Also, linear forms for small towns were less favorable.

Coronary artery disease (CAD) has dominated mortality for most of the past century, not just in Europe and North America but worldwide. Treatments for CAD, both pharmaceutical and surgical, have become leading sectors of the healthcare economy. This paper focuses on the therapeutic landscape for CAD in the United States. We hope to add texture to the broader conversation of pharmaceuticalization explored in this issue by situating pharmaceutical therapies as just one element in the broader therapeutic terrain, alongside cardiac surgery and interventional cardiology. Patients with CAD must navigate a therapeutic landscape with three intersecting paths: lifestyle change, pharmaceuticals, and surgery. While pharmaceuticals are often seen as a quick fix, a way of avoiding more difficult lifestyle changes, it is surgery and angioplasty that promise patients the quickest fix of all. There also is another option, often overlooked by analysts but popular among physicians and patients: inaction. The U.S. context is often critiqued as a site of excessive treatment with respect to both drugs and procedures, and yet there is deep stratification within it – over-treatment in many populations and under-treatment in others. People who experience the serious risks of CAD do so in a racialized terrain of durable preoccupations with difference and unequal access to care. While the pharmaceuticalization literature disproportionately attends to lifestyle drugs, which some observers consider to be medically inappropriate or unnecessary, CAD does remain the leading cause of death. Thus, the stakes are high. Examination of the pharmaceuticalization of CAD in light of surgical treatments and racial disparities offers a window into the pervasiveness and persuasiveness of pharmaceuticals in an increasingly consumer-driven medicine, as well as the limits of their appeal and their reach., History of Science

This paper explores the menu of options for renormalizing public debt levels relative to nominal activity in the long run, should governments eventually decide to do so. Although debt ratios may need to rise further in some cases, a vision of longer-term options is key to weighing alternative medium-term stabilization strategies. Orthodox ones, the standard fare of officialdom, include enhancing growth, running primary budget surpluses, and privatizing government assets. Heterodox polices include restructuring debt contracts, generating unexpected inflation, taxing wealth, and repressing private finance. Advanced countries have relied far more on heterodox approaches than many observers choose to remember., Economics

Research consistently shows that college choice in an important predictor of college completion and labor market outcomes. These longer term implications of college choice, combined with suboptimal choices made by many low-income but high-achieving students, has sparked several large-scale initiatives to improve college choice. Strategically targeting those students most susceptible to making questionable decisions in the college-choice process remains challenging, as variation in college choice is largely unexplained by easily measurable socio-demographic characteristics. This paper explores the potential to improve upon existing models and, more generally, to better understand college choice by documenting the similarities in college enrollment patterns between younger and older siblings. To do so, we identify siblings in the millions of SAT test-takers between the 2004 and 2011 high school graduation cohorts. We find that younger siblings enroll in the same college as their older sibling 21.2 percent of the time. Also, conditional on their own SAT scores, we find that younger siblings whose older siblings enrolled in four-year colleges and the most selective colleges are 17.4 and 21.3 percentage points, respectively, more likely to themselves enroll in four-year and the most selective colleges. Overall, adding characteristics and enrollment decisions of older siblings to standard college choice models improves model fit and consequently, are valuable pieces of information for explanatory and predictive power., Economics

The concept of "exorbitant privilege" has received great attention from policy makers as well as academics worldwide. The idea originally referred to the willingness of foreigners to hold large quantities of US government debt at extremely low interest rates, due to the dollar's world reserve currency status. In recent years, the term exorbitant privilege has been expanded to explain why the US appears to be enjoying excess return from its external assets over liabilities across all asset classes, including foreign direct investment, equities and other forms of portfolio investment. In this paper, we give a brief review of the recent literature on exorbitant privilege, and then proceed to discuss exorbitant privilege in the context of another country, Japan, which has been the world's largest creditor nation for more than two decades. In contrast to the common perception that Japan has been a particularly poor international investor, we find that Japan enjoys exorbitant privilege in both the broad and narrow sense. Japan also earns higher expected returns from maturity transformation. Thus although the dollar is the reserve currency, the yen also has enjoyed a safe haven effect in the recent period., Economics

