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The aim of this paper is to review esophageal electrical impedance technologies and to discuss the use of these technologies for physiological measurements, diagnostics, and therapy of esophageal disease. In order to develop a better understanding of the pathophysiology of and improve the diagnosis of esophageal disorders, such as gastroesophageal reflux disease (GERD) and achalasia, several new diagnostic tests, including intraluminal impedance, esophageal mucosal impedance, and the functional luminal imaging probe, have been developed. These technologies have proven valuable for assessment of the esophagus in recent years. They provide information on esophageal flow properties, mucosal integrity, lumen shape, and distensibility in esophageal disorders, in particular for GERD and achalasia. Despite their promise and novel clinical studies, the potential of these technologies has been far from realized. New multidisciplinary approaches will contribute to our understanding and interpretation of esophageal impedance data and disease mechanisms. [ABSTRACT FROM AUTHOR]

Atmospheric rivers (ARs) are narrow regions of strong horizontal water vapor transport that play important roles in the global water cycle, weather, and hydrology. Motivated by challenges in simulating ARs with state-of-the-art global models, this paper diagnoses model errors with a focus on relative contributions of moisture convergence, evaporation, and precipitation to AR column-integrated water vapor (IWV) budget. Using 20-year simulations by 24 global weather/climate models, budget terms are calculated for four AR sectors: postfrontal, frontal, prefrontal, and pre-AR, with biases assessed against two reanalysis products. The results indicate that each sector is unique in terms of the dominant water vapor balance, and that the terms exhibiting the largest intermodel spread are the same terms dominating thewater vapor balance in each sector. Overall, simulated bulk AR characteristics (e.g., geometry, frequency, and intensity) aremore sensitive to biases in IVT convergence andIWVtendency than to biases in evaporation and precipitation, although evaporation/precipitation biases do affect key AR bulk characteristics in selected sectors. The large intermodel spread (particularly for precipitation) and, in certain cases, discrepancies between the reanalysis references themselves (particularly for precipitation types) highlight the need for observational efforts that target better constraining AR processes in weather/climate models and reanalyses. [ABSTRACT FROM AUTHOR]

Our paper reviews recent progress in the study and understanding of observed trends in extreme rainfall events in the Metropolitan Area of São Paulo (MASP). These are discussed in relation to hydrometeorological hazards that trigger natural disasters, such as flash floods, landslides, and droughts, that affect the population and local economies. A review of the most updated literature on rainfall and extremes in the MASP shows a significant increase in the total volume of rainy-season rainfall during the last seven decades. While there were practically no days with heavy rain (more than 50 mm) in the 1950s, these days have been occurring two to five times a year in the last 10 years. This, together with the inappropriate occupation of risky areas, such as slopes and banks of watercourses, leads to inundation, flooding, and landslides. Changes in extremes can be partly due to natural climate variability but can also be related to global warming and/or urbanization. There is ample evidence of an increasing risk of rainfall-related hazards in theMASP. This is particularly so for landslides in vulnerable areas. Exposure will continue to lead to risk increases. This calls for significant improvement in climate and disaster risk reduction and management efforts in theMASP region. [ABSTRACT FROM AUTHOR]

The multiple micronutrient supplement (MMS) based on the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) formula provides women and their offspring with a healthy start to life in an efficacious, safe, and cost‐effective way. To date, however, no precise and transparent specifications exist to support the manufacturing and distribution of UNIMMAP–MMS globally. To palliate for this need, the MMS Technical Advisory Group at the New York Academy of Sciences and the Micronutrient Forum convened a technical consultation to develop an open access UNIMMAP–MMS Product Specification for the manufacturing of this product. The specifications offered in this paper cover: ingredients, excipients, and processing aids used in the manufacturing of UNIMMAP–MMS; stability studies recommended under different testing conditions and climatic zones; packaging considerations; manufacturing standards, including pharmacopeia standards, manufacturing practices, certificates of analysis, change control, and quality agreement; finished product specifications, including tablet characterization and purity, potency assay; analytical test methods; and storage and transportation requirements. [ABSTRACT FROM AUTHOR]

Few studies have evaluated the impact of nutritional supplementation among pregnant adolescents. We examined the effects of the Rang Din Nutrition Study (RDNS) interventions on children born to mothers <20 years of age. The RDNS was a cluster‐randomized effectiveness trial with four arms: (1) women and children both received small‐quantity lipid‐based nutrient supplements (LNS‐LNS), (2) women received iron and folic acid (IFA) and children received LNS (IFA‐LNS), (3) women received IFA and children received micronutrient powder (MNP) (IFA‐MNP), and (4) women received IFA and children received no supplements (IFA‐Control). We enrolled 4011 women at <20 weeks gestation; 1552 were adolescents. Among adolescents, prenatal LNS reduced newborn stunting by 25% and small head size by 28% and had a marginally significant effect on newborn wasting, compared with IFA. Low birth weight and preterm birth were reduced only among adolescents with lower food security. Effects on subsequent growth status were observed only among female children in the LNS‐LNS group: less stunting at 18 months (versus IFA‐MNP) and lower prevalence of small head circumference and wasting at 24 months (versus IFA‐Control). Initiatives targeting pregnant adolescents in similar settings should consider inclusion of small‐quantity LNS, particularly for adolescents living in food‐insecure households.Few studies have evaluated the impact of nutritional supplementation among pregnant adolescents. This paper examines the effects of nutritional interventions on children born to mothers <20 years of age in Bangladesh. Its findings suggest that initiatives targeting pregnant adolescents in similar settings should consider inclusion of small‐quantity lipid‐based nutrient supplements, particularly for adolescents living in food‐insecure households. [ABSTRACT FROM AUTHOR]