Silicon is a promising anode material for lithium-ion batteries due to its enormous theoretical energy density. Fracture during electrochemical cycling has limited the practical viability of silicon electrodes, but recent studies indicate that fracture can be prevented by taking advantage of lithiation-induced plasticity. In this paper, we provide experimental insight into the nature of plasticity in amorphous LixSi thin films. To do so, we vary the rate of lithiation of amorphous silicon thin films and simultaneously measure stresses. An increase in the rate of lithiation results in a corresponding increase in the flow stress. These observations indicate that rate-sensitive plasticity occurs in a-LixSi electrodes at room temperature and at charging rates typically used in lithium-ion batteries. Using a simple mechanical model, we extract material parameters from our experiments, finding a good fit to a power law relationship between the plastic strain rate and the stress. These observations provide insight into the unusual ability of a-LixSi to flow plastically, but fracture in a brittle manner. Moreover, the results have direct ramifications concerning the rate-capabilities of silicon electrodes: faster charging rates (i.e., strain rates) result in larger stresses and hence larger driving forces for fracture., Engineering and Applied Sciences

Objectives: The human dimensions of healthcare—core values and skilled communication necessary for every healthcare interaction—are fundamental to compassionate, ethical, and safe relationship-centered care. The objectives of this paper are to: describe the development of the International Charter for Human Values in Healthcare which delineates core values, articulate the role of skilled communication in enacting these values, and provide examples showing translation of the Charter’s values into action. Methods: We describe development of the Charter using combined qualitative research methods and the international, interprofessional collaboration of institutions and individuals worldwide. Results: We identified five fundamental categories of human values for every healthcare interaction—Compassion, Respect for Persons, Commitment to Integrity and Ethical Practice, Commitment to Excellence, and Justice in Healthcare—and delineated subvalues within each category. We have disseminated the Charter internationally and incorporated it into education/training. Diverse healthcare partners have joined in this work. Conclusion: We chronicle the development and dissemination of the International Charter for Human Values in Healthcare, the role of skilled communication in demonstrating values, and provide examples of educational and clinical programs integrating these values. Practice implications: The Charter identifies and promotes core values clinicians and educators can demonstrate through skilled communication and use to advance humanistic educational programs and practice.

Aspirational Goal 3 of the National Action Alliance for Suicide Prevention’s Research Prioritization Task Force is to predict who is at risk for attempting suicide in the near future. Despite decades of research devoted to the study of risk and protective factors for suicide and suicidal behavior, surprisingly little is known about the short-term prediction of these behaviors. In this paper, we propose several questions that, if answered, could improve the identification of short-term, or imminent, risk for suicidal behavior. First, what factors predict the transition from suicidal thoughts to attempts? Second, what factors are particularly strong predictors of making this transition over the next hours, days, or weeks? Third, what are the most important objective markers of short-term risk for suicidal behavior? And fourth, what method of combining information about risk and protective factors yields the best prediction? We propose that the next generation of research on the assessment and prediction of suicidal behavior should shift, from cross-sectional studies of bivariate risk and protective factors, to prospective studies aimed at identifying multivariate, short-term prediction indices, examining methods of synthesizing this information, and testing the ability to predict and prevent suicidal events., Psychology

Dating business cycles entails ascertaining economy-wide turning points. Broadly speaking, there are two approaches in the literature. The first approach, which dates to Burns and Mitchell (1946), is to identify turning points individually in a large number of series, then to look for a common date that could be called an aggregate turning point. The second approach, which has been the focus of more recent academic and applied work, is to look for turning points in a few, or just one, aggregate. This paper examines these two approaches to the identification of turning points. We provide a nonparametric definition of a turning point (an estimand) based on a population of time series. This leads to estimators of turning points, sampling distributions, and standard errors for turning points based on a sample of series. We consider both simple random sampling and stratified sampling. The empirical part of the analysis is based on a data set of 270 disaggregated monthly real economic time series for the US, 1959–2010., Economics

This paper studies how land reform and population growth affect land inequality and landlessness, focusing particularly on indirect effects owing to their influence on household divisions and land market transactions. Theoretical predictions of a model of household division and land transactions are successfully tested using household panel data from West Bengal spanning 1967–2004. The tenancy reform lowered inequality through its effects on household divisions and land market transactions, but its effect was quantitatively dominated by inequality-raising effects of population growth. The land distribution program lowered landlessness, but this was partly offset by targeting failures and induced increases in immigration.

In ergative constructions, the agent of a transitive verb is in the ergative case and the theme is in the absolutive case. By contrast, in biabsolutive constructions, both the agent and theme of a transitive verb appear in the absolutive case. This paper presents and analyzes the biabsolutive construction in two Nakh-Dagestanian languages, Lak and Tsez. Despite many surface similarities, the biabsolutive constructions in Lak and Tsez call for different syntactic analyses. We argue that the biabsolutive construction in Lak is an instance of restructuring in the presence of an aspectual head bearing a progressive (imperfective) feature. Tsez biabsolutive constructions, on the other hand, are biclausal; we argue that the theme and the lexical verb are contained in a PP complement selected by a light verb. Related languages may be classified as “Lak-type” or “Tsez-type” based on the behavior of their biabsolutives. The existence of two underlying structures for one surface pattern in Nakh-Dagestanian poses a learnability problem for a child acquiring a language with biabsolutive constructions. We outline a set of strategies used by a learner who must compare the available input data with a set of structural hypotheses., Linguistics

This paper examines the relationship between stature and later life health in 6 emerging economies, each of which are expected to experience significant increases in the mean age of their populations over the coming decades. Using data from the WHO Study on Global Ageing and Adult Health (SAGE) and pilot data from the Longitudinal Ageing Study in India (LASI), I show that various measures of health are associated with height, a commonly used proxy for childhood environment. In the pooled sample, a 10 cm increase in height is associated with between a 2 and 3 percentage point increase in the probability of being in very good or good self-reported health, a 3 percentage point increase in the probability of reporting no difficulties with activities of daily living or instrumental activities of daily living, and between a fifth and a quarter of a standard deviation increase in grip strength and lung function. Adopting a methodology previously used in the research on inequality, I also summarise the height-grip strength gradient for each country using the concentration index, and provide a decomposition analysis.

As demonstrated by the email game of Rubinstein (1989), the predictions of the standard equilibrium models of game theory are sensitive to assumptions about the fine details of the higher order beliefs. This paper shows that models of bounded depth of reasoning based on level-k thinking or cognitive hierarchy make predictions that are independent of the tail assumptions on the higher order beliefs. The framework developed here provides a language that makes it possible to identify general conditions on depth of reasoning, instead of committing to a particular model such as level-k thinking or cognitive hierarchy., Economics

Few research papers in economics have examined the extent, causes or consequences of physical stature decline in aging populations. Using repeated observations on objectively measured data from the English Longitudinal Study of Aging (ELSA), we document that reduction in height is an important phenomenon among respondents aged 50 and over. On average, physical stature decline occurs at an annual rate of between 0.08% and 0.10% for males, and 0.12% and 0.14% for females—which approximately translates into a 2–4 cm reduction in height over the life course. Since height is commonly used as a measure of long-run health, our results demonstrate that failing to take age-related height loss into account substantially overstates the health advantage of older birth cohorts relative to their younger counterparts. We also show that there is an absence of consistent predictors of physical stature decline at the individual level. However, we demonstrate how deteriorating health and reductions in height occur simultaneously. We document that declines in muscle mass and bone density are likely to be the mechanism through which these effects are operating. If this physical stature decline is determined by deteriorating health in adulthood, the coefficient on measured height when used as an input in a typical empirical health production function will be affected by reverse causality. While our analysis details the inherent difficulties associated with measuring height in older populations, we do not find that significant bias arises in typical empirical health production functions from the use of height which has not been adjusted for physical stature decline. Therefore, our results validate the use of height among the population aged over 50.