Bone marrow is a cellular tissue that forms within the pore space and hollow diaphysis of bones. As a tissue, its primary function is to support the hematopoietic progenitor cells that maintain the populations of both erythroid and myeloid lineage cells in the bone marrow, making it an essential element of normal mammalian physiology. However, bone's primary function is load bearing, and deformations induced by external forces are transmitted to the encapsulated marrow. Understanding the effects of these mechanical inputs on marrow function and adaptation requires knowledge of the material behavior of the marrow at multiple scales, the loads that are applied, and the mechanobiology of the cells. This paper reviews the current state of knowledge of each of these factors. Characterization of the marrow mechanical environment and its role in skeletal health and other marrow functions remains incomplete, but research on the topic is increasing, driven by interest in skeletal adaptation and the mechanobiology of cancer metastasis. [ABSTRACT FROM AUTHOR]

Carbapenem‐resistant Enterobacteriaceae (CRE) have been listed by the WHO as high‐priority pathogens owing to their high association with mortalities and morbidities. Resistance to multiple β‐lactams complicates effective clinical management of CRE infections. Using plasmid typing methods, a wide distribution of plasmid replicon groups has been reported in CREs around the world, including IncF, N, X, A/C, L/M, R, P, H, I, and W. We performed a literature search for English research papers, published between 2013 and 2018, reporting on plasmid‐mediated carbapenem resistance. A rise in both carbapenemase types and associated plasmid replicon groups was seen, with China, Canada, and the United States recording a higher increase than other countries. blaKPC was the most prevalent, except in Angola and the Czech Republic, where OXA‐181 (n = 50, 88%) and OXA‐48–like (n = 24, 44%) carbapenemases were most prevalent, respectively; blaKPC‐2/3 accounted for 70% (n = 956) of all reported carbapenemases. IncF plasmids were found to be responsible for disseminating different antibiotic resistance genes worldwide, accounting for almost 40% (n = 254) of plasmid‐borne carbapenemases. blaCTX‐M, blaTEM, blaSHV, blaOXA‐1/9, qnr, and aac‐(6′)‐lb were mostly detected concurrently with carbapenemases. Most reported plasmids were conjugative but not present in multiple countries or species, suggesting limited interspecies and interboundary transmission of a common plasmid. A major limitation to effective characterization of plasmid evolution was the use of PCR‐based instead of whole‐plasmid sequencing–based plasmid typing. [ABSTRACT FROM AUTHOR]

Anemia is an important public health challenge and accurate prevalence estimates are needed for program planning and tracking progress. While venous blood assessed by automated hematology analyzers is considered gold standard, most population‐based surveys use point‐of‐care diagnostics and capillary blood to estimate population prevalence of anemia. Several factors influence hemoglobin (Hb) concentration, including human and analytic error, analysis method, and type of instrument, but it is unclear whether biological variability exists between venous and capillary blood. The objective of this paper was to systematically review sources of Hb variability and the potential biological basis for venous and capillary differences. We use data from a recent survey in the state of Uttar Pradesh, India, to illustrate the implications on anemia prevalence estimates. Significant differences in Hb concentration between capillary and venous blood samples are common. Most but not all find capillary Hb concentration to be higher than venous. Instrument/method variability and human error play an important role, but cannot fully explain these differences. A normative guide to data collection, analysis, and anemia diagnosis is needed to ensure consistent and appropriate interpretation. Further research is needed to fully understand the biological implications of venous and capillary Hb variability. [ABSTRACT FROM AUTHOR]

Iodine is an essential trace element required for the regulation of physiological processes involving the thyroid gland. However, inadequate and excessive intake of iodine are responsible for health problems, such as iodine deficiency disorders, hypothyroidism, hyperthyroidism, thyroiditis, thyroid papillary cancer, and thyrotoxicosis. The Universal Salt Iodization (USI) program has become successful in providing supplemental iodine at the population level globally. Packaging quality, fortification level, and transportation and storage conditions of iodized salt determine the availability of iodine. Previous studies have reported severe health issues caused by excessive iodine intake after the implementation of the USI program. To understand the levels of iodine, we collected 2117 household salt samples from seven districts of Nepal and tested them for iodine content; among them, 98.1% were iodized. Overall median concentration of iodine was 53.9 ppm (range: 43.5–61.4 ppm). The majority (67.2%) of samples had iodine in the range of 45–75 ppm. Approximately 0.9% of samples had inadequate, 13.3% contained adequate, and 83.9% had excessive iodine than the World Health Organization‐recommended value. Iodine content varied among the sampling districts and seasons, to some extent. Our study confirmed that iodized salt is widely used in Nepal and is excessively iodized. Excessive intake of iodine through iodized salt requires further attention by policy makers. The iodine level may need adjustment to address the health impact. [ABSTRACT FROM AUTHOR]

This paper defines the attributes of distributed data networks and outlines the data and analytic infrastructure needed to build and maintain a successful network. We use examples from one successful implementation of a large-scale, multisite, healthcare-related distributed data network, the U.S. Food and Drug Administration-sponsored Sentinel Initiative. Analytic infrastructure-development concepts are discussed from the perspective of promoting six pillars of analytic infrastructure: consistency, reusability, flexibility, scalability, transparency, and reproducibility. This paper also introduces one use case for machine learning algorithm development to fully utilize and advance the portfolio of population health analytics, particularly those using multisite administrative data sources. [ABSTRACT FROM AUTHOR]

The goal of this paper is to briefly introduce and defend the idea that God is the source of our moral obligations. In contrast to Michael Shermer's paper, which defends a naturalistic position about the foundations of morality, this approach is explicitly supernaturalistic. The paper begins by defining how 'God' will be understood, and then spells out some of the details of how, on the proposed view, moral obligations are to depend upon God. The third section briefly reviews some of the leading arguments for this view, before the paper concludes with a discussion of the Euthyphro dilemma. [ABSTRACT FROM AUTHOR]

In Ghana, iodine deficiency was first reported in 1994 among 33% of the population. A nationwide Universal Salt Iodization (USI) program plus other complementary interventions were subsequently implemented as a response. Our paper reviews the current risks of excess iodine status in Ghana and identifies policy and research gaps. A mixed methods review of 12 policies and institutional reports and 13 peer‐reviewed articles was complemented with consultations with 23 key informants (salt producers and distributors, food processors, regulatory agency officials, and healthcare providers) purposively sampled between May and August 2017. The findings show a strong policy environment indicated by regulations on food and salt fortification (Act 851), including the USI regulation. However, currently, only a third of Ghanaian households use adequately iodized salt. Recent evidence shows that voluntarily fortified processed foods (including condiments) supply a considerable amount of iodine to the food system. Limited biological impact data suggest possible household exposure to excessive dietary iodine (>15 parts per million). Currently, there is no systematic tracking of iodine content from fortified foods and other sources. Cross‐sectoral actions are needed to understand this situation better. Key research gap is the lack of comprehensive data on iodine content and intake from other sources in Ghana. [ABSTRACT FROM AUTHOR]

The excessive consumption of certain vitamins and minerals could have deleterious consequences on health and development of individuals and populations. Simultaneous micronutrient‐delivery interventions could be challenging in terms of safety as the target populations may overlap, posing a risk of excessive intake of certain micronutrients. The Evidence and Programme Guidance Unit of the Department of Nutrition for Health and Development of the World Health Organization convened a technical consultation on the risk of excessive intake of vitamins and minerals delivered through public health interventions in October 2017. The technical consultation's working groups identified important and emerging technical issues, lessons learned, and research priorities related to (1) planning, implementing, monitoring, and evaluating nutrition programs for the detection and control of the risk of excessive intakes; (2) safety, quality control, and assurance considerations; (3) coordination between public health nutrition interventions and other interventions and sectors; and (4) the legislative framework and policy coherence needed for simultaneous nutrition interventions. This paper provides the background and rationale of the technical consultation, synopsizes the presentations, and provides a summary of the main considerations proposed by the working groups. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 11 (GDF11), a secreted member of the transforming growth factor‐β (TGF‐β) superfamily, has been reported to have the capacity to reverse age‐related pathologic changes and regulate organ regeneration after injury; however, the role of GDF11 in fracture healing and bone repair is still unclear. Here, we established a fracture model in 12‐week‐old male mice to observe two healing states: the cartilaginous callus and bony callus formation phases. Our results showed that recombinant GDF11 (rGDF11) injection inhibits cartilaginous callus maturation and hard callus formation, thereby impairing fracture healing in vivo. In vitro, rGDF11 administration inhibited chondrocyte differentiation and maturation by phosphorylating SMAD2/3 protein and inhibiting RUNX2 expression. Notably, inhibition of TGF‐β activity by a SMAD‐specific inhibitor attenuated GDF11 effects. Thus, our study demonstrates that, rather than acting as a rejuvenating agent, rGDF11 impairs fracture healing by inhibiting chondrocyte differentiation and maturation. Growth differentiation factor 11 (GDF11) has been reported to reverse age‐related pathologic changes and regulate organ regeneration after injury, but its role in fracture healing and bone repair is unclear. This paper demonstrates that, rather than acting as a rejuvenating agent, rGDF11 impairs fracture healing by inhibiting chondrocyte differentiation and maturation. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 11 (GDF11), a secreted member of the transforming growth factor‐β (TGF‐β) superfamily, has been reported to have the capacity to reverse age‐related pathologic changes and regulate organ regeneration after injury; however, the role of GDF11 in fracture healing and bone repair is still unclear. Here, we established a fracture model in 12‐week‐old male mice to observe two healing states: the cartilaginous callus and bony callus formation phases. Our results showed that recombinant GDF11 (rGDF11) injection inhibits cartilaginous callus maturation and hard callus formation, thereby impairing fracture healing in vivo. In vitro, rGDF11 administration inhibited chondrocyte differentiation and maturation by phosphorylating SMAD2/3 protein and inhibiting RUNX2 expression. Notably, inhibition of TGF‐β activity by a SMAD‐specific inhibitor attenuated GDF11 effects. Thus, our study demonstrates that, rather than acting as a rejuvenating agent, rGDF11 impairs fracture healing by inhibiting chondrocyte differentiation and maturation. Growth differentiation factor 11 (GDF11) has been reported to reverse age‐related pathologic changes and regulate organ regeneration after injury, but its role in fracture healing and bone repair is unclear. This paper demonstrates that, rather than acting as a rejuvenating agent, rGDF11 impairs fracture healing by inhibiting chondrocyte differentiation and maturation. [ABSTRACT FROM AUTHOR]

Cities modify their local climate, and at the same time they suffer from the local impacts of climate change. Our paper discusses the progress and obstacles in three active research topics that contribute to increasing the capability within the urban climate research community for transferring local climate knowledge to society. The first is linked to the production of urban surface descriptions useful for urban climate studies. The concept of local climate zones is now widely used to represent urban climate variability at the neighborhood scale. Land‐use, morphological, architectural, and social data are also needed, and those are being gathered using different approaches. The second is linked to the necessity for producing information directly connected to their effects on society. This requires a strong multidisciplinary approach, and nowadays impact studies are not limited to one dimension but instead cover multiple dimensions. The third is to transfer all this information to city practitioners, so that urban climate features are considered, among many other aspects, in city management. For urban planning, cartographic tools have been introduced to include urban climate diagnosis as well as recommendations for future urbanization. Cities modify their local climate, and at the same time they suffer from the local impacts of climate change. This perspective article discusses the progress and obstacles in three active research areas in urban climate research that contribute to increasing the capability of researchers for transferring local climate knowledge to urban planners. [ABSTRACT FROM AUTHOR]

This paper reports on the influence that extreme values in the tails of the North Atlantic Oscillation (NAO) Index probability density function (PDF) can exert on temperatures in Europe. When the NAO Index enters into its lowest (10% quantile or less) and highest (90% quantile or higher) modes, European temperatures often exhibit large negative or positive departures from their mean values, respectively. Analyses of the joint quantiles of the Index and temperatures (i.e., the simultaneous exceedance of particular quantile thresholds by the two variables) show that temperatures enter into the upper or lower tails of their PDF when the NAO Index also enters into its extreme tails, more often that could be expected from random statistics. Studies of this nature help further our understanding of the manner by which mechanisms of decadal‐scale climate variability can influence extremes of temperature—and thus perhaps improve the forecasting of extreme temperatures in weather and climate models. [ABSTRACT FROM AUTHOR]