On the basis of geological evidence, it is often stated that the early martian climate was warm enough for liquid water to flow on the surface thanks to the greenhouse effect of a thick atmosphere. We present 3D global climate simulations of the early martian climate performed assuming a faint young Sun and a CO2 atmosphere with surface pressure between 0.1 and 7 bars. The model includes a detailed radiative transfer model using revised CO2 gas collision induced absorption properties, and a parameterisation of the CO2 ice cloud microphysical and radiative properties. A wide range of possible climates is explored using various values of obliquities, orbital parameters, cloud microphysic parameters, atmospheric dust loading, and surface properties. Unlike on present day Mars, for pressures higher than a fraction of a bar, surface temperatures vary with altitude because of the adiabatic cooling and warming of the atmosphere when it moves vertically. In most simulations, CO2 ice clouds cover a major part of the planet. Previous studies had suggested that they could have warmed the planet thanks to their scattering greenhouse effect. However, even assuming parameters that maximize this effect, it does not exceed +15 K. Combined with the revised CO2 spectroscopy and the impact of surface CO2 ice on the planetary albedo, we find that a CO2 atmosphere could not have raised the annual mean temperature above 0 °C anywhere on the planet. The collapse of the atmosphere into permanent CO2 ice caps is predicted for pressures higher than 3 bar, or conversely at pressure lower than 1 bar if the obliquity is low enough. Summertime diurnal mean surface temperatures above 0 °C (a condition which could have allowed rivers and lakes to form) are predicted for obliquity larger than 40° at high latitudes but not in locations where most valley networks or layered sedimentary units are observed. In the absence of other warming mechanisms, our climate model results are thus consistent with a cold early Mars scenario in which nonclimatic mechanisms must occur to explain the evidence for liquid water. In a companion paper by Wordsworth et al. we simulate the hydrological cycle on such a planet and discuss how this could have happened in more detail., Engineering and Applied Sciences

This paper considers the estimation of approximate dynamic factor models when there is temporal instability in the factor loadings. We characterize the type and magnitude of instabilities under which the principal components estimator of the factors is consistent, and find that these instabilities can be larger than earlier theoretical calculations suggest. We further characterize the rate of convergence of the estimated factors as a function of the magnitude of the time variation in the factor loadings for general types of parameter instability, and provide numerical evidence that this consistency rate is tight in the special case of random walk parameter variation. We also discuss implications of these results for the robustness of regressions based on the estimated factors and of estimates of the number of factors in the presence of parameter instability., Economics

BACKGROUND: High prevalences of depression and suicidality have been found among gay men. This paper assesses the possible impact of Blues-out, a depression awareness campaign based on the European Alliance Against Depression targeting the gay/lesbian community in Geneva, Switzerland. METHODS: In 2007 and 2011, pre- and post-intervention surveys were conducted among two distinct samples of gay men in Geneva, recruited by probability-based time-space sampling. Effect sizes and net percent changes are reported for mental health literacy and mental health outcomes in 2007 and 2011 as well as among men aware and unaware of Blues-out in 2011. RESULTS: 43% of the respondents correctly recognized depression in 2011 with no change vis-à-vis 2007. Despite small effect sizes, significant net decreases (from -18% to -28%) were seen in lifetime suicide plans, 12-month suicidal ideation, lifetime depression, and 4-week psychological distress between 2007 and 2011. These decreases were not accompanied by changes in any of the numerous items on attitudes/knowledge, found only when comparing men aware and unaware of Blues-out in 2011. More men aware of Blues-out found specialists and psychological therapies helpful than their counterparts and correctly identified depression and gay men's greater risk for depression. LIMITATIONS: Community-level assessment with no control. CONCLUSIONS: Although improvement in depression recognition and decrease in suicide attempts could not be replicated unequivocally in this adapted intervention among gay men, there are indications that this evidence-based depression awareness campaign may have lessened suicidality and mental morbidity and improved mental health literacy and help-seeking.

This paper addresses the quantification of glacier retreat through remote sensing. Specifically, we use multi-spectral Landsat satellite images for the estimation of glacier termini locations. Different frequency bands—including visual, infrared, thermal, and processed bands—are examined with respect to their utility in identifying the location of glacier termini and the associated standard error across several scenes. The methodology is to extract an intensity profile along the glacier path from the spatially registered Landsat imagery such that the complexity of the problem is reduced from 2D (image intensity) to 1D (glacier profile intensity). Local polynomial regression is then used to smooth the 1D glacier intensity profile, where the underlying function is assumed to be corrupted with correlated noise. The glacier terminus is then detected by locating an inflection point in the smoothed glacier profile, where a constrained bandwidth selection method is introduced to ensure a single inflection point along the glacier path. Using our method with thermal band B62 and a standard processed band called normalized difference snow index (NDSI) often permits for separating ice from soil but does not lead to a consistent identification of termini location, relative to ground based observations. We therefore introduce a new processed band that combines B62 and NDSI, termed normalized difference thermal snow index (NDTSI). Applying our method along with NDTSI to multiple frames from the Franz Josef, Gorner, Rhone, and Nigardsbreen glaciers indicates an ability to accurately and robustly identify the position of glacier termini, though confirmation of skill awaits application to a larger population of observations., Earth and Planetary Sciences

Understanding the contextual factors associated with why adults walk is important for those interested in increasing walking as a mode of transportation and leisure. This paper investigates the relationships between neighborhood-level sociodemographic context, individual level sociodemographic characteristics and walking for leisure and transport. Data from two community-based studies of adults (n = 550) were used to determine the association between the Area Sociodemographic Environment (ASDE), calculated from U.S. Census variables, and individual-level SES as potential correlates of walking behavior. Descriptive statistics, mean comparisons and Pearson’s correlations coefficients were used to assess bivariate relationships. Generalized estimating equations were used to model the relationship between ASDE, as quartiles, and walking behavior. Adjusted models suggest adults engage in more minutes of walking for transportation and less walking for leisure in the most disadvantaged compared to the least disadvantaged neighborhoods but adding individual level demographics and SES eliminated the significant results. However, when models were stratified for free or reduced cost lunch, of those with children who qualified for free or reduced lunch, those who lived in the wealthiest neighborhoods engaged in 10.7 min less of total walking per day compared to those living in the most challenged neighborhoods (p < 0.001). Strategies to increase walking for transportation or leisure need to take account of individual level socioeconomic factors in addition to area-level measures.

This paper argues that the 2009 pledge of $100 billion in 2020 by rich countries for mitigation and adaptation should not be used for mitigation by commercial firms in developing countries, since that would artificially create competitive advantage for such firms and provoke protectionist reactions in the rich countries where firms must bear the costs of mitigation, thereby undermining the world trading system. The costs of heating the earth's surface should be borne by all emitters, just as the price of copper and other scarce resources is paid by all users, rich or poor. That will still leave scope for rich country help in adaptation to climate change and in bringing to fruition new technologies to reduce emissions., Economics

This paper presents an analysis of phage-displayed libraries of peptides using Illumina. We describe steps for the preparation of short DNA fragments for deep sequencing and MatLab software for the analysis of the results. Screening of peptide libraries displayed on the surface of bacteriophage (phage display) can be used to discover peptides that bind to any target. The key step in this discovery is the analysis of peptide sequences present in the library. This analysis is usually performed by Sanger sequencing, which is labor intensive and limited to examination of a few hundred phage clones. On the other hand, Illumina deep-sequencing technology can characterize over 107 reads in a single run. We applied Illumina sequencing to analyze phage libraries. Using PCR, we isolated the variable regions from M13KE phage vectors from a phage display library. The PCR primers contained (i) sequences flanking the variable region, (ii) barcodes, and (iii) variable 5′-terminal region. We used this approach to examine how diversity of peptides in phage display libraries changes as a result of amplification of libraries in bacteria. Using HiSeq single-end Illumina sequencing of these fragments, we acquired over 2 × 107 reads, 57 base pairs (bp) in length. Each read contained information about the barcode (6 bp), one complimentary region (12 bp) and a variable region (36 bp). We applied this sequencing to a model library of 106 unique clones and observed that amplification enriches ∼150 clones, which dominate ∼20% of the library. Deep sequencing, for the first time, characterized the collapse of diversity in phage libraries. The results suggest that screens based on repeated amplification and small-scale sequencing identify a few binding clones and miss thousands of useful clones. The deep sequencing approach described here could identify under-represented clones in phage screens. It could also be instrumental in developing new screening strategies, which can preserve diversity of phage clones and identify ligands previously lost in phage display screens., Chemistry and Chemical Biology