Although an association between cancer progression and matrix metalloproteinase (MMP) 2 and MPP9 expression has been known, the expression, nuclear localization, and physiologically controlled activation of these two MMPs have not been investigated in malignant mesothelioma cells. We examined the expression and intracellular localization of MMP2/9 in ZL55 malignant mesothelioma cells, as well as their regulation by ADP. Using real‐time PCR, we showed that activation of the P2Y1 receptor by ADP increased the expression of MMP2/9 mRNAs; MMP2/9 collected from conditioned media also showed an increase in activity; and ADP induced the nuclear localization of MMP2/9. The effects of ADP on transcription of the MMPs were due to activation of c‐Src, Akt, and NF‐κB, while ERK1/2 phosphorylation was needed for the increase in enzymatic activity and the regulation of nuclear import. We also showed that the nuclear localization of MMP2/9 induced by ADP causes the cleavage and inactivation of poly‐ADP‐ribose polymerase‐1. These findings may help to elucidate the mechanisms regulating MMP2/9 activation in ZL55 human epithelioid mesothelioma cells, and perhaps other cells. Therapeutic approaches that promote ADP accumulation in a tumor environment may constitute an effective means to induce anticancer activity. This paper examines the expression, intracellular localization, and function of matrix metalloproteinase (MMP) 2 and MMP9 in ZL55 human epithelioid mesothelioma cells, as well as their regulation by ADP. We found that ADP activates an intracellular transduction system based on NF‐κB, c‐Src, Akt, and ERK1/2 that causes nuclear localization of MMP2/9, resulting in degradation of the DNA repair enzyme poly‐ADP‐ribose polymerase‐1. [ABSTRACT FROM AUTHOR]

Thiamine is an essential micronutrient that plays a key role in energy metabolism. Many populations worldwide may be at risk of clinical or subclinical thiamine deficiencies, due to famine, reliance on staple crops with low thiamine content, or food preparation practices, such as milling grains and washing milled rice. Clinical manifestations of thiamine deficiency are variable; this, along with the lack of a readily accessible and widely agreed upon biomarker of thiamine status, complicates efforts to diagnose thiamine deficiency and assess its global prevalence. Strategies to identify regions at risk of thiamine deficiency through proxy measures, such as analysis of food balance sheet data and month‐specific infant mortality rates, may be valuable for understanding the scope of thiamine deficiency. Urgent public health responses are warranted in high‐risk regions, considering the contribution of thiamine deficiency to infant mortality and research suggesting that even subclinical thiamine deficiency in childhood may have lifelong neurodevelopmental consequences. Food fortification and maternal and/or infant thiamine supplementation have proven effective in raising thiamine status and reducing the incidence of infantile beriberi in regions where thiamine deficiency is prevalent, but trial data are limited. Efforts to determine culturally and environmentally appropriate food vehicles for thiamine fortification are ongoing. This paper describes the current state of thiamine research and the significance of thiamine deficiency in low‐ and middle‐income countries from public health and clinical perspectives. The map shows countries where the estimated per capita availability of thiamine in the national food supply (as per food balance sheets) is below the recommended nutrient intake for men (in turquoise), and countries where rice or wheat flour fortification are in place to address low thiamine availability (in yellow). [ABSTRACT FROM AUTHOR]

Abstract: The objective of our paper is to develop a mechanistic conceptual framework for how food webs recover from natural physical disturbances. We summarize our work on the effect of hurricanes on island food webs and review other studies documenting how other types of physical disturbances (including fires, floods, and volcanic eruptions) alter food–web interactions. Based on these case studies, we propose that four factors play an important role in food‐web succession: (1) disturbance intensity, (2) sequential recovery/colonization of successively higher trophic levels, (3) tradeoffs between growth rate of organisms at different successional stages and susceptibility to consumers, and (4) detritus including autochthonous and allochthonous sources. Studies on river flooding and islands disturbed by hurricanes indicate that energy flow is higher and trophic cascades are stronger during recovery than when the food web is at a steady state. We suggest that as consumer species colonize during succession, they may change the species or phenotypic composition of their food supply from highly vulnerable to less vulnerable items, thereby weakening both bottom‐up and top‐down effects throughout the food web. High inputs of detritus caused by disturbances can amplify bottom‐up effects during early succession, and subsequently alter top‐down effects. [ABSTRACT FROM AUTHOR]

Abstract: Socioeconomic‐based disparities in physical health outcomes are well established, with individuals from lower socioeconomic status (SES) backgrounds being more likely to experience chronic disease morbidity and early mortality compared to those from higher SES strata. While numerous studies in recent decades have focused on understanding the contextual, psychosocial, and biological mechanisms linking SES and health, the neural pathways that contribute to this relationship are currently underinvestigated. The present paper reviews and synthesizes the small number of published studies that have explored links between SES and health‐relevant neural functioning. Specifically, current knowledge of the relationship between socioeconomic factors and neural systems that may be affected by low SES contexts, including those related to processing threat and stress, responding to reward, and engaging in emotion regulation, is reviewed. Gaps in our knowledge that could be filled by health neuroscience research are emphasized, in an effort to catalyze future studies in this area. Understanding the neural mechanisms linking SES and health is crucial for building comprehensive models of the pathways by which social inequalities become health inequalities and may help identify novel targets for intervention to prevent health disparities. Health neuroscience research has a critical role to play in this important area of research. [ABSTRACT FROM AUTHOR]

Abstract: Auditory short‐term memory (STM) is a fundamental ability to make sense of auditory information as it unfolds over time. Whether separate STM systems exist for different types of auditory information (music and speech, in particular) is a matter of debate. The present paper reviews studies that have investigated both musical and verbal STM in healthy individuals and in participants with neurodevelopmental and neurological disorders. Overall, the results are in favor of only partly shared networks for musical and verbal STM. Evidence for a distinction in STM for the two materials stems from (1) behavioral studies in healthy participants, in particular from the comparison between nonmusicians and musicians; (2) behavioral studies in congenital amusia, where a selective pitch STM deficit is observed; and (3) studies in brain‐damaged patients with cases of double dissociation. In this review we highlight the need for future studies comparing STM for the same perceptual dimension (e.g., pitch) in different materials (e.g., music and speech), as well as for studies aiming at a more insightful characterization of shared and distinct mechanisms for speech and music in the different components of STM, namely encoding, retention, and retrieval. [ABSTRACT FROM AUTHOR]