Randomization of treatment assignment in experiments generates treatment groups with approximately balanced baseline covariates. However, in observational studies, where treatment assignment is not random, patients in the active treatment and control groups often differ on crucial covariates that are related to outcomes. These covariate imbalances can lead to biased treatment effect estimates. The propensity score is the probability that a patient with particular baseline characteristics is assigned to active treatment rather than control. Though propensity scores are unknown in observational studies, by matching or subclassifying patients on estimated propensity scores, we can design observational studies that parallel randomized experiments, with approximate balance on observed covariates. Observational study designs based on estimated propensity scores can generate approximately unbiased treatment effect estimates. Critically, propensity score designs should be created without access to outcomes, mirroring the separation of study design and outcome analysis in randomized experiments. This paper describes the potential outcomes framework for causal inference and best practices for designing observational studies with propensity scores. We discuss the use of propensity scores in two studies assessing the effectiveness and risks of antifibrinolytic drugs during cardiac surgery., Statistics

Upon returning to their communities, children formerly associated with armed forces and armed groups–commonly referred to as child soldiers–often confront significant community stigma. Much research on the reintegration and rehabilitation of child soldiers has focused on exposure to past war-related violence and mental health outcomes, yet no empirical work has yet examined the role that post-conflict stigma plays in shaping long-term psychosocial adjustment. Two waves of data are used in this paper from the first prospective study of male and female former child soldiers in Sierra Leone. We examined the role of stigma (manifest in discrimination as well as lower levels of community and family acceptance) in the relationship between war-related experiences and psychosocial adjustment (depression, anxiety, hostility and adaptive behaviors). Former child soldiers differ from one another with regard to their post-war experiences, and these differences profoundly shape their psychosocial adjustment over time. Consistent with social stress theory, we observed that post-conflict factors such as stigma can play an important role in shaping psychosocial adjustment in former child soldiers. We found that discrimination was inversely associated with family and community acceptance. Additionally, higher levels of family acceptance were associated with decreased hostility, while improvements in community acceptance were associated with adaptive attitudes and behaviors. We found that post-conflict experiences of discrimination largely explained the relationship between past involvement in wounding/killing others and subsequent increases in hostility. Stigma similarly mediated the relationship between surviving rape and depression. However, surviving rape continued to demonstrate independent effects on increases in anxiety, hostility and adaptive/prosocial behaviors after adjusting for other variables. These findings point to the complexity of psychosocial adjustment and community reintegration in these youth and have a number of programmatic and policy implications.

It is widely recognized that the economics of distant-future events, like climate change, is critically dependent upon the choice of a discount rate. Unfortunately, it is unclear how to discount distant-future events when the future discount rate itself is unknown. In previous work, an analytically-tractable approach called ‘‘gamma discounting’’ was proposed, which gave a declining discount rate schedule as a simple closed-form function of time. This paper extends the previous gamma approach by using a Ramsey optimal growth model, combined with uncertainty about future productivity, in order to ‘‘risk adjust’’ all probabilities by marginal utility weights. Some basic numerical examples are given, which suggest that the overall effect of risk-adjusted gamma discounting on lowering distant-future discount rates may be significant. The driving force is a ‘‘fear factor’’ from risk aversion to permanent productivity shocks representing catastrophic future states of the world., Economics

The majority of the population of the planet (6.6 billion) now live in urban areas, which have distinct impacts upon climate at scales from the local to the global. This urban effect is due to the physical form of the city (its three-dimensional geometry and material composition) and its functions (the day-to-day activity patterns that generate emissions of waste heat and materials into the overlying air). While a substantial body of knowledge on the science of urban climates has been developed over the past fifty years, there is little evidence that this knowledge is incorporated into urban planning and design practice. This paper focuses on this gap by examining the nature of urban climate expertise and the needs of those that make decisions about urban areas. In conclusion it makes recommendations to maintain and enhance urban observations and data; to improve understanding of local, regional and global climate linkages; to develop tools for practical planning; and to disseminate urban climate knowledge and its relevance to urban planning to both practicing meteorologists and urban decision makers.

This paper proposes the use of the surface based Laplace-Beltrami and the volumetric Laplace eigenvalues and -functions as shape descriptors for the comparison and analysis of shapes. These spectral measures are isometry invariant and therefore allow for shape comparisons with minimal shape pre-processing. In particular, no registration, mapping, or remeshing is necessary. The discriminatory power of the 2D surface and 3D solid methods is demonstrated on a population of female caudate nuclei (a subcortical gray matter structure of the brain, involved in memory function, emotion processing, and learning) of normal control subjects and of subjects with schizotypal personality disorder. The behavior and properties of the Laplace-Beltrami eigenvalues and -functions are discussed extensively for both the Dirichlet and Neumann boundary condition showing advantages of the Neumann vs. the Dirichlet spectra in 3D. Furthermore, topological analyses employing the Morse-Smale complex (on the surfaces) and the Reeb graph (in the solids) are performed on selected eigenfunctions, yielding shape descriptors, that are capable of localizing geometric properties and detecting shape differences by indirectly registering topological features such as critical points, level sets and integral lines of the gradient field across subjects. The use of these topological features of the Laplace-Beltrami eigenfunctions in 2D and 3D for statistical shape analysis is novel.

This paper investigates the effects of the education level, product market rigidities and employment protection legislation on growth. It exploits macro-panel data for OECD countries. For countries close to the technological frontier, education and rigidities are significantly related to TFP growth. The contribution of the interaction between product market regulation and labour market rigidity seems particularly substantial., Economics

Subcellular fractionation has been an important tool in investigating human eosinophil structure and function, including localizing of cytokine/chemokines within granules, investigating granule protein translocation and intracellular transport during eosinophil secretion, and studying secretory mechanisms of granules. The resolution of organelles obtained by subcellular fractionation was improved considerably after the introduction of nonionic iodinated density-gradient metrizamide and Nycodenz media that, unlike sucrose, exhibit relatively low tonicity throughout the gradient. However, the structure and membrane preservation of isolated organelles were still compromised due to the lack of gradient isoosmolarity. This paper describes a detailed protocol of subcellular fractionation of nitrogen cavitated eosinophils on an isoosmotic iodinated density gradient (iodixanol – OptiPrep) and the isolation of well preserved and functional membrane-bound specific granules.

The majority of theoretical models have defined stigma as occurring psychologically and limit its negative effects to individual processes. This paper, via an analysis of how 'face' is embodied in China, deepens an articulation of how the social aspects of stigma might incorporate the moral standing of both individual and collective actors defined within a local context. We illustrate (1) how one's moral standing is lodged within a local social world; (2) how one's status as a 'moral' community member is contingent upon upholding intrapersonal and social-transactional obligations; and (3) how loss of face and fears of moral contamination might lead to a 'social death'. We first draw from Chinese ethnographies that describe the process of human cultivation before one can achieve fully 'moral' status in society. We integrate findings from empirical studies describing how social-exchange networks in China are strictly organized based on the reciprocation of favors, moral positioning, and 'face'. We further ground these Chinese constructs within a theoretical framework of different forms of capital, and discuss the severe social consequences that loss of face entails. By utilizing the examples of schizophrenia and AIDS to illustrate how loss of moral standing and stigma is interwoven in China, we propose a model highlighting changes in moral status to describe how stigma operates. We suggest that symbolic restoration of moral status for stigmatized groups takes place as local-level stigma interventions. By analyzing the moral aspects of 'face', we propose that across cultures, stigma is embedded in the moral experience of participants, whereby stigma is conceived as a fundamentally moral issue: stigmatized conditions threaten what matters most for those in a local world. We further propose that stigma jeopardizes an actor's ability to mobilize social capital to attain essential social statuses., Anthropology

As the luminosity of an accreting black hole drops to a few percent of Eddington, the spectrum switches from the familiar soft state to a hard state that is well-described by a distended and tenuous advection-dominated accretion flow (ADAF). An ADAF is a poor radiator, and the ion temperature can approach 1012 K near the center, although the electrons are cooler, with their temperature typically capped at ∼ 109−11 K. The foundational papers predicted that the large thermal energy in an ADAF would drive strong winds and jets, as later observed and also confirmed in computer simulations. Of chief interest, however, is the accreting gas that races inward. It carries the bulk of the accretion energy as stored thermal energy, which vanishes without a trace as the gas passes through the hole’s event horizon. One thus expects black holes in the ADAF regime to be unusually faint. Indeed, this is confirmed by a comparison of accreting stellar-mass black holes and neutron stars, which reside in very similar transient X-ray binary systems. The black holes are on average observed to be fainter by a factor of ∼ 100 − 1000. The natural explanation is that a neutron star must radiate the advected thermal energy from its surface, whereas a black hole can hide the energy behind its event horizon. The case for an event horizon in Sagittarius A∗, which is immune to caveats on jet outflows and is furthermore independent of the ADAF model, is especially compelling. These two lines of evidence for event horizons are impervious to counterarguments that invoke strong gravity or exotic stars., Astronomy