This paper discusses meditation from the unique perspective of the nondual approach and explores the possible relevance of this approach to applications of love and compassion meditation in clinical settings. It contrasts the nondual approach with the better known gradual or goal-oriented, dualistic view of meditation. This paper also introduces one of the central ideas of the nondual approach-that love and compassion, like other positive qualities that are ordinarily considered as goals of meditation practice, can be found to be already present within oneself as innate dimensions of one's authentic being. [ABSTRACT FROM AUTHOR]

Globally, urbanization is rapidly growing cities and towns at a historically unprecedented rate, and this rapid urban growth is influencing many facets of the environment. This paper reviews the effectiveness of conservation interventions that are designed to increase urban sustainability. It presents evidence for an apparent urban-environmental paradox: while the process of urban growth converts natural habitat to other land covers and degrades natural resources and ecosystem function, the increase in human population can increase demand for natural resources and ecosystem services. The fundamental problem that many conservation interventions try to address is that most facets of the environment are common or public goods, and are hence undervalued in decision making (market failure). The paper presents a threefold classification of conservation interventions in cities: conservation in the city (protecting biodiversity), conservation by the city (reducing per capita resource and energy use), and conservation for cities (projects that maintain or enhance ecosystem services). It ends by discussing methods for spatially targeting conservation interventions of all three types and for quantifying the effectiveness of interventions retrospectively. [ABSTRACT FROM AUTHOR]

An incredibly high failure rate in the pharmaceutical industry has positioned personalized medicine with its prerequisite drug-diagnostic codevelopment, commonly known as companion diagnostics (CDx), in the frontline as an potential rescuer. This hopefulness is potentiated by the recent major advances and competitiveness in molecular diagnostics, making laboratory tests widely accessible at affordable prices. If executed correctly, biomarkers and CDx can potentially help the drug industry by enhancing the probability of success and possibly accelerating time to market; help the diagnostics industry develop tests utilizing precious, clinically annotated human samples; and, more importantly, benefit patients by supporting accurate diagnosis and selection of the most efficacious and least toxic therapies. However, this spectacular road is not yet paved, and it faces an enormous number of challenges. This paper will list these challenges and highlight some critical problems with representative examples of imminent but still overlooked preanalytical and analytical variables that can defeat the whole purpose of biomarkers and CDx and mislead drug developers and clinicians. The paper will provide some suggestions for mitigation. [ABSTRACT FROM AUTHOR]

Undernutrition among women and children contributes to almost half the global burden of child mortality in developing countries. The impact of nutrition on economic development has highlighted the need for evidence-based solutions and yielded substantial global momentum. However, it is now recognized that the impact of evidence-based interventions is limited by the lack of evidence on the best operational strategies for scaling up nutrition interventions. With the goal of encouraging greater engagement in implementation research in nutrition and generating evidence on implementation and utilization of nutrition interventions, this paper brings together a framework and a broad analysis of literature to frame and highlight the crucial importance of research on the delivery and utilization of nutrition interventions. The paper draws on the deliberations of a high-level working group, an e-consultation, a conference, and the published literature. It proposes a framework and areas of research that have been quite neglected, and yet are critical to better understanding through careful research to enable better translation of global and national political momentum for nutrition into public health impact. [ABSTRACT FROM AUTHOR]

This paper reviews some of the existing food security indicators, discussing the validity of the underlying concept and the expected reliability of measures under reasonably feasible conditions. The main objective of the paper is to raise awareness on existing trade-offs between different qualities of possible food security measurement tools that must be taken into account when such tools are proposed for practical application, especially for use within an international monitoring framework. The hope is to provide a timely, useful contribution to the process leading to the definition of a food security goal and the associated monitoring framework within the post-2015 Development Agenda. [ABSTRACT FROM AUTHOR]

In India, progress against undernutrition has been slow. Given its importance for income generation, improving diets, care practices, and maternal health, the agriculture sector is widely regarded as playing an important role in accelerating the reduction in undernutrition. This paper comprehensively maps existing evidence along agriculture-nutrition pathways in India and assesses both the quality and coverage of the existing literature. We present a conceptual framework delineating six key pathways between agriculture and nutrition. Three pathways pertain to the nutritional impacts of farm production, farm incomes, and food prices. The other three pertain to agriculture-gender linkages. After an extensive search, we found 78 research papers that provided evidence to populate these pathways. The literature suggests that Indian agriculture has a range of important influences on nutrition. Agriculture seems to influence diets even when controlling for income, and relative food prices could partly explain observed dietary changes in recent decades. The evidence on agriculture-gender linkages to nutrition is relatively weak. Sizeable knowledge gaps remain. The root causes of these gaps include an interdisciplinary disconnect between nutrition and economics/agriculture, a related problem of inadequate survey data, and limited policy-driven experimentation. Closing these gaps is essential to strengthening the agriculture sector's contribution to reducing undernutrition. [ABSTRACT FROM AUTHOR]

This paper introduces convergent innovation (CI) as a form of meta-innovation-an innovation in the way we innovate. CI integrates human and economic development outcomes, through behavioral and ecosystem transformation at scale, for sustainable prosperity and affordable universal health care within a whole-of-society paradigm. To this end, CI combines technological and social innovation (including organizational, social process, financial, and institutional), with a special focus on the most underserved populations. CI takes a modular approach that convenes around roadmaps for real world change-a portfolio of loosely coupled complementary partners from the business community, civil society, and the public sector. Roadmaps serve as collaborative platforms for focused, achievable, and time-bound projects to provide scalable, sustainable, and resilient solutions to complex challenges, with benefits both to participating partners and to society. In this paper, we first briefly review the literature on technological innovation that sets the foundations of CI and motivates its feasibility. We then describe CI, its building blocks, and enabling conditions for deployment and scaling up, illustrating its operational forms through examples of existing CI-sensitive innovation. [ABSTRACT FROM AUTHOR]