SWAN (Semantic Web Application in Neuromedicine) is a project to construct a semantically-organized, community-curated, distributed knowledge base of Theory, Evidence, and Discussion in biomedicine. Unlike Wikipedia and similar approaches, SWAN’s ontology is designed to represent and foreground both harmonizing and contradictory assertions within the total community discourse. Releases of the software, content and ontology will be initially by and for the Alzheimer Disease (AD) research community, with the obvious potential for extension into other disease research areas. The Alzheimer Research Forum, a 4,000-member web community for AD researchers, will host SWAN’s initial public release, currently scheduled for late 2007. This paper presents the current version of SWAN’s ontology of scientific discourse and presents our current thinking about its evolution including extensions and alignment with related communities, projects and ontologies.

Objective Randomized controlled trials in patient education often have difficulty enrolling vulnerable populations – specifically, older, poorer and less educated individuals. We undertook a randomized controlled trial (RCT) of an educational intervention for arthritis management, which included strategies to remove literacy-related barriers to participation. This paper reports on the multi-stage recruitment process and assesses whether refusal to participate was related to education, age, gender, working status or insurance status. Methods The recruitment protocol was designed to eliminate literacy-related barriers to participation. Patients were never asked to read or fill out forms. Interactions were oral, using everyday terms and short, clear sentences. Patients who declined during a screening call were considered Stage 1 Refusers. Patients who initially expressed interest but neither completed a baseline questionnaire nor provided consent were considered Stage 2 Refusers. Patients who consented were considered Enrollees. Age, gender, and insurance status were compared between Stage 1 Refusers and Enrollees. A second analysis compared these variables, plus educational attainment and working status, between Stage 2 Refusers and Enrollees. Results Of 408 eligible patients, there were 193 (47.3%) Stage 1 Refusers, 81 (19.9%) Stage 2 Refusers and 134 (32.8%) Enrollees. A higher proportion of Stage 1 Refusers than Enrollees were ≥65 years old (58% vs. 37%, p=.0003). Multivariate analysis, adjusting for gender and insurance status, confirmed the effect of older age on refusal (OR=2.3 (1.4, 3.6)). There were no significant differences between Stage 2 Refusers and Enrollees. Conclusion We found no evidence of refusal to participate due to educational attainment, working status, insurance status, or gender. Older patients were more likely to refuse participation at the first stage of recruitment. Practice Implications Researchers should continue efforts to increase participation among older patients, particularly when studies are designed to be generalized to an elderly population as is the case with arthritis research. Strategies used in this recruitment protocol designed to remove literacy-related barriers to recruitment may be responsible for the observation that subjects with lower education did not have lower refusal rates. Such strategies deserve further study.

In this paper, we present a set of techniques for the evaluation of brain tissue classifiers on a large data set of MR images of the head. Due to the difficulty of establishing a gold standard for this type of data, we focus our attention on methods which do not require a ground truth, but instead rely on a common agreement principle. Three different techniques are presented: the Williams’ index, a measure of common agreement; STAPLE, an Expectation Maximization algorithm which simultaneously estimates performance parameters and constructs an estimated reference standard; and Multidimensional Scaling, a visualization technique to explore similarity data. We apply these different evaluation methodologies to a set eleven different segmentation algorithms on forty MR images. We then validate our evaluation pipeline by building a ground truth based on human expert tracings. The evaluations with and without a ground truth are compared. Our findings show that comparing classifiers without a gold standard can provide a lot of interesting information. In particular, outliers can be easily detected, strongly consistent or highly variable techniques can be readily discriminated, and the overall similarity between different techniques can be assessed. On the other hand, we also find that some information present in the expert segmentations is not captured by the automatic classifiers, suggesting that common agreement alone may not be sufficient for a precise performance evaluation of brain tissue classifiers.