The paper outlines how the principles of convergent innovation (CI) can be applied to bring about a transformation in the pulse value chain. The paper presents three pioneering CI initiatives--two in conception and one in operation--by various actors in the pulse ecosystem, which are delivering economic and human development impact in particular segments of the pulse value chain. It goes on to propose the way forward to scale up these efforts and connect them into a roadmap so as to achieve transformation throughout society, calling into action a number of actors in the ecosystem. [ABSTRACT FROM AUTHOR]

The causes of many vexing challenges facing 21st-century society are at the nexus of systems involved in agriculture, health and wealth production, consumption, and distribution. Using food as a test bed, and on the basis of emerging roadmaps that set achievable objectives over a 1- to 3-year horizon, we introduce this special feature with convergence thinking and practice at its core. Specifically, we discuss academic papers structured around four themes: (1) evidence for a need for convergence and underlying mechanisms at the individual and societal levels; (2) strategy for mainstreaming convergence as a driver of business engagement and innovation; (3) convergence in policy and governance; (4) convergence in metrics and methods. Academic papers under each theme are accompanied by a roadmap paper reporting on the current status of concrete transformative convergence-building projects associated with that theme. We believe that the insights provided by these papers have the potential to enable all actors throughout society to singly and collectively work to build supply and demand for nutritious food, in both traditional and modern food systems, while placing the burdens of malnutrition and ill health on their core strategic agendas. [ABSTRACT FROM AUTHOR]

This paper investigates the mathematical representation of time in physics. In existing theories, time is represented by the real numbers, hence their formal properties represent properties of time: these are surveyed. The central question of the paper is whether the existing representation of time is adequate, or whether it can or should be supplemented: especially, do we need a physics incorporating some kind of 'dynamical passage' of time? The paper argues that the existing mathematical framework is resistant to such changes, and might have to be rejected by anyone seeking a physics of passage. Then it rebuts two common arguments for incorporating passage into physics, especially the claim that it is an element of experience. Finally, the paper investigates whether, as has been claimed, causal set theory provides a physics of passage. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, I describe the development of the Irie Classroom Toolbox, a school‐based violence prevention, teacher training program for use with children aged 3–6 years. In‐depth interviews were conducted with Jamaican preschool teachers, who had participated in a trial of a classroom behavior management program, at posttest (n = 35) and 5 years later (n = 20). An on‐going process evaluation was also conducted. Teachers’ preferred behavior management strategies and training methods were documented, and enablers and barriers to implementation were identified. Teachers were most likely to adopt strategies that they liked, found easy to use, and were effective. These included paying attention to positive behavior and explicitly teaching children the expected behavior. Teachers preferred active, hands‐on training strategies based on social–cognitive theories. Enablers to intervention implementation included positive teacher–facilitator relationships, choice, collaborative problem solving, teachers recognizing benefits of the intervention, group support, and provision of materials. Barriers to intervention implementation were also identified. These data were integrated with behavior change theory (i.e., the behavior change wheel and theoretical domains framework) to develop an intervention grounded in common core elements of evidence‐based programs while also utilizing teachers’ perspectives. The resulting program is a low cost, adaptable intervention that should be suitable for training preschool teachers in other low‐resource settings. [ABSTRACT FROM AUTHOR]

Abstract: We summarize the state of the field of implementation research and practice for early child development and propose recommendations. First, conclusions are drawn regarding what is generally known about the implementation of early childhood development programs, based on papers and discussions leading to a published series on the topic. Second, recommendations for short‐term activities emphasize the use of newly published guidelines for reporting data collection methods and results for implementation processes; knowledge of the guidelines and a menu of measures allows for planning ahead. Additional recommendations include careful documentation of early‐stage implementation, such as adapting a program to a different context and assessing feasibility, as well as the process of sustaining and scaling up a program. Using existing implementation information by building on and improving past programs and translating them into policy are recommended. Longer term goals are to identify implementation characteristics of effective programs and determinants of these characteristics. [ABSTRACT FROM AUTHOR]

Abstract: Research in early childhood development (ECD) has established the need for scaling‐up multisectoral interventions for nurturing care to promote ECD, for improved socioeconomic outcomes for sustainable societies. However, key elements and processes for implementation and scale‐up of such interventions are not well understood. This special series on implementation research and practice for ECD brings together evidence to inform effectiveness, quality, and scale in nurturing care programs; identifies knowledge gaps; and proposes further directions for research and practice. This paper frames the dimensions and components fundamental to the understanding of implementation processes for nurturing care interventions, factors for improving implementation of interventions, and strategies to scale by embedding interventions in delivery systems. We discuss emerging issues in implementation research for ECD, including (1) the role of context in adaptation and implementation, (2) standardized reporting of implementation research, (3) the importance of feasibility studies to inform scale‐up and capacity building, (4) fidelity and program quality improvement, and (5) intervention integration into existing systems. Effective implementation of nurturing care interventions is at the heart of achieving positive developmental outcomes for young children. It is pivotal to adapt and implement these interventions based on evidence for high impact, especially in low‐resource settings. [ABSTRACT FROM AUTHOR]

Nurse home visiting (NHV) offers a potential platform to both address the factors that limit access to services for families experiencing adversity and provide effective interventions. Currently, the ability to examine program implementation is hampered by a lack of detailed description of actual, rather than expected, program development and delivery in published studies. Home visiting implementation remains a black box in relation to quality and sustainability. However, previous literature would suggest that efforts to both report and improve program implementation are vital for NHV to have population impact and policy sustainability. In this paper, we provide a case study of the design, testing, and implementation of the right@home program, an Australian NHV program and randomized controlled trial. We address existing gaps related to implementation of NHV programs by describing the processes used to develop the program to be trialed, summarizing its effectiveness, and detailing the quality processes and implementation evaluation. The weight of our evidence suggests that NHV can be a powerful and sustainable platform for addressing inequitable outcomes, particularly when the program focuses on parent engagement and partnership, delivers evidence‐based strategies shown to improve outcomes, includes fidelity monitoring, and is adapted to and embedded within existing service delivery systems. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we analyze the need for consistent and accurate cost data on early childhood development (ECD) interventions as a basis for increasing and improving the effectiveness of current spending on ECD. We establish the key components necessary in a costing model and present a new standardized costing tool intended for use across a broad range of stakeholders and contexts. Learnings from piloting the tool in Bangladesh, Malawi, Mali, Mexico, and Mozambique are shared. Providing a standardized methodology for costing ECD is an important contribution to the field and has the potential to improve both the volume and effectiveness of ECD financing. [ABSTRACT FROM AUTHOR]

Abstract: Effectiveness trials of increasing childhood development interventions across low‐ and middle‐income countries have shown significant variability. The strength and consistency of benefits for children are dependent on program quality, and this requires paying attention to program implementation. In this paper, we summarize findings on program quality and teacher practices and perceptions for the aeioTU program, a center‐based Reggio‐inspired program in Colombia, now serving more than 13,000 children. The research found engaged, committed staff who valued the emergent approach and understood the children as requiring opportunities to express themselves, being the source for the curriculum, and having relationships with the materials around them. Although the average classroom quality was low in 2011, it increased significantly by 2014, particularly in the language and reasoning and interactions items. Indicator‐level analyses showed that higher‐order interactions and language processes were observed in a large proportion of classrooms by 2014. Teachers' self‐reports on the environment and their teaching and learning showed high levels of quality by 2013. These findings illustrate the significance of process data for program improvement, especially when a program is young. Program quality can be raised after teachers improve their skills, have experience enacting a curriculum, and after training has been strengthened in response to information, while simultaneously scaling up the program. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we describe ways to measure variables of interest when evaluating the implementation of a program to improve early childhood development (ECD). The variables apply to programs delivered to parents in group sessions and home or clinic visits, as well as in early group care for children. Measurements for four categories of variables are included: training and assessment of delivery agents and supervisors; program features such as quality of delivery, reach, and dosage; recipients’ acceptance and enactment; and stakeholders’ engagement. Quantitative and qualitative methods are described, along with when measures might be taken throughout the processes of planning, preparing, and implementing. A few standard measures are available, along with others that researchers can select and modify according to their goals. Descriptions of measures include who might collect the information, from whom, and when, along with how information might be analyzed and findings used. By converging on a set of common methods to measure implementation variables, investigators can work toward improving programs, identifying gaps that impede the scalability and sustainability of programs, and, over time, ascertain program features that lead to successful outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Meta‐analyses of interventions such as parenting, stimulation, and early childhood education have reported consistent medium‐to‐high effect sizes on early childhood development (ECD) and early learning outcomes. However, few effective interventions promoting ECD have achieved scale. In order to increase the access to effective or high‐quality services, greater focus on implementation research of interventions promoting ECD is necessary. In this paper, we describe the development of reporting guidelines for implementation research of nurturing care interventions designed to promote ECD following an expert consensus‐building process. The goal of these guidelines is to support a transparent and standard reporting of implementation evidence on nurturing care interventions designed to promote early childhood development. [ABSTRACT FROM AUTHOR]

Abstract: Immune dysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) syndrome is a rare disorder that increasingly has gained attention as a model of genetic autoimmunity. Numerous papers documenting the key clinical and molecular characteristics of IPEX have provided a detailed understanding of this devastating disease. IPEX is a primary immunodeficiency caused by mutations in the gene FOXP3, which encodes an essential transcription factor required for maintenance of thymus‐derived regulatory T (tTreg) cells. tTreg cell dysfunction is the main pathogenic event leading to multiorgan autoimmunity in IPEX. In addition to the traditional clinical presentation (i.e., severe enteropathy, type 1 diabetes, and eczema), IPEX may encompass other variable and distinct clinical manifestations. As IPEX awareness and characterization have increased, so has identification of FOXP3 mutations, with at least 70 to date. Thus, while FOXP3 is the unifying gene, IPEX is a complex and diverse clinical continuum of disorders. Despite understanding IPEX pathogenesis, new treatment options have remained elusive, although early diagnosis led to hematopoietic stem cell transplantation (HSCT) and immunosuppression treatment and improved patient outcomes. Here, we review current knowledge about IPEX syndrome and highlight findings that could lead to novel targeted treatments. [ABSTRACT FROM AUTHOR]

In this paper we review the evidence basis for prevention of folic acid-sensitive neural tube defects (NTDs) through public health interventions in women of reproductive age (WRA), the proven vehicles for delivery of folic acid, and what is needed to effectively scale these, and provide a snapshot of potential innovations that require future research.Our primary focus is on the global situation affecting large-scale food fortification (LSFF) with folic acid, in particular the fortification of wheat flour and maize meal. Our overarching conclusion is that folic acid fortification is an evidence-based intervention that reduces the prevalence of NTDs, and that LSFF with folic acid is underutilized. Thus, food fortification with folic acid should be a component of most national public health strategies, in particular where folate status is insufficient and a fortifiable food vehicle, processed by a centralized industry, is consumed regularly by WRA. The evidence shows that there is still much work needed (1) to build the enabling environment and expand programs where there is currently no legislation, (2) to improve the low quality of delivery of existing programs, and (3) to measure and sustain programs by generating new coverage data and demonstrating evidence of impact in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Abstract: Obesity is a chronic, relapsing disease that necessitates a multidisciplinary approach to management. Behavioral changes are the foundation to management, but adjunctive therapy is often warranted, including pharmacologic therapies and/or bariatric surgery. Until recently, treatment options included only short‐term therapy (≤12 weeks), and paths beyond that schedule were challenging, as knowledge of the biology of obesity was lacking. With increased recognition of obesity as a chronic, complex medical disease, newer agents have been approved as long‐term therapy, and the cornerstone of treatment is chronic behavior and lifestyle change. In the last decade, the Food and Drug Administration (FDA) has approved several new weight loss medications for the chronic management of obesity. In this review paper, we provide the latest updates on obesity pharmacotherapy. The main areas we will cover include (1) pharmacological management of obesity, (2) a review of FDA‐approved weight loss medications, (3) comanagement of obesity and its metabolic sequelae (type 2 diabetes mellitus, hypertension, and dyslipidemia), and (4) obesity‐centric prescribing for mental illness, neurological disorders, and contraceptive planning. [ABSTRACT FROM AUTHOR]

Biomarkers are biological characteristics that can be used to indicate health or disease. This paper reviews studies on biomarkers of low back pain (LBP) in human subjects. LBP is the leading cause of disability, caused by various spine-related disorders, including intervertebral disc degeneration, disc herniation, spinal stenosis, and facet arthritis. The focus of these studies is inflammatory mediators, because inflammation contributes to the pathogenesis of disc degeneration and associated pain mechanisms. Increasingly, studies suggest that the presence of inflammatory mediators can be measured systemically in the blood. These biomarkers may serve as novel tools for directing patient care. Currently, patient response to treatment is unpredictable with a significant rate of recurrence, and, while surgical treatments may provide anatomical correction and pain relief, they are invasive and costly. The review covers studies performed on populations with specific diagnoses and undefined origins of LBP. Since the natural history of LBP is progressive, the temporal nature of studies is categorized by duration of symptomology/disease. Related studies on changes in biomarkers with treatment are also reviewed. Ultimately, diagnostic biomarkers of LBP and spinal degeneration have the potential to shepherd an era of individualized spine medicine for personalized therapeutics in the treatment of LBP. [ABSTRACT FROM AUTHOR]

Musculoskeletal injuries that disrupt the structure and function of diarthrodial joints can cause permanent biomechanical alterations and lead to a more severe, chronic condition. Despite advancements that have been made to restore tissue function and delay the need for joint replacement, there are currently no disease-modifying therapies for osteoarthritis (OA). To reduce the risk of OA, innovative preventive medicine approaches have been developed over the last decade to treat the underlying pathology. Several biological approaches are promising treatment modalities for various stages of OA owing to their minimally invasive nature and actively dynamic physiological mechanisms that attenuate tissue degradation and inflammatory responses. Individualized growth factor and cytokine therapies, tissue-engineered biomaterials, and cell-based therapies have revolutionary potential for orthopedic applications; however, the paucity of standardization and categorization of biological components and their counterparts has made it difficult to determine their clinical and biological efficacy. Cell-based therapies and tissue-engineered biologics have become lucrative in sports medicine and orthopedics; nonetheless, there is a continued effort to produce a biological treatment modality tailored to target intra-articular structures that recapitulates tissue function. Advanced development of these biological treatment modalities will potentially optimize tissue healing, regeneration, and joint preservation strategies. Therefore, the purpose of this paper is to review current concepts on several biological treatment approaches for OA. [ABSTRACT FROM AUTHOR]

Staple diets that are deficient in thiamine can result in low body thiamine levels, which may be subclinical or may manifest as a thiamine-deficiency syndrome. In many communities in the developing countries of Africa, the staple diets of polished rice or processed cassava are deficient in thiamine, and thus the communities are at high risk for marginal or frank thiamine deficiency unless their diets are supplemented by other sources of thiamine, such as protein meals and vegetables. African communities with large numbers of individuals in low socioeconomic strata are more likely to subsist on a monotonous diet of rice or cassava with minimal or no protein supplementation and are therefore particularly at risk of thiamine-deficiency disorders. Indeed, there is evidence of widespread biochemical thiamine deficiency from community-based studies in Africa. The protean manifestations of thiamine deficiency disorders in the developing countries of Africa are presented in this paper. We present evidence supporting the contention that there is a diagnosis and treatment gap for thiamine-deficiency disorders in Africa. We discuss research and clinical options for bridging the putative diagnosis and treatment gap for thiamine-deficiency disorders in the developing countries of Africa. [ABSTRACT FROM AUTHOR]

Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. [ABSTRACT FROM AUTHOR]

We are at least as dream deprived as we are sleep deprived. Many of the health concerns attributed to sleep loss result from a silent epidemic of REM sleep deprivation. REM/dream loss is an unrecognized public health hazard that silently wreaks havoc with our lives, contributing to illness, depression, and an erosion of consciousness. This paper compiles data about the causes and extent of REM/dream loss associated with commonly used medications, endemic substance use disorders, rampant sleep disorders, and behavioral and lifestyle factors. It examines the consequences of REM/dream loss and concludes with recommendations for restoring healthy REM/dreaming. [ABSTRACT FROM AUTHOR]

Integrating neuropsychology with psychoanalytic thinking and experience, this paper offers a new view of the unconscious that veers away from more traditional conceptualizations. Rather, it emphasizes the ever-present influence of ongoing unconscious processes on much of our behaviors and mental states. Importantly, this new understanding is based on the functional unity of the brain/mind. [ABSTRACT FROM AUTHOR]

Rhizoma Alismatis (RA), the dried rhizome of Alisma orientale (Sam.) Juzep, is a common traditional herbal medicine named Ze Xie in Chinese. RA is an important herbal component of a number of well-known Chinese medicinal preparations. It has been used to treat various ailments, such as dysuria, edema, nephropathy, hyperlipidemia, and diabetes. A wide range of chemical compounds, mainly triterpenoids, sesquiterpenoids, and diterpenoids, have been isolated from RA; among which the protostane-type triterpenoids, termed alisols, have attracted the most attention owing to their unique chemical structures and various biological activities. The extract and active compounds of RA possess a wide spectrum of pharmacological effects (e.g., diuretic, antimetabolic disorder, hepatoprotective, immunomodulatory, antiosteoporotic, anti-inflammatory, antitumor, antibacterial, and antiviral activities). Previous toxicological evaluations indicated that the RA extracts are relatively safe and have no serious side effects within certain dose ranges. This paper reviews the up-to-date information on the ethnomedicinal application, phytochemistry, pharmacology, and toxicology of RA. This information will be useful for a better understanding of the therapeutic potential of RA. [ABSTRACT FROM AUTHOR]